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Nasr G, Ali DME, Fawzy MA, Ali FEM, Fathy M. Combined quercetin with phosphodiesterase inhibitors; sildenafil and pentoxifylline alleviated CCl 4-induced chronic hepatic fibrosis: Role of redox-sensitive pathways. Food Chem Toxicol 2025; 201:115442. [PMID: 40220882 DOI: 10.1016/j.fct.2025.115442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 04/02/2025] [Accepted: 04/09/2025] [Indexed: 04/14/2025]
Abstract
Liver fibrosis is a common pathological condition that is caused by complicated molecular and cellular processes. This study evaluated the therapeutic potential of combined quercetin (QU) with either sildenafil (Sild) or pentoxifylline (PTX) in chronic carbon tetrachloride (CCl4)-induced liver fibrosis in Wistar albino rats. Fibrosis was induced by CCl4 injections (1.5 mg/kg, i.p.) three times weekly for 10 weeks. After six weeks, rats received oral QU (50 mg/kg/day), Sild (50 mg/kg/day), or PTX (10 mg/kg twice/day) individually or in combination for the remaining four weeks. Results showed significant alterations in liver biochemical markers, histopathology, oxidative stress, inflammation, apoptosis, and hypoxic responses due to CCl4 exposure. These changes included reduced expression of Nrf-2, HO-1, and cytoglobin, alongside increased levels of NF-κB, cleaved caspase-3, TNF-α, IL-1β, and HIF-1. Notably, QU, Sild, and PTX, individually or in combination, improved these parameters. The combination of QU with Sild or PTX proved more effective than single treatments, modulating anti-oxidant (Nrf2/HO-1/cytoglobin), anti-inflammatory (NF-κB/TNF-α), and hypoxic signaling pathways (HIF-1α). In conclusion, QU combined with phosphodiesterase inhibitors shows promise as a therapy for liver fibrosis, offering enhanced protection through anti-oxidants and anti-inflammatory mechanisms.
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Affiliation(s)
- Gehad Nasr
- Department of Biochemistry, Faculty of Pharmacy, Sohag University, Sohag, 82524, Egypt
| | | | - Michael A Fawzy
- Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt
| | - Fares E M Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt; Michael Sayegh, Faculty of Pharmacy, Aqaba University of Technology, Aqaba, 77110, Jordan.
| | - Moustafa Fathy
- Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; Biochemistry Department, Faculty of Pharmacy, Minia National University, New Minia, Egypt
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Zaiou M, Joubert O. Racial and Ethnic Disparities in NAFLD: Harnessing Epigenetic and Gut Microbiota Pathways for Targeted Therapeutic Approaches. Biomolecules 2025; 15:669. [PMID: 40427561 PMCID: PMC12109303 DOI: 10.3390/biom15050669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 04/28/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern, impacting approximately 32.4% of the worldwide population. As a disease linked to metabolic dysfunction, NAFLD continues to rise alongside global increases in obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. There is considerable evidence indicating that NAFLD disproportionately affects racial, ethnic, and minority groups, although the exact reasons for these disparities remain elusive. Contributing factors to this disease may include socioeconomic status, cultural influences, stress, genetic factors, and lifestyle choices. Emerging evidence suggests that these causal factors could influence epigenetic mechanisms, particularly DNA methylation and histone modifications, as well as the composition and diversity of gut microbiota. Nevertheless, there is a scarcity of research that comprehensively examines the interplay between epigenetic changes and gut microbiome variations in relation to NAFLD disparities across different racial and ethnic populations globally. This paper intends to (i) explore the connections between NAFLD, ethnic disparities, gut microbiota composition, and epigenetic alterations, while reviewing pertinent studies that illustrate how these factors contribute to health inequities among various ethnic groups impacted by this disease; (ii) explore potential therapeutic targets and biomarkers to advance the management of NAFLD; and (iii) provide insights to enhance our understanding of the mechanisms associated with this disease, thereby promoting further research in this field. Advancements in this area are anticipated to enhance our understanding of disease susceptibilities in at-risk groups and to provide new therapeutic options for NAFLD and its associated complications.
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Affiliation(s)
- Mohamed Zaiou
- Université de Lorraine, CNRS, IJL, F-54000 Nancy, France;
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Wen C, Tang J, Wu M, Liu H, Lin X, Fan M, Liu G, Zhang J, Liang L, Liu X, Li Y, Duan Y, Xu X. Preparation, characterization, and stability of pectin-whey protein isolate-based nanoparticles with mitochondrial targeting ability. Int J Biol Macromol 2025; 301:140383. [PMID: 39880250 DOI: 10.1016/j.ijbiomac.2025.140383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/13/2025] [Accepted: 01/25/2025] [Indexed: 01/31/2025]
Abstract
Quercetin (Que) is a polyhydroxy flavonoid with strong inhibitory activity against cancer cells. However, the poor water solubility and low bioavailability of Que. limit its application in the functional food industry. In the present study, the nanoparticle loaded with Que. was prepared with whey isolate protein (WPI) stabilized by triphenylphosphonium bromide (TPP) and pectin (P) as wall materials. The formation mechanism, release of Que., and antitumor activity of nanoparticles were investigated. The results showed that the optimal ratio of WPI: TPP: Que.: P in the preparation of nanoparticles (WPI-TPP-Que-P) was 50:8:1:20 (w/w/w/w). The encapsulation rate of Que. in the WPI-TPP-Que-P was 82.64 % with a particle size of 261.7 nm and a zeta potential of -42.1 mV. Compared with WPI-TPP-Que, the retention rate of WPI-TPP-Que-P increased by 4.03 % after in vitro digestion. The release kinetic result indicated that WPI-TPP-Que-P release was dominated by non-Fickian diffusion. In addition, WPI-TPP-Que-P was taken in and achieved intracellular targeting to mitochondria and promoted apoptosis (apoptosis rate: 83.6 %) by decreasing mitochondrial membrane potential and IL-10 content and improving the content of TNF-α in HepG-2 cells. This study highlights the promising application of P-modified mitochondria-targeted nanocarriers for enhanced Que. delivery.
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Affiliation(s)
- Chaoting Wen
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China
| | - Jialuo Tang
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China
| | - Maowei Wu
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China
| | - Huimin Liu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
| | - Xinying Lin
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China
| | - Meidi Fan
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China
| | - Guoyan Liu
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China
| | - Jixian Zhang
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China.
| | - Li Liang
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China
| | - Xiaofang Liu
- School of Tourism and Cuisine, Yangzhou University, Yangzhou 225127, China
| | - Youdong Li
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China
| | - Yuqing Duan
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Xin Xu
- College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China.
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Zhra M, Elahi MA, Tariq A, Abu-Zaid A, Yaqinuddin A. Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma. Cells 2025; 14:466. [PMID: 40136715 PMCID: PMC11941559 DOI: 10.3390/cells14060466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/12/2025] [Accepted: 03/13/2025] [Indexed: 03/27/2025] Open
Abstract
Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The gut microbiome interacts with the liver via a bidirectional relationship with the gut-liver axis. Microbial metabolites, sirtuins, and immune responses are pivotal in different metabolic diseases. This extensive review explores the complex and multifaceted interrelationship between sirtuins and gut microbiota, highlighting their importance in health and disease, particularly metabolic dysfunction and hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as a group of NAD+-dependent deacetylases, serve as crucial modulators of a wide spectrum of cellular functions, including metabolic pathways, the inflammatory response, and the process of senescence. Their subcellular localization and diverse functions link them to various health conditions, including NAFLD and cancer. Concurrently, the gut microbiota, comprising diverse microorganisms, significantly influences host metabolism and immune responses. Recent findings indicate that sirtuins modulate gut microbiota composition and function, while the microbiota can affect sirtuin activity. This bidirectional relationship is particularly relevant in metabolic disorders, where dysbiosis contributes to disease progression. The review highlights recent findings on the roles of specific sirtuins in maintaining gut health and their implications in metabolic dysfunction and HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked to metabolic dysregulation and liver pathology.
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Affiliation(s)
- Mahmoud Zhra
- Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;
| | - Muhammad Affan Elahi
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (M.A.E.); (A.A.-Z.)
| | - Aamira Tariq
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Islamabad 45550, Pakistan
| | - Ahmed Abu-Zaid
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (M.A.E.); (A.A.-Z.)
| | - Ahmed Yaqinuddin
- Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;
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Babar M, Aslam B, Faisal MN, Malik A, Akhtar S, Fatima S, Majeed W, Umer A, Farooq MA. Phytochemical characterization and anti-arthritic potential of green-synthesized CuO nanoparticles derived from the Bistorta amplexicaulis root extract. Front Pharmacol 2024; 15:1474592. [PMID: 39741627 PMCID: PMC11685013 DOI: 10.3389/fphar.2024.1474592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 11/22/2024] [Indexed: 01/03/2025] Open
Abstract
Introduction Rheumatoid arthritis is an autoimmune disease that mainly causes joint damage. The patient experiences loss of appetite, pain, fever, and fatigue. The present study was designed to phytochemically characterize and evaluate the anti-arthritic activity of green-synthesized copper oxide (CuO) nanoparticles (NPs) using the hydroalcoholic extract of Bistorta amplexicaulis roots in an adjuvant-induced arthritic rat model. Material and Methods For this purpose, crude powdered plant material was used for proximate analysis, and the plant extract was assessed for qualitative phytochemical analysis, mineral contents, and flavonoid and phenolic contents, as well as quantitative phytochemical analysis through reversed-phase high-performance liquid chromatography (RP-HPLC) and Fourier-transform infrared (FTIR) spectroscopy. The in vitro antioxidant activity of both extracts was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The biosynthesized CuO NPs from the Bistorta amplexicaulis extract showed anti-arthritic activity due to the presence of flavonoids and phenols, which showed a pain reliever effect by blocking the cyclo-oxygenase enzyme and has immune suppressant activity, thus securing the joint from destruction. The nanoparticles were characterized by zeta size, zeta potential, scanning electron microscopy (SEM), and FTIR spectroscopy. Forty-eight albino rats were divided randomly into six treatment groups. Results and Disscussion The zeta size and zeta potential of the nanoparticles were 186.8 nm and -9.23 mV, respectively. Joint stiffness, spleen weight, thymus weight, and paw thickness showed a significant decrease after treatment with NPs. The hematological parameters such as red blood cells (RBCs) and hemoglobin showed a significant increase, while platelets and white blood cells (WBCs) showed a significant decrease in NP-treated groups. C-reactive protein (CRP), rheumatoid factor (RF), liver and kidney function biomarkers, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels showed a significant decrease at both low and high doses of green-synthesized CuO nanoparticles from the Bistorta amplexicaulis root extract. The final data were analyzed by one way and two-way analysis of variance (ANOVA) and Tukey's multi-comparison test. Conclusion So, from this study, it was concluded that both the plant root extract and green-synthesized CuO nanoparticles have anti-arthritic potential, but CuO NPs showed remarkable results.
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Affiliation(s)
- Mahrukh Babar
- Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan
| | - Bilal Aslam
- Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan
| | - Muhammad Naeem Faisal
- Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan
| | - Abdul Malik
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Suhail Akhtar
- Department of Biochemistry, A.T. Still University of Health Sciences, Kirksville, MO, United States
| | - Sabiha Fatima
- Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Wafa Majeed
- Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan
| | - Asher Umer
- Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan
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Katsaros I, Sotiropoulou M, Vailas M, Kapetanakis EI, Valsami G, Tsaroucha A, Schizas D. Quercetin's Potential in MASLD: Investigating the Role of Autophagy and Key Molecular Pathways in Liver Steatosis and Inflammation. Nutrients 2024; 16:3789. [PMID: 39599578 PMCID: PMC11597035 DOI: 10.3390/nu16223789] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 10/27/2024] [Accepted: 11/01/2024] [Indexed: 11/29/2024] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MASLD) is a widespread liver disorder characterized by excessive fat accumulation in the liver, commonly associated with metabolic syndrome components such as obesity, diabetes, and dyslipidemia. With a global prevalence of up to 30%, MASLD is projected to affect over 100 million people in the U.S. and 20 million in Europe by 2030. The disease ranges from Steatotic Lived Disease (SLD) to more severe forms like metabolic dysfunction-associated steatohepatitis (MASH), which can progress to cirrhosis and hepatocellular carcinoma. Autophagy, a cellular process crucial for lipid metabolism and homeostasis, is often impaired in MASLD, leading to increased hepatic lipid accumulation and inflammation. Key autophagy-related proteins, such as Beclin1, LC3A, SQSTM1 (p62), CD36, and Perilipin 3, play significant roles in regulating this process. Disruption in these proteins contributes to the pathogenesis of MASLD. Quercetin, a natural polyphenolic flavonoid with antioxidant and anti-inflammatory properties, has promising results in mitigating MASLD. It may reduce hepatic lipid accumulation, improve mitochondrial function, and enhance autophagy. However, further research is needed to elucidate its mechanisms and validate its therapeutic potential in clinical settings. This underscores the need for continued investigation into autophagy and novel treatments for MASLD.
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Affiliation(s)
- Ioannis Katsaros
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 17 AgiouThoma Str., Athens 11527, Greece; (M.S.); (M.V.); (D.S.)
| | - Maria Sotiropoulou
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 17 AgiouThoma Str., Athens 11527, Greece; (M.S.); (M.V.); (D.S.)
| | - Michail Vailas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 17 AgiouThoma Str., Athens 11527, Greece; (M.S.); (M.V.); (D.S.)
| | - Emmanouil Ioannis Kapetanakis
- Department of Thoracic Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens12462, Greece;
| | - Georgia Valsami
- Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens 15774, Greece;
| | - Alexandra Tsaroucha
- Laboratory of Experimental Surgery, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis 68100, Greece;
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 17 AgiouThoma Str., Athens 11527, Greece; (M.S.); (M.V.); (D.S.)
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Bonfiglio C, Tatoli R, Donghia R, Guido D, Giannelli G. Exploratory Role of Flavonoids on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a South Italian Cohort. Antioxidants (Basel) 2024; 13:1286. [PMID: 39594428 PMCID: PMC11591465 DOI: 10.3390/antiox13111286] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/10/2024] [Accepted: 10/21/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most recent definition for steatotic liver disease associated with metabolic syndrome. The results of recent metabolic and observational studies suggest a potential beneficial effect of food-derived flavonoids in some chronic diseases, including MASLD. The study aims to evaluate the protective role of diet flavonoids in subjects with and without MASLD belonging to a cohort living in the South of Italy. METHODS The study cohort comprised 1297 participants assessed in the NUTRIHEP cohort (2015-2018), divided into two groups, based on presence or absence of MASLD. RESULTS The results indicated statistically significant flavonoid consumption, showing a protective role against MASLD, at an optimal concentration of 165 mg/day, with an OR value of 0.63, (p = 0.001, 95% C.I.: 0.47; 0.83 t). The OR remained almost unchanged when the intake increased from 165 mg per day to 185 mg per day. CONCLUSIONS In conclusion, our study results show a protective role of flavonoids against MASLD. Consuming only 165 mg of flavonoids daily can activate this protective function, reducing the risk of MASLD.
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Affiliation(s)
- Caterina Bonfiglio
- Unit of Data Science, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (R.D.); (D.G.)
| | - Rossella Tatoli
- Unit of Data Science, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (R.D.); (D.G.)
| | - Rossella Donghia
- Unit of Data Science, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (R.D.); (D.G.)
| | - Davide Guido
- Unit of Data Science, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (R.D.); (D.G.)
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy;
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Wang S, Chen B, Du R, Zhong M, Zhang C, Jin X, Cui X, Zhou Y, Kang Q, Xu H, Li Y, Wu Q, Tong G, Luo L. An herbal formulation "Shugan Xiaozhi decoction" ameliorates methionine/choline deficiency-induced nonalcoholic steatohepatitis through regulating inflammation and apoptosis-related pathways. JOURNAL OF ETHNOPHARMACOLOGY 2024; 329:118127. [PMID: 38583728 DOI: 10.1016/j.jep.2024.118127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 03/26/2024] [Accepted: 03/28/2024] [Indexed: 04/09/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Shugan Xiaozhi (SGXZ) decoction is a traditional Chinese medicine used for treating nonalcoholic steatohepatitis (NASH). It has been used clinically for over 20 years and proved to be effective; however, the molecular mechanism underlying the effects of SGXZ decoction remains unclear. AIM OF THE STUDY We analyzed the chemical components, core targets, and molecular mechanisms of SGXZ decoction to improve NASH through network pharmacology and in vivo experiments. MATERIALS AND METHODS The chemical components, core targets, and related signaling pathways of SGXZ decoction intervention in NASH were predicted using network pharmacology. Molecular docking was performed to verify chemical components and their core targets. The results were validated in the NASH model treated with SGXZ decoction. Mouse liver function was assessed by measuring ALT and AST levels. TC and TG levels were determined to evaluate lipid metabolism, and lipid deposition was assessed via oil red O staining. Mouse liver damage was determined via microscopy following hematoxylin and eosin staining. Liver fibrosis was assessed via Masson staining. Western blot (WB) and immunohistochemical (IHC) analyses were performed to detect inflammation and the expression of apoptosis-related proteins, including IL-1β, IL-6, IL-18, TNF-α, MCP1, p53, FAS, Caspase-8, Caspase-3, Caspase-9, Bax, Bid, Cytochrome c, Bcl-2, and Bcl-XL. In addition, WB and IHC were used to assess protein expression associated with the TLR4/MyD88/NF-κB pathway. RESULTS Quercetin, luteolin, kaempferol, naringenin, and nobiletin in SGXZ decoction were effective chemical components in improving NASH, and TNF-α, IL-6, and IL-1β were the major core targets. Molecular docking indicated that these chemical components and major core targets might interact. KEGG pathway analysis showed that the pathways affected by SGXZ decoction, primarily including apoptosis and TLR4/NF-κB signaling pathways, interfere with NASH. In vivo experiments indicated that SGXZ decoction considerably ameliorated liver damage, fibrosis, and lipid metabolism disorder in MCD-induced NASH mouse models. In addition, WB and IHC verified the underlying molecular mechanisms of SGXZ decoction as predicted via network pharmacology. SGXZ decoction inhibited the activation of apoptosis-related pathways in MCD-induced NASH mice. Moreover, SGXZ decoction suppressed the activation of TLR4/MyD88/NF-κB pathway in MCD-induced NASH mice. CONCLUSION SGXZ decoction can treat NASH through multiple targets and pathways. These findings provide new insights into the effective treatment of NASH using SGXZ decoction.
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Affiliation(s)
- Shuai Wang
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, 999078, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Bohao Chen
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Ruili Du
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Mei Zhong
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Chunmei Zhang
- School of Basic Medical Science of Luoyang Polytechnic, No. 6 Keji Avenue, Yibin District, Henan, 471099, China
| | - Xiaoming Jin
- Department of Nephrology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Xiang Cui
- Ankang Traditional Chinese Medicine Hospital, Ankang, 725000, Shaanxi, China
| | - Yuhang Zhou
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Qinyang Kang
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Hang Xu
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Yuting Li
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China
| | - Qibiao Wu
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, 999078, China.
| | - Guangdong Tong
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, 999078, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China.
| | - Lidan Luo
- Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China; Shenzhen Key Laboratory of Liver Diseases of Traditional Chinese Medicine, No.15, Yingchun Road, Luohu District, Guangdong, 518033, China.
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Shao G, Liu Y, Lu L, Wang L, Ji G, Xu H. Therapeutic potential of traditional Chinese medicine in the prevention and treatment of digestive inflammatory cancer transformation: Portulaca oleracea L. as a promising drug. JOURNAL OF ETHNOPHARMACOLOGY 2024; 327:117999. [PMID: 38447616 DOI: 10.1016/j.jep.2024.117999] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/19/2024] [Accepted: 02/28/2024] [Indexed: 03/08/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese medicine (TCM) has been used for centuries to treat various types of inflammation and tumors of the digestive system. Portulaca oleracea L. (POL), has been used in TCM for thousands of years. The chemical composition of POL is variable and includes flavonoids, alkaloids, terpenoids and organic acids and other classes of natural compounds. Many of these compounds exhibit powerful anti-inflammatory and anti-cancer-transforming effects in the digestive system. AIM OF STUDY In this review, we focus on the potential therapeutic role of POL in NASH, gastritis and colitis and their associated cancers, with a focus on the pharmacological properties and potential mechanisms of action of the main natural active compounds in POL. METHODS The information and data on Portulaca oleracea L. and its main active ingredients were collated from various resources like ethnobotanical textbooks and literature databases such as CNKI, VIP (Chinese literature), PubMed, Science Direct, Elsevier and Google Scholar (English literatures), Wiley, Springer, Tailor and Francis, Scopus, Inflibnet. RESULTS Kaempferol, luteolin, myricetin, quercetin, genistein, EPA, DHA, and melatonin were found to improve NASH and NASH-HCC, while kaempferol, apigenin, luteolin, and quercetin played a therapeutic role in gastritis and gastric cancer. Apigenin, luteolin, myricetin, quercetin, genistein, lupeol, vitamin C and melatonin were found to have therapeutic effects in the treatment of colitis and its associated cancers. The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. CONCLUSION The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. However, clinical data describing the mode of action of the naturally active compounds of POL are still lacking. In addition, pharmacokinetic data for POL compounds, such as changes in drug dose and absorption rates, cannot be extrapolated from animal models and need to be measured in patients in clinical trials. On the one hand, a systematic meta-analysis of the existing publications on TCM containing POL still needs to be carried out. On the other hand, studies on the hepatic and renal toxicity of POL are also needed. Additionally, well-designed preclinical and clinical studies to validate the therapeutic effects of TCM need to be performed, thus hopefully providing a basis for the validation of the clinical benefits of POL.
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Affiliation(s)
- Gaoxuan Shao
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China
| | - Ying Liu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China
| | - Lu Lu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China
| | - Lei Wang
- Department of Hepatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China.
| | - Hanchen Xu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China.
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Tian C, Huang R, Xiang M. SIRT1: Harnessing multiple pathways to hinder NAFLD. Pharmacol Res 2024; 203:107155. [PMID: 38527697 DOI: 10.1016/j.phrs.2024.107155] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 03/04/2024] [Accepted: 03/21/2024] [Indexed: 03/27/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. It is the primary cause of chronic liver disorders, with a high prevalence but no approved treatment. Therefore, it is indispensable to find a trustworthy therapy for NAFLD. Recently, mounting evidence illustrates that Sirtuin 1 (SIRT1) is strongly associated with NAFLD. SIRT1 activation or overexpression attenuate NAFLD, while SIRT1 deficiency aggravates NAFLD. Besides, an array of therapeutic agents, including natural compounds, synthetic compounds, traditional Chinese medicine formula, and stem cell transplantation, alleviates NALFD via SIRT1 activation or upregulation. Mechanically, SIRT1 alleviates NAFLD by reestablishing autophagy, enhancing mitochondrial function, suppressing oxidative stress, and coordinating lipid metabolism, as well as reducing hepatocyte apoptosis and inflammation. In this review, we introduced the structure and function of SIRT1 briefly, and summarized the effect of SIRT1 on NAFLD and its mechanism, along with the application of SIRT1 agonists in treating NAFLD.
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Affiliation(s)
- Cheng Tian
- Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Rongrong Huang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ming Xiang
- Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Meng D, Zhang F, Yu W, Zhang X, Yin G, Liang P, Feng Y, Chen S, Liu H. Biological Role and Related Natural Products of SIRT1 in Nonalcoholic Fatty Liver. Diabetes Metab Syndr Obes 2023; 16:4043-4064. [PMID: 38089432 PMCID: PMC10715014 DOI: 10.2147/dmso.s437865] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 11/26/2023] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease(NAFLD) is an umbrella term for a range of diseases ranging from hepatic fat accumulation and steatosis to non-alcoholic steatohepatitis (NASH) in the absence of excessive alcohol consumption and other definite liver damage factors. The incidence of NAFLD has increased significantly in recent years and will continue to grow in the coming decades. NAFLD has become a huge health problem and economic burden. SIRT1 is a member of Sirtuins, a group of highly conserved histone deacetylases regulated by NAD+, and plays a vital role in regulating cholesterol and lipid metabolism, improving oxidative stress, inflammation, and insulin resistance through deacetylating some downstream transcription factors and thus improving NAFLD. Although there are no currently approved drugs for treating NAFLD and some unresolved limitations in developing SIRT1 activators, SIRT1 holds promise as a proper therapeutic target for NAFLD and other metabolic diseases. In recent years, natural products have played an increasingly important role in drug development due to their safety and efficacy. It has been discovered that some natural products may be able to prevent and treat NAFLD by targeting SIRT1 and its related pathways. This paper reviews the mechanism of SIRT1 in the improvement of NALFD and the natural products that regulate NAFLD through SIRT1 and its associated pathways, and discusses the potential of SIRT1 as a therapeutic target for treating NAFLD and the effectiveness of these related natural products as clinical drugs or dietary supplements. These works may provide some new ideas and directions for finding new therapeutic targets for NAFLD and the development of anti-NAFLD drugs with good pharmacodynamic properties.
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Affiliation(s)
- Decheng Meng
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China
| | - Fengxia Zhang
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China
| | - Wenfei Yu
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China
| | - Xin Zhang
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China
| | - Guoliang Yin
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China
| | - Pengpeng Liang
- Shenzhen Hospital, Shanghai University of Traditional Chinese Medicine, Shenzhen, 518001, People’s Republic of China
| | - Yanan Feng
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China
| | - Suwen Chen
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China
| | - Hongshuai Liu
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China
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Zhu J, Cheng X, Naumovski N, Hu L, Wang K. Epigenetic regulation by quercetin: a comprehensive review focused on its biological mechanisms. Crit Rev Food Sci Nutr 2023; 65:627-646. [PMID: 38062765 DOI: 10.1080/10408398.2023.2278760] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
Abstract
Epigenetics regulates gene expression and play significant roles across diverse disease states. Epigenetics mechanisms, including DNA methylation, histone modifications, microRNAs/lncRNA, and N6-methyladenosine (m6A) RNA methylation, elicit heritable but reversible modifications in gene expression without modifying the DNA sequence. Recent research suggests that certain natural phytochemicals with chemopreventive properties have the potential to function as epigenetic regulators. Quercetin, a derivative of natural flavonoid glycosides and a constituent of the human diet, is linked to a variety of health benefits including anti-inflammatory, anticancer activity, antiapoptotic, antihypertensive, and neuroprotective effects. Recent findings suggest that quercetin possesses the ability to modulate canonical biochemical signaling pathways and exert an impact on epigenetic networks. This review aims to synthesize the most recent research findings that elucidate the potential biological effects of quercetin and its influence on in vitro and in vivo models via epigenetic mechanisms. In light of our findings, it is evident that quercetin possesses the potential to function as an exemplary instance of naturally derived phytochemicals, which can be effectively employed as a pivotal constituent in functional foods and dietary supplements aimed at the amelioration of various ailments. More specifically, its mechanism of action involves the alteration of diverse epigenetic targets.
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Affiliation(s)
- Jinfeng Zhu
- School for Radiological and interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions. Soochow University, Suzhou, China
- Department of Experimental Medicine, TOR, University of Rome Tor Vergata, Roma, Italy
| | - Xiaju Cheng
- School for Radiological and interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions. Soochow University, Suzhou, China
| | - Nenad Naumovski
- Discipline of Nutrition and Dietetics, Faculty of Health, University of Canberra, Bruce, Canberra, ACT, Australia
- Functional Foods and Nutrition Research (FFNR) Laboratory, University of Canberra, Ngunnawal Country, Canberra, ACT, Australia
- University of Canberra Research Institute for Sport and Exercise (UCRISE), University of Canberra, Canberra, ACT, Australia
- Department of Nutrition-Dietetics, Harokopio University, Athens, Greece
| | - Lin Hu
- School for Radiological and interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions. Soochow University, Suzhou, China
| | - Kai Wang
- State Key Laboratory of Resource Insects, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing, China
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13
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Arabi SM, Shahraki Jazinaki M, Chambari M, Bahrami LS, Maleki M, Sukhorukov VN, Sahebkar A. The effects of Quercetin supplementation on cardiometabolic outcomes: An umbrella review of meta-analyses of randomized controlled trials. Phytother Res 2023; 37:5080-5091. [PMID: 37654199 DOI: 10.1002/ptr.7971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 07/05/2023] [Accepted: 07/16/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND Quercetin is a bioactive flavonoid, but the effect of it on cardiometabolic factors has remained uncertain and previous findings from meta-analyses have been controversial. OBJECTIVE To provide an overview of the effects of Quercetin on cardiometabolic factors based on meta-analyses of randomized controlled trials (RCTs). METHOD MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched to identify eligible publications. As part of the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. A GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to rate the certainty of evidence. RESULTS Five meta-analyses including 18 eligible RCTs plus 5 RCTs that were not included in previous meta-analyses were found. The results indicated Quercetin does not affect diastolic blood pressure (DBP), lipid profile, inflammation, anthropometric indices, fasting plasma glucose (FBG), and homeostatic model assessment for insulin resistance (HOMA-IR). However, Quercetin supplementation could significantly reduce systolic blood pressure (SBP) (weighted mean difference (WMD): -1.9, 95% CI = -3.2 to -0.6, I2 = 88.3%) and insulin level (WMD: -1.07, 95% CI = -1.9 to -0.1, I2 = 75.0%). The certainty of evidence ranged from very low to moderate. CONCLUSION Quercetin supplementation has reducing effects on SBP and insulin levels but not other cardiometabolic parameters. More high-quality trials with longer follow-up durations may be required to obtain a more robust conclusion.
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Affiliation(s)
- Seyyed Mostafa Arabi
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mahla Chambari
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Leila Sadat Bahrami
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Maleki
- Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | | | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Cao P, Wang Y, Zhang C, Sullivan MA, Chen W, Jing X, Yu H, Li F, Wang Q, Zhou Z, Wang Q, Tian W, Qiu Z, Luo L. Quercetin ameliorates nonalcoholic fatty liver disease (NAFLD) via the promotion of AMPK-mediated hepatic mitophagy. J Nutr Biochem 2023; 120:109414. [PMID: 37423322 DOI: 10.1016/j.jnutbio.2023.109414] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 06/12/2023] [Accepted: 07/05/2023] [Indexed: 07/11/2023]
Abstract
The global incidence of nonalcoholic fatty liver disease (NAFLD) has been surging in recent years, however, no drug is currently approved to treat this disease. Quercetin, a natural flavonoid abundant in plants and fruits, has been reported to alleviate NAFLD, however, the exact molecular mechanism remains unclear. This study aims to further elucidate its potential mechanism of action. The beneficial effects and the underlying mechanism of quercetin in alleviating NAFLD were explored both in vitro and in vivo, by employing chemical inhibitors of autophagosomes (3-methyladenine, 3-MA), autolysosomes (chloroquine, CQ), AMPK (Compound C, CC) and SIRT1 (selisistat, EX-527). The levels of intracellular lipids, reactive oxygen species, mitochondria function, autophagy, and mitophagy were assessed by fluorescent labeling and examined using flow cytometry or confocal microscopy. Key protein expressions of autophagy, mitophagy, and inflammation were also determined. In vivo, quercetin was shown to dose-dependently effectively alleviate NAFLD, but intraperitoneal injection of 3-MA could block the beneficial effects of quercetin on body weight, liver weight, serum ALT/AST, hepatic ROS and inflammation. In vitro, quercetin could reduce intracellular lipids (Nile Red staining) and ROS/DHE accumulation, which could be also blocked by 3-MA or CQ. Furthermore, we found that CC could abrogate the protective effects of quercetin on lipid and ROS accumulation in vitro. Also, CC abolished the proautophagic and anti-inflammatory effects of quercetin, as shown by western blot determination and Lyso-Tracker labeling. Importantly, mitophagy, a specific form of mitochondria-targeted autophagy, was enhanced by quercetin, as demonstrated by PINK1/Parkin protein variation and immunofluorescence colocalization of autophagosomes and mitochondria, which could also be blocked by the intervention of CC. This study demonstrates that quercetin prevents NAFLD through AMPK-mediated mitophagy and suggests that promoting mitophagy via an upregulation of AMPK may be a promising therapeutic strategy against NAFLD.
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Affiliation(s)
- Peng Cao
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Yi Wang
- Department of Critical Care Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, China
| | - Cong Zhang
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Mitchell A Sullivan
- Translational Research Institute, Glycation and Diabetes, Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - Wen Chen
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Jing
- The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong, China
| | - Huifan Yu
- Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, China
| | - Fei Li
- Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, China
| | - Qu Wang
- The First Clinical College, Guangdong Medical University, Zhanjiang, China
| | - Zhongshi Zhou
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Qi Wang
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Wen Tian
- The First Clinical College, Guangdong Medical University, Zhanjiang, China
| | - Zhenpeng Qiu
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
| | - Lianxiang Luo
- The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong, China.
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15
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Cogorno L, Formisano E, Vignati A, Prigione A, Tramacere A, Borgarelli C, Sukkar SG, Pisciotta L. Non-alcoholic fatty liver disease: Dietary and nutraceutical approaches. LIVER RESEARCH 2023; 7:216-227. [PMID: 39958388 PMCID: PMC11791914 DOI: 10.1016/j.livres.2023.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 07/20/2023] [Accepted: 08/24/2023] [Indexed: 02/18/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD), defined as the presence of fat accumulation in imaging or histology in more than 5% of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation, is one of the major causes of chronic liver disease worldwide. Metabolic syndrome is associated with an increased risk of progression from NAFLD to non-alcoholic steatohepatitis (NASH), fibrosis, and forthcoming liver failure. Also, genetic predisposition contributes to the risk of NAFLD development. This review explores the role of diets and nutraceuticals in delaying the development and the evolution of NAFLD to chronic liver disease. The Mediterranean diet, high-protein diet, low-carbohydrate/high-fat diet, high-carbohydrate/low-fat diet, and intermittent fasting are the dietary approaches investigated given the presence of relevant literature data. Moreover, this review focused on nutraceuticals with proven efficacy in ameliorating NAFLD and grouped them into four different categories: plant-based nutraceuticals (Ascophyllum nodosum and Fucus vesiculosus, Silymarin, Berberine, Curcumin, Resveratrol, Nigella sativa, Quercetin), vitamin-like substances (vitamin E, vitamin D, vitamin C, coenzyme Q10, inositol), fatty acids (omega-3), and microbiota-management tools (probiotics).
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Affiliation(s)
- Ludovica Cogorno
- Department of Experimental Medicine-Medical Pathophysiology, Food Science and Endocrinology Section, Sapienza University of Rome, Rome, Italy
| | - Elena Formisano
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
| | - Andrea Vignati
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Amalia Prigione
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | | | | | - Samir Giuseppe Sukkar
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
| | - Livia Pisciotta
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
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Choudhary R, Singh A, Upadhyay A, Singh R, Thangalakshmi S, Dar AH, Bajpai VK, Shukla S. Exotic god fruit, persimmon (
Diospyros kaki
): Pharmacological importance and human health aspects. EFOOD 2023. [DOI: 10.1002/efd2.52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Rita Choudhary
- TERI‐Deakin Nanobiotechnology Centre, Division of Sustainable Agriculture The Energy and Resources Institute, Gwal Pahari Haryana Gurugram India
| | - Anurag Singh
- Department of Food Science and Technology National Institute of Food Technology Entrepreneurship and Management, Kundli Sonipat Haryana India
| | - Ashutosh Upadhyay
- Department of Food Science and Technology National Institute of Food Technology Entrepreneurship and Management, Kundli Sonipat Haryana India
| | - Rakhi Singh
- Department of Food Science and Technology National Institute of Food Technology Entrepreneurship and Management, Kundli Sonipat Haryana India
| | - S. Thangalakshmi
- Department of Food Engineering National Institute of Food Technology Entrepreneurship and Management, Kundli Sonipat Haryana India
| | - Aamir H. Dar
- Department of Food Technology Islamic University of Sciences and Technology Awantipora Kashmir India
| | - Vivek K. Bajpai
- Department of Energy and Materials Engineering Dongguk University Seoul Republic of Korea
| | - Shruti Shukla
- TERI‐Deakin Nanobiotechnology Centre, Division of Sustainable Agriculture The Energy and Resources Institute, Gwal Pahari Haryana Gurugram India
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Quercetin: A Functional Food-Flavonoid Incredibly Attenuates Emerging and Re-Emerging Viral Infections through Immunomodulatory Actions. Molecules 2023; 28:molecules28030938. [PMID: 36770606 PMCID: PMC9920550 DOI: 10.3390/molecules28030938] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/05/2023] [Accepted: 01/10/2023] [Indexed: 01/20/2023] Open
Abstract
Many of the medicinally active molecules in the flavonoid class of phytochemicals are being researched for their potential antiviral activity against various DNA and RNA viruses. Quercetin is a flavonoid that can be found in a variety of foods, including fruits and vegetables. It has been reported to be effective against a variety of viruses. This review, therefore, deciphered the mechanistic of how Quercetin works against some of the deadliest viruses, such as influenza A, Hepatitis C, Dengue type 2 and Ebola virus, which cause frequent outbreaks worldwide and result in significant morbidity and mortality in humans through epidemics or pandemics. All those have an alarming impact on both human health and the global and national economies. The review extended computing the Quercetin-contained natural recourse and its modes of action in different experimental approaches leading to antiviral actions. The gap in effective treatment emphasizes the necessity of a search for new effective antiviral compounds. Quercetin shows potential antiviral activity and inhibits it by targeting viral infections at multiple stages. The suppression of viral neuraminidase, proteases and DNA/RNA polymerases and the alteration of many viral proteins as well as their immunomodulation are the main molecular mechanisms of Quercetin's antiviral activities. Nonetheless, the huge potential of Quercetin and its extensive use is inadequately approached as a therapeutic for emerging and re-emerging viral infections. Therefore, this review enumerated the food-functioned Quercetin source, the modes of action of Quercetin for antiviral effects and made insights on the mechanism-based antiviral action of Quercetin.
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Ma Z, Wang S, Miao W, Zhang Z, Yu L, Liu S, Luo Z, Liang H, Yu J, Huang T, Li M, Gao J, Su S, Li Y, Zhou L. The Roles of Natural Alkaloids and Polyphenols in Lipid Metabolism: Therapeutic Implications and Potential Targets in Metabolic Diseases. Curr Med Chem 2023; 30:3649-3667. [PMID: 36345246 DOI: 10.2174/0929867330666221107095646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 09/05/2022] [Accepted: 09/30/2022] [Indexed: 11/10/2022]
Abstract
The prevalence of obesity and its associated diseases has increased dramatically, and they are major threats to human health worldwide. A variety of approaches, such as physical training and drug therapy, can be used to reduce weight and reverse associated diseases; however, the efficacy and the prognosis are often unsatisfactory. It has been reported that natural food-based small molecules can prevent obesity and its associated diseases. Among them, alkaloids and polyphenols have been demonstrated to regulate lipid metabolism by enhancing energy metabolism, promoting lipid phagocytosis, inhibiting adipocyte proliferation and differentiation, and enhancing the intestinal microbial community to alleviate obesity. This review summarizes the regulatory mechanisms and metabolic pathways of these natural small molecules and reveals that the binding targets of most of these molecules are still undefined, which limits the study of their regulatory mechanisms and prevents their further application. In this review, we describe the use of Discovery Studio for the reverse docking of related small molecules and provide new insights for target protein prediction, scaffold hopping, and mechanistic studies in the future. These studies will provide a theoretical basis for the modernization of anti-obesity drugs and promote the discovery of novel drugs.
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Affiliation(s)
- Zeqiang Ma
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Shengnan Wang
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Shaanxi, China
| | - Weiwei Miao
- Institute of Oncology, Department of Otolaryngology & Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, China
| | - Zhiwang Zhang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Lin Yu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Siqi Liu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Zupeng Luo
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Huanjie Liang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Jingsu Yu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Tengda Huang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Mingming Li
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Jiayi Gao
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Songtao Su
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Yixing Li
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Lei Zhou
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
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19
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Tong J, Zeng Y, Xie J, Xiao K, Li M, Cong L. Association between flavonoid and subclasses intake and metabolic associated fatty liver disease in U.S. adults: Results from National Health and Nutrition Examination Survey 2017-2018. Front Nutr 2022; 9:1074494. [PMID: 36532560 PMCID: PMC9751205 DOI: 10.3389/fnut.2022.1074494] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 11/14/2022] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND Metabolic associated fatty liver disease (MAFLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Flavonoid is considered a promising candidate for metabolic disease prevention although few studies have explored the relationship between flavonoid intake and MAFLD. PURPOSE To assess the relationship between flavonoid intake and MAFLD prevalence in the U.S. adult population. MATERIALS AND METHODS The data of this cross-sectional study was obtained from National Health and Nutrition Examination Survey (NHANES) and Food and Nutrient Database for Dietary Studies (FNDDS) 2017-2018. Flavonoid and subclasses intake was assessed by two 24h recalls. MAFLD was diagnosed according to the consensus definitions. Multivariate logistic regression model was performed to examine the association between flavonoid intake and MAFLD with adjustments for confounders. RESULTS A total of 4,431 participants were included in this cross-sectional analysis. MAFLD had a weighted prevalence of 41.93% and was not associated with total flavonoid intake. A higher anthocyanin and isoflavone intake, on the other hand, was associated with a lower prevalence of MAFLD. The protective effect of higher anthocyanin intake was significant among male, Non-Hispanic White, and Non-Hispanic Asia participants. Higher isoflavone intake was associated with a lower risk of MAFLD in participants of younger (age < 50), Non-Hispanic Black, Non-Hispanic Asia, and higher HEI-2015 scores compared with the lowest quartile of isoflavone intake. Stratified analysis showed that compared with the lowest quartile of anthocyanin intake, the effect of anthocyanin intake on MAFLD varied by racial groups (P interaction = 0.02). A positive correlation existed between HDL and anthocyanidin intake (P = 0.03), whereas a negative correlation existed between FPG and isoflavone intake (P = 0.02). CONCLUSION MAFLD was adversely linked with flavonoid subclasses, anthocyanin and isoflavone. This modifiable lifestyle provides a potential opportunity to prevent MAFLD. These findings promote future research into the links and mechanisms between anthocyanin and isoflavone intake and MAFLD.
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Affiliation(s)
- Junlu Tong
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Yingjuan Zeng
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Jianhui Xie
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Kecen Xiao
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Man Li
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China
- Center for Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Li Cong
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
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20
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Total Flavonoids from Chimonanthus nitens Oliv. Leaves Ameliorate HFD-Induced NAFLD by Regulating the Gut–Liver Axis in Mice. Foods 2022; 11:foods11142169. [PMID: 35885412 PMCID: PMC9322569 DOI: 10.3390/foods11142169] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 07/08/2022] [Accepted: 07/16/2022] [Indexed: 12/15/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the chronic liver diseases with high incidence in the world. This study aimed to investigate whether total flavonoids from Chimonanthus nitens Oliv. leaves (TFC) can ameliorate NAFLD. Herein, a high-fat diet (HFD)-induced NAFLD mice model was established, and TFC was administered orally. The results showed that TFC reduced the body weight and liver index and decreased the serum and hepatic levels of triglyceride (TG) and total cholesterol (TC). TFC significantly reduced the activity of liver functional transaminase. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased by 34.61% and 39.57% in serum and 22.46% and 40.86% in the liver, respectively. TFC regulated the activities of oxidative-stress-related enzymes and upregulated the protein expression of nuclear factor E2-related factor (Nrf2)/heme oxygenase (HO-1) pathway in NAFLD mice, and the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) in serum were increased by 89.76% and 141.77%, respectively. In addition, TFC reduced the levels of free fatty acids (FFA), endotoxin (ET), and related inflammatory factors in mouse liver tissue and downregulated the expression of proteins associated with inflammatory pathways. After TFC treatment, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β in the liver tissues of NAFLD mice were downregulated by 67.10%, 66.56%, and 61.45%, respectively. Finally, TFC reduced liver fat deposition, oxidative stress, and inflammatory response to repair liver damage and alleviate NAFLD. Further studies showed that TFC regulated the expression of intestinal-barrier-related genes and improved the composition of gut microbiota. Therefore, TFC reduced liver inflammation and restored intestinal homeostasis by regulating the gut–liver axis. Overall, our findings revealed a novel function of TFC as a promising prophylactic for the treatment of NAFLD.
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21
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Molecular Mechanism of Crataegi Folium and Alisma Rhizoma in the Treatment of Dyslipidemia Based on Network Pharmacology and Molecular Docking. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:4891370. [PMID: 35722157 PMCID: PMC9200514 DOI: 10.1155/2022/4891370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/04/2022] [Indexed: 11/17/2022]
Abstract
Background Dyslipidemia has become a critical global issue for public health, with elevating prevalence and morbidity closely related to many cardiovascular diseases (CVD) with high incidence rates. Crataegi Folium (known as Shanzhaye in China, SZ, the leaves of Crataegus pinnatifida Bge. var. major N.E. Br. or Crataegus pinnatifida Bge) and Alisma rhizoma (known as Zexie in China, ZX, the dried tuber of Alisma orientale (Sam.) Juzep or Alisma plantago-aquatica Linn), a classic combination of herbs, have been widely used to treat dyslipidemia. However, the therapeutic mechanism of this pair still remains unclear. Hence, this study aimed to elucidate the molecular mechanism of the Shanzhaye-Zexie herb pair (SZHP) in the treatment of dyslipidemia with the use of a network pharmacology analysis approach. Methods Active compounds, targets of the SZHP, and targets for dyslipidemia were screened based on the public database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on the database for annotation, visualization, and integrated discovery (DAVID 6.8). The compound-target-disease-pathway network was visualized using the Cytoscape software, and SYBYL was used for molecular docking. Results Twelve active compounds in the SZHP were screened out, which were closely connected to 186 dyslipidemia-related targets. The network analysis revealed that sitosterol, stigmasterol, isorhamnetin, kaempferol, and quercetin might be candidate agents and CCND1, CASP3, HIF1A, and ESR1 genes were potential drug targets. GO analysis revealed 856 biological processes (BP), 139 molecular functions (MF), and 89 cellular components (CC). The KEGG pathway enrichment analysis indicated that the lipid level and atherosclerosis might influence the treatment of dyslipidemia. Molecular docking showed that quercetin bound well to CCND1, HIF1A, MYC, AKT1, and EGFR genes. These findings were in accord with the prediction obtained through the network pharmacology approach. Conclusions This study revealed the primary pharmacological effects and relevant mechanisms of the SZHP in treating dyslipidemia. Our findings may facilitate the development of the SZHP or its active compounds as an alternative therapy for dyslipidemia. Still, more pharmacological experiments are needed for verification.
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22
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Komeili-Movahhed T, Bassirian M, Changizi Z, Moslehi A. SIRT1/NFκB pathway mediates anti-inflammatory and anti-apoptotic effects of rosmarinic acid on in a mouse model of nonalcoholic steatohepatitis (NASH). J Recept Signal Transduct Res 2022; 42:241-250. [PMID: 33787460 DOI: 10.1080/10799893.2021.1905665] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 03/07/2021] [Accepted: 03/16/2021] [Indexed: 12/13/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) is considered as a common liver disease. SIRT1, a pivotal sensor, controls activation of metabolic, inflammatory and apoptotic pathways. Rosmarinic acid (RA) has positive effects on the liver injuries; nevertheless, its mechanisms are not completely studied. The aim of this study was to explore the role of rosmarinic acid on the pathways involved by SIRT1 for amelioration of a mouse model of NASH. To do this, C57/BL6 mice were divided into four equal groups (6 in each group). Animals received saline and rosmarinic acid as the control groups. NASH was induced by methionine-choline-deficient (MCD) diet. In the NASH + RA group, Rosmarinic acid was injected daily in mice fed on an MCD diet. Rosmarinic acid decreased plasma triglyceride, cholesterol, liver Steatosis and oxidative stress. Rosmarinic acid administration also increased SIRT1, Nrf2 and PPARα and decreased SREBP1c, FAS, NFκB and caspase3 expressions. Moreover, TNFα, IL6, P53, Bax/Bcl2 ratio and caspase3 expressions decreased. Our study demonstrated that remarkable effects of rosmarinic acid on the mice with NASH might be due to activation of SIRT1/Nrf2, SIRT1/NFκB and SIRT1/PPARα pathways, which alleviate hepatic steatosis, oxidative stress, inflammation and apoptosis.
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Affiliation(s)
| | - Mahdi Bassirian
- Student Research Committee, Qom University of Medical Sciences, Qom, Iran
| | | | - Azam Moslehi
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
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23
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Jiao P, Chaoyang L, Wenhan Z, Jingyi D, Yunlin Z, Zhenggang X. Integrative Metabolome and Transcriptome Analysis of Flavonoid Biosynthesis Genes in Broussonetia papyrifera Leaves From the Perspective of Sex Differentiation. FRONTIERS IN PLANT SCIENCE 2022; 13:900030. [PMID: 35668799 PMCID: PMC9163962 DOI: 10.3389/fpls.2022.900030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 04/15/2022] [Indexed: 06/15/2023]
Abstract
Flavonoids are important secondary metabolites involved in plant development and environmental responses. Sex differences in flavonoids are common in plants. Broussonetia papyrifera is a dioecious plant that is rich in flavonoids. However, few studies have been done on its molecular mechanism, especially sex differences. In the present study, we performed an integrated transcriptomics and metabolomics analysis of the sex differences in the accumulation of flavonoids in B. papyrifera leaves at different developmental stages. In general, flavonoids accumulated gradually with developmental time, and the content in female plants was higher than that in male plants. The composition of flavonoids in female and male plants was similar, and 16 kinds of flavonoids accumulated after flowering. Correspondingly, a significant enrichment of differentially expressed genes and metabolites was observed in the flavonoid biosynthesis pathway. WGCNA and qRT-PCR analyses identified several key genes regulating the accumulation of flavonoids, such as those encoding CHS, CHI and DFR. In addition, 8 TFs were found to regulate flavonoid biosynthesis by promoting the expression of multiple structural genes. These findings provide insight into flavonoid biosynthesis in B. papyrifera associated molecular regulation.
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Affiliation(s)
- Peng Jiao
- Hunan Research Center of Engineering Technology for Utilization of Environmental and Resources Plant, Central South University of Forestry and Technology, Changsha, China
| | - Li Chaoyang
- Central South Inventory and Planning Institute of National Forestry and Grassland Administration, Changsha, China
| | - Zhai Wenhan
- College of Forestry, Northwest A&F University, Yangling, China
| | - Dai Jingyi
- Hunan Research Center of Engineering Technology for Utilization of Environmental and Resources Plant, Central South University of Forestry and Technology, Changsha, China
| | - Zhao Yunlin
- Hunan Research Center of Engineering Technology for Utilization of Environmental and Resources Plant, Central South University of Forestry and Technology, Changsha, China
| | - Xu Zhenggang
- Hunan Research Center of Engineering Technology for Utilization of Environmental and Resources Plant, Central South University of Forestry and Technology, Changsha, China
- College of Forestry, Northwest A&F University, Yangling, China
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24
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Parmar AB, Patel VR, Patel JM, Ramani UV, Desai DN. Efficacy of dietary quercetin supplementation with high-energy diet model in broilers: implications on zootechnical parameters, serum biochemistry, antioxidant status, patho-morphology and gene expression studies. ANIMAL PRODUCTION SCIENCE 2022. [DOI: 10.1071/an21218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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25
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Guo Z, Cheng J, Zheng L, Xu W, Xie Y. Mechanochemical-Assisted Extraction and Hepatoprotective Activity Research of Flavonoids from Sea Buckthorn ( Hippophaë rhamnoides L.) Pomaces. Molecules 2021; 26:molecules26247615. [PMID: 34946689 PMCID: PMC8704866 DOI: 10.3390/molecules26247615] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 12/10/2021] [Accepted: 12/10/2021] [Indexed: 11/16/2022] Open
Abstract
Pomaces of sea buckthorn berry were usually side-products during the processing of juice. Due to a lack of an economical and effective extraction method, it was typically recognized as waste. For the purpose of resource utilization, the mechanochemical-assisted extraction (MCAE) method was applied to develop an ecofriendly extraction method and product with better pharmacology activity. The parameters were investigated through response surface methodology (RSM) design experiments. The processing conditions were optimized as follows: amount of Na2CO3 40%, ball-to-material rate 29:1 g/g, milling speed 410 rpm, milling time 24 min, extraction temperature 25 °C, extraction time 20 min and the solid-to-solution ratio 1:10 g/mL. Under these conditions, the yields of flavonoids from sea buckthorn pomaces were 26.82 ± 0.53 mg/g, which corresponds to an increase of 2 times in comparison with that extracted by the heat reflux extraction method. Meanwhile, the hepatoprotective activity of sea buckthorn pomaces extracts was studied by the liver injury induced by ip injection of tetracycline. Biochemical and histopathological studies showed that biomarkers in serum and liver of nonalcoholic fatty liver disease (NAFLD) mice were significantly ameliorated when sea buckthorn flavonoids extracted by MCAE were used. Altogether, these results demonstrate that, as a green and efficient extraction, MCAE treatment could increase the extraction yield of sea buckthorn flavonoids, meanwhile it could exhibit significant activity of improving liver function. This research provided a new way to use pomaces of sea buckthorn as a functional food. It also has great value on the comprehensive utilization of nature’s resources.
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Affiliation(s)
| | | | | | - Wenhao Xu
- Correspondence: (W.X.); (Y.X.); Tel.: +86-189-5805-7635 (W.X. & Y.X.)
| | - Yuanyuan Xie
- Correspondence: (W.X.); (Y.X.); Tel.: +86-189-5805-7635 (W.X. & Y.X.)
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26
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Sun P, Zhao L, Zhang N, Zhou J, Zhang L, Wu W, Ji B, Zhou F. Bioactivity of Dietary Polyphenols: The Role in LDL-C Lowering. Foods 2021; 10:2666. [PMID: 34828946 PMCID: PMC8617782 DOI: 10.3390/foods10112666] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Revised: 10/27/2021] [Accepted: 10/31/2021] [Indexed: 12/18/2022] Open
Abstract
Cardiovascular diseases are the leading causes of the death around the world. An elevation of the low-density lipoprotein cholesterol (LDL-C) level is one of the most important risk factors for cardiovascular diseases. To achieve optimal plasma LDL-C levels, clinal therapies were investigated which targeted different metabolism pathways. However, some therapies also caused various adverse effects. Thus, there is a need for new treatment options and/or combination therapies to inhibit the LDL-C level. Dietary polyphenols have received much attention in the prevention of cardiovascular diseases due to their potential LDL-C lowering effects. However, the effectiveness and potential mechanisms of polyphenols in lowering LDL-C is not comprehensively summarized. This review focused on dietary polyphenols that could reduce LDL-C and their mechanisms of action. This review also discussed the limitations and suggestions regarding previous studies.
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Affiliation(s)
- Peng Sun
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (P.S.); (N.Z.); (J.Z.); (L.Z.); (B.J.)
| | - Liang Zhao
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, China;
| | - Nanhai Zhang
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (P.S.); (N.Z.); (J.Z.); (L.Z.); (B.J.)
| | - Jingxuan Zhou
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (P.S.); (N.Z.); (J.Z.); (L.Z.); (B.J.)
| | - Liebing Zhang
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (P.S.); (N.Z.); (J.Z.); (L.Z.); (B.J.)
| | - Wei Wu
- College of Engineering, China Agricultural University, Beijing 100083, China;
| | - Baoping Ji
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (P.S.); (N.Z.); (J.Z.); (L.Z.); (B.J.)
| | - Feng Zhou
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (P.S.); (N.Z.); (J.Z.); (L.Z.); (B.J.)
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27
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Sotiropoulou M, Katsaros I, Vailas M, Lidoriki I, Papatheodoridis GV, Kostomitsopoulos NG, Valsami G, Tsaroucha A, Schizas D. Nonalcoholic fatty liver disease: The role of quercetin and its therapeutic implications. Saudi J Gastroenterol 2021; 27:319-330. [PMID: 34810376 PMCID: PMC8656328 DOI: 10.4103/sjg.sjg_249_21] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 08/29/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting almost one-third of the general population and 75% of obese patients with type 2 diabetes. The aim of this article is to review the current evidence concerning the role of quercetin, a natural compound and flavonoid, and its possible therapeutic effects on this modern-day disease. Despite the fact that the exact pathophysiological mechanisms through which quercetin has a hepatoprotective effect on NAFLD are still not fully elucidated, this review clearly demonstrates that this flavonoid has potent antioxidative stress action and inhibitory effects on hepatocyte apoptosis, inflammation, and generation of reactive oxygen species, factors which are linked to the development of the disease. NAFLD is closely associated with increased dietary fat consumption, especially in Western countries. The hepatoprotective effect of quercetin against NAFLD merits serious consideration and further validation by future studies.
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Affiliation(s)
- Maria Sotiropoulou
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Ioannis Katsaros
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Michail Vailas
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Irene Lidoriki
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Nikolaos G Kostomitsopoulos
- Center of Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece
| | - Georgia Valsami
- Department of Pharmacy, Laboratory of Biopharmaceutics-Pharmacokinetics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Tsaroucha
- Laboratory of Experimental Surgery, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dimitrios Schizas
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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Foresight regarding drug candidates acting on the succinate-GPR91 signalling pathway for non-alcoholic steatohepatitis (NASH) treatment. Biomed Pharmacother 2021; 144:112298. [PMID: 34649219 DOI: 10.1016/j.biopha.2021.112298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/29/2021] [Accepted: 10/05/2021] [Indexed: 11/24/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. In the pathogenesis of NASH, the signal transduction pathway involving succinate and the succinate receptor (G-protein-coupled receptor 91, GPR91) regulates inflammatory cell activation and liver fibrosis. This review describes the mechanism of the succinate-GPR91 signalling pathway in NASH and summarizes the drugs that act on this pathway, with the aim of providing a new approach to NASH treatment.
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29
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Stephen Robert J, Peddha MS, Srivastava AK. Effect of Silymarin and Quercetin in a Miniaturized Scaffold in Wistar Rats against Non-alcoholic Fatty Liver Disease. ACS OMEGA 2021; 6:20735-20745. [PMID: 34423182 PMCID: PMC8374897 DOI: 10.1021/acsomega.1c00555] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 07/26/2021] [Indexed: 05/02/2023]
Abstract
Silymarin and quercetin (SQ) are known antioxidants with substantial free radical scavenging activities. The efficacy of SQ activity is restricted due to poor absorption and availability. This study aims to increase the hepatoprotective activity of SQ by a newer delivery technique. We have optimized a technique, miniaturized scaffold (MS), for the delivery of active compounds of SQ. SQ molecules were embedded in MS and characterized by morphology, particle size, miniaturization efficiency, and functional group. Further, the hepatoprotective effects of MSQ were investigated through in vitro and in vivo methods. Hepatotoxicity was induced in rats by carbon tetrachloride (CCl4), and subsequently, hepatotoxic rats were treated with the miniaturized scaffold of SQ (MSQ) for 8 weeks. The body weight were significantly high in groups fed with MSQ. A substantial decrease in triglyceride, total cholesterol, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase activities were observed in rats treated with MSQ. Similarly, rats treated with MSQ exhibited lower lipid accumulation in the hepatocytes. The experiments clearly demonstrated the efficacy of MSQ as a superior hepatoprotective agent against non-alcoholic fatty liver disease simulated through toxicity induced by CCl4.
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Affiliation(s)
- Jaisheela
Marry Stephen Robert
- Department
of Food Safety and Analytical Quality Control Laboratory, CSIR- Central Food Technological Research Institute, Mysuru, Karnataka 570 020, India
- Academy
of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Muthukumar Serva Peddha
- Department
of Biochemistry, CSIR- Central Food Technological
Research Institute, Mysuru, 570 020 Karnataka, India
- Academy
of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Alok Kumar Srivastava
- Department
of Food Safety and Analytical Quality Control Laboratory, CSIR- Central Food Technological Research Institute, Mysuru, Karnataka 570 020, India
- Academy
of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
- .
Phone: 91-821-2514972. Fax: 91-821-2517233
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The Therapeutic Effects and Mechanisms of Quercetin on Metabolic Diseases: Pharmacological Data and Clinical Evidence. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:6678662. [PMID: 34257817 PMCID: PMC8249127 DOI: 10.1155/2021/6678662] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/17/2021] [Accepted: 06/08/2021] [Indexed: 12/27/2022]
Abstract
Metabolic diseases have become major public health issues worldwide. Searching for effective drugs for treating metabolic diseases from natural compounds has attracted increasing attention. Quercetin, an important natural flavonoid, is extensively present in fruits, vegetables, and medicinal plants. Due to its potentially beneficial effects on human health, quercetin has become the focus of medicinal attention. In this review, we provide a timely and comprehensive summary of the pharmacological advances and clinical data of quercetin in the treatment of three metabolic diseases, including diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). Accumulating evidences obtained from animal experiments prove that quercetin has beneficial effects on these three diseases. It can promote insulin secretion, improve insulin resistance, lower blood lipid levels, inhibit inflammation and oxidative stress, alleviate hepatic lipid accumulation, and regulate gut microbiota disorders in animal models. However, human clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. More clinical trials with larger sample sizes and longer trial durations are needed to verify its true effectiveness in human subjects. Moreover, another important issue that needs to be resolved in future research is to improve the bioavailability of quercetin. This review may provide valuable information for the basic research, drug development, and clinical application of quercetin in the treatment of metabolic diseases.
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Zhao X, Wang J, Deng Y, Liao L, Zhou M, Peng C, Li Y. Quercetin as a protective agent for liver diseases: A comprehensive descriptive review of the molecular mechanism. Phytother Res 2021; 35:4727-4747. [PMID: 34159683 DOI: 10.1002/ptr.7104] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/12/2021] [Accepted: 03/19/2021] [Indexed: 02/06/2023]
Abstract
Quercetin is the major representative of the flavonoid subgroup of flavones, with good pharmacological activities for the treatment of liver diseases, including liver steatosis, fatty hepatitis, liver fibrosis, and liver cancer. It can significantly influence the development of liver diseases via multiple targets and multiple pathways via antifat accumulation, anti-inflammatory, and antioxidant activity, as well as the inhibition of cellular apoptosis and proliferation. Despite extensive research on understanding the mechanism of quercetin in the treatment of liver diseases, there are still no targeted therapies available. Thus, we have comprehensively searched and summarized the different targets of quercetin in different stages of liver diseases and concluded that quercetin inhibited inflammation of the liver mainly through NF-κB/TLR/NLRP3, reduced PI3K/Nrf2-mediated oxidative stress, mTOR activation in autophagy, and inhibited the expression of apoptotic factors associated with the development of liver diseases. In addition, quercetin showed different mechanisms of action at different stages of liver diseases, including the regulation of PPAR, UCP, and PLIN2-related factors via brown fat activation in liver steatosis. The compound inhibited stromal ECM deposition at the liver fibrosis stage, affecting TGF1β, endoplasmic reticulum stress (ERs), and apoptosis. While at the final liver cancer stage, inhibiting cancer cell proliferation and spread via the hTERT, MEK1/ERK1/2, Notch, and Wnt/β-catenin-related signaling pathways. In conclusion, quercetin is an effective liver protectant. We hope to explore the pathogenesis of quercetin in different stages of liver diseases through the review, so as to provide more accurate targets and theoretical basis for further research of quercetin in the treatment of liver diseases.
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Affiliation(s)
- Xingtao Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jing Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ying Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Li Liao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mengting Zhou
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Quercetin and non-alcoholic fatty liver disease: A review based on experimental data and bioinformatic analysis. Food Chem Toxicol 2021; 154:112314. [PMID: 34087406 DOI: 10.1016/j.fct.2021.112314] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 05/18/2021] [Accepted: 05/29/2021] [Indexed: 02/08/2023]
Abstract
Quercetin, a polyphenol widely present in the plant kingdom, has received great interest due to pleiotropic effects. As evidenced by animal and cellular studies, quercetin exerts hepatoprotection against non-alcoholic fatty liver disease (NAFLD), particularly in hepatic steatosis and hepatitis. Mechanically, various hypotheses of such protective effects have been actively proposed, including improving fatty acid metabolism, anti-inflammation, anti-oxidant, modulating gut microbiota and bile acid, etc. Here, the role of quercetin in NAFLD was summarized. With a particular focus on molecular mechanism, we comprehensively discussed the pathways of quercetin on NAFLD based on the analysis from Gene Expression Omnibus (GEO) database and experimental evidence.
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Postnatally induced metabolic and oxidative changes associated with maternal high-fat consumption were mildly affected by Quercetin-3-O-rutinoside treatment in rats. Heliyon 2021; 7:e06847. [PMID: 33997389 PMCID: PMC8102762 DOI: 10.1016/j.heliyon.2021.e06847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 01/05/2021] [Accepted: 04/14/2021] [Indexed: 11/30/2022] Open
Abstract
Oxidative stress is usually associated with prolonged intake of high-fat diet (HFD). However, little is known about the impact of maternal HFD on endogenous modulation of antioxidant-defence-enzyme-network, its link to adverse fetal growth and overall effects of Quercetin-3-o-rutinoside (QR) supplementation. Sprague-Dawley rats were initially assigned to normal diet (ND) or HFD for 8 weeks and mated. Post-conception, rats were further divided into four groups, of which two groups had diets supplemented with QR while others continued with their respective diets until delivery. Measurements include food and water consumption, physical parameters (body weight, body mass index (BMI) and fur appearance), oral glucose tolerance, lipid profiles, and placental/liver oxidative changes. We observed that water consumption was significantly increased in dams fed HFD without marked differences in food intake, body weight, BMI and glucose tolerance. Surprisingly, offspring of HFD-fed dams had reduced body weight marked by delayed fur appearance compared to the ND offspring. In dams, there were alterations in lipid profile. Lipid peroxidation was increased in the placenta and liver of gestational day (GD) 19 HFD-fed dams and their postnatal day (PND) 21 male offspring. There was evidence of HFD-induced nitrosative stress in dams and PND28 female offspring. Adaptive defence indicate decreased placenta and liver superoxide dismutase (SOD) levels as well as differential changes in total antioxidant capacity (TAC) and catalase (CAT) activity in HFD treated dams and their progenies. Overall, the results indicate that intrauterine metabolic alterations associated with maternal high-fat consumption may induce oxidative challenge in the offspring accompanied by mild developmental consequences, while QR supplementation has little or no beneficial effects.
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Liu Y, Wu H, Wang Z, Wu J, Ying S, Huang M, Li Y. Integrated expression profiles of mRNA and miRNA in a gerbil model of fatty liver fibrosis treated with exenatide. Clin Res Hepatol Gastroenterol 2021; 45:101312. [PMID: 33592427 DOI: 10.1016/j.clinre.2019.07.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 06/27/2019] [Accepted: 07/12/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The morbidity of nonalcoholic fatty liver disease (NAFLD) has increased consistently in recent years. Exenatide could reverse liver fibrosis and lower the occurrence of fatty liver. The aim of the study was to identify and characterize mRNA and miRNA expression to elucidate the mechanism of exenatide in the gerbil model. METHODS Gerbils were fed a high-fat diet for 8 weeks to induce a fibrosis model; then, the gerbil models were treated with exenatide for 4 weeks. The total RNA extracted from the liver tissue samples was used to prepare the library and sequence on a HiSeq 2000. Bioinformatic methods were employed to analyze the sequence data to identify the mRNAs and miRNAs and to acquire the miRNA-mRNA regulatory network. RESULTS By RNA-seq, 2344 differentially expressed genes (DEGs) and 72 miRNAs were found in the model group. Compared with the model group, 591 DEGs and 19 miRNAs were found in the quercetin group, whereas 876 DEGs and 18 miRNAs were found in the treatment group. The miRNA-mRNA regulatory network was constructed in a gerbil model. Immunohistochemistry and RNA sequencing confirmed that the therapeutic effect of exenatide may be derived from extrahepatic signal transduction. The key differential genes are CYP3A, CYP4A11, ACAA1, ACSM, PHX1, MAO, FMO, UGT, ACOX2, ABAT, PIK3C and PLCG1. The key miRNAs are miR-15a, miR-27b, miR-532-3P, miR-627, miR-3596, miR-142-3P, Let-7e-5p, miR-214-5, miR-101-3p, miR-378d. New miRNAs, such as novel_127, novel_143, novel_15, novel_204 are associated with liver fibrosis, while novel_127, novel_15, and novel_54 are associated with reverse treated with exenatide. CONCLUSIONS Our research represents the first description of mRNA/miRNA profiles in a gerbil model of fatty liver fibrosis treated with exenatide, which may provide insights into the pathogenesis or treatment of the metabolic syndrome.
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Affiliation(s)
- Yuehuan Liu
- Zhejiang Academy of Medical Sciences, Hangzhou, China
| | - Hongru Wu
- Department of Gastroenterology, The first Affiliated Hospital, College of Medicine, Zhejiang University, 79, Qignchun Road, Hangzhou 310003, China
| | - Zhiyuan Wang
- Zhejiang Academy of Medical Sciences, Hangzhou, China
| | - Jiusheng Wu
- College of animal sciences, Zhejiang university, Hangzhou, China
| | - Shibo Ying
- Zhejiang Academy of Medical Sciences, Hangzhou, China
| | - Minjie Huang
- College of animal sciences, Zhejiang university, Hangzhou, China
| | - Youming Li
- Department of Gastroenterology, The first Affiliated Hospital, College of Medicine, Zhejiang University, 79, Qignchun Road, Hangzhou 310003, China.
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Zhou H, Ma C, Wang C, Gong L, Zhang Y, Li Y. Research progress in use of traditional Chinese medicine monomer for treatment of non-alcoholic fatty liver disease. Eur J Pharmacol 2021; 898:173976. [PMID: 33639194 DOI: 10.1016/j.ejphar.2021.173976] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 02/09/2021] [Accepted: 02/19/2021] [Indexed: 02/06/2023]
Abstract
With the improvement of people's living standards and the change of eating habits, non-alcoholic fatty liver disease (NAFLD) has gradually become one of the most common chronic liver diseases in the world. However, there are no effective drugs for the treatment of NAFLD. Therefore, it is urgent to find safe, efficient, and economical anti-NAFLD drugs. Compared with western medicines that possess fast lipid-lowering effect, traditional Chinese medicines (TCM) have attracted increasing attention for the treatment of NAFLD due to their unique advantages such as multi-targets and multi-channel mechanisms of action. TCM monomers have been proved to treat NAFLD through regulating various pathways, including inflammation, lipid production, insulin sensitivity, mitochondrial dysfunction, autophagy, and intestinal microbiota. In particular, peroxisome proliferator-activated receptor α (PPAR-α), sterol regulatory element-binding protein 1c (SREBP-1c), nuclear transcription factor kappa (NF-κB), phosphoinositide 3-kinase (PI3K), sirtuin1 (SIRT1), AMP-activated protein kinase (AMPK), p53 and nuclear factor erythroid 2-related factor 2 (Nrf2) are considered as important molecular targets for ameliorating NAFLD by TCM monomers. Therefore, by searching PubMed, Web of Science and SciFinder databases, this paper updates and summarizes the experimental and clinical evidence of TCM monomers for the treatment of NAFLD in the past six years (2015-2020), thus providing thoughts and prospects for further exploring the pathogenesis of NAFLD and TCM monomer therapies.
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Affiliation(s)
- Honglin Zhou
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Cheng Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Cheng Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Lihong Gong
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yafang Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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Mehrbod P, Hudy D, Shyntum D, Markowski J, Łos MJ, Ghavami S. Quercetin as a Natural Therapeutic Candidate for the Treatment of Influenza Virus. Biomolecules 2020; 11:E10. [PMID: 33374214 PMCID: PMC7824064 DOI: 10.3390/biom11010010] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 12/16/2020] [Accepted: 12/21/2020] [Indexed: 12/12/2022] Open
Abstract
The medical burden caused by respiratory manifestations of influenza virus (IV) outbreak as an infectious respiratory disease is so great that governments in both developed and developing countries have allocated significant national budget toward the development of strategies for prevention, control, and treatment of this infection, which is seemingly common and treatable, but can be deadly. Frequent mutations in its genome structure often result in resistance to standard medications. Thus, new generations of treatments are critical to combat this ever-evolving infection. Plant materials and active compounds have been tested for many years, including, more recently, active compounds like flavonoids. Quercetin is a compound belonging to the flavonols class and has shown therapeutic effects against influenza virus. The focus of this review includes viral pathogenesis as well as the application of quercetin and its derivatives as a complementary therapy in controlling influenza and its related symptoms based on the targets. We also touch on the potential of this class of compounds for treatment of SARS-COV-2, the cause of new pandemic.
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Affiliation(s)
- Parvaneh Mehrbod
- Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran 1316943551, Iran
| | - Dorota Hudy
- Department of Laryngology, Faculty of Health Sciences in Katowice, Medical University of Silesia, 40-027 Katowice, Poland; (D.H.); (J.M.)
| | - Divine Shyntum
- Biotechnology Center, Silesian University of Technology, 44-100 Gliwice, Poland;
| | - Jarosław Markowski
- Department of Laryngology, Faculty of Health Sciences in Katowice, Medical University of Silesia, 40-027 Katowice, Poland; (D.H.); (J.M.)
| | - Marek J. Łos
- Department of Pathology, Pomeranian Medical University, 71-344 Szczecin, Poland;
| | - Saeid Ghavami
- Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada;
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Sayed AM, Hassanein EH, Salem SH, Hussein OE, Mahmoud AM. Flavonoids-mediated SIRT1 signaling activation in hepatic disorders. Life Sci 2020; 259:118173. [DOI: 10.1016/j.lfs.2020.118173] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/18/2020] [Accepted: 07/27/2020] [Indexed: 02/07/2023]
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Gad RA, Abdel-Reheim ES, Shehab GMG, Hafez HS, Abuelsaad ASA. Evaluation of Insulin Resistance Induced Brain Tissue Dysfunction in Obese Dams and their Neonates: Role of Ipriflavone Amelioration. Comb Chem High Throughput Screen 2020; 24:767-780. [PMID: 32772909 DOI: 10.2174/1386207323666200808181148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 06/13/2020] [Accepted: 06/17/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Nonalcoholic steatohepatitis (NASH) is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. A high fat high cholesterol diet (HFD) was provided to female albino rats to establish a NASH model. It is well known that the offspring of obese mothers have an increased risk of obesity and diabetes. The present study aimed at evaluating the ameliorative effects of ipriflavone (IP) as a natural food supplement on lipid metabolism, improving insulin sensitivity, reducing oxidative stress and inflammation, modifying metabolic risk factors and/or reduce brain damage, in both neonates and their dams. MATERIALS AND METHODS The present aim was achieved by evaluating the oxidative stress and antioxidant defense system biomarkers, as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) activities. In addition, the neurotransmitter acetylcholine (Ach) and acetylcholine esterase (AchE) activities, as well as levels of the apolipoprotein E4 (APOE4); β-secretase, hyper phosphor-tau and β-amyloid 42; 3-hydroxy- 3-methyl glutaryl coenzyme A reductase (HMG CoA R)" and COX-II by immunoblotting assays in the brain tissue of neonates and their dams in all the studied groups. RESULTS A very significant amelioration in acetylcholine and acetylcholine esterase neurotransmitters, Alzheimer's makers (β-amyloid), antioxidants (reduced glutathione (GSH) contents, catalase (CAT) and superoxide dismutase (SOD); and inflammatory cytokines in NASH model is observed upon administrating ipriflavone (IP) as a natural food supplement. The multifunctional activities of ipriflavone as an antioxidant, anti-inflammatory and anti-insulin resistance drug were discussed and correlated with other investigations. CONCLUSION Regarding steatohepatitis, the present study confirmed the anti-inflammatory effects of the ipriflavone (IP). Therefore, future studies should focus on hepatic fatty acid uptake, hepatic lipogenesis, and fatty acid oxidation and the role of IP in regulating hepatic fat metabolism. In addition, natural products like IP could be combined with the highly used pharmaceutical drugs to reduce the side effects of nonalcoholic steatohepatitis, and minimize progression of dementia. Moreover, the present study supports further attempts to heal the neural dysfunction via antioxidant and anti-inflammatory cascade activities using ipriflavone (IP).
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Affiliation(s)
- Rania A Gad
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef (NUB), Beni-Suef, 62511, Egypt
| | - Eman S Abdel-Reheim
- Physiology Divisions; Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt
| | - Gaber M G Shehab
- Department of Biochemistry, College of Medicine, Taif University, Taif 21944, Saudi Arabia
| | - Hani S Hafez
- Zoology Department, Faculty of Science, Suez University, Suez, Egypt
| | - Abdelaziz S A Abuelsaad
- Immunology Divisions; Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt
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Herranz-López M, Olivares-Vicente M, Rodríguez Gallego E, Encinar JA, Pérez-Sánchez A, Ruiz-Torres V, Joven J, Roche E, Micol V. Quercetin metabolites from Hibiscus sabdariffa contribute to alleviate glucolipotoxicity-induced metabolic stress in vitro. Food Chem Toxicol 2020; 144:111606. [PMID: 32738368 DOI: 10.1016/j.fct.2020.111606] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 07/08/2020] [Accepted: 07/09/2020] [Indexed: 12/17/2022]
Abstract
Polyphenols from Hibiscus sabdariffa (HS) alleviate obesity-related metabolic complications but the metabolites responsible for such effects are unknown. We aimed to elucidate which of the potential plasma metabolites from a polyphenol-enriched HS (PEHS) extract contributed for the reversion of glucolipotoxicity-induced metabolic stress using 3T3-L1 adipocyte and INS 832/13 pancreatic β-cell models under glucolipotoxic conditions. PEHS extract, quercetin (Q) and quercetin-3-O-glucuronide (Q3GA) showed stronger capacity to decrease glucolipotoxicity-induced ROS generation than ascorbic acid or chlorogenic acid. PEHS extract, Q and Q3GA decreased secretion of cytokines (leptin, TNF-α, IGF-1, IL-6, VEGF, IL-1α, IL-1β and CCL2) and reduced CCL2 expression at transcriptional level. In addition, PEHS extract, Q and Q3GA reduced triglyceride accumulation, which occurred through fatty acid synthase (FASN) downregulation, AMPK activation and mitochondrial mass and biogenesis restoration via PPARα upregulation. Electron microscopy confirmed that PEHS extract and Q3GA decreased mitochondrial remodeling and mitophagy. Virtual screening leads us to postulate that Q and Q3GA might act as agonists of these protein targets at specific sites. These data suggest that Q and Q3GA may be the main responsible compounds for the capacity of PEHS extract to revert glucolipotoxicity-induced metabolic stress through AMPK-mediated decrease in fat storage and increase in fatty acid oxidation, though other compounds of the extract may contribute to this capacity.
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Affiliation(s)
- María Herranz-López
- Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) e Instituto de Biología Molecular y Celular (IBMC). Miguel Hernández University (UMH), Elche, 03202, Alicante, Spain.
| | - Mariló Olivares-Vicente
- Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) e Instituto de Biología Molecular y Celular (IBMC). Miguel Hernández University (UMH), Elche, 03202, Alicante, Spain
| | - Esther Rodríguez Gallego
- Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43007, Tarragona, Spain
| | - Jose Antonio Encinar
- Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) e Instituto de Biología Molecular y Celular (IBMC). Miguel Hernández University (UMH), Elche, 03202, Alicante, Spain
| | - Almudena Pérez-Sánchez
- Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) e Instituto de Biología Molecular y Celular (IBMC). Miguel Hernández University (UMH), Elche, 03202, Alicante, Spain
| | - Verónica Ruiz-Torres
- Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) e Instituto de Biología Molecular y Celular (IBMC). Miguel Hernández University (UMH), Elche, 03202, Alicante, Spain
| | - Jorge Joven
- Universitat Rovira i Virgili, Departament de Cirurgia i Medicina, Unitat de Recerca Biomèdica, 43201, Reus, Tarragona, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Spain
| | - Enrique Roche
- Institute of Bioengineering and Department of Applied Biology-Nutrition, University Miguel Hernandez, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain; CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (CB12/03/30038), 28220, Madrid, Spain
| | - Vicente Micol
- Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) e Instituto de Biología Molecular y Celular (IBMC). Miguel Hernández University (UMH), Elche, 03202, Alicante, Spain; CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (CB12/03/30038), 28220, Madrid, Spain
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Hosseinikia M, Oubari F, Hosseinkia R, Tabeshfar Z, Salehi MG, Mousavian Z, Abbasi M, Samadi M, Pasdar Y. Quercetin supplementation in non-alcoholic fatty liver disease. NUTRITION & FOOD SCIENCE 2020; 50:1279-1293. [DOI: 10.1108/nfs-10-2019-0321] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Purpose
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease which has become a public health concern, whose growing prevalence has been reported as around 33.9% in Iran. As oxidative stress plays a crucial role in the pathogenesis of NAFLD, antioxidant compounds such as quercetin could ameliorate the side effect of oxidative stress. The aim of the current study was to assess the effect of quercetin on lipid profile, liver enzymes and inflammatory indices in NAFLD patients.
Design/methodology/approach
In a randomized, double-blind, placebo-controlled trial conducted as a pilot study, 90 patients with NAFLD were supplemented with either a quercetin or a placebo capsule twice daily (500 mg) for 12 weeks. Both groups were advised to follow an energy-balanced diet with physical activity recommendations. Blood sample was obtained for laboratory parameters at baseline and the end of week 12.
Findings
At the end of the follow-up, quercetin group had significantly greater reduction in anthropometric parameters, cholesterol (−15 ± (−41, 0.00) in Q group versus −1± (−8, 2) in control group, p = 0.004), TG (−56.7 ± 22.7) in Q group versus −13.4 ± 27.7 in control group, p = 0.04), and tumor necrosis factor-α (TNF-α) (−49.5 ± (−99, 21) in Q group versus −5 ± (−21, 0.30) in the control group, p < 0.0001) compared to the control group. However, changes in fatty liver grade, liver enzymes, as well as high density lipoprotein-cholesterol and high-sensitivity C-reactive protein were not significantly different between the two groups.
Originality/value
To the best of the authors’ knowledge, this was the first study which assessed the effect of quercetin supplementation on liver enzymes, lipid profile and inflammatory indices of NAFLD patients as a double-blind placebo-controlled pilot study.
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Amirinejad A, Hekmatdoost A, Ebrahimi A, Ranjbaran F, Shidfar F. The effects of hydroalcoholic extract of spinach on prevention and treatment of some metabolic and histologic features in a rat model of nonalcoholic fatty liver disease. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2020; 100:1787-1796. [PMID: 31849065 DOI: 10.1002/jsfa.10215] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Revised: 12/16/2019] [Accepted: 12/18/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND This study evaluated the effects of hydroalcoholic extract of spinach (HES) on nonalcoholic fatty liver disease (NAFLD). In the prevention phase, 18 Sprague-Dawley rats were fed a high-fat diet, a high-fat diet plus 400 mg kg-1 HES, or a chow diet for 7 weeks. For the treatment phase, after the induction of NAFLD, they were fed a high-fat diet, a high-fat diet plus 400 mg kg-1 HES, a chow diet, or chow diet plus 400 mg kg-1 HES for 4 weeks (n = 6). RESULTS Weight gain (P = 0.01), food intake (P < 0.01), serum glucose (P = 0.01), triglyceride (TG) (P = 0.02), low-density lipoprotein cholesterol (LDL-c) (P = 0.01), aspartate aminotransferase (AST) (P = 0.02), liver steatosis, and the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) (P < 0.01) in the high-fat group were statistically higher than in the other groups at the end of the prevention phase. Feeding spinach extract to rats on a high-fat diet decreased serum glucose (P = 0.01), total cholesterol (TCh) (P < 0.01), AST (P = 0.01), alkaline phosphatase (ALP) (P < 0.01), and liver steatosis (P < 0.01) in the treatment phase. CONCLUSION Overall, spinach extract showed beneficial effects in the prevention and treatment of NAFLD. © 2019 Society of Chemical Industry.
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Affiliation(s)
- Ali Amirinejad
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdolali Ebrahimi
- Department of Pathology, Imam Hossein Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Ranjbaran
- School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Farzad Shidfar
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
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Wu Z, Zhang Y, Gong X, Cheng G, Pu S, Cai S. The preventive effect of phenolic-rich extracts from Chinese sumac fruits against nonalcoholic fatty liver disease in rats induced by a high-fat diet. Food Funct 2020; 11:799-812. [PMID: 31930271 DOI: 10.1039/c9fo02262g] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The objective of this study is to investigate the preventive effect of phenolic-rich extracts from Chinese sumac (Rhus chinensis Mill.) fruits against NAFLD in rats induced by a high-fat diet and to clarify the underlying mechanisms.
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Affiliation(s)
- Zihuan Wu
- Faculty of Agriculture and Food
- Yunnan Institute of Food Safety
- Kunming University of Science and Technology
- Kunming
- People's Republic of China
| | - Yan Zhang
- The First People's Hospital of Yunnan Province and the Affiliated Kunhua Hospital of Kunming University of Science and Technology
- Kunming
- People's Republic of China
| | - Xiarong Gong
- The First People's Hospital of Yunnan Province and the Affiliated Kunhua Hospital of Kunming University of Science and Technology
- Kunming
- People's Republic of China
| | - Guiguang Cheng
- Faculty of Agriculture and Food
- Yunnan Institute of Food Safety
- Kunming University of Science and Technology
- Kunming
- People's Republic of China
| | - Shibiao Pu
- Chinese Materia Medica
- Yunnan University of Chinese Medicine
- Kunming
- People's Republic of China
| | - Shengbao Cai
- Faculty of Agriculture and Food
- Yunnan Institute of Food Safety
- Kunming University of Science and Technology
- Kunming
- People's Republic of China
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Vovkun TV, Yanchuk PI, Shtanova LY, Veselsky SP, Filimonova NB, Komarov IV. Corvitin modulates the content of lipids in rat liver bile. UKRAINIAN BIOCHEMICAL JOURNAL 2019. [DOI: 10.15407/ubj91.06.112] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Rafiei H, Omidian K, Bandy B. Phenolic Breakdown Products of Cyanidin and Quercetin Contribute to Protection against Mitochondrial Impairment and Reactive Oxygen Species Generation in an In Vitro Model of Hepatocyte Steatosis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:6241-6247. [PMID: 31117508 DOI: 10.1021/acs.jafc.9b02367] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
A question in cell culture and dietary studies on protection by flavonoids against conditions such as hepatocyte steatosis is whether effects might be due to phenolic breakdown/digestion products. In HepG2 hepatocytes, treatment with quercetin, cyanidin, or their phenolic breakdown/digestion products (protocatechuic acid, 2,4,6-trihydroxybenzaldehyde, and caffeic acid), starting 2 h prior to oleic acid for 24 h, protected similarly against increases in intracellular lipid and reactive oxygen species and decreased mitochondrial membrane potential. Cyanidin or the phenolic products also protected against decreased mitochondrial content. After preincubation for only 1 h (to limit spontaneous degradation) and removal prior to oleic acid, only the phenolic products protected against decreased mitochondrial content, and without adding oleic acid, only protocatechuic acid and caffeic acid, and less so cyanidin, induced mitochondrial content. The results suggest that phenolic breakdown/digestion products of cyanidin and quercetin contribute to the protective effects in vitro, and perhaps in vivo.
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Affiliation(s)
- Hossein Rafiei
- College of Pharmacy and Nutrition , University of Saskatchewan , Saskatoon , Saskatchewan S7N 5B5 , Canada
| | - Kosar Omidian
- College of Pharmacy and Nutrition , University of Saskatchewan , Saskatoon , Saskatchewan S7N 5B5 , Canada
| | - Brian Bandy
- College of Pharmacy and Nutrition , University of Saskatchewan , Saskatoon , Saskatchewan S7N 5B5 , Canada
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Rafiei H, Omidian K, Bandy B. Dietary Polyphenols Protect Against Oleic Acid-Induced Steatosis in an in Vitro Model of NAFLD by Modulating Lipid Metabolism and Improving Mitochondrial Function. Nutrients 2019; 11:nu11030541. [PMID: 30832407 PMCID: PMC6471211 DOI: 10.3390/nu11030541] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 02/27/2019] [Accepted: 02/27/2019] [Indexed: 12/13/2022] Open
Abstract
In this study, we aimed to determine the relative effectiveness of common dietary polyphenols or the isoquinoline alkaloid berberine in protecting against molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD) involving changes to cellular lipid metabolism and bioenergetics. In a model of steatosis using HepG2 hepatocytes, exposure of the cells to 1.5 mM oleic acid (OA) for 24 h caused steatosis and distorted cell morphology, induced the expression of mRNA for enzymes that are involved in lipogenesis and fatty acid oxidation (FAS and CPT1A), and impaired indices of aerobic energy metabolism (PPARγ mRNA expression, mitochondrial membrane potential (MMP), and galactose-supported ATP production). Co-treatment with 10 µM of selected polyphenols all strongly protected against the steatosis and changes in cell morphology. All polyphenols, except cyanidin, inhibited the effects on FAS and PPARγ and further increased CPT1A1 expression, suggesting a shift toward increased β-oxidation. Resveratrol, quercetin, catechin, and cyanidin, however not kuromanin or berberine, ameliorated the decreases in MMP and galactose-derived ATP. Berberine was unique in worsening the decrease in galactose-derived ATP. In further investigations of the mechanisms involved, resveratrol, catechin, and berberine increased SIRT1 enzyme activity and p-AMPKαThr172 protein, which are involved in mitochondrial biogenesis. In conclusion, selected polyphenols all protected against steatosis with similar effectiveness, however through different mechanisms that increased aerobic lipid metabolism and mitochondrial function.
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Affiliation(s)
- Hossein Rafiei
- Nutrition Division, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada.
| | - Kosar Omidian
- Nutrition Division, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada.
| | - Brian Bandy
- Nutrition Division, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada.
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Zeng H, Guo X, Zhou F, Xiao L, Liu J, Jiang C, Xing M, Yao P. Quercetin alleviates ethanol-induced liver steatosis associated with improvement of lipophagy. Food Chem Toxicol 2018; 125:21-28. [PMID: 30580029 DOI: 10.1016/j.fct.2018.12.028] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 12/06/2018] [Accepted: 12/18/2018] [Indexed: 02/07/2023]
Abstract
Although emerging evidence demonstrated that quercetin could be explored as a potential candidate for the early intervention of alcoholic liver disease (ALD), the exact mechanisms against ethanol-induced hepatic steatosis haven't been fully elucidated. Herein, we investigated the effect of quercetin on liver steatosis caused by chronic-plus-single-binge ethanol feeding, focusing on lipophagy. Adult male mice were pair-fed with liquid diets containing ethanol (28% of total calories) and treated with quercetin for 12 weeks. Chronic-plus-binge ethanol consumption led to lipid droplets accumulation and liver damage as evidenced by histopathological changes, the increased content of triglyceride in serum and liver, and the elevated of serum ALT and AST level, which were greatly attenuated by quercetin. Moreover, quercetin blocked autophagy suppression by chronic-binge ethanol intake as manifested by the morphological improvement of mitochondrial characteristics, the increased number of autolysosome and restoration of autophagy-related protein expression. Furthermore, quercetin promoted lipophagy confirmed by the decreased perilipin 2 (PLIN2) level, activated AMPK activity and increased co-localization of liver LC3II and PLIN2 proteins. Collectively, these findings suggest that regular consumption of dietary quercetin has a role in preventing hepatic steatosis induced by chronic-plus-binge ethanol feeding, which mechanism may associate with the evident regulatory effect of quercetin on lipophagy.
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Affiliation(s)
- Hongmei Zeng
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiaoping Guo
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Feng Zhou
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Lin Xiao
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Jingjing Liu
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Chunjie Jiang
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Mingyou Xing
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Ping Yao
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Mazidi M, Katsiki N, Banach M. A higher flavonoid intake is associated with less likelihood of nonalcoholic fatty liver disease: results from a multiethnic study. J Nutr Biochem 2018; 65:66-71. [PMID: 30623852 DOI: 10.1016/j.jnutbio.2018.10.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 09/23/2018] [Accepted: 10/03/2018] [Indexed: 02/07/2023]
Abstract
Limited information exists on the impact of flavonoid intake on nonalcoholic fatty liver disease (NAFLD). We evaluated the link between flavonoid intake, liver tests and risk of NAFLD in a randomly selected sample of US adults (from the National Health and Nutrition Examination Survey, NHANES, 2005-2010). Of the 17,685 participants, 46.9% were men and 45.4% had NAFLD. NAFLD patients had a significantly lower mean flavonoid intake than healthy individuals (111.3±3.6 vs. 201.3±2.3 mg/d, respectively; P<.001). Fatty liver index (FLI) and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly higher in the first tertile (T1) of flavonoid intake compared with the highest tertile (T3: with the highest flavonoid intake) (FLI: 67.1 vs. 36.2, AST: 31.2 VS 26.8 U/L and, ALT: 34.2 vs. 24.2 U/L, respectively; P<.001 for all comparisons). Adjusted linear regression displayed significant and negative associations between FLI, AST, ALT and flavonoid intake (P<.001 for all comparisons). Multivariable logistic regression showed that the risk for NAFLD significantly decreased as flavonoid intake tertiles increased in a stepwise manner (odds ratio: 0.81, 95% confidence interval: 0.78-0.86). Moderation analysis revealed that C-reactive protein (CRP) strongly modulated the impact of flavonoid intake on FLI; participants with higher CRP levels benefited less from flavonoid intake compared with those with lower CRP concentrations. In conclusions, our results suggest a reverse significant association between flavonoid consumption, liver tests and the risk for NAFLD. Furthermore, CRP was shown to essentially moderate this relationship. These findings support recommendations for consumption of flavonoid-rich foods to prevent cardiometabolic diseases.
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Affiliation(s)
- Mohsen Mazidi
- Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, SE-412 96, Gothenburg, Sweden.
| | - Niki Katsiki
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Maciej Banach
- Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland
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48
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Ding Y, Chen X, Wang B, Yu B, Ge J, Shi X. Quercetin suppresses the chymotrypsin-like activity of proteasome via inhibition of MEK1/ERK1/2 signaling pathway in hepatocellular carcinoma HepG2 cells. Can J Physiol Pharmacol 2018; 96:521-526. [PMID: 29394494 DOI: 10.1139/cjpp-2017-0655] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The proteasomal system is a promising target for cancer treatment. Quercetin (Que), a flavonoid compound with antitumor ability, displays the inhibitory effect on proteasome activity. However, the underlying molecular mechanisms are ill defined. The present study found that Que treatment significantly reduced the chymotrypsin-like protease activity of proteasome whereas the trypsin- and caspase-like protease activities remained unchanged in HepG2 cancer cells, along with activation of p38 MAPK and JNK and reduction of ERK1/2 phosphorylation. Que-reduced proteasome activity could not be reverted by inhibition of p38 MAPK and JNK signaling pathway. In addition, MEK1 overexpression or knockdown upregulated or downregulated the chymotrypsin-like protease activity of proteasome, respectively. Both Que and MEK1/ERK1/2 inhibitor attenuated the expression levels of proteasome β subunits. These results indicate that Que-induced suppression of MEK1/ERK1/2 signaling and subsequent reduction of proteasome β subunits is responsible for its inhibitory impacts on proteasome activity.
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Affiliation(s)
- Youming Ding
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Xiaoyan Chen
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Bin Wang
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Bin Yu
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Jianhui Ge
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Xiaokang Shi
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Department of Hepatobiliary & Laparascopic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
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Zhu X, Xiong T, Liu P, Guo X, Xiao L, Zhou F, Tang Y, Yao P. Quercetin ameliorates HFD-induced NAFLD by promoting hepatic VLDL assembly and lipophagy via the IRE1a/XBP1s pathway. Food Chem Toxicol 2018; 114:52-60. [PMID: 29438776 DOI: 10.1016/j.fct.2018.02.019] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 02/05/2018] [Accepted: 02/07/2018] [Indexed: 12/12/2022]
Abstract
The consumption of a quercetin-rich diet has been well-established as a feasible method against non-alcoholic fatty liver disease (NAFLD); however, the molecular mechanisms underlying the progression of NAFLD and its intervention by quercetin remain largely obscure. Male Sprague-Dawley rats fed high-fat diet (HFD), and HepG2 cells stimulated with free fatty acid, were treated with quercetin and various pharmacological reagents to explore the effect of signaling pathways involved in endoplasmic reticulum stress on very low-density lipoprotein (VLDL) assembly and lipophagy. Quercetin intake decreased hepatic TG content by 39%, with a 1.5-fold increase in VLDL, and up-regulated spliced X-box binding protein 1 (XBP1s) expression compared with the HFD group. Thapsigargin or STF-083010 (an IRE1α endonuclease inhibitor) decreased VLDL content in a dose-dependent manner, partially counteracting the protective effects of quercetin, 4-PBA or APY-29 (an IRE1α endonuclease activator). Additionally, microsomal TG-transfer protein complex expression was increased with quercetin-treated and down-regulated by STF-083010. Moreover, quercetin increased co-localization of lysosomes with lipid droplets (LDs) accompanied by decreased p62 accumulation. STF-083010 partially abolished the effect of quercetin on LDs autophagy in an mTOR-independent manner. Collectively, these findings demonstrate that hepatic VLDL assembly and lipophagy are the main targets of quercetin against NAFLD via the IRE1a/XBP1s pathway.
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Affiliation(s)
- Xinhong Zhu
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ting Xiong
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Peiyi Liu
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiaoping Guo
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Lin Xiao
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Feng Zhou
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yuhan Tang
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Ping Yao
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Li C, Guo H, Dai F, Huo X, Li Z, Zhang S, Fu R, He Z, Gu M, Du X, Chen Z. SREBP‑2 expression pattern contributes to susceptibility of Mongolian gerbils to hypercholesterolemia. Mol Med Rep 2018; 17:3288-3296. [PMID: 29257228 DOI: 10.3892/mmr.2017.8195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Accepted: 11/17/2017] [Indexed: 11/05/2022] Open
Abstract
Gerbils are susceptible to dietary cholesterol and prone to hypercholesterolemia and non‑alcoholic fatty liver disease. The present study aimed to explore the role of sterol regulatory element binding protein (SREBP)‑2 and 3‑hydroxy‑3‑methylglutaryl CoA reductase (HMGCR) in hypercholesterolemia susceptibility in gerbils. Male gerbils were fed the normal diet or a high‑fat diet (HFD) for 2 weeks, or the HFD for 2 weeks followed with the normal diet for an additional 2 weeks. Serum lipid levels and hepatic fat deposition were measured, and mRNA and protein levels of SREBP‑2 and HMGCR were evaluated by quantitative polymerase chain reaction and Western blotting. In addition, the role of SREBP‑2 function in cholesterol synthesis from the gerbil primary hepatic cells was also investigated by modulation of SERBP‑2 expression via the transfection of SREBP‑2 overexpression and knockdown plasmids, respectively. The data demonstrated that the total cholesterol and low‑density lipoprotein cholesterol levels in the gerbil serum samples were rapidly and significantly elevated in response to HFD. In addition, the effect of the HFD was rapidly attenuated in the gerbils following a return to the normal diet. HMGCR expression and activation were not altered by dietary cholesterol consumption in the livers from the gerbils in model or recovery groups. HMGCR expression and activation were effectively regulated in cultured hepatic cells from the gerbils. These results indicated that the activation of SREBP‑2 to HMGCR was not terminated in gerbil livers during cholesterol intake. Therefore, stable SREBP‑2 expression contributes to the susceptibility of gerbils to hypercholesterolemia.
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Affiliation(s)
- Changlong Li
- Department of Medical Genetics and Developmental Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Honggang Guo
- Zhejiang Center of Laboratory Animals, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China
| | - Fangwei Dai
- Zhejiang Center of Laboratory Animals, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China
| | - Xueyun Huo
- Department of Medical Genetics and Developmental Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Zhenkun Li
- Department of Medical Genetics and Developmental Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Shuangyue Zhang
- Department of Medical Genetics and Developmental Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Rui Fu
- Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, P.R. China
| | - Zhengming He
- Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, P.R. China
| | - Meng Gu
- Department of Medical Genetics and Developmental Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Xiaoyan Du
- Department of Medical Genetics and Developmental Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
| | - Zhenwen Chen
- Department of Medical Genetics and Developmental Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China
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