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Gharakhanlou BJ, Bonab SB, Amaghani A, Shiri-Shahsavar MR. Curcumin supplementation combined with high intensity interval training modulates serum irisin and lipid profile in obese women: "A randomized double-blind clinical trial". Contemp Clin Trials Commun 2025; 44:101464. [PMID: 40092644 PMCID: PMC11909447 DOI: 10.1016/j.conctc.2025.101464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 02/18/2025] [Accepted: 02/20/2025] [Indexed: 03/19/2025] Open
Abstract
Background Curcumin is the most widely known active substance of turmeric extract, which attributed numerous functional properties, including anti-inflammatory and cardioprotective properties. Inactivity and changes in lifestyle and subsequent overweight/obesity are becoming major health risk factors. Objective the aim of this study was to determine the effect of curcumin supplementation combined with high intensity interval trainings (HIIT) exercise on serum irisin and lipid profile in obese women. Methods 40 inactive women (aged 30-35 years, and body mass index 30 and above) allocated in four groups (10 in each) as followed; curcumin (C), exercise plus curcumin (EC), placebo (P), and exercise plus placebo (EP). All subjects completed an eight-week HIIT program. The C and EC groups received one capsule containing 80 mg curcumin nanomicelle daily throughout study. Blood samples were taken in the beginning and after eight weeks to measure changes in the study variables (irisin and lipid profile). The ANCOVA and Bonferroni's post hoc test was used to compare variables between 4 groups and pairwise at a significance level of ≤0.05 using SPSS-22. Results The results revealed that mean serum irisin (p = 0.023), cholesterol (p = 0.019), triglyceride (p = 0.022), high-density lipoprotein (p = 0.009) and low-density lipoprotein (p = 0.011) were significantly changed in all intervention groups compared to the placebo group. Conclusion Based on these results, it can be concluded that HIIT training with curcumin consumption has a greater significancy on obesity reduction in women; Therefore, curcumin and HIIT exercise can be considered as a therapeutic approach to reduce the negative outcomes of obesity. Clinical trial registry number IRCT20141004019397N2, link. Statement of significance This study investigated the effects of curcumin supplementation combined with high-intensity interval training (HIIT) on human serum Irisin levels for the first time, in a clinical randomized trial. This suggests that HIIT training alongside curcumin consumption may be a promising therapeutic approach to reduce the negative health consequences of obesity in women.
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Affiliation(s)
| | - Solmaz Babaei Bonab
- Department of Sports Sciences, Faculty of Humanities, University of Maragheh, Maragheh, Iran
| | - Akram Amaghani
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Reza Shiri-Shahsavar
- Metabolic Diseases Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
- Clinical Trial Research Center, School of Medicine, University College Dublin, Dublin, Ireland
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Balaji D, Balakrishnan R, Srinivasan D, Subbarayan R, Shrestha R, Srivastava N, Chauhan A. The Impact of SARS-CoV-2 on Liver Diseases and Potential Phytochemical Treatments. INFECTIOUS MICROBES AND DISEASES 2024; 6:177-188. [DOI: 10.1097/im9.0000000000000161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Abstract
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has brought about numerous challenges. One of these challenges is the impact of SARS-CoV-2 on the liver. Although this virus primarily affects the lungs, it can induce elevated transaminase levels and the development of scar tissue in the liver, exacerbating preexisting liver conditions. Individuals with preexisting conditions, such as nonalcoholic fatty liver disease, alcohol-induced liver disease and hepatocellular carcinoma, face an increased risk of mortality from COVID-19. However, drugs currently used to treat COVID-19 have undesirable side effects, which make them unsuitable for patients with preexisting liver conditions. In this review, we explore the potential of phytochemicals, such as apigenin, berberine, curcumin, epigallocatechin-3-gallate, quercetin, resveratrol and silymarin, for treatment of the liver conditions, including nonalcoholic fatty liver disease, alcohol-induced liver disease and hepatocellular carcinoma. We also discuss significant associations between phytochemicals and COVID-19 by depicting their molecular interactions. Based on the discussed overlapping functions, it is important to assess the therapeutic efficacy of phytochemicals that possess hepatoprotective properties as potential alternative treatments for COVID-19.
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Affiliation(s)
- Dhanvee Balaji
- Centre for Advanced Biotherapeutics and Regenerative Medicine, Faculty of Research, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India
| | - Ranjith Balakrishnan
- Centre for Advanced Biotherapeutics and Regenerative Medicine, Faculty of Research, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India
| | - Dhasarathdev Srinivasan
- Centre for Advanced Biotherapeutics and Regenerative Medicine, Faculty of Research, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India
| | | | | | | | - Ankush Chauhan
- Centre for Herbal Pharmacology and Environmental Sustainability, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India
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Jasaputra DK, Rahardjo TM, Gunadi JW, Stefani S, Sutrisno II. Synergistic Effects of Turmeric, Strawberry and Broccoli in Improving Lipid Profile in Adult Patients with Hypercholesterolemia. Pak J Biol Sci 2024; 27:587-593. [PMID: 39731428 DOI: 10.3923/pjbs.2024.587.593] [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] [Indexed: 12/29/2024]
Abstract
<b>Background and Objective:</b> Turmeric, strawberries and broccoli are popular in the community for their beneficial effects in improving lipid profile, but poor bioavailability and absorption of their phytochemical compounds might reduce their effects while given separately. Therefore, their combination might provide a synergistic enhancement of their property as hypolipidemic agents. This study aims to examine the effects of turmeric, strawberry and broccoli in improving lipid profile in adult patients with hypercholesterolemia. <b>Materials and Methods:</b> Twenty hypercholesterolemic adult patients from Unggul Karsa Medika Hospital in Bandung, Indonesia were recruited for the study, they were given 600 mg/day of turmeric/curcuminoid, 100 g of fresh strawberry and 100 g of boiled broccoli for 30 days. The measurement of the patient's characteristics (body weight, height, BMI) and biochemical parameters in the blood (total cholesterol, triglyceride, LDL-C, HDL-C, SGOT, SGPT, urea and creatinine) were conducted before and after the treatment. <b>Results:</b> The mean age of the patients was 49.15±1.9 years old, with mean height 1.56±0.014 m, weight 61.43±1.96 kg and mean body mass index 25.25±0.87 kg/m<sup><a href="86677_op">2</a></sup>. Lipid profile before the treatment: Total cholesterol 239.75±6.56 mg/dL, LDL-C 172.9±6.53 mg/dL, HDL-C 66.55±3.37 mg/dL and triglyceride 193.7±18.45 mg/dL; after the treatment: Total cholesterol 220.7±9.39 mg/dL, LDL-C 153.95±9.98 mg/dL, HDL-C 59.2±2.45 mg/dL and triglyceride 145±16.55 mg/dL. The result showed a significant reduction of total cholesterol (p = 0.014), LDL-C (p = 0.036), HDL-C (p = 0.001) and triglyceride (p = 0.015) after the treatment. Other biochemical parameters (SGOT, SGPT, urea and creatinine) showed normal levels before and after the treatment. <b>Conclusion:</b> In summary, supplementation of turmeric, strawberry and broccoli improves lipid profile in adult patients with hypercholesterolemia.
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Leng T, Zhang L, Ma J, Qu X, Lei B. Intrinsically bioactive multifunctional Poly(citrate-curcumin) for rapid lung injury and MRSA infection therapy. Bioact Mater 2024; 41:158-173. [PMID: 39131630 PMCID: PMC11314446 DOI: 10.1016/j.bioactmat.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 07/01/2024] [Accepted: 07/02/2024] [Indexed: 08/13/2024] Open
Abstract
Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.
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Affiliation(s)
- Tongtong Leng
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Long Zhang
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - Junping Ma
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Xiaoyan Qu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Bo Lei
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
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Liu Q, Chen T, Chen L, Zhao R, Ye X, Wang X, Wu D, Hu J. High Internal Phase Emulsions Stabilized with Ultrasound-Modified Spirulina Protein for Curcumin Delivery. Foods 2024; 13:1324. [PMID: 38731694 PMCID: PMC11083376 DOI: 10.3390/foods13091324] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 04/23/2024] [Accepted: 04/24/2024] [Indexed: 05/13/2024] Open
Abstract
Spirulina protein (SP) is recognized as a nutritious edible microbial protein and holds potential as a natural emulsifier. Due to the inherent challenges SP faces in stabilizing high internal phase emulsions (HIPEs), ultrasonic techniques were utilized for modification. Noticeable alterations in the structural and functional properties of SP were observed following ultrasonic treatment at various power levels (0, 100, 300, and 500 W). Ultrasound treatment disrupted non-covalent interactions within the protein polymer structure, leading to the unfolding of molecular structures and the exposure of hydrophobic groups. Importantly, the particle size of SP was reduced the most at an ultrasonic power of 300 W, and the three-phase contact angle reached its peak at 84.3°. The HIPEs stabilized by SP modified with 300 W ultrasonication have high apparent viscosity and modulus values and strong storage stability under different environmental conditions. Additionally, the encapsulation of curcumin in HIPEs led to improved retention of curcumin across various settings. The bioavailability increased to 35.36, which is 2.8 times higher than the pure oil. These findings suggest that ultrasound-modified SP is a promising emulsifier for HIPEs, and is expected to encapsulate hydrophobic nutrients such as curcumin more effectively.
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Affiliation(s)
- Qing Liu
- State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, China; (Q.L.); (T.C.); (L.C.); (X.Y.); (X.W.); (D.W.)
- School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Tao Chen
- State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, China; (Q.L.); (T.C.); (L.C.); (X.Y.); (X.W.); (D.W.)
- School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Lihang Chen
- State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, China; (Q.L.); (T.C.); (L.C.); (X.Y.); (X.W.); (D.W.)
- School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Runan Zhao
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China;
| | - Ximei Ye
- State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, China; (Q.L.); (T.C.); (L.C.); (X.Y.); (X.W.); (D.W.)
- School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Xinchuang Wang
- State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, China; (Q.L.); (T.C.); (L.C.); (X.Y.); (X.W.); (D.W.)
- School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Di Wu
- State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, China; (Q.L.); (T.C.); (L.C.); (X.Y.); (X.W.); (D.W.)
- School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Jiangning Hu
- State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, China; (Q.L.); (T.C.); (L.C.); (X.Y.); (X.W.); (D.W.)
- School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
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Bertoncini-Silva C, Vlad A, Ricciarelli R, Giacomo Fassini P, Suen VMM, Zingg JM. Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment. Antioxidants (Basel) 2024; 13:331. [PMID: 38539864 PMCID: PMC10967568 DOI: 10.3390/antiox13030331] [Citation(s) in RCA: 29] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/02/2024] [Accepted: 03/05/2024] [Indexed: 01/06/2025] Open
Abstract
Curcumin, a natural polyphenolic component from Curcuma longa roots, is the main bioactive component of turmeric spice and has gained increasing interest due to its proposed anti-cancer, anti-obesity, anti-inflammatory, antioxidant, and lipid-lowering effects, in addition to its thermogenic capacity. While intake from dietary sources such as curry may be sufficient to affect the intestinal microbiome and thus may act indirectly, intact curcumin in the body may be too low (<1 microM) and not sufficient to affect signaling and gene expression, as observed in vitro with cultured cells (10-20 microM). Several strategies can be envisioned to increase curcumin levels in the body, such as decreasing its metabolism or increasing absorption through the formation of nanoparticles. However, since high curcumin levels could also lead to undesired regulatory effects on cellular signaling and gene expression, such studies may need to be carefully monitored. Here, we review the bioavailability of curcumin and to what extent increasing curcumin levels using nanoformulations may increase the bioavailability and bioactivity of curcumin and its metabolites. This enhancement could potentially amplify the disease-preventing effects of curcumin, often by leveraging its robust antioxidant properties.
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Affiliation(s)
- Caroline Bertoncini-Silva
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil; (C.B.-S.); (P.G.F.)
| | - Adelina Vlad
- Department of Functional Sciences I/Physiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Roberta Ricciarelli
- Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy;
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Priscila Giacomo Fassini
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil; (C.B.-S.); (P.G.F.)
| | - Vivian Marques Miguel Suen
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil; (C.B.-S.); (P.G.F.)
| | - Jean-Marc Zingg
- Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
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Mohammadi F, Mohsenpour MA, Sohrabi Z, Niakousari M, Jeddi M, Hassanzadeh J, Ferns GA, Eftekhari MH. The effects of powdered drinks enriched with curcumin and probiotics on lipid profile and atherogenic indices in patients with metabolic syndrome: A randomized, double-blinded, placebo-controlled clinical trial. Food Sci Nutr 2024; 12:1257-1267. [PMID: 38370069 PMCID: PMC10867475 DOI: 10.1002/fsn3.3839] [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: 07/20/2023] [Revised: 10/27/2023] [Accepted: 11/03/2023] [Indexed: 02/20/2024] Open
Abstract
Cardiovascular disease is prevalent globally and is the most common complication of metabolic syndrome (MetS). Previous studies have suggested that curcumin and probiotics may improve the lipid profile, so we aimed to investigate the effects of the edible powder enriched with these substances on lipid profile level and atherogenic indices such as Atherogenic Coefficient (AC), Castelli Risk Index-I (CRI-I), Castelli Risk Index-II (CRI-II), and Atherogenic Index of Plasma (AIP). In the present parallel randomized double-blinded placebo-controlled clinical trial, 124 people with MetS with overweight or obesity were randomly allocated to 4 groups and were followed up for 8 weeks. The participants received a low-calorie diet and a daily sachet of enriched powder drink. The sachets contained either 109 CFU of probiotics or 1 g of curcumin, or probiotic + curcumin (pro + cur), or placebo, respectively. The fasting lipid profile and atherogenic indices were measured at the beginning and end of the study. One hundred and fourteen participants completed the study. At the end of the study, the within- and between-group comparisons showed no significant differences in lipid profile and atherogenic indices (p > .05). Based on the results of the current study, taking an oral powder containing 1 g curcumin and 109 CFU probiotics for 8 weeks had no effect on the lipid profile level and atherogenic indices; however, more studies are recommended.
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Affiliation(s)
- Farzaneh Mohammadi
- Department of Clinical Nutrition, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
- Student Research Committee, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
| | - Mohammad Ali Mohsenpour
- Department of Clinical Nutrition, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
- Student Research Committee, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
| | - Zahra Sohrabi
- Nutrition Research Center, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
| | - Mehrdad Niakousari
- Department of Food Science and Technology, College of AgricultureShiraz UniversityShirazIran
| | - Marjan Jeddi
- Endocrinology and Metabolism Research CenterShiraz University of Medical SciencesShirazIran
| | - Jafar Hassanzadeh
- Department of Epidemiology, School of Health, Research Center for Health Sciences, Institute of HealthShiraz University of Medical SciencesShirazIran
| | - Gordon A. Ferns
- Department of Medical EducationBrighton & Sussex Medical SchoolBrightonUK
| | - Mohammad Hassan Eftekhari
- Department of Clinical Nutrition, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
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Zhou M, Huang J, Zhou J, Zhi C, Bai Y, Che Q, Cao H, Guo J, Su Z. Anti-Obesity Effect and Mechanism of Chitooligosaccharides Were Revealed Based on Lipidomics in Diet-Induced Obese Mice. Molecules 2023; 28:5595. [PMID: 37513467 PMCID: PMC10384603 DOI: 10.3390/molecules28145595] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 07/16/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023] Open
Abstract
Chitooligosaccharide (COS) is a natural product from the ocean, and while many studies have reported its important role in metabolic diseases, no study has systematically elaborated the anti-obesity effect and mechanism of COS. Herein, COSM (MW ≤ 3000 Da) was administered to diet-induced obese mice by oral gavage once daily for eight weeks. The results show that COSM administration reduced body weight; slowed weight gain; reduced serum Glu, insulin, NEFA, TC, TG, and LDL-C levels; increased serum HSL and HDL-C levels; improved inflammation; and reduced lipid droplet size in adipose tissue. Further lipidomic analysis of adipose tissue revealed that 31 lipid species are considered to be underlying lipid biomarkers in COS therapy. These lipids are mainly enriched in pathways involving insulin resistance, thermogenesis, cholesterol metabolism, glyceride metabolism and cyclic adenosine monophosphate (cAMP), which sheds light on the weight loss mechanism of COS. The Western blot assay demonstrated that COSM intervention can improve insulin resistance, inhibit de novo synthesis, and promote thermogenesis and β-oxidation in mitochondria by the AMPK pathway, thereby alleviating high-fat diet-induced obesity. In short, our study can provide a more comprehensive direction for the application of COS in obesity based on molecular markers.
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Affiliation(s)
- Minchuan Zhou
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Jingqing Huang
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Department of Pharmacy, Affiliated Hospital of Guilin Medical University, Guilin 541001, China
| | - Jingwen Zhou
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Cuiting Zhi
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yan Bai
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China
| | - Qishi Che
- Guangzhou Rainhome Pharm & Tech Co., Ltd., Science City, Guangzhou 510663, China
| | - Hua Cao
- School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458, China
| | - Jiao Guo
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Zhengquan Su
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
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9
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Zhang X, Zhu L, Wang X, Zhang H, Wang L, Xia L. Basic research on curcumin in cervical cancer: Progress and perspectives. Biomed Pharmacother 2023; 162:114590. [PMID: 36965256 DOI: 10.1016/j.biopha.2023.114590] [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: 12/31/2022] [Revised: 03/14/2023] [Accepted: 03/22/2023] [Indexed: 03/27/2023] Open
Abstract
Curcumin is a polyphenolic substance extracted from plants such as Curcuma longa, Curcuma zedoaria, and radix curcumae, and it has attracted much attention because of the anti-inflammatory, antioxidant, anti-tumor, antibacterial and other multiple pharmacological effects. Cervical cancer is one of the most common malignant tumors in women. With the application of HPV (human papillomavirus) vaccine, the incidence of cervical cancer is expected to be reduced, but it remains difficult to promote the vaccine among low-income population. As a commonly used food additive, curcumin has recently been found to have a significant therapeutic effect in the treatment of cervical cancer. In recent years, numerous in vitro and in vivo studies have found that curcumin can have significant efficacy in anti-cervical cancer treatment by promoting apoptosis, inhibiting tumour cell proliferation, metastasis and invasion, inhibiting HPV and inducing autophagy in tumour cells. However, due to poor water solubility, rapid catabolism, and low bioavailability of curcumin, studies on curcumin derivatives and novel formulations are increasing. Curcumin has a wide range of mechanisms of action against cervical cancer and may become a novel antitumor drug in the future, opening up new ideas for the research of curcumin in the field of antitumor. There is a lack of systematic reviews on the mechanism of action of curcumin against cervical cancer. Therefore, this study is a review of the literature based on the mechanism of action of curcumin against cervical cancer, with a view to providing reference information for scientific and clinical practitioners.
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Affiliation(s)
- Xiaoyu Zhang
- School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Lin Zhu
- School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xuezhen Wang
- School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hairong Zhang
- Department of Obstetrics and Gynecology, Shandong Provincial Third Hospital, Jinan, China
| | - Lianzhong Wang
- Department of Respiratory and Critical Care Medicine of Second affiliated hospital, Shandong University of Traditional Chinese Medicine, Jinan, China.
| | - Lei Xia
- Department of Pathology, Shandong University of Traditional Chinese Medicine, Jinan, China.
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Shuai X, Dai T, McClements DJ, Ruan R, Du L, Liu Y, Chen J. Hypolipidemic effects of macadamia oil are related to AMPK activation and oxidative stress relief: In vitro and in vivo studies. Food Res Int 2023; 168:112772. [PMID: 37120222 DOI: 10.1016/j.foodres.2023.112772] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 01/19/2023] [Accepted: 03/24/2023] [Indexed: 03/28/2023]
Abstract
Macadamia oil is rich in monounsaturated fatty acids, especially a high level of palmitoleic acid, which may have beneficial health effects by lowering blood lipid levels. In our study, the hypolipidemic effects of macadamia oil and its potential mechanisms of action were investigated using a combination of in vitro and in vivo assays. The results showed that macadamia oil significantly reduced lipid accumulation, and improved triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels in oleic acid-induced high-fat HepG2 cells. The macadamia oil treatment also exhibited antioxidant effects, as seen by its ability to reduce reactive oxygen species and malondialdehyde (MDA) levels, and increase superoxide dismutase (SOD) activity. The effects of 1000 μg/mL of macadamia oil were comparable to that of 4.19 μg/mL simvastatin. The results of qRT-PCR and western blotting analyses indicated that macadamia oil effectively inhibited hyperlipidemia by reducing the expression levels of SREBP-1c, PPAR-γ, ACC and FAS and by enhancing the expression levels of HO-1, NRF2 and γ-GCS, via AMPK activation and oxidative stress relief, respectively. In addition, different doses of macadamia oil were found to significantly improve liver lipid accumulation, reduce serum and liver TC, TG, and LDL-C levels, increase HDL-C levels, increase antioxidant enzyme (SOD, GSH-Px, and T-AOC) activity, and decrease the MDA content of mice on a high-fat diet. These results indicated that macadamia oil had a hypolipidemic effect and provide insights that might facilitate the development of functional food and dietary supplements.
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Affiliation(s)
- Xixiang Shuai
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Taotao Dai
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | | | - Roger Ruan
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Liqing Du
- South Subtropical Crop Research Institute, China Academy of Tropical Agricultural Sciences, Zhanjiang 524091, China
| | - Yuhuan Liu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Jun Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
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11
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Frattaruolo L, Marra F, Lauria G, Siciliano C, Curcio R, Muto L, Brindisi M, Aiello D, Napoli A, Fiermonte G, Cappello AR, Fiorillo M, Ahmed A, Dolce V. A Picrocrocin-Enriched Fraction from a Saffron Extract Affects Lipid Homeostasis in HepG2 Cells through a Non-Statin-like Mode. Int J Mol Sci 2023; 24:3060. [PMID: 36834472 PMCID: PMC9965904 DOI: 10.3390/ijms24043060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/25/2023] [Accepted: 01/31/2023] [Indexed: 02/08/2023] Open
Abstract
Dyslipidemia is a lipid metabolism disorder associated with the loss of the physiological homeostasis that ensures safe levels of lipids in the organism. This metabolic disorder can trigger pathological conditions such as atherosclerosis and cardiovascular diseases. In this regard, statins currently represent the main pharmacological therapy, but their contraindications and side effects limit their use. This is stimulating the search for new therapeutic strategies. In this work, we investigated in HepG2 cells the hypolipidemic potential of a picrocrocin-enriched fraction, analyzed by high-resolution 1H NMR and obtained from a saffron extract, the stigmas of Crocus sativus L., a precious spice that has already displayed interesting biological properties. Spectrophotometric assays, as well as expression level of the main enzymes involved in lipid metabolism, have highlighted the interesting hypolipidemic effects of this natural compound; they seem to be exerted through a non-statin-like mechanism. Overall, this work provides new insights into the metabolic effects of picrocrocin, thus confirming the biological potential of saffron and paving the way for in vivo studies that could validate this spice or its phytocomplexes as useful adjuvants in balancing blood lipid homeostasis.
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Affiliation(s)
- Luca Frattaruolo
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Federica Marra
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Graziantonio Lauria
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Carlo Siciliano
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Rosita Curcio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Luigina Muto
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Matteo Brindisi
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Donatella Aiello
- Department of Chemistry and Chemical Technologies, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Anna Napoli
- Department of Chemistry and Chemical Technologies, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Giuseppe Fiermonte
- Department of Biosciences, Biotechnologies and Environment, University of Bari, 70125 Bari, Italy
| | - Anna Rita Cappello
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Marco Fiorillo
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Amer Ahmed
- Department of Biosciences, Biotechnologies and Environment, University of Bari, 70125 Bari, Italy
| | - Vincenza Dolce
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
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12
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Bertoncini-Silva C, Zingg JM, Fassini PG, Suen VMM. Bioactive dietary components-Anti-obesity effects related to energy metabolism and inflammation. Biofactors 2022; 49:297-321. [PMID: 36468445 DOI: 10.1002/biof.1921] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 11/18/2022] [Indexed: 12/10/2022]
Abstract
Obesity is the result of the long-term energy imbalance between the excess calories consumed and the few calories expended. Reducing the intake of energy dense foods (fats, sugars), and strategies such as fasting and caloric restriction can promote body weight loss. Not only energy in terms of calories, but also the specific composition of the diet can affect the way the food is absorbed and how its energy is stored, used or dissipated. Recent research has shown that bioactive components of food, such as polyphenols and vitamins, can influence obesity and its pathologic complications such as insulin resistance, inflammation and metabolic syndrome. Individual micronutrients can influence lipid turnover but for long-term effects on weight stability, dietary patterns containing several micronutrients may be required. At the molecular level, these molecules modulate signaling and the expression of genes that are involved in the regulation of energy intake, lipid metabolism, adipogenesis into white, beige and brown adipose tissue, thermogenesis, lipotoxicity, adipo/cytokine synthesis, and inflammation. Higher concentrations of these molecules can be reached in the intestine, where they can modulate the composition and action of the microbiome. In this review, the molecular mechanisms by which bioactive compounds and vitamins modulate energy metabolism, inflammation and obesity are discussed.
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Affiliation(s)
- Caroline Bertoncini-Silva
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Jean-Marc Zingg
- Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Priscila Giacomo Fassini
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Vivian Marques Miguel Suen
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
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13
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Saeedi F, Farkhondeh T, Roshanravan B, Amirabadizadeh A, Ashrafizadeh M, Samarghandian S. Curcumin and blood lipid levels: an updated systematic review and meta-analysis of randomised clinical trials. Arch Physiol Biochem 2022; 128:1493-1502. [PMID: 36264280 DOI: 10.1080/13813455.2020.1779309] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The present study was designed to indicate the protective effects of curcumin on dyslipidemia. Main databases were searched to recognise randomised clinical trials evaluating the effect of curcumin on blood lipid profiles. The pooled odds ratio with a 95% confidence interval (CI) was used to evaluate the effect of curcumin on blood lipid parameters. HDL-C levels in the curcumin group were 0.04-fold lower than placebo (95% CI:-0.36-0.29; Z = 0.23; p = .82). LDL-C levels in the curcumin group reduced by 0.17 versus the placebo group (95% CI: -0.43-0.09; Z = 1.27; p = .2). TC levels in the curcumin group were 0.21 lower versus the placebo group (95% CI: -0.55-0.13; Z = 1.22; p = .22). TG level in the curcumin group were 0.05 lower versus the placebo (95% CI: -0.20-0.11; Z = 0.58; p = .56). This study suggests that curcumin may reduce blood lipid levels and can be used as a hypolipidemic agent.
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Affiliation(s)
- Farhad Saeedi
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Tahereh Farkhondeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Babak Roshanravan
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran
| | - Alireza Amirabadizadeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Saeed Samarghandian
- Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
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14
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Ceja-Galicia ZA, García-Arroyo FE, Aparicio-Trejo OE, El-Hafidi M, Gonzaga-Sánchez G, León-Contreras JC, Hernández-Pando R, Guevara-Cruz M, Tovar AR, Rojas-Morales P, Aranda-Rivera AK, Sánchez-Lozada LG, Tapia E, Pedraza-Chaverri J. Therapeutic Effect of Curcumin on 5/6Nx Hypertriglyceridemia: Association with the Improvement of Renal Mitochondrial β-Oxidation and Lipid Metabolism in Kidney and Liver. Antioxidants (Basel) 2022; 11:2195. [PMID: 36358567 PMCID: PMC9686550 DOI: 10.3390/antiox11112195] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 10/04/2023] Open
Abstract
Chronic kidney disease (CKD) prevalence is constantly increasing, and dyslipidemia in this disease is characteristic, favoring cardiovascular events. However, the mechanisms of CKD dyslipidemia are not fully understood. The use of curcumin (CUR) in CKD models such as 5/6 nephrectomy (5/6Nx) has shown multiple beneficial effects, so it has been proposed to correct dyslipidemia without side effects. This work aimed to characterize CUR's potential therapeutic effect on dyslipidemia and alterations in lipid metabolism and mitochondrial ß-oxidation in the liver and kidney in 5/6Nx. Male Wistar rats were subjected to 5/6Nx and progressed by 4 weeks; meanwhile, CUR (120 mg/kg) was administered for weeks 5 to 8. Our results showed that CUR reversed the increase in liver and kidney damage and hypertriglyceridemia induced by 5/6Nx. CUR also reversed mitochondrial membrane depolarization and β-oxidation disorders in the kidney and the increased lipid uptake and the high levels of proteins involved in fatty acid synthesis in the liver and kidney. CUR also decreased lipogenesis and increased mitochondrial biogenesis markers in the liver. Therefore, we concluded that the therapeutic effect of curcumin on 5/6Nx hypertriglyceridemia is associated with the restoration of renal mitochondrial ß-oxidation and the reduction in lipid synthesis and uptake in the kidneys and liver.
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Affiliation(s)
- Zeltzin Alejandra Ceja-Galicia
- Department of Cardio-Renal Physiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
- Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | | | - Omar Emiliano Aparicio-Trejo
- Department of Cardio-Renal Physiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
| | - Mohammed El-Hafidi
- Department of Cardiovascular Biomedicine, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
| | - Guillermo Gonzaga-Sánchez
- Department of Cardio-Renal Physiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
| | - Juan Carlos León-Contreras
- Department of Experimental Pathology, National Institute of Medical Science and Nutrition “Salvador Zubirán”, Mexico City 14080, Mexico
| | - Rogelio Hernández-Pando
- Department of Experimental Pathology, National Institute of Medical Science and Nutrition “Salvador Zubirán”, Mexico City 14080, Mexico
| | - Martha Guevara-Cruz
- Department of Nutrition Physiology, National Institute of Medical Science and Nutrition “Salvador Zubirán”, Mexico City 14080, Mexico
| | - Armando R. Tovar
- Department of Nutrition Physiology, National Institute of Medical Science and Nutrition “Salvador Zubirán”, Mexico City 14080, Mexico
| | - Pedro Rojas-Morales
- Department of Cardio-Renal Physiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
- Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | - Ana Karina Aranda-Rivera
- Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | | | - Edilia Tapia
- Department of Cardio-Renal Physiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
| | - José Pedraza-Chaverri
- Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico
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15
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Nouri M, Sohaei S, Shalaby MN, Mehrabani S, Ramezani A, Faghih S. Effect of curcumin on body mass index and glycemic indices in females with PCOS: a systematic review and meta-analysis of randomized controlled trial. NUTRITION & FOOD SCIENCE 2022; 52:1129-1141. [DOI: 10.1108/nfs-11-2021-0334] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Purpose
This paper aims to assess the impact of curcumin supplementation body mass index and glycemic indices in women with polycystic ovary syndrome (PCOS).
Design/methodology/approach
A systematic search of the literature was conducted in PubMed, Scopus and ISI web of science to identify all randomized controlled trials (RCTs) published from the earliest record up to February 2021. The authors used a random-effects model to estimate pooled effect sizes.
Findings
A total of four potentially related clinical trials met the inclusion criteria which included a total of 198 participants. Random-effects meta-analysis showed significant effects of curcumin on fasting blood sugar (FBS) (−3.62 mg/dl, 95% CI [−5.65, −1.58], p-value < 0.001, I2 = 0.0%), insulin level (−1.67 µU/mL, 95% CI [−3.06, −0.28], p-value = 0.018, I2 = 0.0%) and homeostasis model of assessment insulin resistance (HOMA-IR) (−0.42, 95% CI [−0.76, −0.09], p-value < 0.01, I2 = 0.0%). No evidence of publication bias was discovered in the meta-analyses.
Originality/value
Present systematic review and meta-analysis of RCTs showed beneficial effects of curcumin consumption on FBS, insulin level and HOMA-IR in patients with PCOS. However, further large-scale studies are needed to confirm these results.
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16
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Vafaeipour Z, Razavi BM, Hosseinzadeh H. Effects of turmeric (Curcuma longa) and its constituent (curcumin) on the metabolic syndrome: An updated review. JOURNAL OF INTEGRATIVE MEDICINE 2022; 20:193-203. [PMID: 35292209 DOI: 10.1016/j.joim.2022.02.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 01/13/2022] [Indexed: 12/16/2022]
Abstract
Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world's adult population is about 20%-25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitro, in vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects.
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Affiliation(s)
- Zeinab Vafaeipour
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
| | - Bibi Marjan Razavi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran; Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
| | - Hossein Hosseinzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran.
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17
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Murakami A. Novel mechanisms underlying bioactivities of polyphenols via hormesis. CURRENT OPINION IN TOXICOLOGY 2022. [DOI: 10.1016/j.cotox.2022.02.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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18
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Ageing, Age-Related Cardiovascular Risk and the Beneficial Role of Natural Components Intake. Int J Mol Sci 2021; 23:ijms23010183. [PMID: 35008609 PMCID: PMC8745076 DOI: 10.3390/ijms23010183] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/14/2021] [Accepted: 12/16/2021] [Indexed: 12/18/2022] Open
Abstract
Ageing, in a natural way, leads to the gradual worsening of the functional capacity of all systems and, eventually, to death. This process is strongly associated with higher metabolic and oxidative stress, low-grade inflammation, accumulation of DNA mutations and increased levels of related damage. Detrimental changes that accumulate in body cells and tissues with time raise the vulnerability to environmental challenges and enhance the risk of major chronic diseases and mortality. There are several theses concerning the mechanisms of ageing: genetic, free radical telomerase, mitochondrial decline, metabolic damage, cellular senescence, neuroendocrine theory, Hay-flick limit and membrane theories, cellular death as well as the accumulation of toxic and non-toxic garbage. Moreover, ageing is associated with structural changes within the myocardium, cardiac conduction system, the endocardium as well as the vasculature. With time, the cardiac structures lose elasticity, and fibrotic changes occur in the heart valves. Ageing is also associated with a higher risk of atherosclerosis. The results of studies suggest that some natural compounds may slow down this process and protect against age-related diseases. Animal studies imply that some of them may prolong the lifespan; however, this trend is not so obvious in humans.
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Turgut R, Kartal M, Akkol EK, Demirbolat İ, Taştan H. Development of Cholesterol-Lowering and Detox Formulations Using Bentonite and Herbal Ingredients. Front Pharmacol 2021; 12:775789. [PMID: 34938189 PMCID: PMC8685422 DOI: 10.3389/fphar.2021.775789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 11/16/2021] [Indexed: 11/17/2022] Open
Abstract
Detoxification enzymes involved in human metabolism works to minimize the potential xenobiotic-induced damage constantly. Studies have revealed that toxin accumulation plays an important role in the etiology of cardiovascular disease. This study has been designed to provide evidence of medicinal use of bentonite, turmeric (Curcuma longa L.), grape (Vitis vinifera L.) seed, flaxseed (Linum usitatissimum L.), and psyllium (Plantago ovata L.) as detoxification and cholesterol-lowering agents using a hypercholesterolemic model in mice. The potential hypocholesterolemic effects and detoxification ability of these ingredients were evaluated at the same time: Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, plasma total antioxidant activity, nitric acid, leptin levels and glutathione, glutathione peroxidase, lipid peroxidation, superoxide dismutase and catalase values were measured. It was determined that GBTF group (grape seed extract, bentonite, turmeric, and flaxseed), GBTP group (grape seed extract, bentonite, turmeric, and psyllium), and GBT group (grape seed extract, bentonite, and turmeric) of the tested materials decreased the serum total cholesterol concentration by 64.8, 57.5, and 48.9%, respectively, in mice fed a high cholesterol diet. In addition, it was determined that some detoxification parameters such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase were statistically significantly reversed in GBTF, GBTP, and GBT groups. Flaxseed, psyllium, and bentonite clay did not show significant effects in reducing total cholesterol; however, GBTF, GBTP, and GBT groups interventions had a significant effect in reducing total cholesterol levels. Moreover, it was observed that adding flaxseed or psyllium to the GBT group increased the cholesterol-lowering effect. Therefore, it can be thought that this significant effect is due to the synergistic effect of the raw materials. When the results obtained were evaluated, it was seen that the cholesterol-lowering and detoxification effects of the combinations were higher than from the effect of natural material used alone. As a result, combinations of some of these ingredients have a positive effect on reducing the risk of cardiovascular disease.
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Affiliation(s)
- Rana Turgut
- Department of Pharmacognosy, Health Sciences Institute, Bezmialem Vakif University, Istanbul, Turkey
| | - Murat Kartal
- Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
| | - Esra Küpeli Akkol
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, Turkey
| | - İlker Demirbolat
- Bezmialem Center of Education, Practice, and Research in Phytotherapy, Bezmialem Vakif University, Istanbul, Turkey
| | - Hakkı Taştan
- Department of Biology, Faculty of Science, Gazi University, Ankara, Turkey
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Ghareghomi S, Rahban M, Moosavi-Movahedi Z, Habibi-Rezaei M, Saso L, Moosavi-Movahedi AA. The Potential Role of Curcumin in Modulating the Master Antioxidant Pathway in Diabetic Hypoxia-Induced Complications. Molecules 2021; 26:molecules26247658. [PMID: 34946740 PMCID: PMC8706440 DOI: 10.3390/molecules26247658] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/09/2021] [Accepted: 12/13/2021] [Indexed: 12/13/2022] Open
Abstract
Oxidative stress is the leading player in the onset and development of various diseases. The Keap1-Nrf2 pathway is a pivotal antioxidant system that preserves the cells' redox balance. It decreases inflammation in which the nuclear trans-localization of Nrf2 as a transcription factor promotes various antioxidant responses in cells. Through some other directions and regulatory proteins, this pathway plays a fundamental role in preventing several diseases and reducing their complications. Regulation of the Nrf2 pathway occurs on transcriptional and post-transcriptional levels, and these regulations play a significant role in its activity. There is a subtle correlation between the Nrf2 pathway and the pivotal signaling pathways, including PI3 kinase/AKT/mTOR, NF-κB and HIF-1 factors. This demonstrates its role in the development of various diseases. Curcumin is a yellow polyphenolic compound from Curcuma longa with multiple bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Since hyperglycemia and increased reactive oxygen species (ROS) are the leading causes of common diabetic complications, reducing the generation of ROS can be a fundamental approach to dealing with these complications. Curcumin can be considered a potential treatment option by creating an efficient therapeutic to counteract ROS and reduce its detrimental effects. This review discusses Nrf2 pathway regulation at different levels and its correlation with other important pathways and proteins in the cell involved in the progression of diabetic complications and targeting these pathways by curcumin.
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Affiliation(s)
- Somayyeh Ghareghomi
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran 1417466191, Iran; (S.G.); (M.R.)
| | - Mahdie Rahban
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran 1417466191, Iran; (S.G.); (M.R.)
| | | | - Mehran Habibi-Rezaei
- School of Biology, College of Science, University of Tehran, Tehran 1417466191, Iran
- Center of Excellence in NanoBiomedicine, University of Tehran, Tehran 1417466191, Iran
- Correspondence: (M.H.-R.); (A.A.M.-M.); Tel.: +98-21-6111-3214 (M.H.-R.); +98-21-6111-3381 (A.A.M.-M.); Fax: +98-21-6697-1941 (M.H.-R.); +98-21-6640-4680 (A.A.M.-M.)
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer,” Sapienza University of Rome, 00185 Rome, Italy;
| | - Ali Akbar Moosavi-Movahedi
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran 1417466191, Iran; (S.G.); (M.R.)
- UNESCO Chair on Interdisciplinary Research in Diabetes, University of Tehran, Tehran 1417466191, Iran
- Correspondence: (M.H.-R.); (A.A.M.-M.); Tel.: +98-21-6111-3214 (M.H.-R.); +98-21-6111-3381 (A.A.M.-M.); Fax: +98-21-6697-1941 (M.H.-R.); +98-21-6640-4680 (A.A.M.-M.)
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21
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Zuraini NZA, Sekar M, Wu YS, Gan SH, Bonam SR, Mat Rani NNI, Begum MY, Lum PT, Subramaniyan V, Fuloria NK, Fuloria S. Promising Nutritional Fruits Against Cardiovascular Diseases: An Overview of Experimental Evidence and Understanding Their Mechanisms of Action. Vasc Health Risk Manag 2021; 17:739-769. [PMID: 34858028 PMCID: PMC8631183 DOI: 10.2147/vhrm.s328096] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 09/06/2021] [Indexed: 12/22/2022] Open
Abstract
Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.
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Affiliation(s)
- Nur Zulaikha Azwa Zuraini
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia
| | - Mahendran Sekar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia
| | - Yuan Seng Wu
- Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia
- Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia
| | - Siew Hua Gan
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, 47500, Malaysia
| | - Srinivasa Reddy Bonam
- Institut National de la Santé et de la Recherche Médicale, Centre de Recherché des Cordeliers, Sorbonne Université, Université de Paris, Paris, France
| | - Nur Najihah Izzati Mat Rani
- Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia
| | - M Yasmin Begum
- Department of Pharmaceutics, College of Pharmacy, King Khalid University (KKU), Asir-Abha, 61421, Saudi Arabia
| | - Pei Teng Lum
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia
| | | | - Neeraj Kumar Fuloria
- Faculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, Malaysia
| | - Shivkanya Fuloria
- Faculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, Malaysia
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22
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Abdelazeem B, Abbas KS, Shehata J, Baral N, Banour S, Hassan M. The effects of curcumin as dietary supplement for patients with polycystic ovary syndrome: An updated systematic review and meta-analysis of randomized clinical trials. Phytother Res 2021; 36:22-32. [PMID: 34517426 DOI: 10.1002/ptr.7274] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/15/2021] [Accepted: 08/25/2021] [Indexed: 11/09/2022]
Abstract
This review aims to evaluate if there are clinical benefits of curcumin (CUR) in patients with polycystic ovary syndrome (PCOS). Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were systematically searched to identify only randomized clinical trials (RCTs) that assessed CUR in patients with PCOS from inception to May 5, 2021. Five RCTs were included with a total of 296 patients, with 148 among the CUR groups and 148 patients among the control group. Revised Cochrane risk-of-bias tool for randomized trials was used to assess the risk of bias, three RCTs provided a low risk of bias and two provided a high risk of bias. Compared with the control group, CUR was associated with a statistically significant improvement in the glycemic control including fasting blood glucose (MD = -3.67; 95% CI = [-5.25, -2.08], p < .00001), insulin level (MD = -1.91; 95% CI = [-2.97, -0.84], p = .0005), homeostasis model assessment of insulin resistance (MD = -0.55; 95% CI = [-0.83, -0.27], p = .0001), and quantitative insulin sensitivity check index (MD = 0.01; 95% CI = [0.00, 0.02], p = .0005). The mean difference in total cholesterol was also statistically significant (MD = -15.55; 95% CI = [-30.33, -0.76], p < .04). The rest of the secondary outcomes, including LDL, HDL, sex hormone, body weight, and CRP, were not statistically significant. This review concluded that among patients with PCOS, the use of CUR demonstrated a significant difference from the control group for glycemic control. Those findings suggest that CUR confers clinical benefits in patients with PCOS. However, due to the limited number of the included studies, further high-quality studies are needed to establish the clinical efficacy of the CUR.
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Affiliation(s)
- Basel Abdelazeem
- Department of Internal Medicine, McLaren Health Care, Flint/Michigan State University, Flint, Michigan, USA
| | | | | | - Nischit Baral
- Department of Internal Medicine, McLaren Health Care, Flint/Michigan State University, Flint, Michigan, USA
| | - Sandi Banour
- Department of Pharmacy, Midwestern University, Glendale, Arizona, USA
| | - Mustafa Hassan
- Department of Internal Medicine, McLaren Health Care, Flint/Michigan State University, Flint, Michigan, USA
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23
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Fu YS, Chen TH, Weng L, Huang L, Lai D, Weng CF. Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential. Biomed Pharmacother 2021; 141:111888. [PMID: 34237598 DOI: 10.1016/j.biopha.2021.111888] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/12/2021] [Accepted: 06/28/2021] [Indexed: 12/11/2022] Open
Abstract
Curcumin, isolated from Curcuma longa L., is a fat-soluble natural compound that can be obtained from ginger plant tuber roots, which accumulative evidences have demonstrated that it can resist viral and microbial infection and has anti-tumor, reduction of blood lipid and blood glucose, antioxidant and removal of free radicals, and is active against numerous disorders various chronic diseases including cardiovascular, pulmonary, neurological and autoimmune diseases. In this article is highlighted the recent evidence of curcuminoids applied in sevral aspects of medical problem particular in COVID-19 pandemics. We have searched several literature databases including MEDLINE (PubMed), EMBASE, the Web of Science, Cochrane Library, Google Scholar, and the ClinicalTrials.gov website via using curcumin and medicinal properties as a keyword. All studies published from the time when the database was established to May 2021 was retrieved. This review article summarizes the growing confirmation for the mechanisms related to curcumin's physiological and pharmacological effects with related target proteins interaction via molecular docking. The purpose is to provide deeper insight and understandings of curcumin's medicinal value in the discovery and development of new drugs. Curcumin could be used in the prevention or therapy of cardiovascular disease, respiratory diseases, cancer, neurodegeneration, infection, and inflammation based on cellular biochemical, physiological regulation, infection suppression and immunomodulation.
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Affiliation(s)
- Yaw-Syan Fu
- Department of Physiology, School of Basic Medicine, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Ting-Hsu Chen
- Department of Physiology, School of Basic Medicine, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Lebin Weng
- Department of Physiology, School of Basic Medicine, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Liyue Huang
- Department of Physiology, School of Basic Medicine, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Dong Lai
- Department of Transfusion, the Second Affiliated Hospital of Xiamen Medical College, Xiamen 361021, Fujian, China.
| | - Ching-Feng Weng
- Department of Physiology, School of Basic Medicine, Xiamen Medical College, Xiamen 361023, Fujian, China.
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24
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Liang WF, Gong YX, Li HF, Sun FL, Li WL, Chen DQ, Xie DP, Ren CX, Guo XY, Wang ZY, Kwon T, Sun HN. Curcumin Activates ROS Signaling to Promote Pyroptosis in Hepatocellular Carcinoma HepG2 Cells. In Vivo 2021; 35:249-257. [PMID: 33402471 DOI: 10.21873/invivo.12253] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 11/02/2020] [Accepted: 11/03/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIM Curcumin is a polyphenol that exerts a variety of pharmacological activities and plays an anti-cancer role in many cancer cells. It was recently reported that gasdermin E (GSDME) is involved in the progression of pyroptosis. MATERIALS AND METHODS HepG2 cells were treated with various concentrations of curcumin and cell viability was examined using MTT assay, apoptosis was analysed using flow cytometry, reactive oxygen species (ROS) levels using dihydroethidium, LDH release using an LDH cytotoxicity assay, and protein expression using western blot. RESULTS Curcumin increased the expression of the GSDME N-terminus and proteins involved in pyrolysis, promoted HspG2 cell pyrolysis and increased intracellular ROS levels. Moreover, inhibition of the production of intracellular ROS with n-acetylcysteine (NAC) improved the degree of apoptosis and pyrolysis induced by curcumin. CONCLUSION Curcumin induces HspG2 cell death by increasing apoptosis and pyroptosis, and ROS play a key role in this process. This study improves our understanding of the potential anti-cancer properties of curcumin in liver cancer.
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Affiliation(s)
- Wan-Feng Liang
- Department of Veterinary Medicine, Agricultural College of Yanbian University, Yanji, P.R. China
| | - Yi-Xi Gong
- Department of Veterinary Medicine, Agricultural College of Yanbian University, Yanji, P.R. China
| | - Hai-Feng Li
- Department of Veterinary Medicine, Agricultural College of Yanbian University, Yanji, P.R. China
| | - Fu-Liang Sun
- Department of Veterinary Medicine, Agricultural College of Yanbian University, Yanji, P.R. China
| | - Wei-Long Li
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China
| | - Dong-Qin Chen
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China
| | - Dan-Ping Xie
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China
| | - Chen-Xi Ren
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China
| | - Xiao-Yu Guo
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China
| | - Zi-Yi Wang
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China
| | - Taeho Kwon
- Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeonbuk, Republic of Korea
| | - Hu-Nan Sun
- College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China;
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25
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Song L, Zhang J, Lai R, Li Q, Ju J, Xu H. Chinese Herbal Medicines and Active Metabolites: Potential Antioxidant Treatments for Atherosclerosis. Front Pharmacol 2021; 12:675999. [PMID: 34054550 PMCID: PMC8155674 DOI: 10.3389/fphar.2021.675999] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 04/16/2021] [Indexed: 12/17/2022] Open
Abstract
Atherosclerosis is a complex chronic disease that occurs in the arterial wall. Oxidative stress plays a crucial role in the occurrence and progression of atherosclerotic plaques. The dominance of oxidative stress over antioxidative capacity generates excess reactive oxygen species, leading to dysfunctions of the endothelium and accelerating atherosclerotic plaque progression. Studies showed that Chinese herbal medicines and traditional Chinese medicine (TCM) might regulate oxidative stress; they have already been used to treat diseases related to atherosclerosis, including stroke and myocardial infarction. This review will summarize the mechanisms of oxidative stress in atherosclerosis and discuss studies of Chinese herbal medicines and TCM preparations treating atherosclerosis, aiming to increase understanding of TCM and stimulate research for new drugs to treat diseases associated with oxidative stress.
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Affiliation(s)
- Luxia Song
- Graduate School, Beijing University of Chinese Medicine, Beijing, China.,National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jie Zhang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China.,National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Runmin Lai
- Graduate School, Beijing University of Chinese Medicine, Beijing, China.,National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiuyi Li
- Graduate School, Beijing University of Chinese Medicine, Beijing, China.,National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jianqing Ju
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hao Xu
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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26
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Enayati A, Johnston TP, Sahebkar A. Anti-atherosclerotic Effects of Spice-Derived Phytochemicals. Curr Med Chem 2021; 28:1197-1223. [PMID: 32368966 DOI: 10.2174/0929867327666200505084620] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 03/29/2020] [Accepted: 04/02/2020] [Indexed: 11/22/2022]
Abstract
Cardiovascular diseases are the leading cause of death in the world. Atherosclerosis is characterized by oxidized lipid deposition and inflammation in the arterial wall and represents a significant problem in public health and medicine. Some dietary spices have been widely used in many countries; however, the mechanism of their action as it relates to the prevention and treatment of atherosclerosis is still poorly understood. In this review, we focus on the properties of various spice-derived active ingredients used in the prevention and treatment of atherosclerosis, as well as associated atherosclerotic risk factors. We provide a summary of the mechanisms of action, epidemiological analyses, and studies of various components of spice used in the clinic, animal models, and cell lines related to atherosclerosis. Most notably, we focused on mechanisms of action by which these spice-derived compounds elicit their lipid-lowering, anti-inflammatory, antioxidant, and immunomodulatory properties, as well as their involvement in selected biochemical and signal transduction pathways. It is suggested that future research should aim to design well-controlled clinical trials and more thoroughly investigate the role of spices and their active components in the prevention/treatment of atherosclerosis. Based on this literature review, it appears that spices and their active components are well tolerated and have few adverse side effects and, therefore, provide a promising adjunctive treatment strategy for patients with atherosclerosis.
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Affiliation(s)
- Ayesheh Enayati
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, United States
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27
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Oxidative Stress, Plant Natural Antioxidants, and Obesity. Int J Mol Sci 2021; 22:ijms22041786. [PMID: 33670130 PMCID: PMC7916866 DOI: 10.3390/ijms22041786] [Citation(s) in RCA: 217] [Impact Index Per Article: 54.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/07/2021] [Accepted: 02/08/2021] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and size of adipocytes, promoting lipogenesis, stimulating differentiation of preadipocytes to mature adipocytes, and regulating the energy balance in hypothalamic neurons that control appetite. This review discusses the participation of oxidative stress in obesity and the important groups of compounds found in plants with antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, and isoflavones), and curcuminoids (b) carotenoids, (c) capsaicinoids and casinoids, (d) isothiocyanates, (e) catechins, and (f) vitamins. Examples are analyzed, such as resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, and garlic. The antioxidant activities of these compounds depend on their activities as reactive oxygen species (ROS) scavengers and on their capacity to prevent the activation of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells), and reduce the expression of target genes, including those participating in inflammation. We conclude that natural compounds have therapeutic potential for diseases mediated by oxidative stress, particularly obesity. Controlled and well-designed clinical trials are still necessary to better know the effects of these compounds.
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28
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Li Y, Wu S. Curcumin inhibits the proteolytic process of SREBP-2 by first inhibiting the expression of S1P rather than directly inhibiting SREBP-2 expression. Food Sci Nutr 2021; 9:209-216. [PMID: 33473285 PMCID: PMC7802558 DOI: 10.1002/fsn3.1985] [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: 07/09/2020] [Revised: 10/18/2020] [Accepted: 10/19/2020] [Indexed: 12/12/2022] Open
Abstract
Many studies have demonstrated that curcumin can downregulate mRNA levels of sterol regulatory element-binding proteins (SREBP-2); however, our study did not find similar results. This study was designed to demonstrate that curcumin inhibits the proteolytic process of SREBP-2 by first inhibiting the expression of membrane-bound transcription factor site-1 protease (S1P) rather than directly inhibiting SREBP-2 expression. After curcumin treatment, Caco-2 cells were collected to observe the dose- and time-dependent dynamics of precursor and mature SREBP-2, transcription factor-specific protein 1 (SP-1), and SREBP cleavage-activating protein (SCAP). After curcumin treatment, SREBP-2 distribution was detected in the cells and S1P protein expression was examined. Curcumin could downregulate mRNA levels of SREBP2, SP-1 and SCAP, but it did not simultaneously downregulate the expression of precursor SREBP-2 (pSREBP-2) and SCAP. Curcumin can inhibit the proteolytic process of SREBP-2, reduce the production of mature SREBP-2 (mSREBP-2), and change the cellular distribution of SREBP-2. The inhibitory effect of curcumin on SP-1 protein expression is short-acting. Curcumin could downregulate the mRNA and protein expression of S1P, but has no obvious inhibitory effect on the mRNA and protein expression of S2P (site-2 protease). Curcumin can inhibit the SREBP-2 proteolytic process to reduce mSREBP-2 which functions as a transcription factor, affecting the regulation of cholesterol metabolism-related genes. Curcumin does not directly inhibit the expression of mSREBP-2 protein, and it has no such inhibitory effect for at least a short period of time, although curcumin does reduce the amount of mSREBP-2 protein. S1P is a key protease in the hydrolysis of pSREBP-2 into mSREBP-2. Therefore, curcumin may decrease the amount of mSREBP-2 by directly inhibiting the expression of S1P mRNA and protein.
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Affiliation(s)
- Yongnan Li
- The Sixth General SurgeryBiliary & Vascular surgeryShengjing Hospital of China Medical UniversityShenyang CityChina
| | - Shuodong Wu
- The Sixth General SurgeryBiliary & Vascular surgeryShengjing Hospital of China Medical UniversityShenyang CityChina
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29
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Mohammadian Haftcheshmeh S, Khosrojerdi A, Aliabadi A, Lotfi S, Mohammadi A, Momtazi-Borojeni AA. Immunomodulatory Effects of Curcumin in Rheumatoid Arthritis: Evidence from Molecular Mechanisms to Clinical Outcomes. Rev Physiol Biochem Pharmacol 2021; 179:1-29. [PMID: 33404796 DOI: 10.1007/112_2020_54] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disorder characterized by the destruction of the joint and bone resorption. The production of pro-inflammatory cytokines and chemokines, dysregulated functions of three important subtypes of T helper (TH) cells including TH1, TH17, and regulator T (Treg) cells are major causes of the initiation and development of RA. Moreover, B cells as a source of the production of several autoantibodies play key roles in the pathogenesis of RA. The last decades have seen increasingly rapid advances in the field of immunopharmacology using natural origin compounds for the management of various inflammatory diseases. Curcumin, a main active polyphenol compound isolated from turmeric, curcuma longa, possesses a wide range of pharmacologic properties for the treatment of several diseases. This review comprehensively will assess beneficial immunomodulatory effects of curcumin on the production of pro-inflammatory cytokines and also dysregulated functions of immune cells including TH1, TH17, Treg, and B cells in RA. We also seek the clinical efficacy of curcumin for the treatment of RA in several recent clinical trials. In conclusion, curcumin has been found to ameliorate RA complications through modulating inflammatory and autoreactive responses in immune cells and synovial fibroblast cells via inhibiting the expression or function of pro-inflammatory mediators, such as nuclear factor-κB (NF-κB), activated protein-1 (AP-1), and mitogen-activated protein kinases (MAPKs). Of note, curcumin treatment without any adverse effects can attenuate the clinical symptoms of RA patients and, therefore, has therapeutic potential for the treatment of the diseases.
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Affiliation(s)
| | - Arezou Khosrojerdi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Aliabadi
- Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shadi Lotfi
- Department of Medical Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Asadollah Mohammadi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
| | - Amir Abbas Momtazi-Borojeni
- Halal Research center of IRI, FDA, Tehran, Iran.
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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30
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Jiang N, Zhang M, Meng X, Sun B. Effects of curcumin on the pharmacokinetics of amlodipine in rats and its potential mechanism. PHARMACEUTICAL BIOLOGY 2020; 58:465-468. [PMID: 32432949 PMCID: PMC7301706 DOI: 10.1080/13880209.2020.1764060] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 04/27/2020] [Indexed: 06/04/2023]
Abstract
Context: Hyperlipidaemia and hypertension are often treated together with curcumin and amlodipine. It is necessary to investigate the drug-drug interaction between curcumin and amlodipine.Objective: The interaction between curcumin and amlodipine was investigated in rats and with rat liver microsomes.Methods: The pharmacokinetics of amlodipine (1 mg/kg) was investigated in rats with or without curcumin pre-treatment (2 mg/kg), six rats in each group. The metabolic stability of amlodipine was investigated with rat liver microsomes.Results: Curcumin significantly increased the Cmax (26.19 ± 2.21 versus 17.80 ± 1.56 μg/L), AUC(0-t) (507.27 ± 60.23 versus 238.68 ± 45.59 μg·h/L), and t1/2 (14.69 ± 1.64 versus 11.43 ± 1.20 h) of amlodipine (p < 0.05). The metabolic stability of amlodipine was significantly increased with the half-life time in rat liver microsomes increased from 34.23 ± 3.33 to 44.15 ± 4.12 min, and the intrinsic rate decreased from 40.49 ± 3.26 to 31.39 ± 2.78 μL/min/mg protein.Discussion and conclusions: These results indicated that drug-drug interaction might appear during the co-administration of curcumin and amlodipine. The potential mechanism may be due to the inhibition of CYP3A4 by curcumin. Thus, this interaction should be given special attention in the clinic and needs further experiments to characterize the effect in humans.
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Affiliation(s)
- Na Jiang
- Department of Emergency, Yidu Central Hospital of Weifang, Weifang, Shandong, China
| | - Meicheng Zhang
- Department of Cardiovascular Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong, China
| | - Xiangzhi Meng
- Department of Cardiovascular Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong, China
| | - Bin Sun
- Department of Emergency, Yidu Central Hospital of Weifang, Weifang, Shandong, China
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31
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Singh A, Raj A, Padmanabhan A, Shah P, Agrawal N. Combating silver nanoparticle-mediated toxicity in Drosophila melanogaster with curcumin. J Appl Toxicol 2020; 41:1188-1199. [PMID: 33146454 DOI: 10.1002/jat.4103] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/11/2020] [Accepted: 10/22/2020] [Indexed: 12/21/2022]
Abstract
Nanoscale materials display unique physical and chemical properties that enable their assimilation into a variety of industrial and consumer products. Amongst the widely used nanomaterials, silver nanoparticles (AgNPs) have gained tremendous recognition for various applications, owing to their extraordinary plasmonic and bactericidal properties. Despite of the extensive usage of AgNPs in various sectors, its impact on human health remains ambiguous. Several studies have established that higher doses of AgNPs are detrimental to organismal health. In order to attain the best from these versatile nanoparticles, a recent advent of green nanotechnology, that is, employment of metal nanoparticles synthesized using plant extracts, has emerged. Here, using Drosophila as a model system, we tested if adding curcumin, a biologically active polyphenolic compound present in turmeric, having multitudes of therapeutic properties, could mitigate AgNP-mediated biotoxicity. We found that co-administration of AgNPs with curcumin in the fly food could alleviate several harmful effects evoked by AgNPs ingestion in Drosophila model. Addition of curcumin superseded reduction in feeding, pupation, eclosion, pigmentation, and fertility caused by AgNPs ingestion. Interestingly, impairment in ovary development observed in flies reared on AgNPs-supplemented food was also partially restored by co-administration of AgNPs with curcumin. Furthermore, substantial alleviation of reactive oxygen species level and cell death was observed in larval tissues upon co-supplementation of AgNPs with curcumin. We therefore propose that curcumin, when administered with AgNPs, can abrogate the toxic manifestations of AgNPs ingestion and hence can be incorporated in various consumer products encompassing it.
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Affiliation(s)
- Akanksha Singh
- Department of Zoology, University of Delhi, Delhi, India
| | - Akanksha Raj
- Department of Zoology, University of Delhi, Delhi, India
| | - Aishwarya Padmanabhan
- Department of Zoology, University of Delhi, Delhi, India.,Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, UK
| | - Prasanna Shah
- Department of Physics, Acropolis Institute of Technology and Research, Indore, India
| | - Namita Agrawal
- Department of Zoology, University of Delhi, Delhi, India
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Xia ZH, Zhang SY, Chen YS, Li K, Chen WB, Liu YQ. Curcumin anti-diabetic effect mainly correlates with its anti-apoptotic actions and PI3K/Akt signal pathway regulation in the liver. Food Chem Toxicol 2020; 146:111803. [PMID: 33035629 DOI: 10.1016/j.fct.2020.111803] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 01/30/2023]
Abstract
This study aimed to investigate the therapeutic effect of curcumin on type 2 diabetes and its underlying mechanisms. A type 2 diabetes mellitus rat model was established by providing high-fat diet and low doses of streptozotocin. Type 2 diabetes mellitus rats were treated with low dose and high dose of curcumin for 8 weeks. The results showed that high-dose curcumin significantly reduced fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase, liver coefficient, and malondialdehyde levels, and BCL2-Associated X expression in the type 2 diabetes mellitus rats. High-dose curcumin increased the levels of liver superoxide dismutase, catalase, and glutathione; as well as the expression of liver B-cell lymphoma-2, phosphatidylinositol 3-kinase, phosphorylated phosphatidylinositol 3-kinase, protein kinase B, and phosphorylated protein kinase B in type 2 diabetes mellitus rats. Furthermore, it ameliorated the histological structure of the liver and pancreas in diabetes mellitus model rats. However, low-dose curcumin had no significant effect on diabetes mellitus model rats. The results suggest that adequate doses of curcumin controls type 2 diabetes mellitus development as well as the mechanism involved in its anti-apoptotic actions and phosphatidylinositol 3-hydroxy kinase/protein kinase B signal pathway regulation in the liver.
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Affiliation(s)
- Zhen-Hong Xia
- College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Sai-Ya Zhang
- College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Yu-Si Chen
- College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Ke Li
- College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Wen-Bo Chen
- College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Yan-Qiang Liu
- College of Life Sciences, Nankai University, Tianjin, 300071, China.
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Tse C, Warner A, Farook R, Cronin JG. Phytochemical Targeting of STAT3 Orchestrated Lipid Metabolism in Therapy-Resistant Cancers. Biomolecules 2020; 10:biom10081118. [PMID: 32731620 PMCID: PMC7464013 DOI: 10.3390/biom10081118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/22/2020] [Accepted: 07/24/2020] [Indexed: 12/12/2022] Open
Abstract
Lipids are critical for maintaining homeostasis and cellular metabolism. However, the dysregulation of lipid metabolism contributes to the pathogenesis of chronic inflammatory diseases and is a hallmark of several cancer types. Tumours exist in a microenvironment of poor vascularization-depleted oxygen and restricted nutrients. Under these conditions, tumours have been shown to increasingly depend on the metabolism of fatty acids for sustained proliferation and survival. Signal transducer and activator of transcription 3 (STAT3) plays a key role in cellular processes such as cell growth, apoptosis and lipid metabolism. Aberrant STAT3 activity, as seen in several cancer types, is associated with tumour progression and malignancy, in addition to propagating crosstalk between tumour cells and the microenvironment. Furthermore, STAT3-regulated lipid metabolism is critical for cancer stem cell self-renewal and therapy resistance. Plant-derived compounds known as phytochemicals are a potential source for novel cancer therapeutic drugs. Dietary phytochemicals are known to modulate key cellular signalling pathways involved in lipid homeostasis and metabolism, including the STAT3 signalling pathways. Targeting STAT3 orchestrated lipid metabolism has shown therapeutic promise in human cancer models. In this review, we summarize the antitumour activity of phytochemicals with an emphasis placed on their effect on STAT3-regulated lipid metabolism and their role in abrogating therapy resistance.
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Abstract
PURPOSE Hyperlipidemia, characterized by an increase in circulating lipid levels, doubles the chance of developing cardiovascular diseases. It prompts inflammation, immune activation, and oxidative stress in the bloodstream and organs of rats. Thus, we theorized that the metabolism of purines, an immunomodulatory mechanism, is altered in cells involved in the development of cardiovascular diseases. METHODS Therefore, we induced acute hyperlipidemia in Wistar rats with Poloxamer-407 and euthanized the animals 36 h later. The leucocyte differential, the rate of purine metabolism on the surface of platelets and heart cells, and markers of oxidative stress in the heart tissue were evaluated. These parameters were also assessed in animals pretreated for 30 days with curcumin and/or rutin. RESULTS Hyperlipidemia increased the hydrolyses of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in platelets. In heart cells, the metabolism of ATP and adenosine (ADO) were increased, while ADP hydrolysis was reduced. Additionally, lipid damage and antioxidant defenses were increased in heart homogenates. Hyperlipidemic rats also exhibited a reduced percentage of eosinophils and lymphocytes. CONCLUSION Together, these findings are indicative of an increased risk of developing cardiovascular diseases in hyperlipidemic rats. The pretreatments with antioxidants reverted some of the changes prompted by hyperlipidemia preventing detrimental changes in the cells and tissues. Graphical Abstract.
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Chen S, Yang S, Wang M, Chen J, Huang S, Wei Z, Cheng Z, Wang H, Long M, Li P. Curcumin inhibits zearalenone-induced apoptosis and oxidative stress in Leydig cells via modulation of the PTEN/Nrf2/Bip signaling pathway. Food Chem Toxicol 2020; 141:111385. [DOI: 10.1016/j.fct.2020.111385] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/29/2020] [Accepted: 04/19/2020] [Indexed: 12/15/2022]
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Nanocurcumin alleviates insulin resistance and pancreatic deficits in polycystic ovary syndrome rats: Insights on PI3K/AkT/mTOR and TNF-α modulations. Life Sci 2020; 256:118003. [PMID: 32589998 DOI: 10.1016/j.lfs.2020.118003] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/13/2020] [Accepted: 06/21/2020] [Indexed: 12/17/2022]
Abstract
INTRODUCTION AND AIMS Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting females. Mechanisms underlying PCOS complicated pathology remain largely unknown, making current treatment only symptomatic. Increasing reports suggest impaired PI3K/AKT/mTOR pathway and tumor necrosis factor-α (TNF-α) levels are involved in cellular proliferation and metabolism-related disorders. However, rare data explored their role in PCOS. Hence, this study investigated TNF-α and pancreatic PI3K/AKT/mTOR levels in PCOS animal model and evaluated their effects on developed pancreatic deficits. Secondly; we explored the impact of nanocurcumin as powerful anti-inflammatory supplement against these developed pancreatic pathologies. METHODS PCOS was induced in rats using letrozole. Nanocurcumin was formulated to increase solubility and bioavailability of curcumin. Transmission electron microscopy (TEM), zeta potential and Infra-red spectroscopy (FT-IR) were used for characterization. Nanocurcumin was orally ingested for 15 days. FINDINGS PCOS group exhibited significant disturbance in sex hormones, oxidative stress markers, and TNF-α levels as determined by immunoassay. Western blotting revealed significant reduction of PI3K/AKT/mTOR levels leading to impaired insulin sensitivity, decreased β cells function and mass as confirmed by HOMA assessments and immunohistochemistry. Nanocurcumin significantly improved oxidative markers, glucose indices and TNF-α levels. It reinstated PI3K/AKT/mTOR levels, alleviated insulin resistance, and retained islets integrity consequently restoring normal sex hormonal levels. SIGNIFICANCE To the best of our knowledge, the study is the first to report pancreatic role of PI3K/AKT/mTOR and TNF-α in PCOS and the first to demonstrate nanocurcumin promising potential against PCOS-related pancreatic molecular and histological pathologies that can indeed offer better control of the disease.
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Mohammadian Haftcheshmeh S, Karimzadeh MR, Azhdari S, Vahedi P, Abdollahi E, Momtazi-Borojeni AA. Modulatory effects of curcumin on the atherogenic activities of inflammatory monocytes: Evidence from in vitro and animal models of human atherosclerosis. Biofactors 2020; 46:341-355. [PMID: 31875344 DOI: 10.1002/biof.1603] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 12/11/2019] [Indexed: 12/14/2022]
Abstract
Atherosclerosis is a complex and long-lasting disorder characterized by chronic inflammation of arteries that leads to the initiation and progression of lipid-rich plaques, in which monocytes/macrophages play the central role in endothelial inflammation and taking up these lipids. Circulating monocytes can adopt a long-term proinflammatory phenotype leading to their atherogenic activities. During atherogenic condition, inflammatory monocytes adhere to the surface of the activated endothelial cells and then transmigrate across the endothelial monolayer into the intima, where they proliferate and differentiate into macrophages and take up the lipoproteins, forming foam cells that derive atherosclerosis progression. Therefore, modulating the atherogenic activities of inflammatory monocytes can provide a valuable therapeutic approach for atherosclerosis prevention and treatment. Curcumin is a naturally occurring polyphenolic compound with numerous pharmacological activities and shows protective effects against atherosclerosis; however, underlying mechanisms are not clearly known yet. In the present review, on the basis of a growing body of evidence, we show that curcumin can exert antiatherosclerotic effect through inhibiting the atherogenic properties of monocytes, including inflammatory cytokine production, adhesion, and transendothelial migration, as well as intracellular cholesterol accumulation.
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Affiliation(s)
| | - Mohammad R Karimzadeh
- Department of Medical Genetics, School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | - Sara Azhdari
- Department of Anatomy and Embryology, School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | - Parviz Vahedi
- Department of Anatomical Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Elham Abdollahi
- Department of Medical Immunology and Allergy, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir A Momtazi-Borojeni
- Halal Research Center of IRI, FDA, Tehran, Iran
- Nanotechnology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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Salehi B, Del Prado-Audelo ML, Cortés H, Leyva-Gómez G, Stojanović-Radić Z, Singh YD, Patra JK, Das G, Martins N, Martorell M, Sharifi-Rad M, Cho WC, Sharifi-Rad J. Therapeutic Applications of Curcumin Nanomedicine Formulations in Cardiovascular Diseases. J Clin Med 2020; 9:746. [PMID: 32164244 PMCID: PMC7141226 DOI: 10.3390/jcm9030746] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 03/02/2020] [Accepted: 03/04/2020] [Indexed: 12/18/2022] Open
Abstract
Cardiovascular diseases (CVD) compromises a group of heart and blood vessels disorders with high impact on human health and wellbeing. Curcumin (CUR) have demonstrated beneficial effects on these group of diseases that represent a global burden with a prevalence that continues increasing progressively. Pre- and clinical studies have demonstrated the CUR effects in CVD through its anti-hypercholesterolemic and anti-atherosclerotic effects and its protective properties against cardiac ischemia and reperfusion. However, the CUR therapeutic limitation is its bioavailability. New CUR nanomedicine formulations are developed to solve this problem. The present article aims to discuss different studies and approaches looking into the promising role of nanotechnology-based drug delivery systems to deliver CUR and its derivatives in CVD treatment, with an emphasis on their formulation properties, experimental evidence, bioactivity, as well as challenges and opportunities in developing these systems.
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Affiliation(s)
- Bahare Salehi
- Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran;
| | - María L. Del Prado-Audelo
- Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior S/N, Del. Coyoacán, Mexico City 04510, Mexico; (M.L.D.P.-A.); (G.L.-G.)
- Laboratorio de Posgrado en Tecnología Farmacéutica, FES-Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlán Izcalli 54740, Mexico
| | - Hernán Cortés
- Laboratorio de Medicina Genómica, Departamento de Genética, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico;
| | - Gerardo Leyva-Gómez
- Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior S/N, Del. Coyoacán, Mexico City 04510, Mexico; (M.L.D.P.-A.); (G.L.-G.)
| | - Zorica Stojanović-Radić
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, 18000 Niš, Serbia;
| | - Yengkhom Disco Singh
- Department of Post-Harvest Technology, College of Horticulture and Forestry, Central Agricultural University, Pasighat 791102, Arunachal Pradesh, India;
| | - Jayanta Kumar Patra
- Research Institute of Biotechnology & Medical Converged Science, Dongguk University-Seoul, Goyangsi 10326, Korea; (J.K.P.); (G.D.)
| | - Gitishree Das
- Research Institute of Biotechnology & Medical Converged Science, Dongguk University-Seoul, Goyangsi 10326, Korea; (J.K.P.); (G.D.)
| | - Natália Martins
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, University of Concepcion, Concepcion 4070386, Chile
- Unidad de Desarrollo Tecnológico, Universidad de Concepción UDT, Concepcion 4070386, Chile
| | - Marzieh Sharifi-Rad
- Research Department of Agronomy and Plant Breeding, Agricultural Research Institute, University of Zabol, Zabol 3585698613, Iran;
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong, China
| | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1991953381, Iran
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Curcumin stimulates exosome/microvesicle release in an in vitro model of intracellular lipid accumulation by increasing ceramide synthesis. Biochim Biophys Acta Mol Cell Biol Lipids 2020; 1865:158638. [PMID: 31988047 DOI: 10.1016/j.bbalip.2020.158638] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 01/22/2020] [Accepted: 01/23/2020] [Indexed: 01/01/2023]
Abstract
Curcumin, a hydrophobic polyphenol found in the rhizome of Curcuma longa, has been shown to reduce intracellular lipid accumulation in mouse models of lysosomal storage diseases such as Niemann-Pick type C. Exosomes are small extracellular vesicles secreted by cells in response to changes in intracellular ceramide composition. Curcumin can induce exosome/microvesicle release in cellular models of lipid deposition; however, the mechanism by which curcumin stimulates this release is unknown. In a model of lipid trafficking impairment in C6 glia cells, we show that curcumin stimulated ceramide synthesis by increasing the intracellular concentration of ceramide-dihydroceramide. Ceramide overload increased exosome/microvesicle secretion 10-fold, thereby reducing the concentration of lipids in the endolysosomal compartment. These effects were blocked by inhibitors of serine palmitoyltransferase (myriocin) and ceramide synthase (fumonisin B1). It is concluded that the decrease in intracellular lipid deposition induced by curcumin is mediated by increased ceramide synthesis and exosome/microvesicle release. This action may represent an additional health benefit of curcumin.
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Abstract
Acute lung injury (ALI) is characterized by acute inflammation and tissue injury results in dysfunction of the alveolar epithelial membrane. If the epithelial injury is severe, a fibroproliferative phase of ALI can develop. During this phase, the activated fibroblast and myofibroblasts synthesize excessive collagenous extracellular matrix that leads to a condition called pulmonary fibrosis. Lung injury can be caused by several ways; however, the present review focus on bleomycin (BLM)-mediated changes in the pathology of lungs. BLM is a chemotherapeutic agent and has toxic effects on lungs, which leads to oxidative damage and elaboration of inflammatory cytokines. In response to the injury, the inflammatory cytokines will be activated to defend the system from injury. These cytokines along with growth factors stimulate the proliferation of myofibroblasts and secretion of pathologic extracellular matrix. During BLM injury, the pro-inflammatory cytokine such as IL-17A will be up-regulated and mediates the inflammation in the alveolar epithelial cell and also brings about recruitment of certain inflammatory cells in the alveolar surface. These cytokines probably help in up-regulating the expression of p53 and fibrinolytic system molecules during the alveolar epithelial cells apoptosis. Here, our key concern is to provide the adequate knowledge about IL-17A-mediated p53 fibrinolytic system and their pathogenic progression to pulmonary fibrosis. The present review focuses mainly on IL-17A-mediated p53-fibrinolytic aspects and how curcumin is involved in the regulation of pathogenic progression of ALI and pulmonary fibrosis.
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Lin K, Chen H, Chen X, Qian J, Huang S, Huang W. Efficacy of Curcumin on Aortic Atherosclerosis: A Systematic Review and Meta-Analysis in Mouse Studies and Insights into Possible Mechanisms. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:1520747. [PMID: 31998433 PMCID: PMC6973199 DOI: 10.1155/2020/1520747] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 11/30/2019] [Accepted: 12/19/2019] [Indexed: 02/08/2023]
Abstract
Since the first report in 2005, accumulating interests have been focused on the effect of curcumin in atherosclerosis with discrepancies. Therefore, we conducted a systematic review and meta-analysis to comprehensively estimate its effect against atherosclerosis. Literature search was performed on the database of PubMed, EMBASE, and Cochrane Library to identify relevant studies which estimated the effect of curcumin in atherosclerosis. Reporting effects on aortic lesion area was the primary outcome while effects on serum lipid profiles and circulating inflammatory markers were the secondary outcome. A total of 10 studies including 14 independent pairwise experiments were included in our analysis. We clarified that curcumin could significantly reduce aortic atherosclerotic lesion area (SMD = -0.89, 95% CI: -1.36 to -0.41, P = 0.0003), decrease serum lipid profiles (Tc, MD = -1.005, 95% CI: -1.885 to -0.124, P = 0.025; TG, MD = -0.045, 95% CI: -0.088 to -0.002, P = 0.042; LDL-c, MD = -0.523, 95% CI: -0.896 to -0.149, P = 0.006) as well as plasma inflammatory indicators (TNF-α, MD = -56.641, 95% CI: -86.848 to -26.433, P < 0.001; IL-1β, MD = -5.089, 95% CI: -8.559 to -1.619, P = 0.004). Dose-response meta-analysis predicted effective dosage of curcumin between 0 and 347 mg/kg BW per day, which was safe and nontoxic according to the existing publications. The underlying mechanisms were also discussed and might be associated with the modulation of lipid transport and inflammation in cells within artery walls as well as indirect modulations in other tissues. Clinical evidence from nonatherosclerosis populations revealed that curcumin would lower the lipid profiles and inflammatory responses as it has in a mouse model. However, standard preclinical animal trial designs are still needed; further studies focusing on the optimal dose of curcumin against atherosclerosis and RCTs directly in atherosclerosis patients are also warranted.
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Affiliation(s)
- Ke Lin
- Department of Cardiology, The Key Lab of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China
| | - Huaijun Chen
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310000, China
| | - Xiaojun Chen
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China
| | - Jinfu Qian
- Department of Cardiology, The Key Lab of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China
| | - Shushi Huang
- Department of Cardiology, The Key Lab of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China
| | - Weijian Huang
- Department of Cardiology, The Key Lab of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China
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Li H, Sureda A, Devkota HP, Pittalà V, Barreca D, Silva AS, Tewari D, Xu S, Nabavi SM. Curcumin, the golden spice in treating cardiovascular diseases. Biotechnol Adv 2020; 38:107343. [DOI: 10.1016/j.biotechadv.2019.01.010] [Citation(s) in RCA: 209] [Impact Index Per Article: 41.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 01/10/2019] [Accepted: 01/29/2019] [Indexed: 02/07/2023]
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Teixeira J, Chavarria D, Borges F, Wojtczak L, Wieckowski MR, Karkucinska-Wieckowska A, Oliveira PJ. Dietary Polyphenols and Mitochondrial Function: Role in Health and Disease. Curr Med Chem 2019; 26:3376-3406. [PMID: 28554320 DOI: 10.2174/0929867324666170529101810] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 04/23/2017] [Accepted: 04/23/2017] [Indexed: 12/12/2022]
Abstract
Mitochondria are cytoplasmic double-membraned organelles that are involved in a myriad of key cellular regulatory processes. The loss of mitochondrial function is related to the pathogenesis of several human diseases. Over the last decades, an increasing number of studies have shown that dietary polyphenols can regulate mitochondrial redox status, and in some cases, prevent or delay disease progression. This paper aims to review the role of four dietary polyphenols - resveratrol, curcumin, epigallocatechin-3-gallate nd quercetin - in molecular pathways regulated by mitochondria and their potential impact on human health. Cumulative evidence showed that the aforementioned polyphenols improve mitochondrial functions in different in vitro and in vivo experiments. The mechanisms underlying the polyphenols' beneficial effects include, among others, the attenuation of oxidative stress, the regulation of mitochondrial metabolism and biogenesis and the modulation of cell-death signaling cascades, among other mitochondrial-independent effects. The understanding of the chemicalbiological interactions of dietary polyphenols, namely with mitochondria, may have a huge impact on the treatment of mitochondrial dysfunction-related disorders.
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Affiliation(s)
- José Teixeira
- CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4169- 007, Portugal.,CNC - Center for Neuroscience and Cell Biology, UC-Biotech, Biocant Park - Cantanhede, University of Coimbra, Portugal
| | - Daniel Chavarria
- CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4169- 007, Portugal
| | - Fernanda Borges
- CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4169- 007, Portugal
| | - Lech Wojtczak
- Nencki Institute of Experimental Biology, Warsaw, Poland
| | | | | | - Paulo J Oliveira
- CNC - Center for Neuroscience and Cell Biology, UC-Biotech, Biocant Park - Cantanhede, University of Coimbra, Portugal
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Sohaei S, Amani R, Tarrahi MJ, Ghasemi-Tehrani H. The effects of curcumin supplementation on glycemic status, lipid profile and hs-CRP levels in overweight/obese women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled clinical trial. Complement Ther Med 2019; 47:102201. [DOI: 10.1016/j.ctim.2019.102201] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 09/24/2019] [Accepted: 09/25/2019] [Indexed: 10/25/2022] Open
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Ghelani H, Razmovski-Naumovski V, Chang D, Nammi S. Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats. BMC Nephrol 2019; 20:431. [PMID: 31752737 PMCID: PMC6873446 DOI: 10.1186/s12882-019-1621-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 11/08/2019] [Indexed: 12/17/2022] Open
Abstract
Background Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders due to the dysregulation of lipoprotein metabolism which progresses kidney disease. The objective of this study is to evaluate the protective effects of curcumin on dyslipidaemia associated with adenine-induced chronic kidney disease in rats. Methods Male SD rats (n = 29) were divided into 5 groups for 24 days: normal control (n = 5, normal diet), CKD control (n = 6, 0.75% w/w adenine-supplemented diet), CUR 50 (n = 6, 50 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), CUR 100 (n = 6, 100 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), and CUR 150 (n = 6, 150 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet). The serum and tissue lipid profile, as well as the kidney function test, were measured using commercial diagnostic kits. Results The marked rise in total cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids in serum, as well as hepatic cholesterol, triglyceride and free fatty acids of CKD control rats were significantly protected by curcumin co-treatment (at the dose of 50, 100 and 150 mg/kg). Furthermore, curcumin significantly increased the serum high-density lipoprotein (HDL) cholesterol compared to the CKD control rats but did not attenuate the CKD-induced weight retardation. Mathematical computational analysis revealed that curcumin significantly reduced indicators for the risk of atherosclerotic lesions (atherogenic index) and coronary atherogenesis (coronary risk index). In addition, curcumin improved kidney function as shown by the reduction in proteinuria and improvement in creatinine clearance. Conclusion The results provide new scientific evidence for the use of curcumin in CKD-associated dyslipidaemia and substantiates the traditional use of curcumin in preventing kidney damage.
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Affiliation(s)
- Hardik Ghelani
- School of Science and Health, Western Sydney University, Sydney, NSW, 2751, Australia.,NICM Health Research Institute, Western Sydney University, Sydney, NSW, 2751, Australia
| | - Valentina Razmovski-Naumovski
- School of Science and Health, Western Sydney University, Sydney, NSW, 2751, Australia.,NICM Health Research Institute, Western Sydney University, Sydney, NSW, 2751, Australia.,South Western Sydney Clinical School School of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia
| | - Dennis Chang
- School of Science and Health, Western Sydney University, Sydney, NSW, 2751, Australia.,NICM Health Research Institute, Western Sydney University, Sydney, NSW, 2751, Australia
| | - Srinivas Nammi
- School of Science and Health, Western Sydney University, Sydney, NSW, 2751, Australia. .,NICM Health Research Institute, Western Sydney University, Sydney, NSW, 2751, Australia.
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Jiang Z, Wan Y, Li P, Xue Y, Cui W, Chen Q, Chen J, Wang F, Mao D. Effect of Curcumin Supplement in Summer Diet on Blood Metabolites, Antioxidant Status, Immune Response, and Testicular Gene Expression in Hu Sheep. Animals (Basel) 2019; 9:E720. [PMID: 31554289 PMCID: PMC6826745 DOI: 10.3390/ani9100720] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 09/15/2019] [Accepted: 09/19/2019] [Indexed: 02/07/2023] Open
Abstract
In summer, the high temperature affects animal growth and reproductive performance. Curcumin is a flavonoid with anti-oxidant and anti-inflammatory effects. To evaluate the effects of dietary curcumin supplement on the blood biochemical parameters and testicular gene expressions in Hu sheep in summer, a total of 144 male Hu sheep aged four months were randomly divided into three groups (Con, Cur1, and Cur2, n = 48). Sheep in Con, Cur1, and Cur2 groups were fed a basal diet supplement with 0, 450, and 900 mg (per sheep) curcumin daily, respectively. Sheep were fed for 35 days, including a pre-feed for seven days. The results showed that the supplement with 450 mg and 900 mg curcumin increased serum free fatty acid (NEFA) and glutathione peroxidase (GPX), as well as IgA and IgM. The supplement with 450 mg curcumin increased the IgG level, while the supplement with 900 mg curcumin had a lower IgG level than the supplement with 450 mg curcumin (p < 0.05). Dietary curcumin supplement increased testicular organ index, serum testosterone level, and testicular star mRNA expression (p < 0.05). Furthermore, dietary curcumin supplement linearly inhibited testicular apoptosis with increased testicular bcl-2 mRNA expression and decreased caspase-3 mRNA expression (p < 0.05). In conclusion, dietary curcumin supplement can promote lipid metabolism, antioxidant capacity, and immune response, as well as testicular development, in Hu sheep, which provides evidence of application of curcumin in sheep production.
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Affiliation(s)
- Zhiyang Jiang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
- National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
| | - Yongjie Wan
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
| | - Peng Li
- Qidong Ruipeng Animal Husbandry Co., Ltd, Nantong 226227, Jiangsu, China.
| | - Yang Xue
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
| | - Wenwen Cui
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
| | - Qi Chen
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
| | - Jianqin Chen
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
| | - Feng Wang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
| | - Dagan Mao
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
- National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
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Valentine C, Ohnishi K, Irie K, Murakami A. Curcumin may induce lipolysis via proteo-stress in Huh7 human hepatoma cells. J Clin Biochem Nutr 2019; 65:91-98. [PMID: 31592057 DOI: 10.3164/jcbn.19-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 05/02/2019] [Indexed: 12/25/2022] Open
Abstract
Curcumin has been shown to have anti-obesity effects in animal studies. Although several molecular mechanisms of action have been reported, the initial or upstream molecular events remain to be revealed. In this study, we found that curcumin or heat shock treatment up-regulated the expression of adipose triglyceride lipase (ATGL) in Huh7 hepatoma cells, which resulted in acceleration of lipolysis. Interestingly, perturbation of protein homeostasis was seen in curcumin-treated cells, as detected by formation of numerous ubiquitinated proteins and conjugated proteins with p62 (SQSTM). Curcumin activated the protein expression of molecular chaperones, such as heat shock protein (HSP)40 and HSP70. Pre-treatment of the cells with 4-phenylbutyric acid, a chemical chaperone, suppressed proteo-stress induced by curcumin and reduced its lipolysis effect. Importantly, the cytotoxicity of curcumin was markedly alleviated when intracellular triglyceride was consumed by the polyphenol. Thus, energy supplementation from lipolysis may play substantial roles in adaptation and survival of curcumin-exposed cells. To support this notion, the cytotoxicity of curcumin was aggravated in ATGL-knockdown cells. Curcumin decreased intracellular ATP for activating AMP-activated protein kinase, which initiates catabolic pathways including ATGL-dependent lipolysis. Taken together, we propose a hypothesis that curcumin induces lipolysis to compensate for ATP reduction due to its proteo-stress effects.
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Affiliation(s)
- Cindy Valentine
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
| | - Kohta Ohnishi
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
| | - Kazuhiro Irie
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
| | - Akira Murakami
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
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48
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Naeini MB, Momtazi AA, Jaafari MR, Johnston TP, Barreto G, Banach M, Sahebkar A. Antitumor effects of curcumin: A lipid perspective. J Cell Physiol 2019; 234:14743-14758. [PMID: 30741424 DOI: 10.1002/jcp.28262] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 01/06/2019] [Accepted: 01/10/2019] [Indexed: 01/24/2023]
Abstract
Lipid metabolism plays an important role in cancer development due to the necessities of rapidly dividing cells to increase structural, energetic, and biosynthetic demands for cell proliferation. Basically, obesity, type 2 diabetes, and other related diseases, and cancer are associated with a common hyperactivated "lipogenic state." Recent evidence suggests that metabolic reprogramming and overproduction of enzymes involved in the synthesis of fatty acids are the new hallmarks of cancer, which occur in an early phase of tumorigenesis. As the first evidence to confirm dysregulated lipid metabolism in cancer cells, the overexpression of fatty acid synthase (FAS) was observed in breast cancer patients and demonstrated the role of FAS in cancer. Other enzymes of fatty acid synthesis have recently been found to be dysregulated in cancer, including ATP-dependent citrate lyase and acetyl-CoA carboxylase, which further underscores the connection of these metabolic pathways with cancer cell survival and proliferation. The degree of overexpression of lipogenic enzymes and elevated lipid utilization in tumors is closely associated with cancer progression. The question that arises is whether the progression of cancer can be suppressed, or at least decelerated, by modulating gene expression related to fatty acid metabolism. Curcumin, due to its effects on the regulation of lipogenic enzymes, might be able to suppress, or even cause regression of tumor growth. This review discusses recent evidence concerning the important role of lipogenic enzymes in the metabolism of cancer cells and whether the inhibitory effects of curcumin on lipogenic enzymes is therapeutically efficacious.
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Affiliation(s)
- Mehri Bemani Naeini
- Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Abbas Momtazi
- Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Reza Jaafari
- Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri
| | - George Barreto
- Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C, Colombia.,Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile
| | - Maciej Banach
- Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Sinjari B, Pizzicannella J, D'Aurora M, Zappacosta R, Gatta V, Fontana A, Trubiani O, Diomede F. Curcumin/Liposome Nanotechnology as Delivery Platform for Anti-inflammatory Activities via NFkB/ERK/pERK Pathway in Human Dental Pulp Treated With 2-HydroxyEthyl MethAcrylate (HEMA). Front Physiol 2019; 10:633. [PMID: 31244665 PMCID: PMC6579913 DOI: 10.3389/fphys.2019.00633] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 05/06/2019] [Indexed: 01/21/2023] Open
Abstract
Curcumin, primary component of the spice turmeric extracted from the rhizomes of Curcuma longa, represents the major anti-oxidant and anti-inflammatory substance found in turmeric, acting thought various mechanisms not completely understood. Curcumin modulates cytokines, growth factors, transcription factors, inflammatory molecules and cell signaling pathways. During restorative dentistry practice, free resin monomers of 2-hydroxyethyl methacrylate (HEMA) propagate through dentin micro-channel and pulp into the bloodstream affecting cellular integrity. The study highlights the significance of application of curcumin bioactive component into liposomal formulations (CurLIP) to restore the homeostasis of dental pulp stem cells (hDPSCs) in response to 3 and 5 mmol L–1 HEMA treatment. Cell proliferation in combination with changes of the morphological features, proinflammatory cytokines secretion as Interleukin (IL) 6, IL8, Monocyte Chemoattractant Protein-1 (MCP1) and Interferon-gamma (IFNγ) were assayed along with the nuclear factor (NF)-kB, an inducible transcription factor involved in the activation of several cell processes associated to extracellular signal-regulated kinases (ERK) and posphorylated (p-) ERK pathway. Our results showed a decreased cell proliferation, morphological changes and upregulation of IL6, IL8, MCP1 and IFNγ in presence of 3 and 5 mmol L–1 HEMA treatment. CurLIP therapy in hDPSCs provokes an increase in cell proliferation and the block of inflammatory cytokines secretion through the inhibitory regulation of NFkB/ERK and pERK signaling cascade. The natural nanocarrier CurLIP influences numerous biochemical and molecular cascades causing anti-inflammatory properties in response to HEMA treatment in human dental pulp stem cells, representing an innovative endodontic formulation able to improve the quality of dental care with a major human community impact.
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Affiliation(s)
- Bruna Sinjari
- Department of Medical Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti, Italy
| | - Jacopo Pizzicannella
- Department of Medical Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti, Italy.,ASL02 Lanciano-Vasto-Chieti, "Ss. Annunziata" Hospital, Chieti, Italy
| | - Marco D'Aurora
- Department of Psychological, Health and Territorial Sciences, University "G. d'Annunzio", Chieti, Italy
| | | | - Valentina Gatta
- Department of Psychological, Health and Territorial Sciences, University "G. d'Annunzio", Chieti, Italy
| | | | - Oriana Trubiani
- Department of Medical Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti, Italy
| | - Francesca Diomede
- Department of Medical Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti, Italy
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50
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Itaya M, Miyazawa T, Zingg JM, Eitsuka T, Azzi A, Meydani M, Miyazawa T, Nakagawa K. The differential cellular uptake of curcuminoids in vitro depends dominantly on albumin interaction. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 59:152902. [PMID: 30981184 DOI: 10.1016/j.phymed.2019.152902] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 02/21/2019] [Accepted: 03/21/2019] [Indexed: 05/23/2023]
Abstract
BACKGROUND Curcuminoids, mainly present in the plant rhizomes of turmeric (Curcuma longa), consist of mainly three forms (curcumin (CUR), bisdemethoxycurcumin (BDMC) and demethoxycurcumin (DMC)). It has been reported that different forms of curcuminoids possess different biological activities. However, the mechanisms associated with these differences are not well-understood. Recently, our laboratory found differences in the cellular uptake of these curcuminoids. Therefore, it has been inferred that these differences contribute to the different biological activities. PURPOSE In this study, we investigated the mechanisms of differential cellular uptake of these curcuminoids. METHOD Based on our previous study, we hypothesized the differential cellular uptake is caused by (I) polarity, (II) transporters, (III) metabolism rate of curcuminoids and (IV) medium components. These four hypotheses were each investigated by (I) neutralizing the polarities of curcuminoids by encapsulation into poly(lactic-co-glycolic) acid nanoparticles (PLGA-NPs), (II) inhibition of polyphenol-related absorption transporters, (III) analysis of the cellular curcuminoids and their metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and (IV) use of different mediums in cell study. RESULTS The differential cellular uptake was not affected by (I-III). However, when investigating (IV), not only CUR but also BDMC and DMC were incorporated into cells when serum free media was used. Furthermore, when we used the serum free medium containing bovine serum albumin (BSA), only CUR was taken up but BDMC and DMC were not. Therefore, we identified that the differential cellular uptake of curcuminoids is caused by the medium components, especially BSA. Also, the fluorescence quenching study suggested that differential cellular uptake is due to the different interaction between BSA and each curcuminoid. CONCLUSION The differential cellular uptake of curcuminoids was caused by the different interaction between curcuminoids and BSA. The results from this study might give clues on the mechanisms by which curcuminoids exhibit different physiological activities.
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Affiliation(s)
- Mayuko Itaya
- Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Taiki Miyazawa
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Tokyo 101-0062, Japan
| | - Jean-Marc Zingg
- Department of Biochemistry and Molecular Biology, University of Miami, 1011 NW 15th St, Miami, Florida 33136-1019, United States
| | - Takahiro Eitsuka
- Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Angelo Azzi
- Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, United States
| | - Mohsen Meydani
- Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, United States
| | - Teruo Miyazawa
- Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Sendai 980-0845, Japan; New Industry Creation Hatchery Center (NICHe), Tohoku University, 6-6-10 Aramaki Aza Aoba, Sendai 980-8579, Japan
| | - Kiyotaka Nakagawa
- Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
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