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Chen Y, Ren F, Yang N, Xiang Q, Gao S, Pu W, Yang Z, Liu Q, Luo S, Rao C. The mechanism study of quercetin isolated from Zanthoxylum bungeanum maxim. inhibiting ferroptosis and alleviating MAFLD through p38 MAPK/ERK signaling pathway based on lipidomics and transcriptomics. Front Pharmacol 2025; 16:1517291. [PMID: 40230695 PMCID: PMC11994740 DOI: 10.3389/fphar.2025.1517291] [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: 10/25/2024] [Accepted: 03/14/2025] [Indexed: 04/16/2025] Open
Abstract
Background As a resource with a variety of medicinal and edible values, Zanthoxylum bungeanum Maxim has been found to improve high-fat diet-induced metabolic-associated fatty liver disease (MAFLD). Aim of the study The aim of this study was to predict the main active metabolites in Z. bungeanum Maxim. Based on network analysis, and to explore and validate their potential mechanisms of action through lipidomics and transcriptomic techniques. Materials and Methods MAFLD mouse model and cell model were established to evaluate the effect of active components in Z. bungeanum Maxim. on MAFLD. Serum biochemical indexes, pathological staining observation, lipid group and transcriptome were used to verify the mechanism of action of active components in Z. bungeanum Maxim. on MAFLD. Results Quercetin can regulate the liver lipid metabolites of MAFLD mice through the Glycerophospholipid metabolic pathway, thereby improving liver lipid accumulation and liver injury. At the same time, quercetin can also improve MAFLD by reducing oleic acid-induced lipid accumulation in HepG2 cells, and inhibit ferroptosis through the p38 MAPK/ERK signaling pathway, thereby alleviating the progression of MAFLD. Conclusion Quercetin isolated from Z. bungeanum Maxim. has ameliorative effects on MAFLD, probably mainly by affecting lipid metabolic pathways and MAPK signaling pathways.
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Affiliation(s)
- Yan Chen
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Fajian Ren
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Nannan Yang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Qiwen Xiang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Song Gao
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Wei Pu
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Zhou Yang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Qiuyan Liu
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Shajie Luo
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Chaolong Rao
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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Xiong J, Chen G, He Y, Zhao C, Chen D, Liu Y, Zhang Z, Wu Y, Xu H. Oxymatrine reduces hepatic lipid synthesis in rat model of nonalcoholic steatohepatitis by regulating Sirt1/AMPK and LXR/Plin2/SREBP-1c pathways. Chem Biol Interact 2025; 407:111370. [PMID: 39746502 DOI: 10.1016/j.cbi.2024.111370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/22/2024] [Accepted: 12/31/2024] [Indexed: 01/04/2025]
Abstract
Nonalcoholic Steatohepatitis (NASH) is a common liver disease with limited treatment options. Oxymatrine (OMT) has been reported to treat liver diseases effectively. This study aims to explore the mechanisms of OMT in NASH. Male Sprague-Dawley rats were fed a high-fat and high-sucrose diet and hepatocytes were stimulated with oleic acid (OA) to establish NASH models, then, NASH models were intervened with OMT. In vivo, liver injury and lipid accumulation extents were evaluated by serum and liver biochemical indexes, and histological analysis. In vitro, cell viability and lipid accumulation degrees were measured. Additionally, the relationships between perilipin 2 (Plin2) and liver X-activated receptor alpha (LXRα) as well as Plin2 and sterol regulatory element binding protein-1c (SREBP-1c), sirtuin 1 (Sirt1)/adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway-, liver X-activated receptor (LXR)/Plin2/SREBP-1c pathway- and lipid synthesis-related proteins were detected both in vivo and in vitro. Finally, Sirt1 was knocked down in hepatocytes. OMT not only reduced serum alanine aminotransferase activity and triglyceride content, liver triglyceride and free fatty acid levels in NASH rats, but also improved hepatic injury and lipid accumulation. In vitro, OMT enhanced viability, and downregulated lipid accumulation in OA-induced hepatocytes. Both in vivo and in vitro results revealed Plin2 directly interacted with LXRα and SREBP-1c, and OMT activated Sirt1/AMPK pathway but inhibited the expressions of LXR/Plin2/SREBP-1c pathway and lipid synthesis (acetyl-CoA carboxylase, fatty acid synthase, stearoyl-Coenzyme A desaturase 1) related proteins in NASH models. Importantly, Sirt1 knockdown reversed the protective effects of OMT in OA-stimulated hepatocytes. OMT may reduce hepatic lipid synthesis in NASH by activating the Sirt1/AMPK pathway and inhibiting the LXR/Plin2/SREBP-1c pathway, suggesting that OMT may be a promising strategy for treating NASH.
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Affiliation(s)
- Jingfang Xiong
- Department of Geriatrics, Hangzhou Red Cross Hospital, Hangzhou, 310003, China
| | - Gaofeng Chen
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ying He
- Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, 310003, China
| | - Changqing Zhao
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Dongya Chen
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, Hangzhou, 310003, China
| | - Yihui Liu
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, Hangzhou, 310003, China
| | - Zhaolin Zhang
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, Hangzhou, 310003, China
| | - Yijun Wu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Hong Xu
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, Hangzhou, 310003, China.
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Wang Z, Gao H, Ma X, Zhu D, Zhao L, Xiao W. Adrenic acid: A promising biomarker and therapeutic target (Review). Int J Mol Med 2025; 55:20. [PMID: 39575474 PMCID: PMC11611323 DOI: 10.3892/ijmm.2024.5461] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 11/06/2024] [Indexed: 01/05/2025] Open
Abstract
Adrenic acid is a 22‑carbon unsaturated fatty acid that is widely present in the adrenal gland, liver, brain, kidney and vascular system that plays a regulatory role in various pathophysiological processes, such as inflammatory reactions, lipid metabolism, oxidative stress, vascular function, and cell death. Adrenic acid is a potential biomarker for various ailments, including metabolic, neurodegenerative and cardiovascular diseases and cancer. In addition, adrenic acid is influenced by the pharmacological properties of several natural products, such as astragaloside IV, evodiamine, quercetin, kaempferol, Berberine‑baicalin and prebiotics, so it is a promising new target for clinical treatment and drug development. However, the molecular mechanisms by which adrenic acid exerts are unclear. The present study systematically reviewed the biosynthesis and metabolism of adrenic acid, focusing on intrinsic mechanisms that influence the progression of metabolic, cardiovascular and neurological disease. These mechanisms regulate several key processes, including immuno‑inflammatory response, oxidative stress, vascular function and cell death. In addition, the present study explored the potential clinical translational value of adrenic acid as a biomarker and therapeutic target. To the best of our knowledge, the present study is first systematic summary of the mechanisms of action of adrenic acid across a range of diseases. The present study provides understanding of the wide range of metabolic activities of adrenic acid and a basis for further exploring the pathogenesis and therapeutic targets of various diseases.
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Affiliation(s)
- Ze Wang
- Shanghai Key Laboratory of Human Performance, Shanghai University of Sport, Shanghai 200438, P.R. China
| | - Haoyang Gao
- Shanghai Key Laboratory of Human Performance, Shanghai University of Sport, Shanghai 200438, P.R. China
| | - Xiaotong Ma
- Shanghai Key Laboratory of Human Performance, Shanghai University of Sport, Shanghai 200438, P.R. China
| | - Danlin Zhu
- Shanghai Key Laboratory of Human Performance, Shanghai University of Sport, Shanghai 200438, P.R. China
| | - Linlin Zhao
- Shanghai Key Laboratory of Human Performance, Shanghai University of Sport, Shanghai 200438, P.R. China
- School of Physical Education, Shanghai Normal University, Shanghai 200234, P.R. China
| | - Weihua Xiao
- Shanghai Key Laboratory of Human Performance, Shanghai University of Sport, Shanghai 200438, P.R. China
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Zheng Z, Yang S, Dai W, Sun Y, Wang J, Zhang X, Zheng Y, Kong J. Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study. Front Endocrinol (Lausanne) 2025; 15:1436827. [PMID: 39916753 PMCID: PMC11798786 DOI: 10.3389/fendo.2024.1436827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 12/23/2024] [Indexed: 02/09/2025] Open
Abstract
Background This study explored the causal connection among the plasma lipidome, nonalcoholic fatty liver disease (NAFLD), and potential metabolome mediators through Mendelian randomization (MR). Methods We obtained summary statistics for 179 plasma lipidome traits (N = 7,174), 1,400 plasma metabolome traits (N = 8,299), and one NAFLD trait from publicly available genome-wide association studies. A two-sample MR analysis was conducted to infer causality. Additionally, multiple sensitivity analyses were conducted to assess the heterogeneity, horizontal pleiotropy, and robustness of the MR findings. MetaboAnalyst 6.0 was used for the pathway analysis of the identified lipids and metabolites. Furthermore, we used mediation analysis to assess whether the effect of plasma lipidome on NAFLD was mediated by plasma metabolome. Results The MR analysis predicted a genetically determined causal relationship between plasma lipidomes and NAFLD. No compelling proof was found that genetically predicted NAFLD influenced the risk of the five plasma lipidomes mentioned earlier. Based on established causal relationships between lipids and metabolites, we identified that eight metabolic pathways are closely associated with NAFLD. Our mediation analysis revealed six mediation relationships, indicating the causal pathway from plasma lipids to NAFLD mediated by five specific metabolites. No potential pleiotropy was found in the sensitivity analysis. Conclusions In summary, our study identified causal relationships between plasma lipidomes, plasma metabolomes, and NAFLD. Certainly, the impact of plasma lipidomes on NAFLD is not limited to plasma metabolomes, indicating a need to further investigate into other possible mediators. These identified factors may become new biomarkers of the NAFLD contributing to its prevention, diagnosis, and treatment.
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Affiliation(s)
- Zhuyuan Zheng
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shaojie Yang
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Wanlin Dai
- Innovation Institute of China Medical University, Shenyang, Liaoning, China
| | - Yang Sun
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Jingnan Wang
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xiaolin Zhang
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yiming Zheng
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Jing Kong
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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Zhang S, Wu Y, Ren Y, Xu Y, An H, Zhao Q, Wang Y, Li H. Widely metabolomic combined with transcriptome analysis to build a bioactive compound regulatory network for the fruit growth cycle in Pseudocydonia sinensis. Food Chem 2024; 456:139933. [PMID: 38852462 DOI: 10.1016/j.foodchem.2024.139933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 03/06/2024] [Accepted: 05/30/2024] [Indexed: 06/11/2024]
Abstract
Neglected and underutilised plants such as Pseudocydonia sinensis (Chinese quince) have garnered global interest as invaluable sources of natural bioactive compounds. Herein, a wide-targeted metabolomics-based approach revealed 1199 concurrent metabolites, with further analysis of their fluctuations across with the five stages of fruit growth. The bioactive compounds in Chinese quince primarily comprised sugars and organic acids, flavonoids, and terpenoids. Moreover, 395 metabolites were identified as having medicinal properties and rutin was the most content of them. Transcriptome analysis further provided a molecular basis for the metabolic changes observed during fruit development. By thoroughly analysing metabolite and transcriptome data, we revealed changes in bioactive compounds and related genes throughout fruit development. This study has yielded valuable insights into the ripening process of Chinese quince fruit, presenting substantial implications for industrial applications, particularly in quality control.
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Affiliation(s)
- Shuangyu Zhang
- Research Institute for Landscape and Ornamental plant, College of Landscape Architecture and Art, Northwest A&F University, Yangling 712100, China.
| | - Yang Wu
- Research Institute for Landscape and Ornamental plant, College of Landscape Architecture and Art, Northwest A&F University, Yangling 712100, China.
| | - Yanshen Ren
- Research Institute for Landscape and Ornamental plant, College of Landscape Architecture and Art, Northwest A&F University, Yangling 712100, China.
| | - Yaping Xu
- Research Institute for Landscape and Ornamental plant, College of Landscape Architecture and Art, Northwest A&F University, Yangling 712100, China.
| | - Hong An
- Research Institute for Landscape and Ornamental plant, College of Landscape Architecture and Art, Northwest A&F University, Yangling 712100, China.
| | - Qianyi Zhao
- Research Institute for Landscape and Ornamental plant, College of Landscape Architecture and Art, Northwest A&F University, Yangling 712100, China.
| | - Yu Wang
- Research Institute for Landscape and Ornamental plant, College of Landscape Architecture and Art, Northwest A&F University, Yangling 712100, China.
| | - Houhua Li
- Research Institute for Landscape and Ornamental plant, College of Landscape Architecture and Art, Northwest A&F University, Yangling 712100, China.
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Sun Z, Wei Y, Xu Y, Jiao J, Duan X. The use of traditional Chinese medicine in the treatment of non-alcoholic fatty liver disease: A review. PHARMACOLOGICAL RESEARCH - MODERN CHINESE MEDICINE 2024; 12:100475. [DOI: 10.1016/j.prmcm.2024.100475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wang Z, Qiu H, Yang Y, Zhang Y, Mou T, Zhang X, Zhang Y. Huanglian-Hongqu herb pair improves nonalcoholic fatty liver disease via NF-κB/NLRP3 pathway in mice: network pharmacology, molecular docking and experimental validation. Hereditas 2024; 161:12. [PMID: 38566171 PMCID: PMC10988798 DOI: 10.1186/s41065-024-00316-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 03/20/2024] [Indexed: 04/04/2024] Open
Abstract
The Huanglian-Hongqu herb pair (HH) is a carefully crafted traditional Chinese herbal compound designed to address disorders related to glucose and lipid metabolism. Its primary application lies in treating hyperlipidemia and fatty liver conditions. This study explored the potential mechanism of HH in treating non-alcoholic fatty liver disease (NAFLD) through network pharmacology, molecular docking, and in vivo animal experiments. Ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UPLC-Q-TOF-MS) was employed to identify the chemical composition of HH. Network pharmacology was used to analyze the related signaling pathways affected by HH. Subsequently, the prediction was verified by animal experiment. Finally, we identified 29 components within HH. Network pharmacology unveiled interactions between HH and 153 NAFLD-related targets, highlighting HH's potential to alleviate NAFLD through NF-κB signaling pathway. Molecular docking analyses illuminated the binding interactions between HH components and key regulatory proteins, including NF-κB, NLRP3, ASC, and Caspase-1. In vivo experiments demonstrated that HH alleviated NAFLD by reducing serum and liver lipid levels, improving liver function, and lowering inflammatory cytokine levels in the serum. Moreover, HH administration downregulated mRNA and protein levels of the NF-κB/NLRP3 pathway. In conclusion, our findings demonstrated that HH has potential therapeutic benefits in ameliorating NAFLD by targeting the NF-κB/NLRP3 pathway, facilitating the broader application of HH in the field of NAFLD.
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Affiliation(s)
- Zheng Wang
- College of Traditional Chinese Medicine and Health Service, Shanxi Datong University, Datong, China
| | - Hairong Qiu
- Department of Chinese Medicine, Medical School, Hubei Minzu University, Enshi, China
| | - Yang Yang
- Institute of Traditional Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, China
| | - Yueyu Zhang
- College of Public health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Taiguo Mou
- College of Public health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaobo Zhang
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
- Traditional Chinese Medicine department, Chinese Medicine Hospital of Chenghua, Chengdu, China.
| | - Yong Zhang
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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8
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Zhang W, Cheng W, Li J, Huang Z, Lin H, Zhang W. New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model. mSystems 2024; 9:e0102723. [PMID: 38421203 PMCID: PMC10949483 DOI: 10.1128/msystems.01027-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 01/29/2024] [Indexed: 03/02/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem due to the high incidence affecting approximately one-third of the world's population. NAFLD is usually linked to obesity and excessive weight. A subset of patients with NAFLD expresses normal or low body mass index; thus, the condition is called non-obese NAFLD or lean NAFLD. However, patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. Furthermore, preclinical results from non-obese animal models with NAFLD are unclear. Gut microbiota and their metabolites in non-obese/lean-NAFLD patients differ from those in obese NAFLD patients. Therefore, we analyzed the biochemical indices, intestinal flora, and intestinal metabolites in a non-obese NAFLD mouse model established using a methionine-choline-deficient (MCD) diet. The significantly lean MCD mice had a remarkable fatty liver with lower serum triglyceride and free fatty acid levels, as well as higher alanine transaminase and aspartate transaminase levels than normal mice. 16S RNA sequencing of fecal DNA showed that the overall richness and diversity of the intestinal flora decreased in MCD mice, whereas the Firmicutes:Bacteroidota ratio was increased. g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium were the predominant species in non-obese NAFLD mice. Fecal metabolomics using liquid chromatography-tandem mass spectrometry revealed the potential biomarkers for the prognosis and diagnosis of non-obese NAFLD, including high levels of tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4'-phosphate, and low levels of 3-carbamoyl-2-phenylpropionaldehyde, N-succinyl-L,L-2,6-diaminopimelate, 4-methyl-5-thiazoleethanol, homogentisic acid, and estriol. Our findings could be useful to identify and develop drugs to treat non-obese NAFLD and lean NAFLD. IMPORTANCE Patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. In fact, about 40% of people with NAFLD worldwide are non-obese, and nearly one-fifth are lean. Lean NAFLD unfortunately may be unnoticed for years and remains undetected until hepatic damage is advanced and the prognosis is compromised. This study focused on the lean NAFLD, screened therapeutic agents, and biomarkers for the prognosis and diagnosis using MCD-induced male C57BL/6J mice. The metabolites tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4'-phosphate, together with the predominant flora including g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium, were specific in non-obese NAFLD mice and might be used as targets for non-obese NAFLD drug exploration. This study is particularly significant for non-obese NAFLDs that need to be more actively noticed and vigilant.
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Affiliation(s)
- Wenji Zhang
- Guangdong Provincial Engineering and Technology Research Center for Tobacco Breeding and Comprehensive Utilization, Key Laboratory of Crop Genetic Improvement of Guangdong Province, Crops Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Wenli Cheng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
- Department of Radiation Oncology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - JingHui Li
- Ningbo Psychiatric Hospital, Ningbo, China
| | - Zhenrui Huang
- Guangdong Provincial Engineering and Technology Research Center for Tobacco Breeding and Comprehensive Utilization, Key Laboratory of Crop Genetic Improvement of Guangdong Province, Crops Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Hui Lin
- Department of Radiation Oncology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Wenjuan Zhang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
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Wu Y, Yin W, Hao P, Chen Y, Yu L, Yu X, Wu Y, Li X, Wang W, Zhou H, Yuan Y, Quan X, Yu Y, Hu B, Chen S, Zhou Z, Sun W. Polysaccharide from Panax japonicus C.A. Mey prevents non-alcoholic fatty liver disease development based on regulating liver metabolism and gut microbiota in mice. Int J Biol Macromol 2024; 260:129430. [PMID: 38228199 DOI: 10.1016/j.ijbiomac.2024.129430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 12/13/2023] [Accepted: 01/09/2024] [Indexed: 01/18/2024]
Abstract
In this study, a new polysaccharide (PSPJ) with specific molecular weight and monosaccharide compositions was isolated and purified from the water extract of Panacis Japonici Rhizoma (PJR). 16S rRNA analysis and untargeted metabolomic analysis were used to assess PSPJ's efficacy in averting non-alcoholic fatty liver disease (NAFLD). This study indicated that PSPJ significantly reduced liver fat accumulation, the increase in blood lipids and ALT caused by HFD, indicating that PSPJ can prevent NAFLD. We demonstrated through cell experiments that PSPJ does not directly affect liver cells. The gut microbiota disorder and alterations in short-chain fatty acids (SCFAs) induced by the high-fat diet (HFD) were ameliorated by PSPJ, as evidenced by the analysis of 16S rRNA. In particular, supplementing PSPJ reduced the abundance of Turicibacter, Dubosiella, and Staphylococcus, and increased the abundance of Bacteroides, Blautia, and Lactobacillus. Untargeted metabolomic analysis shows that PSPJ improves liver metabolic disorders by regulating arachidonic acid metabolism, carbohydrate digestion and absorption, fatty acid biosynthesis, fatty acid metabolism and retinol metabolism. The findings of our investigation indicate that PSPJ has the potential to modulate liver metabolism through alterations in the composition of intestinal bacteria, hence preventing NAFLD.
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Affiliation(s)
- Yi Wu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Wen Yin
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Ping Hao
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yueru Chen
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Lingyun Yu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Xingjian Yu
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento 95817, CA, United States of America
| | - Yu Wu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, Center for Global Health, Nanjing Medical University, Nanjing 211166, China
| | - Xiaocong Li
- College of Medicine, Hubei Three Gorges Polytechnic, No.31 Stadium Road, Yichang 443000, China
| | - Wenjia Wang
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; College of Animal Science and Technology, Ningxia University, China
| | - Hui Zhou
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yuan Yuan
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaoyu Quan
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yue Yu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Bing Hu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Shouhai Chen
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Zhenlei Zhou
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
| | - Wenjing Sun
- Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, College of Biology & Pharmacy, Yulin Normal University, No. 1303 Jiaoyu East Road, Yulin 537000, Guangxi, China.
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10
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Li HJ, Wang YS, Wang YN, Liu AR, Su XH, Ma ZA, Wang LX, Zhang ZY, Lv SQ, Miao J, Cui HT. Mechanical study of alisol B 23-acetate on methionine and choline deficient diet-induced nonalcoholic steatohepatitis based on untargeted metabolomics. Biomed Chromatogr 2024; 38:e5763. [PMID: 37858975 DOI: 10.1002/bmc.5763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 09/21/2023] [Accepted: 10/03/2023] [Indexed: 10/21/2023]
Abstract
Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.
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Affiliation(s)
- Hua-Jun Li
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Yuan-Song Wang
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Ya-Nan Wang
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Ai-Ru Liu
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Xiu-Hai Su
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Zi-Ang Ma
- Graduate School of Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Li-Xin Wang
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Zhong-Yong Zhang
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Shu-Quan Lv
- Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
| | - Jing Miao
- Tianjin Second People's Hospital, Tianjin, China
| | - Huan-Tian Cui
- Yunnan University of Traditional Chinese Medicine, Kunming, China
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11
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Zhou Y, Qian C, Tang Y, Song M, Zhang T, Dong G, Zheng W, Yang C, Zhong C, Wang A, Zhao Y, Lu Y. Advance in the pharmacological effects of quercetin in modulating oxidative stress and inflammation related disorders. Phytother Res 2023; 37:4999-5016. [PMID: 37491826 DOI: 10.1002/ptr.7966] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/27/2023] [Accepted: 07/07/2023] [Indexed: 07/27/2023]
Abstract
Numerous pharmacological effects of quercetin have been illustrated, including antiinflammation, antioxidation, and anticancer properties. In recent years, the antioxidant activity of quercetin has been extensively reported, in particular, its impacts on glutathione, enzyme activity, signaling transduction pathways, and reactive oxygen species (ROS). Quercetin has also been demonstrated to exert a striking antiinflammatory effect mainly by inhibiting the production of cytokines, reducing the expression of cyclooxygenase and lipoxygenase, and preserving the integrity of mast cells. By regulating oxidative stress and inflammation, which are regarded as two critical processes involved in the defense and regular physiological operation of biological systems, quercetin has been validated to be effective in treating a variety of disorders. Symptoms of these reactions have been linked to degenerative processes and metabolic disorders, including metabolic syndrome, cardiovascular, neurodegeneration, cancer, and nonalcoholic fatty liver disease. Despite that evidence demonstrates that antioxidants are employed to prevent excessive oxidative and inflammatory processes, there are still concerns regarding the expense, accessibility, and side effects of agents. Notably, natural products, especially those derived from plants, are widely accessible, affordable, and generally safe. In this review, the antioxidant and antiinflammatory abilities of the active ingredient quercetin and its application in oxidative stress-related disorders have been outlined in detail.
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Affiliation(s)
- Yueke Zhou
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Cheng Qian
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yu Tang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mengyao Song
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Teng Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guanglu Dong
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Weiwei Zheng
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chunmei Yang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chongjin Zhong
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Aiyun Wang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yang Zhao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yin Lu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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Wang Q, Liu Z, Wang R, Li R, Lian X, Yang Y, Yan J, Yin Z, Wang G, Sun J, Peng Y. Effect of Ginkgo biloba extract on pharmacology and pharmacokinetics of atorvastatin in rats with hyperlipidaemia. Food Funct 2023; 14:3051-3066. [PMID: 36916480 DOI: 10.1039/d2fo03238d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Ginkgo biloba extract (GBE) is a common dietary supplement used by people with dyslipidaemia worldwide to reduce the risk of cardiovascular disease. Many studies have found that GBE itself has a variety of pharmacological activities. However, the role of GBE as an adjunct to conventional therapy with chemical drugs remains controversial. Therefore, this study explored the additional benefits of GBE in the treatment of hyperlipidaemia with statins in terms of both pharmacodynamics and pharmacokinetics. A hyperlipidaemia model was established by feeding rats a high-fat diet for a long time. The animals were treated with atorvastatin only, GBE only, or a combination of atorvastatin and GBE. The results showed that statins combined with GBE could significantly improve the blood lipid parameters, reduce the liver fat content, and reduce the size of adipocytes in abdominal fat. The effect was superior to statin therapy alone. In addition, the combination has shown additional liver protection against possible pathological liver injury or statin-induced liver injury. A lipidomic study showed that GBE could regulate the abnormal lipid metabolism of the liver in hyperlipemia. When statins are combined with GBE, this callback effect introduced by GBE on endogenous metabolism has important implications for resistance to disease progression and statin resistance. Finally, in the presence of GBE, there was a significant increase in plasma statin exposure. These results all confirmed that GBE has incremental benefits as a dietary supplement of statin therapy for dyslipidaemia.
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Affiliation(s)
- Qingqing Wang
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Zihou Liu
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Rui Wang
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Run Li
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Xiaoru Lian
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Yanquan Yang
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Jiao Yan
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Zhiqi Yin
- Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, China
| | - Guangji Wang
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Jianguo Sun
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
| | - Ying Peng
- Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, China.
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13
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Liu L, Sun S, Li X. LncRNA ZFAS1 ameliorates injury led by non-alcoholic fatty liver disease via suppressing lipid peroxidation and inflammation. Clin Res Hepatol Gastroenterol 2023; 47:102067. [PMID: 36513253 DOI: 10.1016/j.clinre.2022.102067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/30/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is known to aggravate metabolic disturbance and increase the risk of complications. The purpose of the present study was to explore the mechanism underlying the clinical effects of ZFAS1 on NAFLD. METHODS Expression of the ZFAS1 RNA was quantified in patients with NAFLD through reverse transcription-quantitative polymerase chain reaction. The correlations were assessed using Pearson's correlation coefficient test. The receiver operating characteristic curve was used to evaluate the identification of ZFAS1. Commercial kits were purchased to detect the pertinent parameters to establish mice models. Luciferase report assay was used to identify and confirm the presence of ZFAS1 ceRNA. RESULTS The increase of ZFAS1 expression in patients with NAFLD was noted and the high expression level may be considered a risk factor for NAFLD. In mouse models fed with high-fat diet (HFD), the expression levels of ZFAS1 were increased; furthermore, sh-ZFAS1 reversed ZFAS1 overexpression. HFD administration resulted in liver injury, which was indicated by increased lipid deposition, aggressive oxidative stress, and imbalanced inflammatory reaction. However, sh-ZFAS1 attenuated the abovementioned adverse effects of HFD. MiR-144-5p was a ceRNA of ZFAS1; in addition, the expression of miR-144-5p was reduced in HFD-managed models and patients with NAFLD. ZFAS1 could successfully regulate the expression levels of miR-144-5p. In the present study, the negative relationship between ZFAS1 and miR-144-5p was documented. CONCLUSION Excessive expression of ZFAS1 and its diagnostic potential was noted in patients with NAFLD. It was evident that ZFAS1 may be responsible for exacerbating the worsening of liver function.
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Affiliation(s)
- Lu Liu
- Department of Endocrine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
| | - Sen Sun
- Department of Anesthesiology, Shanghai Pulmonary Hospital, Shanghai 200433, China
| | - Xiaohua Li
- Department of Endocrine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
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14
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Jafari-Garageshlaghi F, Hashtarkhani F, Soraya H, Malekinejad H. Quercetin Protected from Aluminum Phosphide-induced Acute and Subacute Cardio- and Hepatotoxicity in Rats. Curr Pharm Des 2022; 28:3513-3524. [PMID: 36453481 DOI: 10.2174/1381612829666221130123706] [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: 05/18/2022] [Revised: 10/01/2022] [Accepted: 10/14/2022] [Indexed: 12/03/2022]
Abstract
BACKGROUND Aluminum phosphide (ALP) intoxication either accidentally or intentionally, is one of the major health concerns in developing countries. Its poisoning causes severe damage to organs including the heart and liver. OBJECTIVES This study aimed to investigate the hepato- and cardioprotective effects of quercetin (QCN) on the acute/subacute toxicity of ALP in rodent models. METHODS Acute (single dose, 12.5 mg/kg, orally) and subacute (2 mg/kg, orally and 7 days) intoxication of ALP were induced in rats and the protective effects of QCN on altered hepatic/cardiac functional enzyme concentrations, myeloperoxidase activity, oxidative stress biomarkers, and histopathological changes were studied at three doses of 10, 50 and 100 mg/kg BW. To record any heart abnormality, an electrocardiogram (ECG) was recorded 3 h after the last treatment. RESULTS Quercetin reduced the ALP-increased hepatic and cardiac functional enzyme concentrations and myeloperoxidase activity. Moreover, QCN improved remarkably the ALP-induced ECG abnormalities (T inversion, bigeminy in R waves) and arrhythmias. QCN attenuated significantly (p < 0.05) the ALP-induced oxidative/ nitrosative stress and histopathological injuries in the liver and heart. CONCLUSION Our results suggest that QCN is able to protect the ALP-induced cardiac and hepatic injuries in both acute and subacute models and its effects attribute to its antioxidant and anti-inflammatory properties.
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Affiliation(s)
- Fatemeh Jafari-Garageshlaghi
- Experimental & Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran.,Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
| | - Fatemeh Hashtarkhani
- Experimental & Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran.,Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
| | - Hamid Soraya
- Experimental & Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran.,Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
| | - Hassan Malekinejad
- Experimental & Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran.,Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
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15
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Xu Z, Wu FW, Niu X, Lu XP, Li YR, Zhang ST, Ou JZ, Wang XM. Integrated strategy of RNA-sequencing and network pharmacology for exploring the protective mechanism of Shen-Shi-Jiang-Zhuo formula in rat with non-alcoholic fatty liver disease. PHARMACEUTICAL BIOLOGY 2022; 60:1819-1838. [PMID: 36124995 PMCID: PMC9518293 DOI: 10.1080/13880209.2022.2106250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 07/08/2022] [Accepted: 07/22/2022] [Indexed: 06/15/2023]
Abstract
CONTEXT Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD). OBJECTIVE To explore the therapeutic effect and mechanism of SSJZF on NAFLD. MATERIALS AND METHODS Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot. RESULTS High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulated total triglycerides (58%), cholesterol (62%), aspartate aminotransferase (57%), alanine aminotransferase (41%) andγ-glutamyl transpeptidase (36%), as well as the expression of ACC (5.3-fold), FAS (12.1-fold), SREBP1C (2.3-fold), and CD36 (4.4-fold), and significantly reduced collagen deposition (67%). Then we identified 23 compounds of SSJZF that acted on 25 key therapeutic targets of NAFLD by integrating RNA-sequencing and network pharmacology. Finally, we also confirmed that high dose SSJZF increased p-PI3K/PI3K (1.6-fold) and p-AKT/AKT (1.6-fold) in NAFLD rats. DISCUSSION AND CONCLUSION We found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs.
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Affiliation(s)
- Zheng Xu
- Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fan-Wei Wu
- Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xuan Niu
- Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xiao-Peng Lu
- Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Yan-Rong Li
- Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
- Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shu-Ting Zhang
- Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
- Guangdong Agriculture and Reclamation Central Hospital, Zhanjiang, Guangdong
| | - Jun-Zhao Ou
- Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
- Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xue-Mei Wang
- Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
- Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, China
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Li H, Wang S, Wang S, Yu H, Yu W, Ma X, He X. Atorvastatin Inhibits High-Fat Diet-Induced Lipid Metabolism Disorders in Rats by Inhibiting Bacteroides Reduction and Improving Metabolism. Drug Des Devel Ther 2022; 16:3805-3816. [PMID: 36349306 PMCID: PMC9637332 DOI: 10.2147/dddt.s379335] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 10/19/2022] [Indexed: 11/25/2022] Open
Abstract
PURPOSE The prevalence of hyperlipidemia and related illnesses is on its rise, and atorvastatin is the frequently used hypolipidemic agent. However, there is still uncertainty about the mechanisms, especially the relationship between the lipid-lowering effect, intestinal microbiome, and metabolic profiles. We aim to intensively explain the mechanism of the hypolipidemic effect of atorvastatin through multi-omics perspective of intestinal microbiome and metabolomics. METHODS Multi-omics methods play an increasingly important role in the analysis of intestinal triggers and evaluation of metabolic disorders such as obesity, hyperlipidemia, and diabetes. Therefore, we were prompted to explore intestinal triggers, underlying biomarkers, and potential intervention targets of atorvastatin in the treatment of dyslipidemia through multi-omics. To achieve this, SPF Wistar rats were fed a high-fat diet or normal diet for 8 weeks. Atorvastatin was then administered to high-fat diet-fed rats. RESULTS By altering intestinal microbiome, a high-fat diet can affect feces and plasma metabolic profiles. Treatment with atorvastatin possibly increases the abundance of Bacteroides, thereby improving "propanoate metabolism" and "glycine, serine and threonine metabolism" in feces and plasma, and contributing to blood lipid reduction. CONCLUSION Our study elucidated the intestinal triggers and metabolites of high-fat diet-induced dyslipidemia from the perspective of intestinal microbiome and metabolomics. It equally identified potential intervention targets of atorvastatin. This further explains the mechanism of the hypolipidemic effect of atorvastatin from a multi-omics perspective.
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Affiliation(s)
- Huimin Li
- Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China,National Human Genetic Resources Center; National Research Institute for Health and Family Planning; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Shue Wang
- Preventive Medicine Experimental Teaching Center, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China
| | - Shuai Wang
- Department of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China
| | - Hai Yu
- Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China
| | - Wenhao Yu
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China,Institute for Medical Dataology, Shandong University, National Institute of Health Data Science of China, Jinan, Shandong, 250012, People's Republic of China
| | - Xiaomin Ma
- Preventive Medicine Experimental Teaching Center, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China
| | - Xiaodong He
- Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China,Institute for Medical Dataology, Shandong University, National Institute of Health Data Science of China, Jinan, Shandong, 250012, People's Republic of China,Correspondence: Xiaodong He, Tel/Fax +86 531 88382554, Email
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Eupalinolide O Induces Apoptosis in Human Triple-Negative Breast Cancer Cells via Modulating ROS Generation and Akt/p38 MAPK Signaling Pathway. JOURNAL OF ONCOLOGY 2022; 2022:8802453. [PMID: 36185619 PMCID: PMC9519309 DOI: 10.1155/2022/8802453] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/22/2022] [Accepted: 08/23/2022] [Indexed: 11/18/2022]
Abstract
Background Triple-negative breast cancer (TNBC) is a subtype of breast cancer with limited therapeutic options. Eupalinolide O (EO) was reported to inhibit tumor growth. This study is aimed at exploring the role of EO on TNBC both in vivo and in vitro. Methods. In in vitro experiments, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assay were conducted to measure the impact of EO on TNBC cell growth at different concentrations and time points. Flow cytometry was conducted to evaluate cell apoptosis. Mitochondrial membrane potential (MMP) loss, caspase-3 activity, and reactive oxygen species (ROS) generation were assessed. The expressions of apoptosis-related mRNAs and Akt/p38 MAPK signaling pathway-related proteins were measured. In in vivo experiments, by injecting TNBC cells into the nude mice to induce xenograft tumor, mice were treated with EO for 20 days. Then, in vivo bioluminescence imaging system was utilized to monitor the growth and distribution of TNBC cells. Tumor volume and weight were also recorded. Hematoxylin-eosin (HE) staining and ELISA assay were applied to observe tumor tissue morphology and ROS levels. Furthermore, western blotting was conducted to observe the expression of apoptosis-related proteins and Akt/p38 MAPK signaling pathway-associated proteins. Results EO inhibited the cell viability and proliferation of TNBC cells but not normal epithelial cells. Furthermore, EO induced apoptosis, decreased MMP, and elevated caspase-3 activity and ROS content in TNBC cells. Meanwhile, the expression of apoptosis-related mRNAs and Akt/p38 MAPK pathway-related proteins was regulated by EO treatment. Besides, in vivo experiments demonstrated EO not only suppressed tumor growth, Ki67 expression, ROS generation, and Akt phosphorylation but also upregulated caspase-3 expression and p-38 phosphorylation. Conclusion EO may induce cell apoptosis in TNBC via regulating ROS generation and Akt/p38 MAPK pathway, indicating EO may be a candidate drug for TNBC.
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TRIM50 Inhibits Proliferation and Metastasis of Gastric Cancer via Promoting β-Catenin Degradation. JOURNAL OF ONCOLOGY 2022; 2022:5936753. [PMID: 36046365 PMCID: PMC9423946 DOI: 10.1155/2022/5936753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 07/15/2022] [Indexed: 12/02/2022]
Abstract
Background Gastric cancer (GC) is a common malignancy with a poor prognosis. Tripartite motif-containing 50 (TRIM50) belongs to the TRIM family and is reported to be related to numerous cancers. This study aimed to investigate the function of TRIM50 in GC. Methods Three microarray datasets (GSE13911, GSE79973, and GSE19826) containing GC and adjacent nontumor tissues were used for bioinformatics analysis to screen GC-related genes and assess the associations between GC development and TRIM50 expression. Then, TRIM50 expression in GC cells was detected at mRNA and protein levels. After TRIM50 was knockdown or overexpressed, the effect of TRIM50 on the proliferation and metastasis of GC cells was analyzed using Cell Counting Kit-8 (CCK-8), flow cytometry, scratch, and Transwell assays. The interaction between TRIM50 and β-catenin was analyzed. The expression of cell cycle-, migration-, invasion-, and Wnt/β-catenin signaling pathway-related proteins was detected by Western blot. Furthermore, we measured the role of TRIM50 overexpression on tumor growth as well as the Wnt/β-catenin signaling pathway in vivo. In addition, XAV939 (a WNT/β-catenin signaling pathway inhibitor) was used to clarify the mechanism of TRIM50 on GC. Results Bioinformatics revealed that TRIM50 expression was decreased in GC samples and associated with GC development. In vitro study revealed that TRIM50 overexpression impeded the GC cell proliferation and metastasis, while TRIM50 knockdown presented the opposite results. In addition, TRIM50 interacted with β-catenin to induce the degradation of β-catenin. In in vivo assay, TRIM50 overexpression inhibited tumor growth and blocked the Wnt/β-catenin signaling pathway. In addition, TRIM50 knockdown-promoted cell proliferation and metastasis in GC cells were inverted by XAV939. Conclusion TRIM50 overexpression may inhibit cell proliferation and metastasis in GC via β-catenin degradation, indicating that TRIM50 could be a target for the treatment of GC.
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A multiomics and network pharmacological study reveals the neuroprotective efficacy of Fu-Fang-Dan-Zhi tablets against glutamate-induced oxidative cell death. Comput Biol Med 2022; 148:105873. [PMID: 35868043 DOI: 10.1016/j.compbiomed.2022.105873] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 07/08/2022] [Accepted: 07/09/2022] [Indexed: 11/20/2022]
Abstract
Neuroprotective therapy after ischemic stroke remains a significant need, but current measures are still insufficient. The Fu-Fang-Dan-Zhi tablet (FFDZT) is a proprietary Chinese medicine clinically employed to treat ischemic stroke in the recovery period. This work aims to systematically investigate the neuroprotective mechanism of FFDZT. A systems strategy that integrated metabolomics, transcriptomics, network pharmacology, and in vivo and in vitro experiments was used. First, middle cerebral artery occlusion (MCAO) model rats were treated with FFDZT. FFDZT treatment significantly reduced the infarct volume in the brains of middle cerebral artery occlusion (MCAO) model rats. Then, samples of serum and brain tissue were taken for metabolomics and transcriptomics studies, respectively; gene expression profiles of MCF7 cells treated with FFDZT and its 4 active compounds (senkyunolide I, formononetin, drilodefensin, and tanshinone IIA) were produced for CMAP analysis. Computational analysis of metabolomics and transcriptomics results suggested that FFDZT regulated glutamate and oxidative stress-related metabolites (2-hydroxybutanoic acid and 2-hydroxyglutaric acid), glutamate receptors (NMDAR, KA, and AMPA), glutamate involved pathways (glutamatergic synapse pathway; d-glutamine and d-glutamate metabolism; alanine, aspartate and glutamate metabolism), as well as the reactive oxygen species metabolic process. CMAP analysis indicated that two active ingredients of FFDZT (tanshinone ⅡA and senkyunolide I) could act as glutamate receptor antagonists. Next, putative therapeutic targets of FFDZT's active ingredients identified in the brain were collected from multiple resources and filtered by statistical criteria and tissue expression information. Network pharmacological analysis revealed extensive interactions between FFDZT's putative targets, anti-IS drug targets, and glutamate-related enzymes, while the resulting PPI network exhibited modular topology. The targets in two of the modules were significantly enriched in the glutamatergic synapse pathway. The interactions between FFDZT's ingredients and important targets were verified by molecular docking. Finally, in vitro experiments validated the effects of FFDZT and its ingredients in suppressing glutamate-induced PC12 cell injury and reducing the generation of reactive oxygen species. All of our findings indicated that FFDZT's efficacy for treating ischemic stroke could be due to its neuroprotection against glutamate-induced oxidative cell death.
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Zhou L, Li H, Hou G, Wang J, Zhou H, Wang D. Effects of Vine Tea Extract on Meat Quality, Gut Microbiota and Metabolome of Wenchang Broiler. Animals (Basel) 2022; 12:ani12131661. [PMID: 35804560 PMCID: PMC9265100 DOI: 10.3390/ani12131661] [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: 05/16/2022] [Revised: 06/23/2022] [Accepted: 06/27/2022] [Indexed: 11/16/2022] Open
Abstract
This study investigates the effects of vine tea (Ampelopsis grossedentata) extract (AGE) on meat quality, gut microbiota and cecal content metabolites of Wenchang broilers. A total of 240 female Wenchang broilers aged 70 days were randomly allocated into four groups with five replicates of twelve broilers each. Broilers were fed a corn-soybean basal diet supplemented with AGE at 0 (T1), 0.2% (T2), 0.4% (T3) and 0.6% (T4) until 124 days of age. The whole feeding trial lasted 54 days. Results suggest that the content of total triglycerides and low-density lipoprotein cholesterol in serum of broilers are linearly reduced with dietary AGE supplementation (p < 0.05). The T3 and T4 groups had higher (p < 0.05) a* value in thigh and breast muscles than the T1 group. Additionally, the dietary supplementation of AGE decreased the shear force and drip loss of both thigh and breast muscles linearly (p < 0.05). Compared with the T1 group, AGE supplementation increased the levels of inosine monophosphate (IMP) significantly (p < 0.05) in both the thigh and breast muscles. Furthermore, an increase (p < 0.05) in the total unsaturated fatty acid (USFA), polyunsaturated fatty acids (PUFA) and the ratio of unsaturated fatty acids to saturated fatty acid (USFA: SFA) in both the thigh and breast muscles in the T3 group was observed. Higher abundance of Bacteroidota (p < 0.05) and lower abundance of Firmicutes (p < 0.05) were observed in the T3 group. The abundance of Faecalibacterium was significantly decreased (p < 0.05) in the T3 group compared with the T1 group. Cholesterol sulfate and p-cresol sulfate were identified as differential metabolites between the T1 and T3 groups. It suggested that 0.4% of AGE supplementation significantly downregulated the levels of p-cresol sulfate and cholesterol sulfate (p < 0.05) and the hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) activity compared with the control. Our present study demonstrates that dietary supplementation with AGE can improve the quality and flavor by increasing the IMP and PUFA content in the muscle of Wenchang broilers. Furthermore, dietary AGE supplementation with 0.4% can regulate the cholesterol metabolism of Wenchang broilers.
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Affiliation(s)
- Luli Zhou
- Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China; (L.Z.); (G.H.)
| | - Hui Li
- College of Animal Science and Technology, Hainan University, Haikou 570228, China; (H.L.); (J.W.)
| | - Guanyu Hou
- Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China; (L.Z.); (G.H.)
| | - Jian Wang
- College of Animal Science and Technology, Hainan University, Haikou 570228, China; (H.L.); (J.W.)
| | - Hanlin Zhou
- Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524013, China
- Correspondence: (H.Z.); (D.W.)
| | - Dingfa Wang
- Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China; (L.Z.); (G.H.)
- Correspondence: (H.Z.); (D.W.)
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Zhu L, Chen G, Guo Y, Zheng J, Yang H, Sun X, Liu Y, Hu B, Liu H. Structural characterization of Poria cocos oligosaccharides and their effects on the hepatic metabolome in high-fat diet-fed mice. Food Funct 2022; 13:6813-6829. [PMID: 35671132 DOI: 10.1039/d2fo00638c] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In this study, novel Poria cocos oligosaccharides (PCO) were prepared by enzymatic degradation, and their polymerization degree was determined to be 2-6 by LC-MS analysis. By monosaccharide composition analysis, methylation assay, FT-IR, and NMR analysis, PCO were deduced to contain the sugar residues of (1 → 2)-β-D-Glcp, (1 → 2)-α-D-Glcp, and (1 → 4)-α-D-Glcp. Using an HFD-fed mouse model with dyslipidemia, PCO could significantly suppress lipid metabolism disorders, characterized by the reduction of lipid accumulation and inflammatory responses in the blood and liver tissues. Based on the non-targeted metabolomic analysis and Spearman's correlation analysis, we presume that the preventive effect of PCO on dyslipidemia might contribute to the reversal of changed metabolic pathways, which were related to the metabolisms of glycerophospholipids, unsaturated fatty acids, amino acids, choline, bile acids, tryptophan, sphingolipids, and glutathione. Our research shed light on the potential application of PCO for the treatment of dyslipidemia.
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Affiliation(s)
- Lin Zhu
- College of Life Science, Wuchang University of Technology, Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, Engineering Technology Research Center of Biological Peptide Antidiabetics of Hubei Province, Jiangxia Avenue 16, Wuhan 430223, P. R. China.,College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Guangming Chen
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Yanlei Guo
- Chongqing Academy of Chinese Materia Medica, Chongqing 400065, P. R. China
| | - Junping Zheng
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Huabing Yang
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Xiongjie Sun
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Yang Liu
- College of Life Science, Wuchang University of Technology, Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, Engineering Technology Research Center of Biological Peptide Antidiabetics of Hubei Province, Jiangxia Avenue 16, Wuhan 430223, P. R. China
| | - Baifei Hu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Hongtao Liu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
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22
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Flos Carthami Exerts Hepatoprotective Action in a Rat Model of Alcoholic Liver Injury via Modulating the Metabolomics Profile. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8158699. [PMID: 35547657 PMCID: PMC9085312 DOI: 10.1155/2022/8158699] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 02/22/2022] [Accepted: 04/05/2022] [Indexed: 02/06/2023]
Abstract
This study was intended to identify the shifts in the metabolomics profile of the hepatic tissue damaged by alcohol consumption and verify the potential restorative action of flos carthami (the flowers of Carthamus tinctorius, FC) in the protection of alcohol-induced injury by attenuating the level of identified metabolites. Rats were treated with FC and subsequently subjected to alcohol administration. The serum samples were subjected to liquid chromatography-mass spectrometry (LC-MS)-based metabolomics followed by statistical and bioinformatics analyses. The clustering of the samples showed an obvious separation in the principal component analysis (PCA) plot, and the scores plot of the orthogonal partial least squares-discriminant analysis (OPLS-DA) model allowed the distinction among the three groups. Among the 3211 total metabolites, 1088 features were significantly different between the control and alcohol-treated groups, while 367 metabolites were identified as differential metabolites between the alcohol- and FC-treated rat groups. Time series clustering approach indicated that 910 metabolites in profile 6 were upregulated by alcohol but subsequently reversed by FC treatment; among them, the top 10 metabolites based on the variable importance in projection (VIP) scores were 1-methyladenine, phenylglyoxylic acid, N-acetylvaline, mexiletine, L-fucose, propylthiouracil, dopamine 4-sulfate, isoleucylproline, (R)-salsolinol, and monomethyl phthalate. The Pearson correlation analysis and network construction revealed 96 hub metabolites that were upregulated in the alcohol liver injury model group but were downregulated by FC. This study confirmed the hepatoprotective effects of FC against alcohol-induced liver injury and the related changes in the metabolic profiles, which will contribute to the understanding and the treatment of alcohol-induced acute liver injury.
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Lozano-Castellón J, Rocchetti G, Vallverdú-Queralt A, Lucchini F, Giuberti G, Torrado-Prat X, Illán M, Mª Lamuela-Raventós R, Lucini L. New insights into the lipidomic response of CaCo-2 cells to differently cooked and in vitro digested extra-virgin olive oils. Food Res Int 2022; 155:111030. [DOI: 10.1016/j.foodres.2022.111030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 02/12/2022] [Accepted: 02/15/2022] [Indexed: 01/18/2023]
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Liu X, Pan Y, Shen Y, Liu H, Zhao X, Li J, Ma N. Protective Effects of Abrus cantoniensis Hance on the Fatty Liver Hemorrhagic Syndrome in Laying Hens Based on Liver Metabolomics and Gut Microbiota. Front Vet Sci 2022; 9:862006. [PMID: 35498747 PMCID: PMC9051509 DOI: 10.3389/fvets.2022.862006] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 03/14/2022] [Indexed: 11/22/2022] Open
Abstract
As a metabolic disease, fatty liver hemorrhagic syndrome (FLHS) has become a serious concern in laying hens worldwide. Abrus cantoniensis Hance (AC) is a commonly used plant in traditional medicine for liver disease treatment. Nevertheless, the effect and mechanism of the decoction of AC (ACD) on FLHS remain unclear. In this study, ultra-high performance liquid chromatography analysis was used to identify the main phytochemicals in ACD. FLHS model of laying hens was induced by a high-energy low-protein (HELP) diet, and ACD (0.5, 1, 2 g ACD/hen per day) was given to the hens in drinking water at the same time for 48 days. Biochemical blood indicators and histopathological analysis of the liver were detected and observed to evaluate the therapeutic effect of ACD. Moreover, the effects of ACD on liver metabolomics and gut microbiota in laying hens with FLHS were investigated. The results showed that four phytochemicals, including abrine, hypaphorine, vicenin-2, and schaftoside, were identified in ACD. ACD treatment ameliorated biochemical blood indicators in laying hens with FLHS by decreasing aspartate aminotransferase, alanine aminotransferase, triglycerides, low-density lipoprotein cholesterol, and total cholesterol, and increasing high-density lipoprotein cholesterol. In addition, lipid accumulation in the liver and pathological damages were relieved in ACD treatment groups. Moreover, distinct changes in liver metabolic profile after ACD treatment were observed, 17 endogenous liver metabolites mainly associated with the metabolism of arachidonic acid, histidine, tyrosine, and tryptophan were reversed by ACD. Gut microbiota analysis revealed that ACD treatment significantly increased bacterial richness (Chao 1, P < 0.05; Ace, P < 0.01), and upregulated the relative abundance of Bacteroidetes and downregulated Proteobacteria, improving the negative effects caused by HELP diet in laying hens. Taken together, ACD had a protective effect on FLHS by regulating blood lipids, reducing liver lipid accumulation, and improving the dysbiosis of liver metabolomics and gut microbiota.
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Affiliation(s)
- Xu Liu
- College of Veterinary Medicine, Veterinary Biological Technology Innovation Center of Hebei Province, Hebei Agricultural University, Baoding, China
| | - Yinchuan Pan
- College of Veterinary Medicine, Veterinary Biological Technology Innovation Center of Hebei Province, Hebei Agricultural University, Baoding, China
| | - Youming Shen
- Research Institute of Pomology, Chinese Academy of Agricultural Sciences, Xingcheng, China
| | - Hailong Liu
- Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou, China
| | - Xinghua Zhao
- College of Veterinary Medicine, Veterinary Biological Technology Innovation Center of Hebei Province, Hebei Agricultural University, Baoding, China
| | - Jianyong Li
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy of Agricultural Sciences, Lanzhou, China
- Jianyong Li
| | - Ning Ma
- College of Veterinary Medicine, Veterinary Biological Technology Innovation Center of Hebei Province, Hebei Agricultural University, Baoding, China
- *Correspondence: Ning Ma
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Xin Y, Hou Y, Zhang J, Ding T, Guan Z, Zhang D, Wang D, Jia S, Li S, Zhao X. Metabolomics analysis of the effects of quercetin on Cd-induced hepatotoxicityin rats. Free Radic Res 2022; 56:185-195. [PMID: 35414335 DOI: 10.1080/10715762.2022.2064285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Cadmium(Cd) is known to cause damage to the liver. In this study, metabolomics technology was used to investigate the effect of quercetin(QE) on Cd-induced hepatotoxicity. A total of 60 male SD rats were randomly divided into the following 6 groups: control group (C), low and high dose QE group (Q1: 10 mg/kg·bw, Q2: 50 mg/kg·bw), Cd group (D), low and high dose QE and Cd combined intervention group (DQ1, DQ2). The rats were given Cd chloride (CdCl2) at a concentration of 40 mg/L through free drinking water. After 12 weeks of treatment, liver samples of rats were collected for metabonomic analysis. A total of 12 metabolites were identified, the intensities of PC(18:0/14:1(9Z)) and Arachidonate acid were decreased in the Cd-treated group (p < 0.01), whereas the intensities of Chenodeoxyglycocholic acid, Cholic acid, Taurochenodesoxycholic acid, Glycocholic acid, Prostaglandin D2, 15-Deoxy-d-12,14-PGJ2, Oxidized glutathione, Cholesterol, Protoporphyrin IX, Bilirubinwere increased significantly in the Cd-treated group compared with group C(p < 0.01). When rats were given high doses of QE and Cd at the same time, the intensity of the above metabolites was significantly restored in group DQ2. Results suggest that The protective effect of QE on Cd-induced liver injury is associated with antioxidant activity of QE, as well as QE can regulates hepatic bile acid metabolism by affecting FXR and BSEP, and regulates AA metabolism by inhibiting Cd-induced activities of COX-2 and PLA2.
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Affiliation(s)
- Youwei Xin
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Yali Hou
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Jingnan Zhang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Tingting Ding
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Zhiyu Guan
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Dongyan Zhang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Dan Wang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Siqi Jia
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Siqi Li
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
| | - Xiujuan Zhao
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China
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Jiang G, Sun C, Wang X, Mei J, Li C, Zhan H, Liao Y, Zhu Y, Mao J. Hepatoprotective mechanism of Silybum marianum on nonalcoholic fatty liver disease based on network pharmacology and experimental verification. Bioengineered 2022; 13:5216-5235. [PMID: 35170400 PMCID: PMC8974060 DOI: 10.1080/21655979.2022.2037374] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/17/2022] [Accepted: 01/29/2022] [Indexed: 12/12/2022] Open
Abstract
The study aimed to identify the key active components in Silybum marianum (S. marianum) and determine how they protect against nonalcoholic fatty liver disease (NAFLD). TCMSP, DisGeNET, UniProt databases, and Venny 2.1 software were used to identify 11 primary active components, 92 candidate gene targets, and 30 core hepatoprotective gene targets in this investigation, respectively. The PPI network was built using a string database and Cytoscape 3.7.2. The KEGG pathway and GO biological process enrichment, biological annotation, as well as the identified hepatoprotective core gene targets were analyzed using the Metascape database. The effect of silymarin on NAFLD was determined using H&E on pathological alterations in liver tissues. The levels of liver function were assessed using biochemical tests. Western blot experiments were used to observe the proteins that were expressed in the associated signaling pathways on the hepatoprotective effect, which the previous network pharmacology predicted. According to the KEGG enrichment study, there are 35 hepatoprotective signaling pathways. GO enrichment analysis revealed that 61 biological processes related to the hepatoprotective effect of S. marianum were identified, which mainly involved in response to regulation of biological process and immune system process. Silymarin was the major ingredient derived from S. marianum, which exhibited the hepatoprotective effect by reducing the levels of ALT, AST, TC, TG, HDL-C, LDL-C, decreasing protein expressions of IL-6, MAPK1, Caspase 3, p53, VEGFA, increasing protein expression of AKT1. The present study provided new sights and a possible explanation for the molecular mechanisms of S. marianum against NAFLD.
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Affiliation(s)
- Guoyan Jiang
- Department of Emergency, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chunhong Sun
- Department of Emergency, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaodong Wang
- Chongqing Medical and Pharmaceutical College, School of Clinical medicine, Chongqing, China
| | - Jie Mei
- Department of periodontal, Stomatological Hospital of Chongqing Medical University, Chongqing, China
| | - Chen Li
- Department of Biology, Chemistry, Pharmacy, Free University of Berlin, Berlin, Germany
| | - Honghong Zhan
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Yixuan Liao
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Yongjun Zhu
- Department of Orthopedics, The Ninth People’s Hospital of Chongqing, Chongqing, China
| | - Jingxin Mao
- Chongqing Medical and Pharmaceutical College, School of Clinical medicine, Chongqing, China
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
- College of Basic Medical Science, Southwest University, Chongqing, China
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Martin-Grau M, Marrachelli VG, Monleon D. Rodent models and metabolomics in non-alcoholic fatty liver disease: What can we learn? World J Hepatol 2022; 14:304-318. [PMID: 35317178 PMCID: PMC8891675 DOI: 10.4254/wjh.v14.i2.304] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/13/2021] [Accepted: 01/29/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) prevalence has increased drastically in recent decades, affecting up to 25% of the world’s population. NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis, which can progress to fibrosis. Several molecular and metabolic changes are required for the hepatocyte to finally vary its function; hence a “multiple hit” hypothesis seems a more accurate proposal. Previous studies and current knowledge suggest that in most cases, NAFLD initiates and progresses through most of nine hallmarks of the disease, although the triggers and mechanisms for these can vary widely. The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge. Among certain requirements to be met, a good model must imitate certain aspects of the human NAFLD disorder, be reliable and reproducible, have low mortality, and be compatible with a simple and feasible method. Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease. Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding. In this review, we provide a brief introduction to NAFLD hallmarks, the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.
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Affiliation(s)
- Maria Martin-Grau
- Department of Pathology, University of Valencia, Valencia 46010, Spain
| | - Vannina G Marrachelli
- Department of Physiology, University of Valencia, Valencia 46010, Spain
- Health Research Institute INCLIVA, Valencia 46010, Spain
| | - Daniel Monleon
- Department of Pathology, University of Valencia, Valencia 46010, Spain
- Health Research Institute INCLIVA, Valencia 46010, Spain
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Madrid 28029, Spain
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Accumulation Pattern of Flavonoids during Fruit Development of Lonicera maackii Determined by Metabolomics. Molecules 2021; 26:molecules26226913. [PMID: 34834005 PMCID: PMC8624894 DOI: 10.3390/molecules26226913] [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: 10/14/2021] [Revised: 11/12/2021] [Accepted: 11/12/2021] [Indexed: 12/28/2022] Open
Abstract
Lonicera maackii (Caprifoliaceae) is a large, upright shrub with fruits that contain many bioactive compounds. Flavonoids are common active substances in L. maackii. However, there is a dearth of information about the accumulation of these flavonoids and their possible medicinal value. We used targeted metabolomics analysis based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to analyze five developmental stages of L. maackii fruit. A total of 438 metabolites were identified in the five developmental stages, including 81 flavonoids and derivatives. The 81 flavonoids included 25 flavones and derivatives, 35 flavonols and derivatives, two isoflavones, three cyanidins and derivatives, eight procyanidins, and eight flavanones. In addition, we outlined the putative flavonoid biosynthesis pathway and screened their upstream metabolites. More importantly, we analyzed the accumulation patterns of several typical flavones and flavonols. The results reported here improved our understanding of the dynamic changes in flavonoids during fruit development and contributed to making full use of the medicinal value of L. maackii fruit.
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Resveratrol and Quercetin as Regulators of Inflammatory and Purinergic Receptors to Attenuate Liver Damage Associated to Metabolic Syndrome. Int J Mol Sci 2021; 22:ijms22168939. [PMID: 34445644 PMCID: PMC8396326 DOI: 10.3390/ijms22168939] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/15/2021] [Accepted: 08/17/2021] [Indexed: 12/17/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered a manifestation of metabolic syndrome (MS) and is characterized by the accumulation of triglycerides and a varying degree of hepatic injury, inflammation, and repair. Moreover, peroxisome-proliferator-activated receptors (PPARs) play a critical role in the pathophysiological processes in the liver. There is extensive evidence of the beneficial effect of polyphenols such as resveratrol (RSV) and quercetin (QRC) on the treatment of liver pathology; however, the mechanisms underlying their beneficial effects have not been fully elucidated. In this work, we show that the mechanisms underlying the beneficial effects of RSV and QRC against inflammation in liver damage in our MS model are due to the activation of novel pathways which have not been previously described such as the downregulation of the expression of toll-like receptor 4 (TLR4), neutrophil elastase (NE) and purinergic receptor P2Y2. This downregulation leads to a decrease in apoptosis and hepatic fibrosis with no changes in hepatocyte proliferation. In addition, PPAR alpha and gamma expression were altered in MS but their expression was not affected by the treatment with the natural compounds. The improvement of liver damage by the administration of polyphenols was reflected in the normalization of serum transaminase activities.
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Santoru ML, Piras C, Murgia F, Leoni VP, Spada M, Murgia A, Liggi S, Lai MA, Usai P, Caboni P, Manzin A, Atzori L. Metabolic Alteration in Plasma and Biopsies From Patients With IBD. Inflamm Bowel Dis 2021; 27:1335-1345. [PMID: 33512485 DOI: 10.1093/ibd/izab012] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, with periods of latency alternating with phases of exacerbation, and include 2 forms: Crohn disease (CD) and ulcerative colitis (UC). Although the etiology of IBD is still unclear, the identification and understanding of pathophysiological mechanisms underlying IBD could reveal newly targeted intestinal alterations and determine therapeutic approaches. METHODS In this study, by using gas chromatography-mass spectrometry, we characterized plasma and biopsies from the metabolomics profiles of patients with IBD compared with those of a control group. RESULTS The results showed a different metabolomics profile between patients with CD (n = 50) and patients with UC (n = 82) compared with the control group (n = 51). Multivariate statistical analysis of the identified metabolites in CD and UC showed changes in energetic metabolism, and lactic acid and ornithine in particular were altered in both plasma and colon biopsies. Moreover, metabolic changes were evidenced between the normal ileum and colon tissues. These differences disappeared when we compared the inflamed ileum and colon tissues, suggesting a common metabolism. CONCLUSIONS This study showed how the metabolomics profile could be a potential tool to identify intestinal alterations associated with IBD and may have application in precision medicine and for better defining the pathogenesis of the disease.
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Affiliation(s)
| | - Cristina Piras
- Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy
| | - Federica Murgia
- Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy
| | - Vera Piera Leoni
- Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy
| | - Martina Spada
- Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy
| | - Antonio Murgia
- Department of Life and Environmental Sciences, University of Cagliari, Sardinia, Italy
| | - Sonia Liggi
- Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy
| | - Maria Antonia Lai
- Gastroenterology Unit, University Hospital of Cagliari, Sardinia, Italy
| | - Paolo Usai
- Department of Medical Sciences and Public Health, University of Cagliari, Sardinia, Italy
| | - Pierluigi Caboni
- Department of Life and Environmental Sciences, University of Cagliari, Sardinia, Italy
| | - Aldo Manzin
- Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy
| | - Luigi Atzori
- Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy
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The Therapeutic Effects and Mechanisms of Quercetin on Metabolic Diseases: Pharmacological Data and Clinical Evidence. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:6678662. [PMID: 34257817 PMCID: PMC8249127 DOI: 10.1155/2021/6678662] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/17/2021] [Accepted: 06/08/2021] [Indexed: 12/27/2022]
Abstract
Metabolic diseases have become major public health issues worldwide. Searching for effective drugs for treating metabolic diseases from natural compounds has attracted increasing attention. Quercetin, an important natural flavonoid, is extensively present in fruits, vegetables, and medicinal plants. Due to its potentially beneficial effects on human health, quercetin has become the focus of medicinal attention. In this review, we provide a timely and comprehensive summary of the pharmacological advances and clinical data of quercetin in the treatment of three metabolic diseases, including diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). Accumulating evidences obtained from animal experiments prove that quercetin has beneficial effects on these three diseases. It can promote insulin secretion, improve insulin resistance, lower blood lipid levels, inhibit inflammation and oxidative stress, alleviate hepatic lipid accumulation, and regulate gut microbiota disorders in animal models. However, human clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. More clinical trials with larger sample sizes and longer trial durations are needed to verify its true effectiveness in human subjects. Moreover, another important issue that needs to be resolved in future research is to improve the bioavailability of quercetin. This review may provide valuable information for the basic research, drug development, and clinical application of quercetin in the treatment of metabolic diseases.
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Quercetin and non-alcoholic fatty liver disease: A review based on experimental data and bioinformatic analysis. Food Chem Toxicol 2021; 154:112314. [PMID: 34087406 DOI: 10.1016/j.fct.2021.112314] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 05/18/2021] [Accepted: 05/29/2021] [Indexed: 02/08/2023]
Abstract
Quercetin, a polyphenol widely present in the plant kingdom, has received great interest due to pleiotropic effects. As evidenced by animal and cellular studies, quercetin exerts hepatoprotection against non-alcoholic fatty liver disease (NAFLD), particularly in hepatic steatosis and hepatitis. Mechanically, various hypotheses of such protective effects have been actively proposed, including improving fatty acid metabolism, anti-inflammation, anti-oxidant, modulating gut microbiota and bile acid, etc. Here, the role of quercetin in NAFLD was summarized. With a particular focus on molecular mechanism, we comprehensively discussed the pathways of quercetin on NAFLD based on the analysis from Gene Expression Omnibus (GEO) database and experimental evidence.
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Hu C, Wang T, Zhuang X, Sun Q, Wang X, Lin H, Feng M, Zhang J, Cao Q, Jiang Y. Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry. J Transl Med 2021; 19:152. [PMID: 33858428 PMCID: PMC8050915 DOI: 10.1186/s12967-021-02820-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 04/09/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disease that affects 20-30% of individuals worldwide. Liver puncture remains the gold standard for the diagnosis of liver diseases despite limitations regarding invasive nature and sample variability. It is of great clinical significance to find noninvasive biomarkers to detect and predict NAFLD. OBJECTIVE The aims of this study were to identify potential serum markers in individuals with early-stage NAFLD and to advance the mechanistic understanding of this disease using a high-throughput mass spectrometry-based untargeted metabolomics approach. METHODS One hundred and twelve patients with early-stage NAFLD aged 18-55 were recruited according to the guidelines. The control group included 112 healthy participants. The demographic, anthropometric, clinical and laboratory data of all participants were systematically collected. Serum samples were obtained after an overnight fast. The comprehensive serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. The resultant data was processed by Compound Discover and SIMCA-P software to validate the potential biomarkers. Significantly altered metabolites were evaluated by variable importance in projection value (VIP > 1) and ANOVA (p < 0.01). Pathway analysis was performed using MetaboAnalyst 4.0. RESULTS The liver function test of early NAFLD patients showed no statistical differences to control group (p > 0.05). However, obvious differences in blood lipids were observed between subjects with NAFLD and controls (p < 0.001). In total, 55 metabolites showed significant changes in experimental group were identified. The area under curve (AUC) values deduced by receiver operating curve (ROC) analysis indicated that these newly identified biomarkers have high predictability and reliability. Of these, 15 metabolites with AUC greater than 0.9 were of great diagnostic value in early NAFLD patients. CONCLUSION In this study, a total of 15 serum metabolites were found to strongly associate with early NAFLD. These biomarkers may have great clinical significance in the early diagnosis of NAFLD, as well as to follow response to therapeutic interventions.
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Affiliation(s)
- Cheng Hu
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Tao Wang
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China
| | - Xiaoyu Zhuang
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Qiaoli Sun
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Xiaochun Wang
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China
| | - Hui Lin
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China
| | - Mingli Feng
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China
| | - Jiaqi Zhang
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
- Shanghai TCM-Integrated Institute of Vascular Anomalies, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, China.
| | - Qin Cao
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China.
| | - Yuanye Jiang
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China.
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Demyanova EV, Shcherbakova ES, Sall TS, Bakulin IG, Vakhitov TY, Sitkin SI. Non-targeted Serum Metabolomics Identifies Candidate Biomarkers Panels Associated with Nonalcoholic Fatty Liver Disease: A Pilot Study in Russian Male Patients. THE OPEN BIOMARKERS JOURNAL 2021; 11:17-27. [DOI: 10.2174/1875318302111010017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 01/04/2021] [Accepted: 01/07/2021] [Indexed: 09/26/2023]
Abstract
Aims:
The aim of the present study was to explore changes in the serum metabolome of patients with NAFLD relative to healthy controls to identify biomarkers associated with steatosis or Non-Alcoholic Steatohepatitis (NASH).
Background:
The serum metabolome reflects changes at the organismal level. This is especially important in Non-Alcoholic Liver Disease (NAFLD), where changes in hormones, cytokines, enzymes and other metabolic alterations can affect the liver, as well as adipose tissue, skeletal muscle and other systems.
Objective:
The objectives were to conduct non-targeted serum metabolomics, data processing, and identification of candidate biomarkers, as well as panels and assessment of their prognostic value.
Materials and Methods:
Non-targeted metabolomic analysis of blood serum samples from 21 male patients with NAFLD (simple steatosis or NASH) and seven male Control group was performed using gas chromatography-mass spectrometry.
Results:
A total of 319 serum metabolites were detected in NAFLD and Control groups, several of which differed significantly between groups. The most discriminating biomarkers were 3-hydroxybutyric acid, 2-hydroxybutyric acid, 2,3-dihydroxybutyric acid, arabitol and 3-methyl-2-oxovaleric acid. Using a panel of three, four or more markers could distinguish patients with NAFLD from controls, and patients with NASH from those with simple steatosis.
Conclusion:
We identified candidate biomarkers for simple steatosis and NASH. Since NAFLD is a multifactorial disease, it is preferable to use a marker panel rather than individual metabolites. Markers may not only result from dysregulation of metabolic pathways in patients with NAFLD, they may also reflect adaptive responses to disease, including functional changes in the intestinal microbiota.
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Chen P, Wang C, Ren YN, Ye ZJ, Jiang C, Wu ZB. Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain. Mol Brain 2021; 14:50. [PMID: 33750430 PMCID: PMC7941960 DOI: 10.1186/s13041-021-00765-y] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 02/25/2021] [Indexed: 12/17/2022] Open
Abstract
The aim of this study was to explore the relationships among gut microbiota disturbances and serum and spinal cord metabolic disorders in neuropathic pain. 16S rDNA amplicon sequencing and serum and spinal cord metabolomics were used to identify alterations in the microbiota and metabolite profiles in the sham rats and the chronic constriction injury (CCI) model rats. Correlations between the abundances of gut microbiota components at the genus level, the levels of serum metabolites, and pain-related behavioural parameters were analysed. Ingenuity pathway analysis (IPA) was applied to analyse the interaction networks of the differentially expressed serum metabolites. First, we found that the composition of the gut microbiota was different between rats with CCI-induced neuropathic pain and sham controls. At the genus level, the abundances of Helicobacter, Phascolarctobacterium, Christensenella, Blautia, Streptococcus, Rothia and Lactobacillus were significantly increased, whereas the abundances of Ignatzschineria, Butyricimonas, Escherichia, AF12, and Corynebacterium were significantly decreased. Additionally, 72 significantly differentially expressed serum metabolites and 17 significantly differentially expressed spinal cord metabolites were identified between the CCI rats and the sham rats. Finally, correlation analysis showed that changes in the gut microbiota was significantly correlated with changes in serum metabolite levels, suggesting that dysbiosis of the gut microbiota is an important factor in modulating metabolic disturbances in the context of neuropathic pain. In conclusion, our research provides a novel perspective on the potential roles of the gut microbiota and related metabolites in neuropathic pain.
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Affiliation(s)
- Peng Chen
- Basic Medical School, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Chen Wang
- First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yan-Na Ren
- Basic Medical School, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Zeng-Jie Ye
- First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chao Jiang
- Department of Neurology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China.
| | - Zhi-Bing Wu
- First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.
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Guo L, Kuang J, Zhuang Y, Jiang J, Shi Y, Huang C, Zhou C, Xu P, Liu P, Wu C, Hu G, Guo X. Serum Metabolomic Profiling to Reveal Potential Biomarkers for the Diagnosis of Fatty Liver Hemorrhagic Syndrome in Laying Hens. Front Physiol 2021; 12:590638. [PMID: 33633583 PMCID: PMC7900428 DOI: 10.3389/fphys.2021.590638] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Accepted: 01/04/2021] [Indexed: 01/12/2023] Open
Abstract
Fatty liver hemorrhage syndrome (FLHS), a nutritional and metabolic disease that frequently occurs in laying hens, causes serious losses to the poultry industry. Nowadays, the traditional clinical diagnosis of FLHS still has its limitations. Therefore, searching for some metabolic biomarkers and elucidating the metabolic pathway in vivo are useful for the diagnosis and prevention of FLHS. In the present study, a model of FLHS in laying hens induced by feeding a high-energy, low-protein diet was established. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the metabolites in serum at days 40 and 80. The result showed that, in total, 40 differential metabolites closely related to the occurrence and development of FLHS were screened and identified, which were mainly associated with lipid metabolism, amino acid metabolism, and energy metabolism pathway disorders. Further investigation of differential metabolites showed 10 potential biomarkers such as 3-hydroxybutyric acid, oleic acid, palmitoleic acid, and glutamate were possessed of high diagnostic values by analyzing receiver operating characteristic (ROC) curves. In conclusion, this study showed that the metabolomic method based on GC-TOF-MS can be used in the clinical diagnosis of FLHS in laying hens and provide potential biomarkers for early risk evaluation of FLHS and further insights into FLHS development.
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Affiliation(s)
- Lianying Guo
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Jun Kuang
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Yu Zhuang
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Jialin Jiang
- Jiangxi Biological Vocational College, Nanchang University, Nanchang, China
| | - Yan Shi
- School of Computer and Information Engineering, Jiangxi Agricultural University, Nanchang, China
| | - Cheng Huang
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Changming Zhou
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Puzhi Xu
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Ping Liu
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Cong Wu
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Guoliang Hu
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
| | - Xiaoquan Guo
- Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China
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Guan T, Xin Y, Zheng K, Wang R, Zhang X, Jia S, Li S, Cao C, Zhao X. Metabolomics analysis of the effects of quercetin on renal toxicity induced by cadmium exposure in rats. Biometals 2020; 34:33-48. [PMID: 33033991 DOI: 10.1007/s10534-020-00260-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 10/01/2020] [Indexed: 02/08/2023]
Abstract
This study aims to explore the protective effects of quercetin against cadmium-induced nephrotoxicity utilizing metabolomics methods. Male Sprague-Dawley rats were randomly assigned to six groups: control, different dosages of quercetin (10 and 50 mg/kg·bw, respectively), CdCl2 (4.89 mg/kg·bw) and different dosages quercetin plus CdCl2 groups. After 12 weeks, the kidneys were collected for metabolomics analysis and histopathology examination. In total, 11 metabolites were confirmed, the intensities of which significantly changed (up-regulated or down-regulated) compared with the control group (p < 0.00067). These metabolites include xanthosine, uric acid (UA), guanidinosuccinic acid (GSA), hypoxanthine (Hyp), 12-hydroxyeicosatetraenoic acid (tetranor 12-HETE), taurocholic acid (TCA), hydroxyphenylacetylglycine (HPAG), deoxyinosine (DI), ATP, formiminoglutamic acid (FIGLU) and arachidonic acid (AA). When high-dose quercetin and cadmium were given to rats concurrently, the intensities of above metabolites significantly restored (p < 0.0033 or p < 0.00067). The results showed quercetin attenuated Cd-induced nephrotoxicity by regulating the metabolism of lipids, amino acids, and purine, inhibiting oxidative stress, and protecting kidney functions.
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Affiliation(s)
- Tong Guan
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China
| | - Youwei Xin
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China
| | - Kai Zheng
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China
| | - Ruijuan Wang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China
| | - Xia Zhang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China
| | - Siqi Jia
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China
| | - Siqi Li
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China
| | - Can Cao
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China.
| | - Xiujuan Zhao
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China.
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Zou LY, Hu N, Wang N, Wang HL. Hepatoprotective Activities of Polysaccharide From the Fruit of Ribes odoratum Wendl. on High-Fat-Sucrose Diet-Induced Nonalcoholic Fatty Liver Disease in Mice. Nat Prod Commun 2020. [DOI: 10.1177/1934578x20946935] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
To investigate the hepatoprotective activities of a polysaccharide extracted from the fruit of Ribes odoratum Wendl. (ROWFP) in a mouse model of high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). The NAFLD model was induced in C57BL/6 mice by feeding them an HFD for 12 weeks. The mice were randomly divided into the following 5 groups: control group, HFD group, 10-mg/kg ROWFP group, 100-mg/kg ROWFP group, and 200-mg/kg ROWFP group. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total triglycerides (TG), total cholesterol (TC), and high-density lipoprotein (HDL) in the serum were analyzed by enzyme-linked immunosorbent assay. The liver ultrastructure was observed via optical microscopy. The oil red O-stained lipid droplets of the fresh liver samples were analyzed, and the lipid content was semiquantified. CD68 expression in the liver tissue and serum levels of the inflammatory factors (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha [TNF-α]) were measured to reflect the inflammation status. The degree of liver fibrosis was determined by sirius red staining. When compared with the control group, the levels of AST, ALT, TG, TC, IL-1β, IL-6, TNF-α, and CD68 in the HFD group were increased, while the HDL level was decreased. Severe liver damage, lipid accumulation, and liver fibrosis were also observed in the HFD model group. When compared with the model group, ROWFP treatment (100 mg/kg or 200 mg/kg) significantly attenuated the HFD-induced hepatic damage. This study supports the hepatoprotective effect of ROWFP against HFD-induced NAFLD.
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Affiliation(s)
- Lin-you Zou
- Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, P. R. China
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, P. R. China
- Key Laboratory of Tibetan Medicine Research of Qinghai Province, Xining, P. R. China
- University of Chinese Academy of Sciences, Beijing, P. R. China
| | - Na Hu
- Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, P. R. China
- Key Laboratory of Tibetan Medicine Research of Qinghai Province, Xining, P. R. China
| | - Ning Wang
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, P. R. China
- Qinghai Academy of Agriculture and Forestry Science, Xining, P. R. China
| | - Hong-lun Wang
- Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, P. R. China
- Key Laboratory of Tibetan Medicine Research of Qinghai Province, Xining, P. R. China
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Hu Y, Xu J, Chen Q, Liu M, Wang S, Yu H, Zhang Y, Wang T. Regulation effects of total flavonoids in Morus alba L. on hepatic cholesterol disorders in orotic acid induced NAFLD rats. BMC Complement Med Ther 2020; 20:257. [PMID: 32807146 PMCID: PMC7433163 DOI: 10.1186/s12906-020-03052-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/11/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Mulberry leaves are the dried leaves of Morus alba L., flavonoids from mulberry leaves (MLF) has showed regulatory effect on abnormal lipid metabolism, but the regulatory mechanism of MLF on cholesterol metabolism is still missing. This study was designed to investigate the effect of MLF and its active metabolite quercetin on regulating cholesterol disorders. METHODS The mechanism of MLF on alleviating liver injury and regulating cholesterol was examined in dyslipidemic SD rats. The regulatory mechanism of quercetin for cholesterol disorders have also been detected through lipid laden HepG2 cell model. RESULTS Our results showed that MLF significantly inhibited lipid accumulation and alleviate hepatic injury in NAFLD rat model. The hepatic expression level of SREBP2, HMGCR and miR-33a were significantly down-regulated, while CYP7A1 was induced by MLF treatment. In vitro, Quercetin significantly decreased lipid accumulation in HepG2 cells. Mechanistically, quercetin could inhibit the mRNA and protein expression level of SREBP2 and HMGCR with or without LDL treatment. In addition, quercetin could also reduce the LXRβ while induced SR-BI mRNA expression. CONCLUSION Our findings indicate that MLF and quercetin could reduce the excessive cholesterol accumulation in vivo and in vitro. These cholesterol-regulating phenomenon might attribute to its effect on down-regulating the expression of lipid-related markers such as SREBP2 and HMGCR, which may exert a protective role in the NAFLD treatment.
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Affiliation(s)
- Yucheng Hu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Jingqi Xu
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Qian Chen
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Mengyang Liu
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Sijian Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Haiyang Yu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Yi Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
| | - Tao Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
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Sandoval V, Sanz-Lamora H, Arias G, Marrero PF, Haro D, Relat J. Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral. Nutrients 2020; 12:E2393. [PMID: 32785059 PMCID: PMC7469047 DOI: 10.3390/nu12082393] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 08/01/2020] [Accepted: 08/05/2020] [Indexed: 02/07/2023] Open
Abstract
The prevention and treatment of obesity is primary based on the follow-up of a healthy lifestyle, which includes a healthy diet with an important presence of bioactive compounds such as polyphenols. For many years, the health benefits of polyphenols have been attributed to their anti-oxidant capacity as free radical scavengers. More recently it has been described that polyphenols activate other cell-signaling pathways that are not related to ROS production but rather involved in metabolic regulation. In this review, we have summarized the current knowledge in this field by focusing on the metabolic effects of flavonoids. Flavonoids are widely distributed in the plant kingdom where they are used for growing and defensing. They are structurally characterized by two benzene rings and a heterocyclic pyrone ring and based on the oxidation and saturation status of the heterocyclic ring flavonoids are grouped in seven different subclasses. The present work is focused on describing the molecular mechanisms underlying the metabolic impact of flavonoids in obesity and obesity-related diseases. We described the effects of each group of flavonoids in liver, white and brown adipose tissue and central nervous system and the metabolic and signaling pathways involved on them.
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Affiliation(s)
- Viviana Sandoval
- Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food Torribera Campus, University of Barcelona, E-08921 Santa Coloma de Gramenet, Spain; (V.S.); (H.S.-L.); (G.A.); (P.F.M.)
| | - Hèctor Sanz-Lamora
- Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food Torribera Campus, University of Barcelona, E-08921 Santa Coloma de Gramenet, Spain; (V.S.); (H.S.-L.); (G.A.); (P.F.M.)
- Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), E-08921 Santa Coloma de Gramenet, Spain
| | - Giselle Arias
- Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food Torribera Campus, University of Barcelona, E-08921 Santa Coloma de Gramenet, Spain; (V.S.); (H.S.-L.); (G.A.); (P.F.M.)
| | - Pedro F. Marrero
- Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food Torribera Campus, University of Barcelona, E-08921 Santa Coloma de Gramenet, Spain; (V.S.); (H.S.-L.); (G.A.); (P.F.M.)
- Institute of Biomedicine of the University of Barcelona (IBUB), E-08028 Barcelona, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBER-OBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
| | - Diego Haro
- Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food Torribera Campus, University of Barcelona, E-08921 Santa Coloma de Gramenet, Spain; (V.S.); (H.S.-L.); (G.A.); (P.F.M.)
- Institute of Biomedicine of the University of Barcelona (IBUB), E-08028 Barcelona, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBER-OBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
| | - Joana Relat
- Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food Torribera Campus, University of Barcelona, E-08921 Santa Coloma de Gramenet, Spain; (V.S.); (H.S.-L.); (G.A.); (P.F.M.)
- Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), E-08921 Santa Coloma de Gramenet, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBER-OBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
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Sztolsztener K, Chabowski A, Harasim-Symbor E, Bielawiec P, Konstantynowicz-Nowicka K. Arachidonic Acid as an Early Indicator of Inflammation during Non-Alcoholic Fatty Liver Disease Development. Biomolecules 2020; 10:biom10081133. [PMID: 32751983 PMCID: PMC7464179 DOI: 10.3390/biom10081133] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/25/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excessive lipid deposition. Lipid metabolism disturbances are possibly associated with hepatocyte inflammation development and oxidative balance impairment. The aim of our experiment was to examine the first moment when changes in plasma and liver arachidonic acid (AA) levels as a pro-inflammatory precursor may occur during high-fat diet (HFD)-induced NAFLD development. Wistar rats were fed a diet rich in fat for five weeks, and after each week, inflammation and redox balance parameters were evaluated in the liver. The AA contents in lipid fractions were assessed by gas–liquid chromatography (GLC). Protein expression relevant to inflammatory and lipogenesis pathways was determined by immunoblotting. The oxidative system indicators were determined with assay kits. Our results revealed that a high-fat diet promoted an increase in AA levels, especially in the phospholipid (PL) fraction. Importantly, rapid inflammation development via increased inflammatory enzyme expression, elevated lipid peroxidation product content and oxidative system impairment was caused by the HFD as early as the first week of the experiment. Based on these results, we may postulate that changes in AA content may be an early indicator of inflammation and irreversible changes in NAFLD progression.
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Quercetin mitigates monosodium glutamate-induced excitotoxicity of the spinal cord motoneurons in aged rats via p38 MAPK inhibition. Acta Histochem 2020; 122:151554. [PMID: 32622428 DOI: 10.1016/j.acthis.2020.151554] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/19/2020] [Accepted: 04/22/2020] [Indexed: 12/18/2022]
Abstract
Various studies reported the possibility of deterioration of blood-brain barrier (BBB) integrity owing to the aging process. The current work was performed to investigate the ability of Monosodium glutamate (MSG) to cross BBB in aged rats, the damage affecting the anterior horn cells of the spinal cord due to excitotoxicity, and the mechanisms by which quercetin (Que) administration might suppress such damage. Forty male rats aged 18 months were assigned equally to 4 groups: control group, Que group (received Que, 20 mg/kg/d intraperitonealy for 10 days), MSG group (received MSG, 4.0 g/kg/d subcutaneously for 10 days), MSG + Que group (received both Que and MSG as done in the Que and MSG groups respectively). Cervical spinal cord specimens were obtained and prepared for routine histological study, immunohistochemical staining by caspase-3 and glial fibrillary acidic protein (GFAP), assessment of oxidative stress, measurement of cytokines, assessment of caspase-3 activity and GFAP levels as well as for western blotting of phosphorylated activating transcription factor 2 (ATF2pp) as an indicator for the activity of p38 mitogen-activated protein kinase (MAPK). The MSG group revealed variable degenerative and apoptotic changes in the motoneurons and neuroglia, a marked rise in the cytoplasmic caspase-3 expression in motoneurons and a significant reduction (p < 0.001) in the astrocyte surface area percentage. In addition, the spinal cord tissue exhibited a significant elevation (p < 0.001) in the levels of malondialdehyde (MDA), IL-1, IL-6, TNFα, INFɣ, caspase-3 activity and ATF2 pp expression as well as a significant reduction (p < 0.001) in SOD, IL-10 and GFAP levels compared with the control group. On combining Que with MSG, most of the degenerative changes were reversed and all the impaired parameters were nearly normalized except for IL-6 and GFAP levels which were still significantly (p < 0.05) different from those of the control group. Our study suggests that MSG can break through the BBB of the aged rats and induce excitotoxicity dependent changes in spinal cord motoneurons. Most of these changes were reversed by Que probably via targeting the p38 MAPK-ATF2 pathway, antagonizing oxidative stress, anti-inflammatory effect, and promoting GFAP expression.
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Cui H, Li Y, Cao M, Liao J, Liu X, Miao J, Fu H, Song R, Wen W, Zhang Z, Wang H. Untargeted Metabolomic Analysis of the Effects and Mechanism of Nuciferine Treatment on Rats With Nonalcoholic Fatty Liver Disease. Front Pharmacol 2020; 11:858. [PMID: 32581811 PMCID: PMC7295953 DOI: 10.3389/fphar.2020.00858] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 05/26/2020] [Indexed: 12/22/2022] Open
Abstract
Metabolomic analysis has been used to characterize the effects and mechanisms of drugs for nonalcoholic fatty liver disease (NAFLD) at the metabolic level. Nuciferine is an active component derived from folium nelumbinis and has been demonstrated to have beneficial effects on a high-fat diet (HFD) induced hepatic steatosis model. However, the effect of the altered metabolites of nuciferine on NAFLD has not yet been elucidated. In this study, we established a NAFLD rat model using HFD and treated with nuciferine. The lipid content levels, pro-inflammatory cytokines, and oxidative stress were investigated to access the therapeutic effects of nuciferine. Additionally, the metabolic regulatory mechanisms of nuciferine on NAFLD were analyzed using untargeted metabolomics. Gene expression of the key enzymes related to the changed metabolic pathways following nuciferine intervention was also investigated. The results showed that nuciferine treatment significantly reduced the body weight, levels of lipids, and liver enzymes in the blood and improved the hepatic steatosis in the NAFLD rat model. Nuciferine treatment also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the levels of methane dicarboxylic aldehyde (MDA) in the liver. Nuciferine treatment decreased the serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) and upregulated the gene expression of IL-6, IL-1β, and TNF-α in the liver. Metabolomic analysis indicated a metabolism disorder in the NAFLD rat model reflected in a dysfunction of the glycerophospholipid, linoleic acid, alpha-linolenic acid, arginine and proline metabolism. Conversely, treatment with nuciferine improved the metabolic disorder in the NAFLD rat model. Nuciferine treatment also regulated the gene expression of key enzymes related to the glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism pathways in the liver. In conclusion, our study demonstrated an amelioration of the metabolic disorders following nuciferine treatment in NAFLD rat model. Our study contributes to the understanding of the effects and mechanisms of drugs for complex diseases using metabolomic analysis and experimental approaches.
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Affiliation(s)
- Huantian Cui
- Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Yuting Li
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Min Cao
- College of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jiabao Liao
- Department of Emergency, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China
| | - Xiangguo Liu
- Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Jing Miao
- Department of Integrated Traditional and Western Medicine, Tianjin Second People’s Hospital, Tianjin, China
| | - Hui Fu
- College of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ruiwen Song
- College of Management, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Weibo Wen
- Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, China
| | - Zhaiyi Zhang
- College of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Hongwu Wang
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Hosseinikia M, Oubari F, Hosseinkia R, Tabeshfar Z, Salehi MG, Mousavian Z, Abbasi M, Samadi M, Pasdar Y. Quercetin supplementation in non-alcoholic fatty liver disease. NUTRITION & FOOD SCIENCE 2020; 50:1279-1293. [DOI: 10.1108/nfs-10-2019-0321] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Purpose
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease which has become a public health concern, whose growing prevalence has been reported as around 33.9% in Iran. As oxidative stress plays a crucial role in the pathogenesis of NAFLD, antioxidant compounds such as quercetin could ameliorate the side effect of oxidative stress. The aim of the current study was to assess the effect of quercetin on lipid profile, liver enzymes and inflammatory indices in NAFLD patients.
Design/methodology/approach
In a randomized, double-blind, placebo-controlled trial conducted as a pilot study, 90 patients with NAFLD were supplemented with either a quercetin or a placebo capsule twice daily (500 mg) for 12 weeks. Both groups were advised to follow an energy-balanced diet with physical activity recommendations. Blood sample was obtained for laboratory parameters at baseline and the end of week 12.
Findings
At the end of the follow-up, quercetin group had significantly greater reduction in anthropometric parameters, cholesterol (−15 ± (−41, 0.00) in Q group versus −1± (−8, 2) in control group, p = 0.004), TG (−56.7 ± 22.7) in Q group versus −13.4 ± 27.7 in control group, p = 0.04), and tumor necrosis factor-α (TNF-α) (−49.5 ± (−99, 21) in Q group versus −5 ± (−21, 0.30) in the control group, p < 0.0001) compared to the control group. However, changes in fatty liver grade, liver enzymes, as well as high density lipoprotein-cholesterol and high-sensitivity C-reactive protein were not significantly different between the two groups.
Originality/value
To the best of the authors’ knowledge, this was the first study which assessed the effect of quercetin supplementation on liver enzymes, lipid profile and inflammatory indices of NAFLD patients as a double-blind placebo-controlled pilot study.
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Souza Cruz EM, Bitencourt de Morais JM, Dalto da Rosa CV, da Silva Simões M, Comar JF, de Almeida Chuffa LG, Seiva FRF. Long-term sucrose solution consumption causes metabolic alterations and affects hepatic oxidative stress in Wistar rats. Biol Open 2020; 9:bio047282. [PMID: 32086249 PMCID: PMC7055397 DOI: 10.1242/bio.047282] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 02/06/2020] [Indexed: 12/11/2022] Open
Abstract
As the number of overweight and obese people has risen in recent years, there has been a parallel increase in the number of people with metabolic syndrome, diabetes and non-alcoholic fatty liver disease. The consumption of artificially sweetened beverages contributes to these epidemics. This study investigated the long-term effects of ingestion of a 40% sucrose solution on serum and hepatic parameters in male Wistar rats (Rattus norvegicus). After 180 days, the glycemic response, lipid profile and hepatic oxidative stress were compared to those of rats maintained on water. Sucrose ingestion led to higher body weight, increased fat deposits, reduced voluntary food intake and reduced feeding efficiency. Rats that received sucrose solution showed early signs of glucose intolerance and insulin resistance, such as hyperinsulinemia. Serum triacylglycerol (TG), very-low density lipoprotein (VLDL), cholesterol, ALT and AST levels increased after sucrose consumption. Elevated malondialdehyde and superoxide dismutase (SOD) levels and reduced glutathione levels characterize the hepatic oxidative stress due to sucrose ingestion. Liver sample histology showed vacuolar traces and increased fibrotic tissue. Our data showed the harmful effects of chronic consumption of sucrose solution, which can cause alterations that are found frequently in obesity, glucose intolerance and non-alcoholic hepatic disease, characteristics of metabolic syndrome.
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Affiliation(s)
- Ellen Mayara Souza Cruz
- Department of Biology, Biological Science Center, Universidade Estadual do Norte do Paraná - UENP, Luiz Meneghel Campus, Bandeirantes, 8630-000 Paraná, Brazil
| | - Juliana Maria Bitencourt de Morais
- Department of Biology, Biological Science Center, Universidade Estadual do Norte do Paraná - UENP, Luiz Meneghel Campus, Bandeirantes, 8630-000 Paraná, Brazil
| | - Carlos Vinícius Dalto da Rosa
- Department of Biology, Biological Science Center, Universidade Estadual do Norte do Paraná - UENP, Luiz Meneghel Campus, Bandeirantes, 8630-000 Paraná, Brazil
| | - Mellina da Silva Simões
- Department of Biochemistry, Universidade Estadual de Maringá - UEM, Maringá, 87020-900 Paraná, Brazil
| | - Jurandir Fernando Comar
- Department of Biochemistry, Universidade Estadual de Maringá - UEM, Maringá, 87020-900 Paraná, Brazil
| | - Luiz Gustavo de Almeida Chuffa
- Department of Anatomy, Institute of Biosciences of Botucatu, Universidade Estadual Paulista - UNESP, Botucatu, 18618-689 São Paulo, Brazil
| | - Fábio Rodrigues Ferreira Seiva
- Department of Biology, Biological Science Center, Universidade Estadual do Norte do Paraná - UENP, Luiz Meneghel Campus, Bandeirantes, 8630-000 Paraná, Brazil
- Post Graduation Program of Experimental Pathology, Department of Pathology, Universidade Estadual de Londrina - UEL, 86057-970 Paraná, Brazil
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