title: Reduced oxidative stress contributes to the lipid lowering effects of isoquercitrin in free fatty acids induced hepatocytes.
abstract: Oxidative stress interferes with hepatic lipid metabolism at various levels ranging from benign lipid storage to so-called second hit of inflammation activation. Isoquercitrin (IQ) is widely present flavonoid but its effects on hepatic lipid metabolism remain unknown. We used free fatty acids (FFA) induced lipid overload and oxidative stress model in two types of liver cells and measured cell viability, intracellular lipids, and reactive oxygen species (ROS) within hepatocytes. In addition, Intracellular triglycerides (TG), superoxide dismutase (SOD), and malondialdehyde (MDA) were examined. A novel in vitro model was used to evaluate correlation between lipid lowering and antioxidative activities. Furthermore, 34 major cytokines and corresponding ROS levels were analyzed in FFA/LPS induced coculture model between hepatocytes and Kupffer cells. At molecular level AMPK pathway was elucidated. We showed that IQ attenuated FFA induced lipid overload and ROS within hepatocytes. Further, IQ reversed FFA induced increase in intracellular TG SOD and MDA. It was shown that antioxidative activity of IQ correlates with its lipid lowering potentials. IQ reversed major proinflammatory cytokines and oxidative stress in FFA/LPS induced coculture model. Finally, AMPK pathway was found responsible for metabolic benefits at molecular level. IQ strikingly manifests antioxidative and related lipid lowering activities in hepatocytes.
authors.affiliation: National Center for Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Waseem
authors.identifier: 0000-0002-0197-1736
authors.initials: W
authors.lastname: Hassan
authors.affiliation: National Center for Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Rongyin
authors.affiliation: National Center for Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Daoud
authors.affiliation: National Center for Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: National Center for Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Center for Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Center for Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Jing
authors.identifier: 0000-0001-8347-361X
authors.initials: J
authors.lastname: Shang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D007728:Kupffer Cells / Q000166:cytology; D050356:Lipid Metabolism / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects*; D010168:Palmitates / Q000008:administration & dosage; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D010168:Palmitates; D017382:Reactive Oxygen Species; D014280:Triglycerides; C016527:isoquercitrin; D019301:Oleic Acid; D011794:Quercetin