title: Protective effect of total flavonoid C-glycosides from Abrus mollis extract on lipopolysaccharide-induced lipotoxicity in mice.
abstract: Abrus mollis is a widely used traditional Chinese medicine for treating acute and chronic hepatitis, steatosis, and fibrosis. It was found that the total flavonoid C-glycosides from Abrus mollis extract (AME) showed potent antioxidant, anti-inflammatory, and hepatoprotective activities. To further investigate the hepatoprotective effect of AME and its possible mechanisms, lipopolysaccharide (LPS)-induced liver injury models were applied in the current study. The results indicated that AME significantly attenuated LPS-induced lipid accumulation in mouse primary hepatocytes as measured by triglyceride (TG) and total cholesterol (TC) assays and Oil Red O staining. Meanwhile, AME exerted a protective effect on LPS-induced liver injury as shown by decreased liver index, serum aminotransferase levels, and hepatic lipid accumulation. Real-time PCR and immunoblot data suggested that AME reversed the LPS-mediated lipid metabolism gene expression, such as sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1). In addition, LPS-induced overexpression of activating transcription factor 4 (ATF4), X-box-binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP) were dramatically reversed by AME. Furthermore, AME also decreased the expression of LPS-enhanced interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). Here, it is demonstrated for the first time that AME ameliorated LPS-induced hepatic lipid accumulation and that this effect of AME can be attributed to its modulation of hepatic de novo fatty acid synthesis. This study also suggested that the hepatoprotective effect of AME may be related to its down-regulation of unfolded protein response (UPR) activation.
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors: Yun
authors: Y
authors: Wang
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing 210009, China.
authors: Zhen-Zhou
authors: ZZ
authors: Jiang
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors: Mi
authors: M
authors: Chen
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors: Mei-Juan
authors: MJ
authors: Wu
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors: Hong-Li
authors: HL
authors: Guo
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors: Li-Xin
authors: LX
authors: Sun
authors: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors: Hao
authors: H
authors: Wang
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors: Shuang
authors: S
authors: Zhang
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 21009, China.
authors: Tao
authors: T
authors: Wang
authors: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: lyzhang@cpu.edu.cn.
authors: Lu-Yong
authors: LY
authors: Zhang
mesh_terms: D029912:Abrus / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006027:Glycosides / Q000494:pharmacology / Q000627:therapeutic use*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008070:Lipopolysaccharides; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008815:Mice, Inbred Strains; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D000637:Transaminases / Q000097:blood; D014280:Triglycerides / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005419:Flavonoids; D006027:Glycosides; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014280:Triglycerides; D002784:Cholesterol; D000637:Transaminases
keywords: Endotoxin; Flavonoid C-glycosides; Inflammation; Lipid metabolism; Unfolded protein response