Ruscogenin ameliorates experimental nonalcoholic steatohepatitis via suppressing lipogenesis and inflammatory pathway.

Abstract

The aim of the study was to investigate the protective effects of ruscogenin, a major steroid sapogenin in Ophiopogon japonicus, on experimental models of nonalcoholic steatohepatitis. HepG2 cells were exposed to 300 μmol/l palmitic acid (PA) for 24 h with the preincubation of ruscogenin for another 24 h. Ruscogenin (10.0 μmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells. Male golden hamsters were randomly divided into five groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) by gavage once daily for 8 weeks. Ruscogenin alleviated dyslipidemia, liver steatosis, and necroinflammation and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. Hepatic mRNA levels involved in fatty acid oxidation were increased in ruscogenin-treated HFD-fed hamsters. Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis. Gene expression of inflammatory cytokines, chemoattractive mediator, nuclear transcription factor-(NF-) κB, and α-smooth muscle actin were increased in the HFD group, which were attenuated by ruscogenin. Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-κB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins in β-oxidation pathway.

• Authors: Hung-Jen Lu, Thing-Fong Tzeng, Shorong-Shii Liou, Chia Ju Chang, Cheng Yang, Ming-Chang Wu, I-Min Liu
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 652680 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 25136608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• RNA, Messenger
• Spirostans
• Tumor Necrosis Factor-alpha
• ruscogenin

Topics

• Animals
• Cricetinae
• Diet, High-Fat
• Gene Expression Regulation (drug effects)
• Hep G2 Cells
• Humans
• Inflammation (drug therapy, genetics, pathology)
• Lipid Metabolism (drug effects)
• Lipogenesis (drug effects, genetics)
• Male
• Mesocricetus
• Metabolic Networks and Pathways (drug effects)
• NF-kappa B (biosynthesis)
• Non-alcoholic Fatty Liver Disease (drug therapy, genetics, pathology)
• RNA, Messenger (biosynthesis)
• Spirostans (administration & dosage)
• Tumor Necrosis Factor-alpha (biosynthesis)