Scutellarin ameliorates nonalcoholic fatty liver disease through the PPARγ/PGC-1α-Nrf2 pathway.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is characterised by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Scutellarin is a flavonoid glycoside having antioxidative stress activity. Our current study aims to investigate the molecular mechanism of scutellarin ameliorating NAFLD. Scutellarin treatment was applied to male C57BL/6 mice maintained on a high-fat diet (HFD) and HepG2 cells challenged with oleic acid. The antioxidation biochemical indicators and lipid levels in the liver and cells were detected by kits. Liver pathology was observed by light microscope, Oil Red O staining, and transmission electron microscope (TEM). In addition, quantitative real-time polymerase chain reactions (qRT-PCR) and western blot assays were employed to detect the mRNA and protein levels of various antioxidative-related genes in the presence or absence of peroxisome proliferator-activated receptor gamma (PPARγ); inhibitor GW9662. Our results showed that scutellarin could significantly reduce blood lipid levels and enhance antioxidative capacities in both the models. In addition, scutellarin treatment conspicuously activated PPARγ, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear factor erythroid-2-related factor (Nrf2), haem oxygenase-1 (HO-1), glutathione S-transferase (GST), and NAD(P)H quinone dehydrogenase one (NQO1), while it significantly inhibited nuclear factor kappa B (NF-κB), Kelch-like ECH-associated protein 1 (Keap1) at both the mRNA and protein levels. However, after interfered by GW9662, scutellarin effect was significantly decreased. The experimental data demonstrated that scutellarin showed strong hypolipidaemic, antioxidative, and liver protective activity which could be attributed to its regulating activity in the PPARγ/PGC-1α-Nrf2 signaling pathway.

• Authors: Xiaoxue Zhang, Renpeng Ji, Huijun Sun, Jinyong Peng, Xiaodong Ma, ChangYuan Wang, Yufeng Fu, Liuchi Bao, Yue Jin
• Journal: Free radical research (Free Radic Res) Vol. 52 Issue 2 Pg. 198-211 (Feb 2018) ISSN: 1029-2470 [Electronic] England
• PMID: 29400110 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Glucuronates
• Hypolipidemic Agents
• NF-E2-Related Factor 2
• PPAR gamma
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• scutellarin
• Apigenin

Topics

• Animals
• Antioxidants (pharmacology)
• Apigenin (pharmacology)
• Glucuronates (pharmacology)
• Hep G2 Cells
• Humans
• Hypolipidemic Agents (pharmacology)
• Liver (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism)
• PPAR gamma (metabolism)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (metabolism)
• Signal Transduction (drug effects)