Alcohol, NAFLD, Other : Osthol Attenuated Liver Steatosis via Decrease Liver De Novo Triglyceride Synthesis not by Insulin Resistance: Multifaceted Effects of Cindium Monnieri Extract = Alcohol, NAFLD, Other : Osthol Attenuated Liver Steatosis via Decrease Liver De Novo Triglyceride Synthesis not by Insulin Resistance: Multifaceted Effects of Cindium Monnieri Extract

다국어 초록 (Multilingual Abstract)

Background: Osthol is a coumarin compound isolated from the fruit of Cnidium monnieri. Previous studies showed osthol have anti-inflammatory effects on various diseases. Nowadays nonalcoholic fatty liver disease (NAFLD) has been believed as a consequence of a ‘multi-hit’ process. However, there is no multi-faceted and comprehensive evaluation about effects of osthol. The current study evaluated effects of osthol on intrahepatic fat synthesis, β-oxidation, inflammation, and insulin resistance by multifaceted-analysis. Methods: SD rats (n=30) were divided into control, NFLD, and osthol groups. NAFLD and osthol groups were fed high-fat diet for 14 weeks. After 8 weeks osthol group was supplemented orally with osthol 20mg/kg. Oral glucose tolerance test (OGTT) was performed. Immunohistochemical (4-HNE, F4/80) and H&E staining were performed on all tissue samples. SREBP1c, FAS, and SCD-1 mRNA expression were measured to assess intrahepatic fat de novo synthesis. PPAR-α, CROT, MCP-1, IRS-1, and IRS-2 expressions were assessed with RT- PCR. Results: H&E staining revealed that compared to NASH, osthol group showed significantly decreased intrahepatic fat (39.4% vs. 21.0%, P=0.021). SREBP1c expression of NAFLD group increased compared to control group (P=0.0001), while osthol treatment decreased SREBP1c expression (P=0.0059). In osthol group, intrahepatic FAS and SCD-1 expression which are down stream of SREBP1c decreased significantly compare to NAFLD Group. PPAR-α expression of osthol was also significantly higher than NAFLD (P=0.0147). However, there was no statistically difference in expression of carnitine octanoyltransferase which is marker of β-oxidation. IRS-1 and IRS-2 expression which are involving in insulin signal pathway and AUROC of OGGT were not different in NAFLD and osthol group. There was no significant difference in periportal inflammation, intrahepatic fibrosis, and kupffer cell number between the groups. Conclusions: Osthol treatment attenuated liver steatosis via decreasing liver de novo triglyceride synthesis and had nominal effects on insulin resistance and liver in- flammations.