Osthol의 간내 중성지방 감소에 의한 간지방증 개선효과

Abstract

Background: Recently, nonalcoholic fatty liver disease has been considered as a consequence of “multi-hit” processes. Osthol, a coumarin compound, has anti-inflammatory effects on various diseases. However, there is no multi-faceted and comprehensive evaluation about its effects. Therefore, 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 randomly divided into control, NASH, and osthol groups. NASH 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 was performed. Immunohistochemical (4-HNE, F4/80) and H&E staining were performed on all tissue samples. SREBP1c, FAS, SCD-1, PPAR-α, CROT, MCP-1, IRS-1, and IRS-2 mRNA 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 NASH 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, which are down stream of SREBP1c, decreased significantly compare to NASH group. PPAR-α expression of osthol was also significantly higher than NASH (p=0.0147). There was no statistically significant difference in expression of CROT, IRS-1, IRS-2 and OGTT between NASH and osthol groups. Moreover, there was also no significant difference in periportal inflammation, intrahepatic fibrosis, and kupffer cell number between the two groups. Conclusion: Osthol treatment attenuated liver steatosis via decreasing liver de novo triglyceride synthesis and had nominal effects on insulin resistance and liver inflammations.