(LB03-14-24) Preventive Effect of Poricoic Acid Against Nonalcoholic Steatohepatitis

Objectives: Poricoic acid (PoA), a component of Poria cocos Wolf, has a wide range of pharmacological activities; however, little is known about its effects on Nonalcoholic steatohepatitis (NASH). The preventive effects of PoA on NASH were examined in vivo and in vitro by analyzing triglyceride synthesis, inflammation and fibrosis.

Methods: Six-week-old C57BL/6 male mice were fed either a normal diet or high fat and methionine-choline deficient diet (HFMCD) for 4 weeks to induce NASH and then orally administrated with vehicle or PoA once a day at a dose of 5 mg/kg body weight, 10 mg/kg body weight or 20 mg/kg body weight during the last 6 weeks of HFMCD feeding. The protective effects of PoA were evaluated by histological observation and gene expression associated with lipogenesis, inflammation and fibrosis. Further, the effect of PoA was also investigated in AML12 cells exposed to palmitic acid.

Results: In the HFMCD-induced NASH mice, PoA reduced the liver weight and the levels of alanine aminotransferase and aspartate aminotransferase compared with non-treated HFMCD group. The staining with Oil Red O and hematoxylin and eosin revealed that PoA administration reduced red staining and the size of lipid droplet. qPCR analysis showed that PoA also reduced the expression of genes related to triglyceride synthesis. Further, immunostaining with CD68 and qPCR analysis revealed that PoA reduced the staining with CD68 and the expression of inflammatory genes induced by HFMCD. Moreover, PoA reduced the staining with sirius red and antibody of α-smooth muscle actin and also reduced the expression of genes related to fibrosis. The treatment of PoA to AML12 cells reduced the increase in triglyceride amount and expression of genes associated with triglyceride synthesis, inflammation and fibrosis.

Conclusions: Taken together, our study indicate that PoA has therapeutic effect on NASH through preventing triglyceride synthesis, inflammation and fibrosis.

Funding Sources: This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) and a two year research grant of Pusan National University.