Effects of kaerophyllin against hepatic fibrosis in rats

Engulfment of apoptotic bodies (ABs) of hepatocytes is associated with activation of hepatic stellate cells (HSCs) and liver fibrosis in vivo. The present study is to investigate the in vitro and in vivo antifibrotic effects of kaerophyllin [α-(trans-3,4-dimethoxybenzylidene)-β-(3,4-methylenedioxybenzyl)-γ-butyrolactone] from Bupleurum scorzonerifolium. Liver fibrosis was induced by thioacetamide (TAA; 200mg/kg, i.p.) injection twice weekly for 6 weeks. Two groups of rats received either high or low doses (15mg/kg and 30mg/kg, twice daily) of kaerophyllin by gavage in rats. LX 2, a human hepatic stellate cell line, incubated in the presence of UV-induced HepG2 ABs was used to investigate the engulfment of ABs by HSCs and the role of kaerophyllin in the inhibition of HSCs activation. Phagocytosis of ABs by LX 2 induced activation, with production of collagen I and asmooth muscle actin (aSMA), increased motility and NF kB activity. Kaerophyllin inhibited LX2 phagocytosis of ABs and activation. TAA administration induced liver fibrosis, which was attenuated by kaerophyllin treatment, with reduction of GOT and GPT levels and aSMA protein expression. Kaerophyllin reduced TAA-induced liver fibrosis and inhibited HSC activation and engulfment of ABs.