Studies On Hepatoprotective And Anti-fibrosis Activities Of Cornuside And Ginsenosides

The present study elucidates the effects of cornuside on carbon tetrachloride (CC14)-induced hepatotoxicity. Rats were treated intraperitoneally with0.5ml/kg CCI4. At16h after the CC14treatment, the levels of serum aminotransferases, TNF-a, and lipid peroxidation were significantly elevated, whereas the hepatic antioxidative enzyme activities were decreased. These changes were attenuated by cornuside. The histological studies also showed that cornuside inhibited the CC14-induced liver damage. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX-2) were elevated after CC14treatment, while the cytochrome P4502E1(CYP2E1) expression was suppressed. Cornuside treatment inhibited the formation of liver nitrite, reduced the over-expression of iNOS and COX-2proteins, but restored the liver CYP2E1content compared with the CC14-treated rats. Our data demonstrate that cornuside protects the liver from CC14-induced acute hepatotoxicity, which might be due to its ability to restore the CYP2E1function and suppress the inflammatory responses, in combination with its capacity to reduce oxidative stress.The hepatic stellate cell (HSC) is the primary cell type in the liver responsible for excess collagen deposition during fibrosis. HSC changes from a quiescent to an activated situation undergoing a fibrogenic stimulus associated with increased extracellular matrix synthesis and increased cell proliferation. It’s investigated how Ginsenosides czh-A-69mediated MAPK/Akt/TLR4/TAK-1and mitochondria pathways in the balance of HSC activation and apoptosis in hapatic stellate cells. An activated HSC cell line was used in the present study. Western blot was applied to detect the expression of MAPK/Akt/TLR4/TAK-1and bcl-2/bax ratio and cytochrome c in the mitochondria. Ginsenosides czh-A-69significantly inhibited the proliferation of activated HSC in a dosage or time manner. Ginsenosides czh-A-69regulated caspase-3or PARP expression at24h after cultuted with czh-A-693.125μM or1h with6.25μM. Ginsenosides czh-A-69also significantly inhibited TIMP-1, TLR4and TAK-1phosphorylation at1h after adiministation with czh-A-696.25μM. Ginsenosides czh-A-69regulated bcl-2/bax and cytochrome c expression at24h after cultuted with czh-A-693.125and1.56μM, respectively, and at12h or1h with6.25μM. Ginsenosides czh-A-69increased JNK/ERK/p38/MAPK phosphorylation at1h after cultuted with czh-A-696.25μM. Furthermore, ginsenosides czh-A-69significantly inhibited Akt phosphorylation at15min after cultuted with czh-A-696.25μM. Therefore, ginsenosides czh-A-69may inhibit the proliferation of activated HSC cell and mediated MAPK/Akt/TLR4/TAK-1and mitochondria pathways in activated murine hepatic stellate cells. Ginsenosides czh-A-69regulated MAPK/Akt/TLR4/TAK-1signaling in HSCs during active fibrogenesis resulting in inhibition of extracellular matrix deposition and reduce of profibrogenic factors expression. These data suggest that ginsenosides czh-A-69may represent an effective therapeutic medicine for hepatic fibrosis.