iridoids and Cholestasis--Intrahepatic

Traditional medicinal formulation of Yin-zhi-huang (YZH) is widely used in the clinic for the treatment of jaundice and chronic liver diseases in East Asian countries. However, the pharmacologically active components of YZH and the underlying mechanism are still unknown. Geniposide (GEN) was recently identified as one of the most abundant circulating components in YZH. In this study, we investigated the protective effect of GEN against liver injuries induced by alpha-naphthylisothiocyanate (ANIT). 50[Formula: see text]mg/kg of GEN was administered to ICR mice once daily for 5 days, and challenge of ANIT 75[Formula: see text]mg/kg was performed on the 4th day. Blood and liver tissues were collected on day 6 and subjected to biochemical, histopathological and pathway analyses. The biochemical and pathological findings showed that GEN almost totally attenuated ANIT-induced cholestasis and liver injury compared with the vehicle/ANIT group. The altered gene transcription related to bile acid metabolism and transport was normalized by co-treatment with GEN. The expressions of tumor necrosis factor-[Formula: see text] and the suppressor of cytokine signaling 3 were significantly decreased in the GEN/ANIT group. Western blot revealed that GEN inhibited the activation and expression of STAT3 and NF[Formula: see text]B. These data suggest GEN inhibits ANIT-induced hepatotoxicity. The protective effect is associated with the downregulation of STAT3 and NF[Formula: see text]B signaling.

Topics: 1-Naphthylisothiocyanate; Animals; Cholestasis, Intrahepatic; Down-Regulation; Drugs, Chinese Herbal; Humans; Iridoids; Male; Mice; Mice, Inbred ICR; NF-kappa B; Signal Transduction; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha

When a lymphokine, the cholestatic factor, was intravenously injected into rats through a mesenteric vein, a remarkable reduction in bile flow was observed. Using this experimentally induced intrahepatic cholestasis model, we studied the choleretic effects of alpha-iridodiol, an iridoid compound. When alpha-iridodiol was administered 30 min before, at the same time, or 30 min after injection of the cholestatic factor, the reductions in bile flow and bile acid excretion were significantly inhibited. Remarkable choleretic effects were also noted when it was administered to normal rats. These results suggested that alpha-iridodiol may be effective in the treatment of intrahepatic cholestasis.

Topics: Animals; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Cyclopentanes; Guinea Pigs; Iridoids; Molecular Structure; Rats

Topics: 1-Naphthylisothiocyanate; Animals; Cholestasis, Intrahepatic; Iridoids; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Plant Extracts; Plants, Medicinal; Pyrans; Rats; Rats, Inbred Strains