Geniposide Inhibits Alpha-Naphthylisothiocyanate-Induced Intrahepatic Cholestasis: The Downregulation of STAT3 and NFκB Signaling Plays an Important Role

Abstract

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.

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Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARαand L-FABP Expressions in High-Fat-Fed Rats

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PPARα-independent action against metabolic syndrome development by fibrates is mediated by inhibition of STAT3 signalling

“…Processing of liver and adipose samples followed the previously published procedures . The primer sequences, listed in Table , were extracted from http://mouseprimerdepot.nci.nih.gov.…”

“…Processing of liver and adipose samples followed the previously published procedures. [29] The primer sequences, listed in Table S1, were extracted from http://mouseprime rdepot.nci.nih.gov. A 5 ll PCR system was designed for the 384 plate that included 1 ll of total cDNA, 2.5 ll of Light-Cycler 480 SYBR Green I Master Mix, 0.2 ll of forward and reverse primer and 2 ll of nuclease-free water.…”