Abstract
Cholestasis is a clinical disorder defined as an impairment of bile flow, and that leads to toxic bile acid (BA) accumulation in hepatocytes. Here, we investigated the hepatoprotective effect of Yinchenhaotang (YCHT), a well-known formulae for the treatment of jaundice and liver disorders, against the cholestasis using the α-naphthylisothiocyanate (ANIT)-induced cholestasis in male Wistar rats. ANIT feeding induced significant cholestasis with substantially increased intrahepatic retention of hydrophobic BAs. The dynamic changes of serum and liver BAs indicated that YCHT was able to attenuate ANIT-induced BA perturbation, which is consistent with the histopathological findings that YCHT significantly decreased the liver damage. YCHT treatment substantially reduced serum alanine aminotransferase (ALT), alkaline phosphatase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL) with minimal bile duct damage in the ANIT treated rats. Elevated mRNA expression of liver IL-6, IL-17A, IL-17F, TGF-β1, α-SMA, TGR5, NTCP, OATP1a1, and ileum ASBT and decreased liver IL-10, FXR, CAR, VDR, BSEP, MRP2, MRP3, MRP4 was also observed in ANIT-induced cholestasis but were attenuated or normalized by YCHT. Our results demonstrated that the BA profiles were significantly altered with ANIT intervention and YCHT possesses the hepatoprotective potential against cholestatic liver injury induced by hepatotoxin such as ANIT.
Highlights
Cholestasis, an impairment in bile formation, is a common feature in many human liver diseases[1]
ANIT is conjugated with glutathione in hepatocytes and transported through the canalicular efflux transporter (MRP2) into bile, where ANIT dissociates from glutathione
Recent work has focused both on the role of bile acid (BA) in cell signaling as well as the role of sterile inflammation in the pathophysiology
Summary
Cholestasis, an impairment in bile formation, is a common feature in many human liver diseases[1]. Yinchenhaotang (YCHT, Inchin-ko-to or TJ-135 in Japan) is one of the most important and widely used traditional Chinese medicine in clinical practice for jaundice and liver disorders treatment[14], which is composed of Artemisia annua L., Gardenia jasminoides Ellis, and Rheum Palmatum L. Since YCHT has a hepatoprotective property against liver injury induced by various toxicants, it appears to be an attractive formula for therapy of cholestatic liver diseases. Such herbal formula has distinct pharmacological effects, its hepatoprotective mechanisms of action remain unclear. We used YCHT treatment in the same animal model to gain mechanistic insights into their protective effects against ANIT-induced cholestasis
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