Herbal medicine Yinchenhaotang protects against α-naphthylisothiocyanate-induced cholestasis in rats

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.

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

“…34 OA is a TGR5 activator to produce proinflammatory cytokines in the biliary tree implicating in cholestasis 89 pathways, 93 and α-naphthyl isothiocyanate (ANIT)-induced cholestasis is associated with inflammation and marked TGR5 induction in rats. 94 TGR5-mediated increase in pro-inflammatory cytokines by OA correlated with the suppression of Cyp7a1 in murine hepatocytes 89 and in animals. 18,19 Thus, OA activation of TGR5, induction of proinflammatory cytokines and suppression of the rate-limiting bile acid synthetic enzyme Cyp7a1 could contribute to the disturbance of bile acid homeostasis leading to cholestasis.…”

“…Bile acids and/or triterpenoids overdose‐mediated inflammation in the biliary tree may contribute to cholestatic liver injury . In this regards, chenodeoxycholic acid produced cholestasis by activating the NLRP3 inflammasome through TGR5 downstream signalling pathways, and α‐naphthyl isothiocyanate (ANIT)‐induced cholestasis is associated with inflammation and marked TGR5 induction in rats …”

Rats cholestasis instigated by 𝛼-Naphthylisothiocyanate and the impacts of green tea (Camellia sinensis) antioxidant

“…α-Naphthylisothiocyanate (ANIT) is a substance usually used to start cholestasis by harming epithelial cells of the bile conduits and causing serious cholangitis and intrahepatic cholestasis (Yan et al, 2017;Wu et al, 2017;Han et al 2018). A one of a kind treatment of rats explored different avenues regarding αnaphthylisothiocyanate (ANIT) which can harm the liver with intrahepatic cholestasis (Plaa and Clerical, 1976;Kossor et al, 1993;Golbar et al, 2017).…”

“…It is imagined that this hepatic injury with ANIT-initiated cholestasis is valuable for examining the procedures associated with medication instigated cholestasis, since hepatic sores and cholestasis exist on account of the application of certain explicit medications (e.g. Erythromycin estolate, Chlorpromazine, and so forth) to rats and people by emulating the application of ANIT to rats (Kossor et al, 1993;Yan et al, 2017;Han et al,2018). ANIT instruments with cholestasis have been proposed; however, it has not yet been completely explained.…”

“…ANIT instruments with cholestasis have been proposed; however, it has not yet been completely explained. It has been prescribed that lessened hepatic glutathione (GSH) be added to the movement of hepatic inclusion related with ANIT-prompted cholestasis because of its capacity to deliver a reversible ANIT-S conjugate which is basic for the vehicle of ANIT into the bile where it is discharged at high fixations and most likely lethal (Roth and Dahm, 1997;Yan et al, 2017;Wu et al, 2017). Likewise, it has been proposed that neutrophil-intervened aggravation might be added to the enhancement of ANIT-initiated cholestatic liver damage in rats (Roth and Dahm, 1997).…”