Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism

Abstract

Cholestasis is a pathological state that leads to serious liver disease; however, therapeutic options remain limited. Yinchen and Gancao are often used in combination at different ratios in traditional Chinese formulae for the treatment of jaundice and cholestasis. In the present study, we investigated the effect of decoctions containing different ratios of Yinchen and Gancao (YGD) on alpha-naphthyl isothiocyanate (ANIT)-treated intrahepatic cholestasis (IC) in mice, and further explored the underlying mechanism. Treatment with 0:4 and 1:4 YGD significantly reduced plasma total bile acid (TBA), total bilirubin (TBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities; decreased unconjugated and conjugated bile acid levels; and improved hepatocyte necrosis and inflammatory cells recruitment to hepatic sinusoids. Moreover, the expression levels of Toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), C-C ligand 2 (CCL2), and C-X-C ligand 2 (CXCL2) in the liver were significantly reduced. However, treatment with 4:1 and 4:0 YGD increased plasma TBA, TBIL, AST, ALT, and ALP activities and aggravated liver cell injury and inflammation. Moreover, the mRNA expression of the bile salt export pump (BSEP) in the liver was significantly increased in mice treated with 4:0 YGD. The present study demonstrates that YGD containing a high proportion of Gancao, which inhibits the TLR4/NF-κB pathway and reduces the inflammatory response, had protective effects against ANIT-treated IC in mice. However, YGD containing a high proportion of Yinchen aggravated the ANIT-treated IC in mice, which may be related to upregulation of BSEP and boosting bile acid regurgitation from damage cholangiocytes to liver in ANIT-treated IC mice.

Hepatoprotective Effects of Glycyrrhetinic Acid on Lithocholic Acid-Induced Cholestatic Liver Injury Through Choleretic and Anti-Inflammatory Mechanisms

“…Glycyrrhizae, also known as licorice, is the most frequently used Chinese herb or food additive ( Yu et al, 2018 ). We found that a glycyrrhizae decoction prepared from licorice root protected against ANIT-induced cholestatic liver injury of mice through inhibition of the TLRs/NF-κB signaling pathway ( Su et al, 2021 ). Glycyrrhizin is the principal triterpene component of the glycyrrhizae decoction, and it is mainly metabolized to glycyrrhetinic acid (GA) through the intestinal flora ( Akao et al, 1994 ; Su et al, 2021 ).…”

“…We found that a glycyrrhizae decoction prepared from licorice root protected against ANIT-induced cholestatic liver injury of mice through inhibition of the TLRs/NF-κB signaling pathway ( Su et al, 2021 ). Glycyrrhizin is the principal triterpene component of the glycyrrhizae decoction, and it is mainly metabolized to glycyrrhetinic acid (GA) through the intestinal flora ( Akao et al, 1994 ; Su et al, 2021 ). Due to high exposure in the liver and a good therapeutic effect, GA can be a potent agent for cholestasis treatment in the clinic.…”

Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo

“…FuZi, the monarch drug of another TCM formula Fuzi Lizhong decoction, exerted protective effects against non-alcoholic fatty liver disease (NAFLD) through anti-inflammatory responses ( Yang et al, 2018 ; Yang et al, 2020 ). Single Yinchen or the combination of Yinchen with other herbs could protect against hepatocyte apoptosis ( Zhang et al, 2022a ), non-alcoholic fatty liver disease ( Guo et al, 2017 ), or ANIT-induced cholestatic liver injury ( Su et al, 2021 ). Compounds such as salvianolic acid C ( Wu et al, 2019 ) and salvianolic acid A protect against drug-induced acute liver failure or CCl 4 -induced liver fibrosis.…”

Comparative Analysis of Gardenia. jasminoides Ellis and G. jasminoides var. Radicans Makino Based on Network Pharmacology

“…Modern pharmacological research further confirms the role of ALB in regulating inflammation, where it reduces the production of inflammatory mediators and modulates inflammatory responses [30]. TNF, as a vital inflammatory regulatory factor associated with Toll-like receptor 4 (TLR4) activation, induces the release of pro-inflammatory cytokines, thereby promoting the occurrence of jaundice and its inflammatory complications [31]. Therefore, we hypothesize that MG and WG may exert their effects in the treatment of jaundice and related liver diseases by modulating inflammatory factors.…”