Targeted bile acid profiles reveal the liver injury amelioration of Da-Chai-Hu decoction against ANIT- and BDL-induced cholestasis

Abstract

Multiple types of liver diseases, particularly cholestatic liver diseases (CSLDs) and biliary diseases, can disturb bile acid (BA) secretion; however, BA accumulation is currently seen as an important incentive of various types of liver diseases’ progression. Da-Chai-Hu decoction (DCHD) has long been used for treating cholestatic liver diseases; however, the exact mechanisms remain unclear. Currently, our study indicates that the liver damage and cholestasis status of the α-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis and bile duct ligation (BDL)-induced extrahepatic cholestasis, following DCHD treatment, were improved; the changes of BA metabolism post-DCHD treatment were investigated by targeted metabolomics profiling by UPLC-MS/MS. DCHD treatment severely downregulated serum biochemical levels and relieved inflammation and the corresponding pathological changes including necrosis, inflammatory infiltration, ductular proliferation, and periductal fibrosis in liver tissue. The experimental results suggested that DCHD treatment altered the size, composition, and distribution of the BAs pool, led the BAs pool of the serum and liver to sharply shrink, especially TCA and TMCA, and enhanced BA secretion into the gallbladder and the excretion of BAs by the urinary and fecal pathway; the levels of BAs synthesized by the alternative pathway were increased in the liver, and the conjugation of BAs and the pathway of BA synthesis were actually affected. In conclusion, DCHD ameliorated ANIT- and BDL-induced cholestatic liver injury by reversing the disorder of BAs profile.

Detrimental Role of CXCR3 in α-Naphthylisothiocyanate- and Triptolide-Induced Cholestatic Liver Injury

“…46 TUDCA is a derivative of UDCA that enhances the ability to promote the hydrophilic conversion of bile pools and protects hepatocytes and cholangiocytes. 47 ANIT induced remarkable increases in total, unconjugated, glycine-conjugated, and taurine-conjugated BAs, and triptolide induced significant increases in total and taurine-conjugated BAs. An increase in conjugated BAs contributes to BA excretion and inhibition of liver injury.…”

“…An increase in conjugated BAs contributes to BA excretion and inhibition of liver injury. 48 The levels of taurine-conjugated BAs in mice are predominant in the liver and are more sensitive to cholestasis, 47 with the most significant increase seen upon ANIT and triptolide treatment. In contrast, CXCR3 knockout mice did not show significant changes in the BA pool size or the aforementioned BAs after administration.…”

“…GCA, a key signaling molecule for BA secretion, is also significantly elevated in the plasma of C57BL/6 mice after ANIT treatment . TUDCA is a derivative of UDCA that enhances the ability to promote the hydrophilic conversion of bile pools and protects hepatocytes and cholangiocytes . ANIT induced remarkable increases in total, unconjugated, glycine-conjugated, and taurine-conjugated BAs, and triptolide induced significant increases in total and taurine-conjugated BAs.…”

Allocholic acid protects against α‐naphthylisothiocyanate‐induced cholestasis in mice by ameliorating disordered bile acid homeostasis

“…Various liver conditions, including cholestasis and biliary diseases, may interfere with BA secretion. Nevertheless, it is now understood that the accumulation of BAs in the hepatocytes can exacerbate multiple liver diseases (Zhou et al, 2022). In recent years, targeted metabolomics has gained importance in drug metabolism, therapeutic actions, toxicity, and the regulation of BA metabolism (Liu et al, 2022).…”

Natural Chinese herbs for the prevention and treatment of acute pancreatitis: a narrative review

“…Several studies have reported that DCHD exhibits beneficial effects on protecting the liver, cholagogic action, anti-inflammation, and regulating glucose and lipid metabolism. [53] In the research, it was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas, [54] and inhibiting the activation of the transforming growth factor (TGF)-β/ Smad signaling pathway. [55] Meanwhile, the accessory use of DCHD on conventional Western medical treatment can strikingly shorten the course of AMP.…”