Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice

Abstract

Intrahepatic cholestasis is a serious symptom of liver disorders with limited therapies. In this study, we investigated the efficacy of Huangqi decoction (HQD), a two-herb classic traditional Chinese medicine (TCM), in the treatment of alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. HQD treatment ameliorated impaired hepatic function and tissue damage. A metabolomics study revealed that the endogenous metabolites significantly affected by HQD were related to bile acid (BA) biosynthesis and glutathione metabolism pathways. HQD treatment decreased the intrahepatic accumulation of cytotoxic BAs, normalized serum BA levels, and increased biliary and urinary BA excretion. Additionally, HQD restored the hepatic glutathione content and suppressed reactive oxygen species (ROS) in cholestatic mice. Protein and gene analysis revealed that HQD increased the expression of the hepatic metabolizing enzymes cytochrome P450 (CYP) 2B10 and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), as well as multidrug resistance-associated protein 2 (Mrp2), Mrp3, and Mrp4, which play crucial roles in BA homeostasis. Further, HQD increased the protein expression of glutamate-cysteine ligase, which is involved in the synthesis of glutathione. Importantly, HQD increased the nuclear expression of nuclear factor-E2-related factor-2 (Nrf2). In conclusion, HQD protects against intrahepatic cholestasis by reversing the disordered homeostasis of BAs and glutathione.

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

“…It has been demonstrated that several traditional Chinese medicine (TCM) remedies for treating jaundice can reverse the metabolomic fingerprint of ANIT, and therefore, protect against ANIT-induced cholestasis. These treatments include paeoniflorin (from the dried root of Paeonia lactiflora) [83,84], rhubarb [85], Yinchenhao decoction (from the above ground parts of Artemisia annua) [86], chicken bile powder (containing mainly taurochenodeoxycholic acid that is deconjugated in the gut producing the primary BA that is a FXR ligand) [87], Huangqi decoction (a TCM comprising Radix Astragali and Radix Glycyrrhizae) [88], gentiopicroside (from Gentiana rigescens Franch. ex Hemsl.)…”

Buzhongyiqi Decoction Protects Against Loperamide-Induced Constipation by Regulating the Arachidonic Acid Pathway in Rats

“…Metabolomics represents a powerful discipline concerned with the comprehensive analysis of small molecules to discover biomarkers in biological systems (Schrimpe-Rutledge et al, 2016;Zhang et al, 2019). This method provides holistic insights into changes in the metabolic pathways during disease or drug treatment (Wu et al, 2017;Zheng et al, 2019). Therefore, metabolomics study is in perfect accordance with the holistic approach of TCM, and can provide clues to mechanism of action of TCM (Wu et al, 2017;Zheng et al, 2019).…”

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).…”

“…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).…”

“…Besides, in rats treated once with ANIT, it was affirmed that lipid peroxidation instigated by responsive oxygen species (ROS) made by methods for attacking neutrophils in the liver tissues is engaged with the movement of liver sores with cholestasis (Kongo et al, 1999;Cullen et al, 2016). Moreover, it has appeared in ANIT-treated rats that the intrusion of the hepatic disease hindering action framework adds to enhanced cholestasis-related liver harm (Ohta et al, 2001;Nakamura et al, 2013;Wu et al, 2017).…”