Protective effect of herbal medicine Huangqi decoction against chronic cholestatic liver injury by inhibiting bile acid-stimulated inflammation in DDC-induced mice.

Abstract

BACKGROUND:

Huangqi decoction (HQD), a classic traditional herbal medicine, has been used for liver fibrosis, but its effect on intrahepatic chronic cholestatic liver injury remains unknown.

PURPOSE:

In the present study, we investigated the hepatoprotective effect of HQD and the underlying molecular mechanisms in 3, 5-diethoxycarbonyl-1, 4-dihydroxychollidine (DDC)-induced chronic cholestatic mice.

METHODS:

The DDC-induced cholestatic mice were administrated HQD for 4 or 8 weeks. Serum biochemistry and morphology were investigated. The serum and liver bile acid (BA) levels were detected by ultra performance liquid chromatography-tandem mass spectrometry. The liver expression of BA metabolizing enzymes and transporters, and inflammatory and fibrotic markers was measured by real-time polymerase chain reaction, western blotting, and immunohistochemistry.

RESULTS:

HQD treatment for 4 or 8 weeks ameliorated DDC-induced liver injury by improving impaired hepatic function and tissue damage. HQD treatment for 8 weeks further decreased the liver expression of cytokeratin 19, tumor growth factor (TGF)-β, collagen I, and α-smooth muscle actin, and ameliorated ductular reaction and liver fibrosis. HQD markedly decreased the accumulation of serum and liver BA. The expression of BA-metabolizing enzymes, cytochrome P450 2b10 and UDP glucuronosyltransferase 1 A1, and multidrug resistance-associated protein 2, Mrp3, and Mrp4 involved in BA homeostasis was increased by 4 weeks of HQD treatment. The expression of BA uptake transporter Na+-taurocholate cotransporting polypeptide was decreased and that of Mrp4 was increased after 8 weeks of HQD treatment. Nuclear factor-E2-related factor-2 (Nrf2) was remarkably induced by HQD treatment. Additionally, HQD treatment for 8 weeks decreased the liver expression of inflammatory factors, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, monocyte chemoattractant protein-1, and intracellular adhesion molecule-1. HQD suppressed the nuclear factor (NF)-κB pathway.

CONCLUSION:

HQD protected mice against chronic cholestatic liver injury and biliary fibrosis, which may be associated with the induction of the Nrf2 pathway and inhibition of the NF-κB pathway, ameliorating BA-stimulated inflammation.

• Authors: Wen-Kai Li, Guo-Feng Wang, Tian-Ming Wang, Yuan-Yuan Li, Yi-Fei Li, Xin-Yi Lu, Ya-Hang Wang, Hua Zhang, Ping Liu, Jia-Sheng Wu, Yue-Ming Ma
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 62 Pg. 152948 (Sep 2019) ISSN: 1618-095X [Electronic] Germany
• PMID: 31129431 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier GmbH. All rights reserved.

Chemical References

• Bile Acids and Salts
• Drugs, Chinese Herbal
• Enzymes
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, mouse
• Protective Agents
• huangqi decoction
• Dicarbethoxydihydrocollidine

Topics

• Animals
• Bile Acids and Salts (metabolism)
• Cholestasis, Intrahepatic (chemically induced, drug therapy, metabolism, pathology)
• Dicarbethoxydihydrocollidine
• Drugs, Chinese Herbal (chemistry, pharmacology)
• Enzymes (metabolism)
• Hepatitis (drug therapy, etiology)
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis (drug therapy, pathology)
• Male
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Protective Agents (pharmacology)