Liu JJ, Mei HW, Jing YY, Li ZL, Wu SG, Yuan HX, Zhang XB. Yinchenhao decoction alleviates obstructive jaundice liver injury by modulating epidermal growth factor receptor and constitutive androstane receptor signaling. World J Hepatol 2025; 17(3): 101724 [DOI: 10.4254/wjh.v17.i3.101724]
Corresponding Author of This Article
Xi-Bo Zhang, PhD, Full Professor, Department of Hepatobiliary and Pancreatic Surgery 2, Tianjin Nankai Hospital, Tianjin Medical University, No. 6 Changjiang Street, Nankai District, Tianjin 300102, China. nkzxb@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jun-Jian Liu, Zhong-Lian Li, Xi-Bo Zhang, Department of Hepatobiliary and Pancreatic Surgery 2, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300102, China
Jun-Jian Liu, Tianjin Key Laboratory, Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin 300102, China
Han-Wei Mei, Department of Gastrointestinal Surgery 3, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 301617, China
Yan-Yan Jing, Su-Guo Wu, Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Hong-Xia Yuan, College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Co-first authors: Jun-Jian Liu and Han-Wei Mei.
Co-corresponding authors: Hong-Xia Yuan and Xi-Bo Zhang.
Author contributions: Zhang XB and Liu JJ conceptualized and designed the research study; Liu JJ and Mei HW conducted the experiments and collected experimental data; Jing YY and Wu SG performed data analysis and interpretation; Liu JJ and Mei HW drafted the manuscript; Yuan HX and Li ZL critically revised and edited the manuscript for intellectual content; All authors reviewed and approved the final version of the manuscript. Liu JJ and Mei HW contributed equally to this work as co-first authors, with Liu JJ leading the experimental execution and data acquisition, and Mei HW assisting in experimental procedures and manuscript preparation. Zhang XB and Yuan HX served as co-corresponding authors, overseeing the project’s conceptual framework, experimental validation, and manuscript refinement. Zhang XB secured funding and supervised the overall research direction, while Yuan HX provided critical insights into data interpretation and coordinated revisions. Li ZL contributed to technical guidance and manuscript proofreading. This collaborative effort ensured the successful completion and publication of the study.
Supported by Tianjin Municipal Education Commission Scientific Research Program, China, No. 2022KJ271.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (license No. SYXK Jin 2020-0008). The experimental protocol was approved by the Animal Research Committee of Tianjin Medical University Nankai Hospital (approval No. NKYY-DWLL-2023-073).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xi-Bo Zhang, PhD, Full Professor, Department of Hepatobiliary and Pancreatic Surgery 2, Tianjin Nankai Hospital, Tianjin Medical University, No. 6 Changjiang Street, Nankai District, Tianjin 300102, China. nkzxb@163.com
Received: September 24, 2024 Revised: January 18, 2025 Accepted: March 4, 2025 Published online: March 27, 2025 Processing time: 182 Days and 13.3 Hours
Abstract
BACKGROUND
Yinchenhao decoction (YCHD) is a traditional Chinese medicine widely used to treat liver damage caused by obstructive jaundice (OJ). Although YCHD has demonstrated protective effects against liver damage, reduced apoptosis, and mitigated oxidative stress in OJ, the precise molecular mechanisms involved remain poorly understood.
AIM
To investigate the beneficial effects of YCHD on OJ and elucidate the underlying mechanisms.
METHODS
The active constituents of YCHD were identified using liquid chromatography-tandem mass spectrometry, and their potential targets for OJ treatment were predicted through network pharmacology. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. An OJ rat model was established by common bile duct ligation. Rats were divided into three groups: Sham surgery (S Group), model (O Group), and YCHD (Y Group). YCHD was administered to Group Y for one week. Bilirubin levels, liver function parameters, and bile acid concentrations in blood and urine were measured by enzyme-linked immunosorbent assay. The bile acid renal clearance rate (Clr) was calculated. Histopathological evaluation of liver and kidney tissues was performed using hematoxylin-eosin staining. Western blotting was utilized to assess the expression of key bile acid metabolism and transport proteins in both liver and kidney tissues. The expression of the constitutive androstane receptor (CAR) and its nuclear localization were evaluated by immunohistochemistry. Molecular docking studies identified the epidermal growth factor receptor (EGFR) as a potential target of YCHD's active components. An OJ cell model was created using human liver (L02) and renal tubular epithelial (HK-2) cells, which were treated with YCHD-containing serum. Western blotting and immunofluorescence assays were employed to evaluate CAR expression and its nuclear localization in relation to EGFR activation.
RESULTS
Network analysis identified the EGFR signaling pathway as a key mechanism through which YCHD exerts its effects on OJ. In vivo experiments showed that YCHD improved liver function, reduced OJ-induced pathology in liver and kidney tissues, and decreased serum bile acid content by enhancing bile acid Clr and urine output. YCHD also increased CAR expression and nuclear heterotopy, upregulating proteins involved in bile acid metabolism and transport, including CYP3A4, UGT1A1, MRP3, and MRP4 in the liver, and MRP2 and MRP4 in the kidneys. In vitro, YCHD increased CAR expression and nuclear heterotopy in L02 and HK-2 cells, an effect that was reversed by EGFR agonists.
CONCLUSION
YCHD enhances bile acid metabolism in the liver and promotes bile acid excretion in the kidneys, ameliorating liver damage caused by OJ. These effects are likely mediated by the upregulation of CAR and its nuclear translocation.
Core Tip: Yinchenhao decoction (YCHD) alleviates obstructive jaundice-induced liver damage by enhancing bile acid metabolism and excretion. This study reveals that YCHD modulates the epidermal growth factor receptor signaling pathway, upregulates the constitutive androstane receptor, and promotes its nuclear localization, contributing to improved liver and kidney function. These findings provide insights into the molecular mechanisms behind YCHD's therapeutic effects on obstructive jaundice.
