Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2024; 16(2): 264-278
Published online Feb 27, 2024. doi: 10.4254/wjh.v16.i2.264
Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism
Hao Ouyang, Hui Miao, Zhen Li, Duan Wu, Si-Cheng Gao, Yao-Yao Dai, Xiao-Di Gao, Hai-Sheng Chai, Wei-Ye Hu, Jun-Feng Zhu
Hao Ouyang, Zhen Li, Duan Wu, Si-Cheng Gao, Yao-Yao Dai, Xiao-Di Gao, Hai-Sheng Chai, Wei-Ye Hu, Jun-Feng Zhu, Department of Liver, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Hui Miao, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 201203, China
Author contributions: Ouyang H, Miao H, Li Z, Wu D, Gao SC, Dai YY, Gao XD, Chai HS, Hu WY, Zhu JF designed and coordinated the study; Ouyang H, Miao H performed the experiments, acquired and analyzed data; Ouyang H, Miao H, Li Z, Wu D, Gao SC, Dai YY, Gao XD, Chai HS, Hu WY, interpreted the data and discussed the results; Ouyang H and Zhu JF wrote the manuscript.
Supported by Preclinical Study of A New Chinese Herbal Medicine for the Treatment of Ascites of Liver Cirrhosis (Spleen and Kidney Yang Deficiency Type) with the Clinical Formula of Qigui Xiaogu Cataplasm, No. 23S21900100; Traditional Chinese Medicine/Chinese and Western Medicine Advantage Specialty Construction Specialty for Department of Hepatology, No. YW(2023-2024)-01-03; National Natural Science Foundation of China, No 82074386; Construction of Special Disease Alliance of Traditional Chinese Medicine in East China Area and Municipal Level, Shanghai Special Disease Alliance of Traditional Chinese Medicine for Liver Cirrhosis Ascites (Water sickness), and Clinical Research Plan of SHDC, No. SHDC2020CR3095B; and National Funded Postdoctoral Researcher Program, No. GZB20230448.
Institutional animal care and use committee statement: The study was reviewed and approved by the institutional animal care guidelines approved by the Experimental Animal Ethical Committee of Shanghai University of Traditional Chinese Medicine (Approval No. PZSHUTCM190912010).
Informed consent statement: Consent was not needed as the study without exposure to the patients’ data.
Conflict-of-interest statement: The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Jun-Feng Zhu, Doctor, Chief Physician, Department of Liver, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai 201203, China. zhujftongling@163.com
Received: October 18, 2023
Peer-review started: October 18, 2023
First decision: December 26, 2023
Revised: January 9, 2024
Accepted: February 1, 2024
Article in press: February 1, 2024
Published online: February 27, 2024
Processing time: 132 Days and 2.2 Hours
Abstract
BACKGROUND

Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis.

AIM

To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice.

METHODS

To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected.

RESULTS

The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1.

CONCLUSION

YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

Keywords: Yinhuang granule; Liver fibrosis; Hepatic stellate cells; Oxidative injury; Nuclear factor erythroid 2-related factor 2; Inflammation

Core Tip: Yinhuang granule (YHG), a Chinese patent medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos, is traditionally employed for the management of tonsillitis, pharyngitis, as well as upper respiratory tract infections in clinical practice. Here, our study found that YHG effectively alleviated liver fibrosis in carbon tetrachloride-treated mice through various mechanisms, including the inhibition of hepatic stellate cells activation, reduction of inflammation, alleviation of liver oxidative stress damage by prompting nuclear factor erythroid 2-related factor 2 activation, and promotion of liver mitochondrial biogenesis. These findings substantiate the potential clinical use of YHG as a therapy for liver fibrosis.