Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway

Xing-Min Zhang; Yue-Chang Huang; Bai-Zhong Chen; Qian Li; Pan-Pan Wu; Wen-Hua Chen; Ri-Hui Wu; Chen Li

doi:10.3389/fphar.2024.1392338

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway

Front Pharmacol. 2024 Jun 20:15:1392338. doi: 10.3389/fphar.2024.1392338. eCollection 2024.

Authors

Xing-Min Zhang^#^{1

2

3}, Yue-Chang Huang^#^{1

2

3}, Bai-Zhong Chen⁴, Qian Li^{1

2

3}, Pan-Pan Wu^{1

2

3}, Wen-Hua Chen^{1

2

3}, Ri-Hui Wu^{1

2

3}, Chen Li^{1

2

3}

Affiliations

¹ School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, China.
² International Healthcare Innovation Institute (Jiangmen), Jiangmen, China.
³ Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, Wuyi University, Jiangmen, China.
⁴ Guangdong Xinbaotang Biotechnology Co., Ltd., Jiangmen, China.

^# Contributed equally.

Abstract

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury.

Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury.

Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice.

Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

Keywords: Pericarpium citri reticulatae, Amomi fructus; alcoholic liver disease; gut microbiota; inflammatory response; oxidative stress.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the National Natural Science Foundation of China (Nos. 81803390 and 22077020), Natural Science Foundation of Guangdong Province, China (No. 2021A1515010221), Guangdong and Macao Cooperation Project from the Department of Science and Technology of Guangdong Province and Jiangmen Science and Technology Bureau (No. 2022A0505020026), Department of Education of Guangdong Province, China (Nos. 2021ZDZX4041 and 2020KZDZX1202), Jiangmen Science and Technology Plan Project Fund (No. 2021030102620004497), and Science and Technology Planning Project of Guangdong Province, China (No. 2021B1212040016).