Revealing the Mechanism of Huazhi Rougan Granule in the Treatment of Nonalcoholic Fatty Liver Through Intestinal Flora Based on 16S rRNA, Metagenomic Sequencing and Network Pharmacology

Yingying Liu; Yingying Tan; Jiaqi Huang; Chao Wu; Xiaotian Fan; Antony Stalin; Shan Lu; Haojia Wang; Jingyuan Zhang; Fanqin Zhang; Zhishan Wu; Bing Li; Zhihong Huang; Meilin Chen; Guoliang Cheng; Yanfang Mou; Jiarui Wu

doi:10.3389/fphar.2022.875700

Revealing the Mechanism of Huazhi Rougan Granule in the Treatment of Nonalcoholic Fatty Liver Through Intestinal Flora Based on 16S rRNA, Metagenomic Sequencing and Network Pharmacology

Front Pharmacol. 2022 Apr 26:13:875700. doi: 10.3389/fphar.2022.875700. eCollection 2022.

Authors

Affiliations

¹ Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
² Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China.
³ State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Linyi, China.

Abstract

Background: The incidence of Nonalcoholic Fatty Liver (NAFL) is increasing year by year, growing evidence suggests that the intestinal flora plays a causative role in NAFL. Huazhi Rougan Granule (HRG) is commonly used in the clinical treatment of NAFL. It is reported that it can reduce lipids and protect the liver, but no research has confirmed whether the drug's effect is related to the intestinal flora. Therefore, we investigated whether the effect of HRG is related to the regulation of intestinal flora to further explore the mechanism of HRG in the treatment of NAFL through intestinal flora. Methods: In this study, C57BL/6J mice were fed a high-fat diet for 8 weeks, and the high-fat diet plus HRG or polyene phosphatidylcholine capsules were each administered by gavage for 4 weeks. High-throughput sequencing, network pharmacology, and molecular docking were used to explore the mechanism of HRG in the treatment of NAFL through intestinal flora. Results: HRG treatment can reduce body weight gain, lipid accumulation in liver and lipogenesis and reduce serum biochemical indexes in high-fat-fed mice. Analysis of intestinal flora showed that HRG changed the composition of intestinal flora, which was characterized by a decrease in the Firmicutes/Bacteroidetes ratio. Moreover, the species distribution was significantly correlated with AKP, HDL-C, and TG. Metagenetic analysis showed that HRG altered the functional composition and functional diversity of microorganisms, which was mainly characterized by an increase in the abundance of metabolic pathways. The network pharmacology results show that the mechanism of HRG in the treatment of NAFL through intestinal flora is mainly reflected in the biological process of gene function and related to infectious diseases, immune systems, and signal transduction pathways, such as cytokine-cytokine receptor interaction, Chagas disease, IL-17 signaling pathway and other signaling pathways. Conclusion: These results strongly suggest that HRG may alleviate NAFL by preventing IFD.

Keywords: 16s sequencing; high-fat diet; intestinal flora disorder; network pharmacology; nonalcoholic simple fatty liver.

Grants and funding

This work was supported by grants from the Young Scientists Training Program of Beijing University of Chinese Medicine (Grant nos. BUCM-201901001), National Nature Science Foundation of China (Grant nos.82074284) and the Project of Cooperation between Beijing University of Chinese Medicine and Lunan Pharmaceutical (Grant nos. BUCM-2021-JS-FW-028).