Liu Yingying, Tan Yingying, Huang Jiaqi, Wu Chao, Fan Xiaotian, Stalin Antony, Lu Shan, Wang Haojia, Zhang Jingyuan, Zhang Fanqin, Wu Zhishan, Li Bing, Huang Zhihong, Chen Meilin, Cheng Guoliang, Mou Yanfang, Wu Jiarui
Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China.
Front Pharmacol. 2022 Apr 26;13:875700. doi: 10.3389/fphar.2022.875700. eCollection 2022.
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. 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. 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. These results strongly suggest that HRG may alleviate NAFL by preventing IFD.
非酒精性脂肪肝（NAFL）的发病率逐年上升，越来越多的证据表明肠道菌群在NAFL的发病中起致病作用。化滞柔肝颗粒（HRG）常用于NAFL的临床治疗。据报道，它可以降血脂和保护肝脏，但尚无研究证实该药物的作用是否与肠道菌群有关。因此，我们研究了HRG的作用是否与肠道菌群的调节有关，以进一步探索HRG通过肠道菌群治疗NAFL的机制。在本研究中，将C57BL/6J小鼠喂饲高脂饮食8周，然后将高脂饮食加HRG或多烯磷脂酰胆碱胶囊分别灌胃给药4周。采用高通量测序、网络药理学和分子对接技术，探讨HRG通过肠道菌群治疗NAFL的机制。HRG治疗可减轻高脂喂养小鼠的体重增加、肝脏脂质蓄积和脂肪生成，并降低血清生化指标。肠道菌群分析表明，HRG改变了肠道菌群的组成，其特征是厚壁菌门/拟杆菌门比值降低。此外，物种分布与碱性磷酸酶、高密度脂蛋白胆固醇和甘油三酯显著相关。宏基因组分析表明，HRG改变了微生物的功能组成和功能多样性，其主要特征是代谢途径丰度增加。网络药理学结果表明，HRG通过肠道菌群治疗NAFL的机制主要体现在基因功能的生物学过程中，与传染病、免疫系统和信号转导途径有关，如细胞因子-细胞因子受体相互作用、恰加斯病、白细胞介素-17信号通路等信号通路。这些结果强烈表明，HRG可能通过预防感染性疾病来减轻NAFL。
