Fu Tian, Chen Yifei, Li Junkui, Zhu Peili, He Huajuan, Zhang Wei, Yung Ken Kin Lam, Wu Wei
School of Pharmacy, Guilin Medical University, Guilin 541199, China.
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Pharmaceuticals (Basel). 2022 Nov 24;15(12):1457. doi: 10.3390/ph15121457.
Japanese is widely used as a hepatoprotective and anti-inflammatory agent in China. However, the active ingredients in Japanese and their potential mechanisms of action in the treatment of autoimmune hepatitis (AIH) are unknown. The pharmacodynamic substance and mechanism of action of Japanese in the treatment of AIH were investigated using network pharmacology and molecular docking technology in this study. Following that, the effects of Japanese were evaluated using the concanavalin A (Con A)-induced acute liver injury rat model. The active ingredients and targets of Japanese were searched using the Traditional Chinese Medicine Systems Pharmacology database, and hepatitis-related therapeutic targets were identified through GeneCards and Online Mendelian Inheritance in Man databases. A compound-target network was then constructed using Cytoscape software, and enrichment analysis was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular docking technology was used to simulate the docking of key targets, and the AIH rat model was used to validate the expression of key targets. Nineteen active chemical components and 143 key target genes were identified. GO enrichment analysis revealed that the treatment of AIH with Japanese mainly involved DNA-binding transcription factor binding, RNA polymerase II-specific DNA transcription factor binding, cytokine receptor binding, receptor-ligand activity, ubiquitin-like protein ligase binding, and cytokine activity. In the KEGG enrichment analysis, 165 pathways were identified, including the lipid and atherosclerotic pathway, IL-17 signaling pathway, TNF signaling pathway, hepatitis B pathway, and the AGE-RAGE signaling pathway in diabetic complications. These pathways may be the key to effective AIH treatment with Japanese . Molecular docking showed that quercetin and kaempferol have good binding to , , , and . Animal experiments demonstrated that Japanese could increase the expression of and decrease the expression of protein, as well as , in rat liver tissues. This study identified multiple molecular targets and pathways for Japanese in the treatment of AIH. At the same time, the effectiveness of Japanese in treating AIH was verified by animal experiments.
在我国，日本獐牙菜被广泛用作保肝抗炎药。然而，日本獐牙菜中的活性成分及其在自身免疫性肝炎（AIH）治疗中的潜在作用机制尚不清楚。本研究运用网络药理学和分子对接技术，对日本獐牙菜治疗AIH的药效物质及作用机制进行了研究。随后，利用刀豆蛋白A（Con A）诱导的急性肝损伤大鼠模型评估了日本獐牙菜的效果。通过中药系统药理学数据库检索日本獐牙菜的活性成分和靶点，并通过GeneCards和人类孟德尔遗传在线数据库确定肝炎相关治疗靶点。然后使用Cytoscape软件构建化合物-靶点网络，并利用基因本体论（GO）和京都基因与基因组百科全书（KEGG）数据库进行富集分析。运用分子对接技术模拟关键靶点的对接，并使用AIH大鼠模型验证关键靶点的表达。确定了19种活性化学成分和143个关键靶基因。GO富集分析表明，日本獐牙菜治疗AIH主要涉及DNA结合转录因子结合、RNA聚合酶II特异性DNA转录因子结合、细胞因子受体结合、受体-配体活性、泛素样蛋白连接酶结合和细胞因子活性。在KEGG富集分析中，共鉴定出165条通路，包括脂质和动脉粥样硬化通路、IL-17信号通路、TNF信号通路、乙型肝炎通路以及糖尿病并发症中的AGE-RAGE信号通路。这些通路可能是日本獐牙菜有效治疗AIH的关键。分子对接表明，槲皮素和山奈酚与 、 、 和 具有良好的结合能力。动物实验表明，日本獐牙菜可增加大鼠肝组织中 的表达，降低 蛋白以及 的表达。本研究确定了日本獐牙菜治疗AIH的多个分子靶点和通路。同时，动物实验验证了日本獐牙菜治疗AIH的有效性。
