Dilimulati Dilihuma, Nueraihemaiti Nuerbiye, Hailati Sendaer, Han Mengyuan, Abudurousuli Kayisaier, Maihemuti Nulibiya, Baishan Alhar, Aikebaier Alfira, Abulizi Maidina, Zhou Wenting
Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, P.R. China.
Xinjiang Key Laboratory of Active Components and Drug Release Technology of Natural Medicines, Urumqi, Xinjiang, China.
Medicine (Baltimore). 2025 Mar 14;104(11):e41793. doi: 10.1097/MD.0000000000041793.
An estimated 170 million people worldwide suffer from chronic hepatitis C virus (HCV) infection, which is the main reason for liver transplantation in numerous nations. Traditional Chinese medicine is also frequently employed in medicine to treat HCV. Xiaoyandina is frequently employed in traditional medicine, and which has traditionally been used to cure acute and chronic hepatitis, jaundice, acute and chronic cholecystitis, and acute and chronic cholangitis. The information related to active compounds was retrieved from public databases and through literature review which was later combined with differentially expressed genes obtained through microarray datasets; a compound-target genes-disease network was constructed which uncovered that Kaempferol, Sesamin, and Quercetin decisively contributed to the cell growth and proliferation by affecting STAT1, interleukin-6, and CXCL10 proteins. The molecular docking and molecular dynamics simulation of 50 ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. In total, compound targets were obtained separately from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. And 27, 10,894, 6, and 20 disease targets were acquired separately based on OMIM, GeneCard, DrugBank, and PharmGkb databases. Then, we constructed the compound-target network and protein-protein interaction network. Three hundred ninety-four differentially expressed genes were observed (231 up-regulated and 163 downregulated genes). Hub genes were screened through survival analysis, including interleukin-6, STAT1, and CXCL10. Finally, molecular docking and molecular dynamics analysis results showed more stable binding between 3 hub genes and the 2 most active compounds Kaempferol and Quercetin. Our research suggests a novel scientific approach for evaluating the multi-component, multi-target impact of XYDN's active compounds. The present investigation suggested Quercetin, Kaempferol, and Sesamin as possible HCV treatments by combining bioinformatics techniques and network pharmacology. But the findings were not validated in actual patients, so further investigation is needed to confirm the potential use of XYDN towards HCV.
据估计，全球有1.7亿人感染慢性丙型肝炎病毒（HCV），这是许多国家进行肝移植的主要原因。中药也经常被用于治疗HCV。消炎利胆片常用于传统医学，传统上用于治疗急慢性肝炎、黄疸、急慢性胆囊炎和急慢性胆管炎。通过公共数据库检索并结合文献综述获取了与活性化合物相关的信息，随后将其与通过微阵列数据集获得的差异表达基因相结合；构建了一个化合物-靶基因-疾病网络，发现山奈酚、芝麻素和槲皮素通过影响信号转导和转录激活因子1（STAT1）、白细胞介素-6和CXC趋化因子配体10（CXCL10）蛋白，对细胞生长和增殖起决定性作用。50纳秒的分子对接和分子动力学模拟很好地补充了化合物的结合亲和力，并揭示了预测化合物在对接位点的强稳定性。总共从中药系统药理学数据库和分析平台分别获得了化合物靶点。并分别基于在线人类孟德尔遗传数据库（OMIM）、基因卡片数据库（GeneCard）、药物银行数据库（DrugBank）和药物基因组知识库（PharmGkb）数据库获得了27个、10894个、6个和20个疾病靶点。然后，我们构建了化合物-靶标网络和蛋白质-蛋白质相互作用网络。观察到394个差异表达基因（231个上调基因和163个下调基因）。通过生存分析筛选出枢纽基因，包括白细胞介素-6、STAT1和CXCL10。最后，分子对接和分子动力学分析结果表明，3个枢纽基因与2种最具活性的化合物山奈酚和槲皮素之间的结合更稳定。我们的研究提出了一种新的科学方法，用于评估消炎利胆片活性化合物的多成分、多靶点影响。本研究通过结合生物信息学技术和网络药理学，提出槲皮素、山奈酚和芝麻素可能是治疗HCV的药物。但这些发现尚未在实际患者中得到验证，因此需要进一步研究以确认消炎利胆片对HCV的潜在用途。
