Xi Yujiang, Zhao Ting, Shi Mingqin, Zhang Xiaoyu, Bao Yanyuan, Gao Jiamei, Shen Jiayan, Wang Hui, Xie Zhaohu, Wang Qi, Li Zhaofu, Qin Dongdong
The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, China.
School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, China.
Evid Based Complement Alternat Med. 2023 Apr 14;2023:2140327. doi: 10.1155/2023/2140327. eCollection 2023.
A major contributor to older disability is osteoarthritis. Radix Angelicae Biseratae (known as Duhuo in China, DH, the dried rhizome of Angelica pubescens) and Dipsaci Radix (known as Xuduan in China, XD, the dried rhizome of Dipsacus asper Wall) herb pair (DXHP) is widely used to treat osteoarthritis, but the underlying molecular mechanisms still have not been revealed. This research aimed to illustrate the therapeutic mechanism of DXHP against osteoarthritis through the techniques of network pharmacology and molecular docking.
Gene targets for osteoarthritis and active ingredients for DXHP were screened based on the pharmacology public database and the gene-disease target database. The software program Cytoscape was used to visualize the active chemical target-disease gene network. The STRING biological information website was used to investigate protein interactions. On the Metascape bioinformatics website, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out. The molecular docking of the important chemicals and primary targets identified by the aforementioned screening was performed using Autodock software.
Twenty-six active substances from the DXHP that had strong connections to 138 osteoarthritis-related targets were screened out. According to network analysis, TNF, GAPDH, IL-6, AKT-1, IL-1B, and VEGFA are prospective therapeutic targets, while osthole, cauloside A, ammidin, angelicone, beta-sitosterol, and asperosaponin VI may be significant active components. 1705 biological processes (BP), 155 molecular functions (MF), and 89 cellular components (CC) were identified by GO analysis. KEGG analysis indicated that IL-17, NF-kappa B, HIF-1, MAPK, and AGE-RAGE signaling pathways are potentially involved. Molecular docking showed that cauloside A, osthole, and -sitosterol have excellent binding activity with main targets.
This study comprehensively illuminated the active ingredients, potential targets, primary pharmacological effects, and relevant mechanisms of the DXHP in the treatment of OA. These findings provide fresh thoughts into the therapeutic mechanisms of the main active ingredients of DXHP and provide a reference for further exploration and clinical applications of DXHP.
骨关节炎是导致老年人残疾的主要因素之一。独活寄生药对（中国称为独活寄生，DH，为毛当归干燥根茎）和续断（中国称为续断，XD，为川续断干燥根茎）药对（DXHP）被广泛用于治疗骨关节炎，但其潜在分子机制仍未阐明。本研究旨在通过网络药理学和分子对接技术阐明DXHP治疗骨关节炎的作用机制。
基于药理学公共数据库和基因-疾病靶点数据库筛选骨关节炎的基因靶点和DXHP的活性成分。使用Cytoscape软件程序可视化活性化学靶点-疾病基因网络。利用STRING生物信息网站研究蛋白质相互作用。在Metascape生物信息网站上进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。使用Autodock软件对上述筛选鉴定出的重要化学物质和主要靶点进行分子对接。
筛选出DXHP中与138个骨关节炎相关靶点有强关联的26种活性物质。通过网络分析，肿瘤坏死因子（TNF）、甘油醛-3-磷酸脱氢酶（GAPDH）、白细胞介素-6（IL-6）、蛋白激酶B-1（AKT-1）、白细胞介素-1β（IL-1B）和血管内皮生长因子A（VEGFA）是潜在治疗靶点，而蛇床子素、毛蕊花糖苷、氨咪啶、当归酮、β-谷甾醇和川续断皂苷VI可能是重要活性成分。GO分析鉴定出1705个生物学过程（BP）、155个分子功能（MF）和89个细胞成分（CC）。KEGG分析表明白细胞介素-17、核因子κB、缺氧诱导因子-1、丝裂原活化蛋白激酶和晚期糖基化终末产物受体信号通路可能参与其中。分子对接显示毛蕊花糖苷、蛇床子素和β-谷甾醇与主要靶点具有良好的结合活性。
本研究全面阐明了DXHP治疗骨关节炎的活性成分、潜在靶点、主要药理作用及相关机制。这些发现为DXHP主要活性成分的治疗机制提供了新思路，为DXHP的进一步探索和临床应用提供了参考。
