College of Pharmacy, Xinjiang Medical University, Urumqi, 830011, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Comput Biol Chem. 2020 Dec;89:107397. doi: 10.1016/j.compbiolchem.2020.107397. Epub 2020 Oct 1.
Qiang-Huo-Sheng-Shi decoction (QHSSD), a classic traditional Chinese herbal formula, which has been reported to be effective in rheumatoid arthritis (RA) and osteoarthritis (OA). However, the concurrent targeting mechanism of how the aforementioned formula is valid in the two distinct diseases OA and RA, which represents the homotherapy-for-heteropathy principle in traditional Chinese medicine (TCM), have not yet been clarified. In the present study, network pharmacology was adopted to analyze the potential molecular mechanism, and therapeutic effective components of QHSSD on both OA and RA. A total of 153 active ingredients in QHSSD were identified, 142 of which associated with 59 potential targets for the two diseases were identified. By constructing the protein-protein interaction network and the compound-target-disease network, 72 compounds and 10 proteins were obtained as the hub targets of QHSSD against OA and RA. The hub genes of ESR1, PTGS2, PPARG, IL1B, TNF, MMP2, IL6, CYP3A4, MAPK8, and ALB were mainly involved in osteoclast differentiation, the NF-κB and TNF signaling pathways. Moreover, molecular docking results showed that the screened active compounds had a high affinity for the hub genes. This study provides new insight into the molecular mechanisms behind how QHSSD presents homotherapy-for-heteropathy therapeutic efficacy in both OA and RA. For the first time, a two-disease model was linked with a TCM formula using network pharmacology to identify the key active components and understand the common mechanisms of its multi-pathway regulation. This study will inspire more innovative and important studies on the modern research of TCM formulas.
羌活胜湿汤（QHSSD）是一种经典的中药方剂，已被报道对类风湿关节炎（RA）和骨关节炎（OA）有效。然而，对于上述方剂在两种不同疾病 OA 和 RA 中有效的同时靶向机制，代表了中医的同病异治原则，尚未得到明确。本研究采用网络药理学分析 QHSSD 对 OA 和 RA 的潜在分子机制和治疗有效成分。共鉴定出 QHSSD 中的 153 种活性成分，其中 142 种与两种疾病的 59 个潜在靶点相关。通过构建蛋白质-蛋白质相互作用网络和化合物-靶点-疾病网络，得到了 72 种化合物和 10 个作为 QHSSD 治疗 OA 和 RA 的枢纽靶点。ESR1、PTGS2、PPARG、IL1B、TNF、MMP2、IL6、CYP3A4、MAPK8 和 ALB 等枢纽基因主要参与破骨细胞分化、NF-κB 和 TNF 信号通路。此外，分子对接结果表明筛选出的活性化合物与枢纽基因具有很高的亲和力。本研究为 QHSSD 在 OA 和 RA 中表现出同病异治疗效的分子机制提供了新的见解。首次使用网络药理学将两种疾病模型与中药方剂联系起来，以鉴定关键的活性成分并了解其多途径调节的共同机制。这项研究将激发对中药方剂现代研究的更多创新和重要研究。
