Department of Orthopedics, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443001, Hubei, China; Third-Grade Pharmacological Laboratory on Chinese Medicine Approved By State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei, 443002, China.
Third-Grade Pharmacological Laboratory on Chinese Medicine Approved By State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei, 443002, China.
J Ethnopharmacol. 2023 Oct 5;314:116553. doi: 10.1016/j.jep.2023.116553. Epub 2023 May 11.
Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Chaenomeles speciosa (CSP) (Chinese Pinyin: mugua) is a medicinal and food herb that has long been used as a folk medicine for rheumatic diseases, yet its bioactive components and therapeutic mechanisms are not clear.
Exploring anti-inflammatory and chondroprotective effects of CSP on rheumatoid arthritis (RA) and its possible targets of action.
In this study, we performed an integrated approach of network pharmacology, molecular docking and experimental studies to explore the potential mechanism of action of CSP in the treatment of cartilage damage in RA.
Studies have shown that Quercetin, ent-Epicatechin and Mairin may be the main active compounds of CSP in the treatment of RA, while AKT1, VEGFA, IL-1β, IL-6, MMP9 etc. are considered as core target proteins to which the main active compounds in CSP bind, as further confirmed by molecular docking. In addition, the potential molecular mechanism of CSP for the treatment of cartilage damage in RA predicted by network pharmacology analysis was validated by in vivo experiments. CSP was found to downregulate the expression of AKT1, VEGFA, IL-1β, IL-6, MMP9, ICAM1, VCAM1, MMP3, MMP13 and TNF-α and increase the expression of COL-2 in the joint tissue of Glucose-6-Phosphate Isomerase (G6PI) model mice. Thus CSP contributes to the treatment of rheumatoid arthritis cartilage destruction.
This study showed that CSP has multi-component, multi-target and multi-pathway characteristics in treating cartilage damage in RA, which can achieve the effect of treating RA by inhibiting the expression of inflammatory factors, reducing neovascularization and alleviating the damage to cartilage caused by the diffusion of synovial vascular opacities, and reducing the degradation of cartilage by MMPs to play a protective role in RA cartilage damage. In conclusion, this study indicates that CSP is a candidate Chinese medicine for further research in treating cartilage damage in RA.
中药（TCM）在中国已有很长的应用历史，并且在全球范围内正逐渐得到越来越多的认可。木瓜（CSP）（中文拼音：mugua）是一种药食同源的草本植物，长期以来一直被民间用于治疗风湿病，但它的生物活性成分和治疗机制尚不清楚。
探索木瓜治疗类风湿关节炎（RA）的抗炎和软骨保护作用及其可能的作用靶点。
本研究采用网络药理学、分子对接和实验研究相结合的方法，探讨木瓜治疗 RA 软骨损伤的潜在作用机制。
研究表明，槲皮素、表儿茶素和马瑞林可能是 CSP 治疗 RA 的主要活性化合物，而 AKT1、VEGFA、IL-1β、IL-6、MMP9 等被认为是 CSP 主要活性化合物结合的核心靶蛋白，这一点进一步通过分子对接得到了证实。此外，网络药理学分析预测的 CSP 治疗 RA 软骨损伤的潜在分子机制通过体内实验得到了验证。CSP 被发现可下调葡萄糖-6-磷酸异构酶（G6PI）模型小鼠关节组织中 AKT1、VEGFA、IL-1β、IL-6、MMP9、ICAM1、VCAM1、MMP3、MMP13 和 TNF-α 的表达，增加 COL-2 的表达。因此，CSP 有助于治疗类风湿关节炎软骨破坏。
本研究表明，CSP 治疗 RA 软骨损伤具有多成分、多靶点、多途径的特点，通过抑制炎症因子的表达、减少新生血管形成以及减轻滑膜血管通透性扩散对软骨的损伤，降低 MMPs 对软骨的降解，从而发挥对 RA 软骨损伤的保护作用。综上所述，本研究表明 CSP 是治疗 RA 软骨损伤的一种有潜力的中药候选药物。
