Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
J Cell Mol Med. 2024 May;28(9):e18319. doi: 10.1111/jcmm.18319.
Knee osteoarthritis (KOA), a major health and economic problem facing older adults worldwide, is a degenerative joint disease. Glycyrrhiza uralensis Fisch. (GC) plays an integral role in many classic Chinese medicine prescriptions for treating knee osteoarthritis. Still, the role of GC in treating KOA is unclear. To explore the pharmacological mechanism of GC against KOA, UPLC-Q-TOF/MS was conducted to detect the main compounds in GC. The therapeutic effect of GC on DMM-induced osteoarthritic mice was assessed by histomorphology, μCT, behavioural tests, and immunohistochemical staining. Network pharmacology and molecular docking were used to predict the potential targets of GC against KOA. The predicted results were verified by immunohistochemical staining Animal experiments showed that GC had a protective effect on DMM-induced KOA, mainly in the improvement of movement disorders, subchondral bone sclerosis and cartilage damage. A variety of flavonoids and triterpenoids were detected in GC via UPLC-Q-TOF/MS, such as Naringenin. Seven core targets (JUN, MAPK3, MAPK1, AKT1, TP53, RELA and STAT3) and three main pathways (IL-17, NF-κB and TNF signalling pathways) were discovered through network pharmacology analysis that closely related to inflammatory response. Interestingly, molecular docking results showed that the active ingredient Naringenin had a good binding effect on anti-inflammatory-related proteins. In the verification experiment, after the intervention of GC, the expression levels of pp65 and F4/80 inflammatory indicators in the knee joint of KOA model mice were significantly downregulated. GC could improve the inflammatory environment in DMM-induced osteoarthritic mice thus alleviating the physiological structure and dysfunction of the knee joint. GC might play an important role in the treatment of knee osteoarthritis.
膝骨关节炎（KOA）是全球老年人面临的主要健康和经济问题，是一种退行性关节疾病。甘草（GC）在许多经典的中药方剂中发挥着重要作用，用于治疗膝骨关节炎。然而，GC 治疗 KOA 的作用尚不清楚。为了探讨 GC 治疗 KOA 的药理机制，采用 UPLC-Q-TOF/MS 检测 GC 中的主要化合物。通过组织形态学、μCT、行为学测试和免疫组织化学染色评估 GC 对 DMM 诱导的骨关节炎小鼠的治疗作用。采用网络药理学和分子对接预测 GC 治疗 KOA 的潜在靶点。通过免疫组织化学染色验证预测结果。动物实验表明，GC 对 DMM 诱导的 KOA 具有保护作用，主要表现在改善运动障碍、软骨下骨硬化和软骨损伤。通过 UPLC-Q-TOF/MS 检测到 GC 中的多种黄酮类和三萜类化合物，如柚皮素。通过网络药理学分析发现，有 7 个核心靶点（JUN、MAPK3、MAPK1、AKT1、TP53、RELA 和 STAT3）和 3 个主要通路（IL-17、NF-κB 和 TNF 信号通路）与炎症反应密切相关。有趣的是，分子对接结果表明，活性成分柚皮素对抗炎相关蛋白具有良好的结合作用。在验证实验中，GC 干预后，KOA 模型小鼠膝关节中 pp65 和 F4/80 炎症指标的表达水平明显下调。GC 可以改善 DMM 诱导的骨关节炎小鼠的炎症环境，从而缓解膝关节的生理结构和功能障碍。GC 可能在治疗膝骨关节炎方面发挥重要作用。
