Yin Li, Fan Yong, Zhong Xugang, Meng Xiang, He Zeju, Hong Zheping, Chen Jihang, Zhang Qiong, Kong Mingxiang, Wang Jiao, Tong Yu, Bi Qing
Department of Sports Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People's Republic of China.
Postgraduate Training Base Alliance of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
Drug Des Devel Ther. 2024 Nov 27;18:5445-5459. doi: 10.2147/DDDT.S490388. eCollection 2024.
Osteoarthritis (OA), a degenerative disease marked by cartilage erosion and synovial proliferation, has led to an increased interest in natural plant-based compounds to slow its progression. Pristimerin(Pri), a triterpenoid compound derived from Tripterygium wilfordii, has demonstrated anti-inflammatory and antioxidant characteristics. This study explores the protective effects of Pri on OA and its potential mechanisms.
In this study, we examined the impact of Pri on the expression of inflammatory factors and extracellular matrix(ECM) degradation induced by IL-1β in chondrocyte experiments. Bioinformatics analysis was then performed to investigate the potential signaling pathways involved in Pri's protective effects. Finally, the efficacy of Pri in reducing cartilage degradation was further evaluated in a destabilization of the medial meniscus (DMM) mouse model.
Utilizing bioinformatics analysis and in vitro studies, it was revealed that Pri inhibits the activation of NF-κB and MAPK signaling pathways, leading to the reversal of upregulated MMP-13 (matrix metalloproteinases-13), iNOS (inducible nitric oxide synthase), and COX-2(cyclooxygenase-2) elicited by IL-1β stimulation, as well as the partial restoration of Collagen-II levels. Furthermore, in a DMM mouse model, the group treated with Pri exhibited reduced cartilage degradation and slowed OA progression compared to the modeling group.
This research highlights Pri as a potential therapeutic agent for delaying OA progression.
骨关节炎（OA）是一种以软骨侵蚀和滑膜增生为特征的退行性疾病，这使得人们对天然植物化合物减缓其进展的兴趣日益增加。土槿皮乙酸（Pri）是一种从雷公藤中提取的三萜类化合物，已显示出抗炎和抗氧化特性。本研究探讨了Pri对OA的保护作用及其潜在机制。
在本研究中，我们在软骨细胞实验中检测了Pri对白细胞介素-1β诱导的炎症因子表达和细胞外基质（ECM）降解的影响。然后进行生物信息学分析，以研究参与Pri保护作用的潜在信号通路。最后，在内侧半月板不稳定（DMM）小鼠模型中进一步评估Pri减少软骨降解的功效。
利用生物信息学分析和体外研究发现，Pri抑制NF-κB和MAPK信号通路的激活，导致白细胞介素-1β刺激引起的基质金属蛋白酶-13（MMP-13）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）上调的逆转，以及Ⅱ型胶原蛋白水平的部分恢复。此外，在DMM小鼠模型中，与建模组相比，接受Pri治疗的组软骨降解减少，OA进展减缓。
本研究强调Pri作为一种潜在的治疗药物，可延缓OA进展。
