Hederagenin Suppresses Inflammation and Cartilage Degradation to Ameliorate the Progression of Osteoarthritis: An In vivo and In vitro Study
Hederagenin Suppresses Inflammation and Cartilage Degradation to Ameliorate the Progression of Osteoarthritis: An In vivo and In vitro Study
复制标题
常春藤素抑制炎症和软骨降解以改善骨关节炎的进展：一项体内和体外研究
DOI：
10.1007/s10753-022-01763-5
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发表时间：
2022-11-08
期刊：
影响因子：
5.1
通讯作者：
Fu, Qiang
中科院分区：
文献类型：
--
作者：
Shen, Yue;Teng, Li;Fu, Qiang
骨关节炎（Osteoarthritis，OA）是一种常见的退行性关节疾病，以关节软骨的进行性退化和炎症为特征。常春藤皂苷元（HE）是从多种草本植物中提取的一种五环三萜皂苷。它具有抗炎、抗脂质过氧化、抗癌和神经保护活性。然而，其对OA的影响尚未研究。我们的研究发现，HE可能是一种潜在的抗OA药物。在体外实验中，HE可通过上调聚集蛋白聚糖和II型胶原水平，下调基质金属蛋白酶和ADAMTS 5水平，抑制细胞外基质（ECM）降解。它还可以减少促炎和炎性细胞因子或酶的产生，包括TNF-α、IL-6、iNOS、考克斯-2、NO和PGE（2）。此外，HE还能显著降低IL-1 β诱导的C28/I2细胞凋亡和ROS的积累。其机制可能与抑制JAK 2/STAT 3/MAPK信号通路及其相互作用有关。HE通过靶向Keap 1-Nrf 2/HO-1/ROS/Bax/Bcl-2轴发挥抗凋亡和抗氧化作用。在体内，HE显著降低了碘乙酸（MIA）诱导的大鼠软骨破坏，OARSI评分和炎性细胞因子水平较低，进一步证明了其在OA进展中的保护作用。这些结果表明，HE是一种潜在的化合物，用于开发治疗OA的药物。
Osteoarthritis (OA), a common degenerative joint disease, is characterized by the progressive degradation of articular cartilage and inflammation. Hederagenin (HE) is a pentacyclic triterpenoid saponin extracted from many herb plants. It has anti-inflammatory, anti-lipid peroxidative, anti-cancer, and neuroprotective activities. However, its effect on OA has not been investigated. Our study found that HE may be a potential anti-OA drug. In vitro, HE could suppress extracellular matrix (ECM) degradation via up-regulating aggrecan and Collagen II levels as well as downregulating MMPs and ADAMTS5 levels. It could also reduce proinflammatory and inflammatory cytokines or enzymes production, including TNF-alpha, IL-6, iNOS, COX-2, NO, and PGE(2). Besides, HE markedly reduced IL-1 beta-induced C28/I2 cell apoptosis and ROS accumulation. Mechanistically, HE exerted chondroprotective and anti-inflammatory effects by partly inhibiting JAK2/STAT3/MAPK signalling pathway and the crosstalk of the two pathways. Also, HE exhibited anti-apoptotic and anti-oxidative effect via targeting Keap1-Nrf2/HO-1/ROS/Bax/Bcl-2 axis. In vivo, HE significantly reduced monosodium iodoacetate (MIA) induced cartilage destruction of rats with a lower OARSI score and inflammatory cytokine levels, further demonstrating its protective effects in OA progression. These results suggest that HE is a potential compound for the development of drugs to treat OA.