Shen Yue, Teng Li, Qu Yuhan, Huang Yuehui, Peng Yi, Tang Min, Fu Qiang
Key Laboratory of Drug-Targeting and Drug Delivery System of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, China.
School of Food and Biological Engineering, Chengdu University, Chengdu, 610106, China.
Inflammation. 2023 Apr;46(2):655-678. doi: 10.1007/s10753-022-01763-5. Epub 2022 Nov 8.
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-α, IL-6, iNOS, COX-2, NO, and PGE. Besides, HE markedly reduced IL-1β-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.
骨关节炎（OA）是一种常见的退行性关节疾病，其特征在于关节软骨的渐进性退化和炎症。常春藤皂苷元（HE）是从许多草本植物中提取的五环三萜皂苷。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的影响尚未得到研究。我们的研究发现，HE可能是一种潜在的抗OA药物。在体外，HE可通过上调聚集蛋白聚糖和胶原蛋白II水平以及下调基质金属蛋白酶（MMPs）和含血小板反应蛋白基序的解聚蛋白样金属蛋白酶5（ADAMTS5）水平来抑制细胞外基质（ECM）降解。它还可以减少促炎和炎性细胞因子或酶的产生，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、一氧化氮（NO）和前列腺素E（PGE）。此外，HE显著降低白细胞介素-1β（IL-1β）诱导的C28/I2细胞凋亡和活性氧（ROS）积累。机制上，HE通过部分抑制Janus激酶2（JAK2）/信号转导和转录激活因子3（STAT3）/丝裂原活化蛋白激酶（MAPK）信号通路以及这两条通路的相互作用发挥软骨保护和抗炎作用。此外，HE通过靶向 Kelch样环氧氯丙烷相关蛋白1（Keap1）-核因子E2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）/ROS/凋亡相关蛋白Bax/凋亡抑制蛋白Bcl-2轴表现出抗凋亡和抗氧化作用。在体内，HE显著降低碘乙酸钠（MIA）诱导的大鼠软骨破坏，其骨关节炎研究学会国际工作组（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是一种开发治疗OA药物的潜在化合物。
