Teng Li, Shen Yue, Qu Yuhan, Yang Longfei, Yang Yuting, Jian Xi, Fan Shengli, Zhang Lele, Fu Qiang
Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China; School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China.
Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China.
Chin J Nat Med. 2023 Feb;21(2):99-112. doi: 10.1016/S1875-5364(23)60388-7.
Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1β and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1β in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.
骨关节炎是一种全球流行的关节疾病，其特征为炎症反应和软骨降解。牛膝甾酮是一种从川牛膝根部提取的甾体化合物，对多种炎症相关疾病具有保护作用。然而，其对骨关节炎的作用尚不清楚。本研究旨在探究牛膝甾酮潜在的抗骨关节炎活性。分别采用从白细胞介素（IL）-1β诱导的大鼠分离出的原代软骨细胞和碘乙酸钠（MIA）刺激的大鼠模型进行体外和体内实验。体外实验结果表明，牛膝甾酮明显抑制软骨细胞凋亡，增加Ⅱ型胶原蛋白和聚集蛋白聚糖的表达，并抑制软骨细胞中由IL-1β诱导的炎症因子诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、含血小板反应蛋白基序的解聚素和金属蛋白酶-5（ADAMTS-5）、金属蛋白酶-3（MMP-3）以及金属蛋白酶-13（MMP-13）的产生。此外，牛膝甾酮可能通过调节核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路改善骨关节炎的炎症和退变进程。在体内实验中，以地塞米松作为阳性对照，牛膝甾酮显著减轻了碘乙酸钠诱导的大鼠炎症反应和软骨破坏。总体而言，本研究为将牛膝甾酮开发成缓解骨关节炎的有效药物奠定了理论基础。
