Kim Eun-Nam, Lee Hyun-Su, Jeong Gil-Saeng
College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Korea.
Antioxidants (Basel). 2020 Aug 25;9(9):788. doi: 10.3390/antiox9090788.
Osteoarthritis (OA) is a common joint degenerative disease induced by oxidative stress in chondrocytes. Although induced-heme oxygenase-1 (HO-1) has been found to protect cells against oxygen radical damage, little information is available regarding the use of bioactive compounds from natural sources for regulating the HO-1 pathway to treat OA. In this study, we explored the inhibitory effects of cudratricusxanthone O (CTO) isolated from the Bureau () on HO-induced damage of SW1353 chondrocytes via regulation of the HO-1 pathway. CTO promoted HO-1 expression by enhancing the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus without inducing toxicity. Pretreatment with CTO-regulated reactive oxygen species (ROS) production by inducing expression of antioxidant enzymes in HO-treated cells and maintained the functions of HO-damaged chondrocytes. Furthermore, CTO prevented HO-induced apoptosis by regulating the expression of anti-apoptotic proteins. Treatment with the HO-1 inhibitor tin-protoporphyrin IX revealed that these protective effects were exerted due to an increase in HO-1 expression induced by CTO. In conclusion, CTO protects chondrocytes from HO-induced damages-including ROS accumulation, dysfunction, and apoptosis through activation of the Nrf2/HO-1 signaling pathway in chondrocytes and, therefore, is a potential therapeutic agent for OA treatment.
骨关节炎（OA）是一种由软骨细胞氧化应激诱导的常见关节退行性疾病。尽管已发现诱导型血红素加氧酶-1（HO-1）可保护细胞免受氧自由基损伤，但关于利用天然来源的生物活性化合物调节HO-1途径治疗OA的信息却很少。在本研究中，我们探讨了从光叶楮中分离得到的光叶楮酮O（CTO）通过调节HO-1途径对HO诱导的SW1353软骨细胞损伤的抑制作用。CTO通过增强核因子红细胞2相关因子2（Nrf2）向细胞核的转位来促进HO-1表达，且不诱导毒性。CTO预处理通过诱导HO处理细胞中抗氧化酶的表达来调节活性氧（ROS）的产生，并维持HO损伤软骨细胞的功能。此外，CTO通过调节抗凋亡蛋白的表达来阻止HO诱导的细胞凋亡。用HO-1抑制剂锡原卟啉IX处理表明，这些保护作用是由于CTO诱导HO-1表达增加所致。总之，CTO通过激活软骨细胞中的Nrf2/HO-1信号通路保护软骨细胞免受HO诱导的损伤，包括ROS积累、功能障碍和细胞凋亡，因此是一种潜在的OA治疗药物。
