Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Oxid Med Cell Longev. 2022 Jun 8;2022:6821170. doi: 10.1155/2022/6821170. eCollection 2022.
Chondrocytes play an essential role in maintaining the structure and function of articular cartilage. Oxidative stress occurred in chondrocytes accelerates cell senescence and death, which contributes to the development of osteoarthritis (OA). Patchouli alcohol (PA), a kind of sesquiterpene in , processes multiple bioactivities in treatment of many diseases. However, its effects of antisenescence and antioxidation on chondrocytes in a D-gal-induced aging mice model are still obscure. In this study, we found that PA treatment could ameliorate the degradation of cartilage extracellular matrix (ECM) in a D-gal-induced aging mice model. Further analyses through the immunofluorescent staining and western blot revealed that PA inhibited D-gal-induced chondrocyte senescence via the activation of antioxidative system. Besides, the damage caused by D-gal could not be recovered with PA treatment in Nrf2-silencing chondrocytes. In addition, molecular docking analysis between PA and Keap1 further suggested that the mechanism of PA's antisenescence and antioxidation was attributed to the activation of Nrf2/HO-1 pathway. Therefore, our results demonstrated that PA was a promising candidate for preventing the quality loss of aging cartilage through inhibiting oxidative stress-mediated senescence in chondrocytes.
软骨细胞在维持关节软骨的结构和功能方面起着至关重要的作用。软骨细胞中的氧化应激会加速细胞衰老和死亡，这有助于骨关节炎（OA）的发展。 广藿香醇（PA）是倍半萜中的一种，在治疗许多疾病方面具有多种生物活性。然而，其在 D-半乳糖诱导的衰老小鼠模型中对软骨细胞的抗衰老和抗氧化作用仍不清楚。在这项研究中，我们发现 PA 处理可改善 D-半乳糖诱导的衰老小鼠模型中软骨细胞外基质（ECM）的降解。通过免疫荧光染色和 Western blot 进一步分析表明，PA 通过激活抗氧化系统抑制 D-半乳糖诱导的软骨细胞衰老。此外，在 Nrf2 沉默的软骨细胞中，PA 处理不能恢复 D-半乳糖引起的损伤。此外，PA 与 Keap1 之间的分子对接分析进一步表明，PA 的抗衰老和抗氧化作用机制归因于 Nrf2/HO-1 通路的激活。因此，我们的研究结果表明，PA 是一种有前途的候选药物，可通过抑制氧化应激介导的软骨细胞衰老来防止衰老软骨的质量损失。
