Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China.
Sci Rep. 2019 Sep 25;9(1):13906. doi: 10.1038/s41598-019-50471-y.
Osteoarthritis (OA) is a degenerative disease of the cartilage that is prevalent in the middle-aged and elderly demography. Polydatin (PD), a natural resveratrol glucoside, has shown significant anti-inflammatory and anti-arthritic potential in previous studies. This study was designed to evaluate the therapeutic properties of PD in vitro and in vivo, and elucidate their underlying mechanisms. The expression levels of all relevant factors were evaluated by qRT-PCR, western blotting, and immunohistochemistry (IHC) where suitable. Reactive oxygen species (ROS) and apoptosis were analyzed using the suitable probes and flow cytometry. The histological evidence of cartilage was assessed in rat models, moreover, the several serum cytokines levels and autophagy levels were evaluated. The result showed PD displayed significant chondro-protective effects, inferred in terms of reduced inflammation and cartilage degradation, apoptosis inhibition, and lower ROS production. The protective effects were attenuated by the autophagy inhibitor 3-MA, indicating a mediating role of autophagy in PD action. Mechanistically, PD exerted its effects by inhibiting the MAPK and PI3K/Akt signaling pathways which led to the down-regulation of mTOR. In conclusion, PD protects against cartilage degeneration by activating the autophagy flux in the chondrocytes via the MAPK and PI3K/Akt signaling pathways.
骨关节炎（OA）是一种常见于中年和老年人群的软骨退行性疾病。虎杖苷（PD）是一种天然的白藜芦醇糖苷，在之前的研究中表现出显著的抗炎和抗关节炎潜力。本研究旨在评估 PD 的体内和体外治疗特性，并阐明其潜在机制。通过 qRT-PCR、western blot 和免疫组织化学（IHC）评估所有相关因素的表达水平。使用合适的探针和流式细胞术分析活性氧（ROS）和细胞凋亡。在大鼠模型中评估软骨的组织学证据，此外，还评估了几种血清细胞因子水平和自噬水平。结果表明 PD 显示出显著的软骨保护作用，表现在炎症和软骨降解减少、抑制细胞凋亡和降低 ROS 产生。自噬抑制剂 3-MA 减弱了保护作用，表明自噬在 PD 作用中起介导作用。机制上，PD 通过抑制 MAPK 和 PI3K/Akt 信号通路发挥作用，导致 mTOR 下调。总之，PD 通过激活软骨细胞中的自噬流来防止软骨退化，这是通过 MAPK 和 PI3K/Akt 信号通路实现的。
