Abstract Context: Oridonin exhibits various pharmacological and physiological activities, including antioxidant, antibacterial, anti-inflammatory, pro-apoptotic, anticancer and neurological effects. However, its role in rheumatoid arthritis (RA) is yet to be revealed. Objective: We evaluated the effects of oridonin on the survival and autophagy of RA-fibroblast-like synoviocytes (FLSs). Materials and methods: RA-FLSs were treated with oridonin at serial concentrations of 0, 2, 4, 6, 8 and 10 µg/mL for 24, 48 and 72 h. Then, cell proliferation and apoptosis were measured. A GFP-LC3 plasmid was transfected into the cells to determine autophagy. Results: Oridonin suppressed RA-FLS proliferation in a dose-dependent manner. The half maximal inhibitory concentrations (IC50) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 µg/mL, respectively. Treatment with oridonin for 24 h increased apoptosis by 4.1%, and increased the protein levels of Bax and cleaved caspase-3 but significantly decreased the levels of IL-1β in the culture supernatant (p < 0.05). In addition, 6 h of oridonin treatment significantly decreased the number of GFP-LC3 punctate dots and inhibited the protein levels of ATG5 and Beclin1 by 80.01% and 42.12%, respectively. Chloroquine (CQ) significantly reinforced the effects of oridonin on inhibition of autophagy, suppression of proliferation, and induction of apoptosis in RA-FLSs (p < 0.05). Conclusions: Our results indicate that treatment with oridonin in combination with CQ inhibits autophagy and cell proliferation and induces apoptosis in RA-FLSs more effectively than treatment oridonin alone. This finding indicates that oridonin is a potential therapeutic agent for RA.

中文翻译：

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Oridonin抑制类风湿性关节炎成纤维细胞样滑膜细胞的自噬和存活

摘要背景：冬凌草素具有多种药理和生理活性，包括抗氧化、抗菌、抗炎、促凋亡、抗癌和神经系统作用。然而，其在类风湿性关节炎 (RA) 中的作用尚待揭示。目的：我们评估了冬凌草素对 RA 成纤维细胞样滑膜细胞 (FLS) 存活和自噬的影响。材料和方法：RA-FLSs 用冬凌草素以 0、2、4、6、8 和 10 µg/mL 的系列浓度处理 24、48 和 72 小时。然后，测量细胞增殖和凋亡。将 GFP-LC3 质粒转染到细胞中以确定自噬。结果：冬凌草素以剂量依赖性方式抑制 RA-FLS 增殖。冬虫夏草素在 24、48 和 72 小时的半数最大抑制浓度 (IC50) 分别为 8.28、7.88 和 8.35 µg/mL。冬虫夏草素处理 24 小时后，细胞凋亡增加了 4.1%，并增加了 Bax 和裂解的 caspase-3 的蛋白质水平，但显着降低了培养物上清液中的 IL-1β 水平（p < 0.05）。此外，冬凌草素处理6小时显着减少了GFP-LC3点状点的数量，并分别抑制了ATG5和Beclin1的蛋白质水平80.01%和42.12%。氯喹 (CQ) 显着增强了冬凌草素对 RA-FLS 中自噬抑制、增殖抑制和细胞凋亡诱导的作用（p < 0.05）。结论：我们的结果表明，冬凌草甲苷联合 CQ 治疗比单独治疗冬凌草甲苷更有效地抑制自噬和细胞增殖并诱导 RA-FLS 的细胞凋亡。