Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes

• Main Authors: Shou-Di He (Author), Sheng-Guang Huang (Author), Hui-Jun Zhu (Author), Xiao-Guang Luo (Author), Kang-Han Liao (Author), Jie-Yao Zhang (Author), Ning Tan (Author), De-Yu Li (Author)
• Format: Book
• Published: Taylor & Francis Group, 2020-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1388-0209; 1744-5116; 10.1080/13880209.2020.1711783
• Keywords: chloroquine oridonin; rheumatoid arthritis; autophagy; chloroquine; Therapeutics. Pharmacology; RM1-950
• Source: Pharmaceutical Biology, Vol 58, Iss 1, Pp 146-151 (2020)

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.