Background:Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory,
analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an
inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss.
Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the
structure of the synovial intima, playing a crucial role in both the initiation and progression of RA.Objective:In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated
from patients with RA.Methods:Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry,
and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2)
were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β
levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed
GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin
1) to assess autophagy in RA-FLS.Results:Our results show that melittin can significantly impair viability, promote apoptosis and autophagy,
and inhibit IL-1β secretion in RA-FLS.Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.
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 mg/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 (IC 50) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 mg/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-1b 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.
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