3,4-Dihydroxybenzoic acid methyl ester from Vespa velutina auraria Smith against rheumatoid arthritis via modulating the apoptosis and inflammation through NF-κB pathway.

In Yunnan, Vespa velutina auraria Smith is used in production of wasp wine, which is employed for treating rheumatoid arthritis (RA). From compounds extracted from Vespa velutina auraria Smith, 3,4-dihydroxybenzoic acid methyl ester (DBME) showed the most effective anti-inflammatory response in RAW264.7 cells according to our prior investigation. This research was designed to investigate how DBME affects RA. RA rat model and inflammatory model of MH7A cell were employed to determine the effects of DBME on RA. DBME was able to reduce paw swelling, bone damage, and changes in histopathological sections in CIA rats in vivo. Furthermore, DBME lowered the levels of tumor necrosis factor-α (TNF-α), immunoglobulin G (IgG), C-C motif chemokine ligand 5 (CCL5), prostaglandin E2 (PGE-2), interleukin-17 (IL-17), and IL-1β, while enhancing the rate of apoptosis in synovial tissue cells of RA rats. Experiments conducted in vitro demonstrated that DBME decreased the concentrations of matrix metalloproteinase 3 (MMP3), IL-1β, CCL5 and IL-6, and promoted the apoptosis in TNF-α-stimulated MH7A cells. Moreover, DBME decreased the ratios of p-P65 to P65 and phosphorylated inhibitor kappa B α (p-IκBα) to IκBα in TNF-α-stimulated MH7A cells. This indicated that DBME may have anti-inflammatory and pro-apoptotic effects in RA via NF-κB pathway.