Protective effect of wogonin on inflammatory responses in BisGMA‐treated macrophages through the inhibition of MAPK and NFκB pathways

Composites, resins, and sealants that are commonly used in orthopedics and dentistry are based on 2,2‐bis[p‐(2′‐hydroxy‐3′‐methacryloxypropoxy)phenylene]propane (BisGMA), which induces proinflammatory responses in macrophages. The present study aimed to explore the anti‐inflammatory responses of wogonin, which is a natural dihydroxyl flavonoid compound, in BisGMA‐treated macrophages. According to the findings, wogonin exhibits anti‐inflammatory, antiallergic, anticancer, and antioxidative properties. The generation of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) were noted to be inhibited by wogonin in BisGMA‐treated macrophages. Furthermore, the production of proinflammatory cytokines including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐6 was reduced. In addition, BisGMA‐induced nuclear factor (NF)‐κB p65 phosphorylation and inhibitor of κB (IκB) degradation were inhibited. Finally, the BisGMA‐induced phosphorylation of mitogen‐activated protein kinases (MAPKs), including p38 MAPK, extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) was inhibited. All these effects were induced by wogonin in the macrophages in a concentration‐dependent manner. Similar inhibitory effects of wogonin were observed on the production of NO and proinflammatory cytokines, expression of iNOS, phosphorylation of NF‐κB p65 and MAPK, and degradation of IκB. These results indicated that rutin is a potential anti‐inflammatory agent for BisGMA‐treated macrophages that undergo NFκB p65 phosphorylation and IκB degradation through upstream MAPK phosphorylation. Therefore, wogonin inhibits BisGMA‐induced proinflammatory responses in macrophages through the regulation of the NFκB pathway and its upstream factor, MAPK.