Glaucocalyxin A inhibits hydrogen peroxide‐induced oxidative stress and inflammatory response in coronary artery smooth muscle cells

Abstract

Atherosclerosis is a complex chronic inflammatory disease that remains one of the leading causes of death and disability worldwide. A previous study reported that glaucocalyxin A (GLA), a natural ent‐Kaurane diterpenoid triptolide, exhibits anti‐atherosclerotic activity. However, the underlying molecular mechanism has not yet been explored. In the present study, we evaluated the anti‐atherosclerotic effect of GLA and the underlying mechanism in vitro. Human coronary artery smooth muscle cells (HCASMCs) were stimulated by hydrogen peroxide (H₂O₂) to induce oxidative stress and inflammation. The results showed that GLA pretreatment improved the viability of H₂O₂‐induced HCASMCs. The increased reactive oxygen species production and decreased superoxide dismutase and glutathione peroxidase activities in H₂O₂‐induced HCASMCs were reversed by GLA pretreatment. In addition, GLA treatment suppressed the H₂O₂‐induced expression of inducible nitric oxide synthase, NADPH oxidase (NOX) 2, and NOX4 in HCASMCs. Moreover, treatment with GLA reduced the production of several inflammatory cytokines, including tumour necrosis factor‐alpha, interleukin (IL)‐6, and IL‐1β in H₂O₂‐induced HCASMCs. Furthermore, GLA treatment suppressed the phosphorylation of p38, as well as inactivating the NF‐κB signalling pathway. These findings suggested that GLA protected against H₂O₂‐induced oxidative stress and inflammation via inhibition of p38 phosphorylation and NF‐κB activation in HCASMCs.