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

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 (H2 O2 ) to induce oxidative stress and inflammation. The results showed that GLA pretreatment improved the viability of H2 O2 -induced HCASMCs. The increased reactive oxygen species production and decreased superoxide dismutase and glutathione peroxidase activities in H2 O2 -induced HCASMCs were reversed by GLA pretreatment. In addition, GLA treatment suppressed the H2 O2 -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 H2 O2 -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 H2 O2 -induced oxidative stress and inflammation via inhibition of p38 phosphorylation and NF-κB activation in HCASMCs.