Standardized extract of Centella asiatica ECa 233 inhibits lipopolysaccharide-induced cytokine release in skin keratinocytes by suppressing ERK1/2 pathways

Objective: To evaluate the effect of standardized extract of Centella asiatica ECa 233 on inflammatory mediator production through cyclooxygenase-2 (COX-2), extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-kappa B (NF-kappa B) pathway in keratinocyte HaCaT cells. Methods: HaCaT cells were treated with 0.1, 1, 10 and 100 mu g/mL ECa 233 in the presence of lipopolysaccharide (LPS). Proinflammatory cytokines and prostaglandin E2 were assessed with ELISA. Western blotting was used to determine the inhibition of COX-2, ERK1/2 and NF-kappa B protein expression. Results: ECa 233 suppressed LPS-induced release of interleukin- 1 beta, tumor necrosis factor-alpha, and prostaglandin E2. ECa 233 also inhibitedCOX-2, phosphorylation of ERK1/2 and the activation of NF-kappa B. Moreover, the formation of reactive oxygen species (ROS) was decreased in response to LPS-inflamed keratinocytes. Conclusions: ECa 233 inhibits LPS-stimulated production of inflammatory mediators in keratinocytes via suppressing ERK1/2 andNF-kappa B pathways. The suppressive effect of ECa 233 may be related to an inhibition of ROS production.