Centella asiatica Extract Powder Protects Against Paw Edema by Modulating Oxidative Stress, Inflammatory Responses,...

Edema is characterized by abnormal fluid accumulation in tissues, leading to visible swelling. The pathogenesis of edema is multifactorial, including vascular dysfunction, inflammation, and impaired fluid homeostasis. This study investigated the antiedematous effects of the natural product Centelline^TM (Centella asiatica extract powder). Centelline exhibited significant antioxidant activity, as demonstrated by its enhanced radical scavenging capacity in the 2,2-diphenyl-1-picrylhydrazyl assay. It preserved the viability of human umbilical vein endothelial cells (HUVECs) under conditions of H₂O₂-induced oxidative stress. Centelline markedly reduced the production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in lipopolysaccharide-stimulated RAW264.7 macrophages. It significantly reversed the H₂O₂-induced upregulation of endothelial adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) and the reduction of nitric oxide (NO) production in HUVECs. Centelline effectively suppressed H₂O₂-induced vascular hyperpermeability in vitro while upregulating the expression of VE-cadherin. Furthermore, Centelline significantly attenuated acetic acid-induced vascular permeability in an in vivo model and inhibited carrageenan-induced paw edema in rats in a dose-dependent manner. Centelline suppressed the expression of inducible NO synthase and cyclooxygenase-2, as well as inflammatory cell infiltration at the inflammatory site in carrageenan-induced paw tissues. Taken together, these findings demonstrate the potent antiedematous effects of Centelline, mediated by the inhibition of oxidative stress and inflammatory responses and the reinforcement of the endothelial barrier. Centelline can be further developed as a natural therapeutic candidate for preventing and managing edema.