Madecassoside Induces Apoptosis of Keloid Fibroblasts Via a Mitochondrial-Dependent Pathway

Centella asiatica herb is a frequently prescribed drug in southeastern Asia and China that can simultaneously facilitate wound healing and prevent scar formation. The active constituents and underlying mechanisms responsible for these biphasic actions remain unknown. Previous studies in our laboratory demonstrated that madecassoside, the main active triterpene saponin in C. asiatica herbs, was able to treat trauma-caused scars in rabbit ear and facilitate burn wound healing in mice. As the formation and progression of keloid scars is closely related to the excessive proliferation and insufficient apoptosis of dermal fibroblasts, the effects of madecassoside on the proliferation and apoptosis of keloid fibroblasts (KFs) were examined in the present study. Primary KFs, originating from human earlobe keloids, were purified and cultured, and then treated with increasing concentrations of madecassoside (10, 30, and 100 mu M) for 48 h. Madecassoside inhibited the proliferation of KFs in a time-and concentration-dependent manner, and induced KF apoptosis as revealed by Hoechst 33258 staining and flow cytometry analysis. Furthermore, madecassoside activated caspase-9 and caspase-3 rather than caspase-8, depolarized the mitochondrial membrane potential, and regulated expression of Bcl-2 family members in KFs. These findings suggest that madecassoside induced the apoptosis of KFs through a mitochondrial-dependent pathway. Drug Dev Res 72: 315-322, 2011. (C) 2010 Wiley-Liss, Inc.