Comparative Dermatological Bioactivities of Chlorophylized and Dechlorophylized Centella asiatica Extracts

Centella asiatica (L.) Urb. (Apiaceae) is widely incorporated into dermatological and wound-healing formulations, where dechlorophylization is commonly used to improve extract stability, although its biological consequences are not fully understood. In this study, an ethanolic extract of C. asiatica leaves (CAE) was compared with a dechlorophylized C. asiatica extract (DCAE) in terms of cytotoxicity, wound-healing, anti-inflammatory, and antimicrobial activities, complemented by network pharmacology analysis. DCAE exhibited improved cytocompatibility, remaining non-cytotoxic up to 100 µg/mL, whereas CAE showed cytotoxic effects above 25 µg/mL. In contrast, CAE demonstrated superior wound-healing performance, reducing the residual wound area to 21.77% compared with 36.81% for DCAE and inducing higher Ki67 expression (1.94-fold versus 1.58-fold). These findings suggest that chlorophyll-associated constituents may contribute to keratinocyte proliferation and re-epithelialization. Although DCAE was enriched in pentacyclic triterpenes, including asiatic acid, asiaticoside, madecassic acid, and madecassoside, it showed stronger anti-inflammatory effects by more effectively suppressing CXCL10, IL-6, TNF-α, and IL-8 expression. Both extracts displayed weak antibacterial activity but moderate antifungal effects against Candida albicans, likely mediated through membrane disruption. Network pharmacology further indicated that wound-healing activity is associated with the regulation of COL1A1 and VEGFA through quercetin, kaempferol, and asiatic acid by way of the PI3K-Akt and MAPK signaling pathways, whereas anti-inflammatory effects involve modulation of PTGS2 and TNF through the NF-κB and IL-17 pathways. Overall, DCAE enhances cytocompatibility and anti-inflammatory activity, while CAE retains stronger regenerative capacity. These findings support the rational design of tailored formulations for specific dermatological applications, such as promoting wound repair or alleviating chronic skin inflammation.