Clinacanthus nutans (Burm.f.) Lindau is a Southeast Asian medicinal plant traditionally used for treating skin inflammation and infections. This study evaluated its wound-healing potential through anti-inflammatory, cytoprotective, and antiviral mechanisms. HPLC-DAD analysis identified schaftoside as the major flavonoid in the 95% ethanolic leaf extract. In the lipopolysaccharide (LPS)-stimulated murine macrophage cell line (RAW 264.7), both C. nutans extract (5 and 50 μg/mL) and its flavonoid schaftoside (5 and 20 μg/mL) significantly downregulated the expression of pro-inflammatory genes, including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E₂ (PGE₂), under both pre-treatment and post-treatment conditions. ELISA confirmed dose-dependent inhibition of human COX-2 enzymatic activity, reaching up to 99.3% with the extract and 86.9% with schaftoside. In the endothelial cell models (CCL-209), the extract exhibited low cytotoxicity and effectively protected cells from LPS-induced apoptosis, preserving vascular integrity critical to tissue regeneration. Antiviral assays demonstrated suppression of HSV-2 replication, particularly during early infection, which may help prevent infection-related delays in wound healing. Collectively, these findings suggest that C. nutans and schaftoside promote wound repair by attenuating inflammatory responses, supporting endothelial survival, and controlling viral reactivation. These multifunctional properties highlight their potential as natural therapeutic agents for enhancing wound-healing outcomes.

Cutaneous wound healing requires coordinated keratinocyte migration, proliferation, and epithelial remodeling. Natural products, particularly pentacyclic triterpenoids, have emerged as promising agents for tissue repair. Holoptelea integrifolia (Roxb.) Planch., a medicinal plant distributed across South and Southeast Asia and traditionally used for skin disorders and wounds, contains the bioactive triterpenoids friedelin and lupeol. However, the signaling mechanisms underlying the wound-repair effects of its extracts and bioactive compounds remain incompletely understood. This study investigated the wound-repair potential of H. integrifolia bark and leaf extracts and their major triterpenoids, friedelin and lupeol, using in vitro models and molecular analyses. Scratch assays in canine primary epidermal keratinocytes (CPEK) and human keratinocytes (HaCaT) showed that both extracts and triterpenoids significantly enhanced keratinocyte migration and accelerated wound closure in a concentration-dependent manner. Western blotting revealed increased Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) levels, accompanied by reduced mammalian sterile 20-like kinase 1 (MST1) and E-cadherin expression, supporting modulation of Hippo signaling toward a pro-migratory phenotype. Molecular docking predicted favorable interactions of friedelin and lupeol with MST1 and YAP. Collectively, these findings indicate that H. integrifolia extracts and their triterpenoids promote keratinocyte-mediated wound repair through coordinated modulation of Hippo and MAPK signaling, supporting friedelin and lupeol as natural candidates for cutaneous wound healing and skin regeneration.