Therapeutic efficacy of Agathosma betulina (P.J.Bergius) Pillans and Lessertia frutescens (L.) Goldblatt & J.C.Manning in promoting wound healing

Abstract

In developing regions such as Africa, chronic wounds represent a major healthcare challenge. Effective wound management has proven to be particularly difficult for immunocompromised patients in resource-limited areas. Although over 250 South African plant species have been identified for dermatological use, many plants, including Agathosma betulina and Lessertia frutescens, lack comprehensive scientific validation for their wound-healing potential. This study investigated the wound-healing ability, antioxidant capacity and immunomodulatory effects of A. betulina and L. frutescens extracts using an in vitro skin cell-culture model. Cell viability and migration were assessed using the MTT and scratch wound assays, respectively. Antioxidant capacity and intracellular reactive oxygen species (ROS) levels were analysed, while genetic expression of key angiogenic and inflammatory markers were quantified using qRT-PCR. Compared to L. frutescens, A. betulina demonstrated greater antioxidant capacity, significantly reducing intracellular ROS (p < 0.05), and showed higher radical scavenging activity across all biochemical assays. Both A. betulina and L. frutescens enhanced tissue repair, achieving 54% and 56% gap closure, respectively. This regenerative effect corresponds with the up-regulation of VEGF, HIF-1α, iNOS and COX-2, suggesting activation of pro-angiogenesis and inflammatory responses. Collectively, the results suggest that these extracts contribute to wound-healing by modulating distinct, complementary mechanistic pathways, primarily through oxidative stress reduction and stimulation of cell migration and angiogenesis. The findings provide important baseline data supporting the traditional use of these species in South African ethnomedicine.