Exploring the impact of Rubus ulmifolius leaf cream on wound healing in an in vivo model: VEGF, PDGF, and cytokine dynamics.

Abstract

Rubus ulmifolius (RUI) Schott, commonly known as wild blackberry, is a perennial plant recognized for its traditional medicinal uses and diverse biological activities. This study aimed to evaluate the wound-healing efficacy of a topical cream formulated with RUI leaf extract. Thirty Wistar rats were used to assess wound contraction over 14 days. The investigation focused on wound closure progression, cytokine profiling, and histopathological evaluation. A recent LC-MS/MS analysis of the RUI leaf extract identified 49 metabolites, including flavonoids, tannins, saponins, phenolic acids, and sugars, using GNPS molecular networking and fragmentation pattern comparison. The extract's richness in saponins and polyphenols is associated with enhanced tissue regeneration, reduced cell damage, and modulation of the inflammatory response. The topical application of RUI extract cream resulted in dose-dependent improvements in wound appearance and closure rate. Biochemical analysis revealed significant downregulation of pro-inflammatory markers (interleukin-1β and matrix metalloproteinase-9) and upregulation of anti-inflammatory and regenerative markers (IL-10, VEGF, PDGF, and RUNX2). Histopathological examination further supported these findings, showing enhanced granulation tissue formation and re-epithelialization. These results suggest that R. ulmifolius leaf extract cream holds significant promise as a therapeutic agent for promoting effective wound healing.