This study investigates the effect of Pedunculoside (PE) on ulcer recovery using a murine oral ulcer model and in vitro assays with primary oral mucosal fibroblasts.

In vivo, PE treatment significantly accelerated ulcer healing in mice, achieving a 7-day cure rate of 85.7%, which is notably higher than control groups. In vitro, PE promoted fibroblast proliferation and markedly enhanced collagen secretion—both key processes in wound healing. Gene and protein expression analyses revealed that PE significantly upregulated Smad3, Col1a1, and Col3a1, indicating a stimulation of the collagen synthesis pathway. Importantly, PE reversed the inhibitory effects of WP1066 (a STAT3 inhibitor) on STAT3 activation, suggesting that PE exerts its healing effects through STAT3 and Smad3 signaling axes.

While PE did not affect fibroblast migration, its potent effect on proliferation and collagen production positions it as a compelling candidate for oral ulcer therapy. These findings provide a pharmacological foundation for the development of PE as a natural and effective agent for treating oral mucosal injuries. Moreover, this study sheds light on the molecular mechanisms of wound healing, emphasizing the relevance of STAT3 and Smad3 signaling in the regenerative process.

Given its anti-inflammatory and pro-healing properties, PE may offer a safe, low-cost alternative or complementary therapy for oral ulcers, particularly in populations seeking herbal or traditional treatments.