RL-QN15 accelerates vaginal mucosal repair by regulating inflammatory, autophagic, and apoptotic responses

Background Vaginal mucosal injury, caused by infection, trauma, or estrogen deficiency, poses a significant clinical challenge with limited effective therapies. Autophagy and apoptosis are critical regulators of mucosal repair, yet their modulation by therapeutic peptides remains poorly understood. Objective This study aimed to investigate whether the amphibian-derived peptide RL-QN15 promotes vaginal mucosal repair and to elucidate its underlying mechanisms. Methods The therapeutic efficacy and mechanisms of RL-QN15 were investigated in both in vitro and in vivo models of LPS-induced inflammatory injury. In vitro, RL-QN15 treatment was evaluated for its effects on rat vaginal epithelial cell proliferation (CCK-8 and EdU assays), IL-6 secretion (ELISA), apoptosis (TUNEL and Annexin V-FITC/PI flow cytometry), and expression of autophagy/apoptosis markers (LC3-II/I, Beclin1, p62, Bax, Bcl-2, and cleaved caspase-3) by Western blot. Therapeutic outcomes of RL-AN15 against LPS-injured rat vaginal mucosa were evaluated by mucosal thickness and IL-6 levels, and the autophagy and apoptosis pathway key markers were analyzed via Western blot to confirm RL-QN15-mediated regulation at the tissue level. Results RL-QN15 significantly reversed LPS-induced suppression of proliferation and autophagy, while inhibiting apoptosis and IL-6 expression in vitro . In vivo , RL-QN15 reduced mucosal thickness, enhanced epithelial integrity, and suppressed IL-6, outperforming erythromycin ointment via direct statistical comparison. Mechanistically, RL-QN15 restored autophagic flux (LC3-II/I, Beclin1, p62) and rebalanced apoptosis (Bax/Bcl-2, caspase-3) in both cellular and tissue models. Conclusions RL-QN15 promotes vaginal mucosal regeneration by modulating autophagy, apoptosis and alleviating inflammation, positioning it as a promising multitarget peptide therapeutic for mucosal injury.