Evaluation of Desmidorchis adenensis for wound-healing: Targeting inflammation, redox balance, and FOXO1/MIP-2 signaling in a murine model.

Yemen has long employed the ethnomedical plant Desmidorchis adenensis (Deflers) Meve & Liede (syn. Caralluma. adenensis (Deflers) A.Berger) for its anti-diabetic, anti-ulcer, anti-inflammatory, anti-parasitic, and anti-pyretic properties. Its aerial parts are rich in pregnane glycosides. The purpose of this study was to assess the wound-healing potential of the total methanolic extract (DAd-TM) and mother liquor fraction (DAd-MR) from D. adenensis (Deflers) Meve & Liede in vitro and in a murine full-thickness excision wound model, focusing on oxidative stress, inflammation, and FOXO1/MIP-2 signaling pathway. In vitro, DAd-MR showed the lowest cytotoxicity (IC50 = 232.63 ± 7.88 μg/mL) and the highest wound closure rate (85.19 ± 2.82%) in the scratch assay. In vivo, topical application of 5% DAd-TM and 5% DAd-MR for 10 days in male Swiss mice significantly accelerated wound closure to 91% and 97% (P < 0.05), and compared to Mebo® (a commercial reference β-sitosterol-based preparation) by 41% and 52% (P < 0.05). Both fractions markedly reduced malondialdehyde (MDA) levels while increasing glutathione (GSH), collagen type I, MIP-2 (a key chemokine involved in inflammatory cell recruitment), and FOXO1 (a transcription factor that regulates oxidative stress response and keratinocyte migration/re-epithelialization). Histopathological examination with semi-quantitative scoring confirmed enhanced re-epithelialization, collagen deposition, and reduced inflammation, particularly with 5% DAd-MR. The study provides the first comprehensive scientific evidence that total extract, more effectively, mother liquor of D. adenensis has skin healing potential via antioxidant, anti-inflammatory, and pro-regenerative mechanisms involving FOXO1 and MIP-2 pathways, as well as stimulating skin extracellular matrix components synthesis and reepithelialization. These findings were confirmed by histological testing. The latter was specifically investigated to enrich polar pregnane glycosides while reducing cytotoxicity associated with non-polar constituents. These findings provide scientific validation for its traditional use and highlight DAd-MR as a promising natural wound-healing agent.