Zeinoside B, a pregnane glycoside from Caralluma adenensis (Defler) A. Berger, accelerates excisional wound healing in mice through antioxidant and reparative mechanisms.

2026-06
Journal of ethnopharmacology 364
- Ola E Abdel-Sattar
- Riham A El-Shiekh
- Manal M Sabry
- Ali M El-Halawany
- Othman S S Al-Hawshabi
- Abeer Salama
- Essam Abdel-Sattar
- Meselhy R Meselhy

PubMed: 41831744
DOI: 10.1016/j.jep.2026.121503

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 24
Population: 24 male Swiss mice
Methods: Randomized into four groups (normal skin, untreated wound, Mebo®-treated, 1.0% ZB-treated), treated once daily for 10 days following standardized full-thickness dorsal skin excision
Duration: 10 days
Funding: Unclear

Animal Study

Ethnopharmacological relevance

Wound healing is a complex and coordinated process that includes phases of hemostasis, inflammation, proliferation, and remodeling. Caralluma adenensis (Defler) A.Berger is ethnomedicinal plant traditionally used in Yemen for Anti-diabetic, anti-ulcer, anti-inflammatory, anti-parasitic, and anti-pyretic agents. This plant is rich in pregnane glycosides. Zeinoside B (ZB), a newly isolated pregnane glycoside with benzoyl esters at C-15/C-20 and a trisaccharide chain at C-3, was evaluated for its wound-healing potential.

Aim of the study

This study aimed to evaluate the in vivo wound-healing efficacy and mechanism pathway of topically applied ZB in a full-thickness excisional wound model, with particular emphasis on oxidative stress and FOXO1/MIP-2-related pathways.

Methods

Male Swiss mice (n = 24) were randomized into four groups: normal skin, untreated wound, Mebo®-treated, and 1.0% ZB-treated, and were treated once daily for 10 days following standardized full-thickness dorsal skin excision. Areas of wound contraction were monitored on days 0, 3, 7, and 10. On day 10, skin homogenates were assayed for malondialdehyde (MDA), reduced glutathione (GSH), macrophage inflammatory protein-2 (MIP-2), collagen type I, and forkhead box protein O1 (FOXO1) via ELISA and colorimetric kits. Histopathological evaluation (H&E) was recoded for re-epithelialization, granulation tissue, collagen deposition, and inflammatory infiltrate.

Results

ZB accelerated wound healing by approximately five times compared to the untreated wound and by 70% higher compared to Mebo® (P < 0.05). Biochemically, ZB reduced MDA levels by 68%, increased GSH by 194%, and elevated FOXO1 by 380% compared to untreated wound, surpassing Mebo® in all oxidative markers. The pro-regenerative effects included a 14-fold increase in MIP-2 and a 228% rise in collagen type I, promoting inflammatory resolution and extracellular matrix remodeling. Histological analysis showed nearly complete re-epithelialization, dense granulation tissue, and minimal inflammatory infiltrate in wounds treated with ZB.

Conclusion

ZB enhanced wound healing in association with oxidative stress (↓MDA, ↑GSH/FOXO1) and modulation repair-related pathways (↑MIP-2/collagen type I). Demonstrating superiority over Mebo®, ZB supports the ethnopharmacological reputation of C. adenensis (Defler) A.Berger and presents itself as a promising, nature-derived topical treatment for wound care in both veterinary and human applications.