Wound Healing and Antioxidant Capabilities of Zizyphus mauritiana Fruits: In-Vitro, In-Vivo, and Molecular Modeling Study

Abstract

LC-HRMS-assisted chemical profiling of Zizyphus mauritiana fruit extract (ZFE) led to the dereplication of 28 metabolites. Furthermore, wound healing activity of ZFE in 24 adult male New Zealand Dutch strain albino rabbits was investigated in-vivo supported by histopathological investigation. Additionally, the molecular mechanism was studied through different in-vitro investigations as well as, studying both relative gene expression and relative protein expression patterns. Moreover, the antioxidant activity of ZFE extract was examined using two in-vitro assays including hydrogen peroxide and superoxide radical scavenging activities that showed promising antioxidant potential. Topical application of the extract on excision wounds showed a significant increase in the wound healing rate (p < 0.001) in comparison to the untreated and MEBO®-treated groups, enhancing TGF-β1, VEGF, Type I collagen expression, and suppressing inflammatory markers (TNF-α and IL-1β). Moreover, an in silico molecular docking against TNFα, TGFBR1, and IL-1β showed that some of the molecules identified in ZFE can bind to the three wound-healing related protein actives sites. Additionally, PASS computational calculation of antioxidant activity revealed potential activity of three phenolic compounds (Pa score > 0.5). Consequently, ZFE may be a potential alternative medication helping wound healing owing to its antioxidant and anti-inflammatory activities.