Efficacy and mechanism of Schisandra chinensis active component Gomisin A on diabetic skin wound healing: network pharmacology and in vivo experimental validation

Ethnopharmacological relevance: Schisandra chinensis (Turcz.) Baill., a common traditional Chinese herbal medicine, has been used for the treatment of diabetes mellitus and its complications. However, the major active component for treating diabetic foot ulcers, a serious complication of diabetes mellitus, was unclear. This study aimed to predict the treatment effect of the active components in Schisandra chinensis against diabetic skin wound using network pharmacology and to confirm the underlying mechanism using a diabetic skin wound model in vivo. Aim of the study: To study the effects and underlying mechanisms of Schisandra chinensis and its main component Gomisin A on diabetic skin wound healing by network pharmacology and high-fat diet (HFD)-induced obese mice model in vivo. Materials and methods: To determine the effectiveness of Schisandra chinensis on diabetic skin wound, network pharmacology was first used. Components of Schisandra chinensis were obtained from the Traditional Chinese Medicine Systems Pharmacology database. The active components were further verified through absorption, distribution, metabolism and excretion. The potential targets of the active components were identified from the Traditional Chinese Medicine Systems Pharmacology, SwissTargetPrediction, TargetNet, and the Comparative Toxicogenomics Database. Targets related to diabetic skin wound were collected from the GeneCards, OMIM, DisGeNET, and PharmGKB databases. The interaction network formed by the intersection of the two datasets was analyzed using Gephi. Network-based proximity was used to predict the network distance between the active components of Schisandra chinensis and diabetic skin wound. Gomisin A was found to have the lowest Z-score and was administered either orally or via topical injection to HFD-induced obese mice daily until the wounds healed, and its effects on skin wound healing were evaluated. Results: Only five active ingredients of Schisandra chinensis were screened in our system: Gomisin A, Longikaurin A, Deoxyharringtonine, Wuweizisu C, and Interiotherin B, which can regulate biological processes related to diabetic skin wound, including positive regulation of phosphorous metabolic process, positive regulation of cell migration, and response to wounding. Network proximity analysis found that Gomisin A has the closest distance- based Z-score among the diabetic skin wound modules and drug targets in the human protein-protein interaction network. The HFD-induced obese mice model further revealed that Gomisin A accelerated skin wound healing by increasing insulin sensitivity and decreasing the advanced glycation end-products mediated toll-like receptor 4 (TLR4)-p38 MAPK-IL6 inflammation signaling pathway. Conclusions: The network pharmacology and in vivo studies indicated that Gomisin A from Schisandra chinensis played a crucial role in improving diabetic skin wound healing.