NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2024, Vol. 36 ›› Issue (11): 1959-1971. doi: 10.16333/j.1001-6880.2024.11.016 cstr: 32307.14.1001-6880.2024.11.016

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Network pharmacology analysis and experimental verification of hypaphorine for the treatment of wound healing

CAI Wei-wei,ZHANG Shi-jie,WEN Yuan-yuan,HOU Bao,SUN Hai-jian,QIU Li-ying*   

  1. Wuxi Medical College,Jiangnan University,Wuxi 214122,China
  • Online:2024-11-25 Published:2024-11-25

Abstract:

To explore the mechanism of the natural compound hypaphorine in promoting wound healing,network pharmacology and in vitro and in vivo experimental models was used.The target of hypaphorine was digged through the SwissTargetPrediction database and wound healing targets were obtained through the GeneCards database;Then,intersecting targets between drug targets and disease targets were screened through Venn online and protein interaction networks (PPI) were constructed through a String database and Cytoscape 3.7.1;Further,the Micro Bioinformatics Online Bioinformatics Platform and Metascape were utilized to conduct GO and KEGG enrichment analysis on the core targets;Finally,cellular inflammation and the mouse model of back injury in diabetes rats were established for in vitro and in vivo experimental verification.The results showed that there were 100 targets for the action of hypaphorine,6 612 targets for wound healing,60 common targets,and 5 core targets.The KEGG enrichment pathway mainly includes signaling pathways related to cancer pathogenesis,PPAR signaling pathway,chemical carcinogenesis reactive oxygen species,and so on.In vitro cell experiments have shown that HYP can inhibit the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3),interleukin-1 beta (IL-1β),tumour necrosis factor-α (TNF-α) and reactive oxygen species (ROS) to inhibit the inflammation process in RAW 264.7 cells and upregulate the expression of peroxisome proliferator-activated receptor γ (PPARγ) and phospho-Akt (p-Akt) to promotes fibroblast migration.Animal experiments showed that HYP could significantly promote the healing of chronic wounds in diabetes rats.The results of HE and Masson staining showed that HYP promoted the re-epithelization of wound sites in diabetes rats.Immunohistochemical and western blot results indicate that HYP inhibits the release of inflammatory factors in chronic wounds,accelerating the transition from the inflammatory phase to tissue regeneration phase.In summary,this study explores that HYP may regulate PPARγ pathway to inhibit the expression of NLRP3,IL-1β,TNF-α and iNOS,and promote the fibroblast proliferation,which play a role in promoting chronic wound healing.

Key words: chronic trauma, diabetes, hypaphorine, network pharmacology, experimental verification

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