A network pharmacology approach to explore mechanisms of bombyx batryticatus in keloid treatments

Background: Skin injuries and irritants, including wounds, insect bites, etc., may cause keloids and hypertrophic scars. However, identifying potential keloid treatment drugs remains an important task. Objective: To reveal the mechanism of bombyx batryticatus (BB) in the treatment of keloid. Methods: By using network pharmacology, this study investigated the molecular targets, metabolites, and KEGG signaling pathways of BB in keloid treatment. Furthermore, drug intervention was divided into different groups (control group: Different concentrations of BB groups: Beauvericin group; And P13K/Akt inhibitor LY294002). The expression levels of MMP-1, MMP-9, Akt, P-Akt, beta-Actin, PI3K p85 alpha, p38 MAPK, GAPDH, and NF-xB in human hypertrophic scar fibroblasts (hHSFs) were evaluated respectively by western blotting. In addition, three main chemical constituents [Beauvericin, Cyclo (D)-Pro-(D) -Phe and (+)-Pinoresinol] and four key keloid intervention targets (MMP1, MMP9, MMP13, and P13k) were used to explore further their interactions in molecular docking procedures Results: 73 drug-disease intersection target genes, 148 molecular signaling pathways were identified in the networks. Compared with the control group, the expression levels of MMP-1, MMP-9, P-Akt, p38 MAPK, and NF-xB in the BB, beauvericin, and LYC294002 groups during the interventions of hHSFs were significantly decreased (P<0.05). Based on Autodock Vina 1.1.2, the results showed the three compounds [Beauvericin, Cyclo (D)-Pro-(D) -Phe and (+)-Pinoresinol] may potentially act on four targets (MMP1, MMP9, MMP13, and P13k) as the same time. Conclusion: Bombyx batryticatus could effectively inhibit the proliferation and invasion of hHSF's, as well as BB synergistically, inhibits the P13K/MMP1/MMP9/MMP13 signaling pathways by acting on multiple targets.