A NETWORK PHARMACOLOGY APPROACH TO EXPLORE MECHANISMS OF BOMBYX BATRYTICATUS IN KELOID TREATMENTS

Na Li^1,2, Yue Dong Liu^{2, *}, PingLi Zhou, Xiansheng Meng³, Yongrui Bao³, Jiangli Shen¹, Ximin Qiao⁴, Yibing Zhang³

¹Xianyang Central Hospital, Xianyang, Shaanxi Province, China - ²The Third Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, China - ³School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning Province, China - ⁴Dean's Office, Xianyang Central Hospital, Xianyang 712000, Shaanxi Province, China

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 PI3K/Akt inhibitor LY294002). The expression levels of MMP-1, MMP-9, Akt, P-Akt, beta-Actin, P13K p85α, p38 MAPK, GAPDH, and NF-κB 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 PI3k) 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-κB in the BB, beauvericin, and LY294002 groups during the intervention 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 PI3k) at the same time.

Conclusion: Bombyx batryticatus could effectively inhibit the proliferation and invasion of hHSFs, as well as BB synergistically, inhibits the PI3K/MMP1/MMP9/MMP13 signaling pathways by acting on multiple targets.