Table 6_Network pharmacology and molecular docking analysis on molecular targets and mechanisms of scar healing ointment in the treatment of hypertrophic scars.xlsx

IntroductionHypertrophic scars (HSs) are characterized by complex mechanisms and impose substantial economic and psychological burdens on patients with wounds. Recent studies have reported that various extracts from traditional Chinese medicines can help prevent and treat HSs. Scar healing ointment (SHO), a modified traditional Chinese prescription applied externally, has demonstrated potential in the clinical treatment of HSs, though its underlying mechanisms remain unexplored.
MethodsIn this study, we systematically identified the active ingredients of the SHO formula and their potential targets using multiple databases (TCMSP, HERB, UniProt, GeneCards, DisGeNet, OMIM, PharmGKB, TTD) and explored the possible underlying mechanisms by which SHO treats HSs using bioinformatic analyses, including protein-protein interaction (PPI) network analysis, GO and KEGG enrichment analyses, and molecular docking.
ResultsOur results indicated that the primary active ingredients in the SHO formula include quercetin, beta-sitosterol, kaempferol, stigmasterol, luteolin, alloimperatorin, acacetin, and (E)-2,3-bis(7-methoxy-2-oxochromen-8-yl)prop-2-enal. Protein-protein interaction network analysis revealed that the hub target proteins of the SHO formula are AKT1, MAPK1, CCND1, TP53, GSK3B, BCL2, CDKN1A, ESR1, and MYC. GO and KEGG enrichment analyses showed that these hub target genes are involved in processes and pathways related to apoptosis and responses to oxidants. Molecular docking analysis demonstrated that the MAPK1-stigmasterol and ESR1-alloimperatorin complexes exhibited strong binding affinities (–5.31 and –6.09) and formed multiple hydrogen bonds (3 and 2, respectively).
DiscussionThese findings suggest that SHO may exert its effects by modulating MAPK1 and ESR1 proteins, thereby contributing to the prevention and treatment of HSs. This study offers new drugs and target candidates for the prevention and treatment of HSs and provides theoretical support for further research and application of the SHO formula. Nevertheless, additional in vivo and in vitro studies are necessary to validate these mechanisms.

引言：增生性瘢痕(Hypertrophic scars, HSs)发病机制复杂，给伤口患者带来沉重的经济与心理负担。现有研究表明，多种中药提取物可用于增生性瘢痕的预防与治疗。疤痕愈合软膏(Scar healing ointment, SHO)是一种外用改良中药方剂，其在增生性瘢痕的临床治疗中已展现出应用潜力，但其具体作用机制尚未阐明。
方法：本研究通过多个数据库（TCMSP、HERB、UniProt、GeneCards、DisGeNet、OMIM、PharmGKB、TTD）系统筛选了SHO方剂的活性成分及其潜在作用靶点，并借助生物信息学分析手段——包括蛋白质-蛋白质相互作用(protein-protein interaction, PPI)网络分析、基因本体(Gene Ontology, GO)与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)富集分析以及分子对接技术——探究了SHO治疗增生性瘢痕的潜在作用机制。
结果：本研究结果显示，SHO方剂中的主要活性成分包括槲皮素(quercetin)、β-谷甾醇(beta-sitosterol)、山奈酚(kaempferol)、豆甾醇(stigmasterol)、木犀草素(luteolin)、别欧前胡素(alloimperatorin)、金合欢素(acacetin)以及(E)-2,3-双(7-甲氧基-2-氧代色满-8-基)丙-2-烯醛((E)-2,3-bis(7-methoxy-2-oxochromen-8-yl)prop-2-enal)。蛋白质-蛋白质相互作用网络分析表明，SHO方剂的核心靶点蛋白包括AKT1、MAPK1、CCND1、TP53、GSK3B、BCL2、CDKN1A、ESR1以及MYC。基因本体与京都基因与基因组百科全书富集分析结果显示，这些核心靶点基因参与了细胞凋亡与氧化应激应答相关的生物学过程及信号通路。分子对接分析证实，MAPK1-豆甾醇复合物与ESR1-别欧前胡素复合物具有较强的结合亲和力（结合能分别为-5.31与-6.09），并分别形成了3个与2个氢键。
讨论：本研究结果表明，SHO可能通过调控MAPK1与ESR1蛋白发挥治疗作用，进而参与增生性瘢痕的预防与治疗。本研究为增生性瘢痕的防治提供了新型药物候选与靶点候选方案，并为SHO方剂的后续研究与临床应用提供了理论支撑。不过，仍需开展更多体内外实验以验证上述作用机制。