The Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, China; Department of Dermatology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712099, China.
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200437, China.
Comput Biol Med. 2023 Mar;155:106660. doi: 10.1016/j.compbiomed.2023.106660. Epub 2023 Feb 10.
A diabetic ulcer (DU) is a dreaded and resistant complication of diabetes mellitus with high morbidity. Fu-Huang ointment (FH ointment) is a proven recipe for treating chronic refractory wounds; however, its molecular mechanisms of action are unclear. In this study, we identified 154 bioactive ingredients and their 1127 target genes in FH ointment through the public database. The intersection of these target genes with 151 disease-related targets in DUs resulted in 64 overlapping genes. Overlapping genes were identified in the PPI network and enrichment analyses. The PPI network identified 12 core target genes, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that upregulation of the PI3K/Akt signalling pathway was involved in the role of FH ointment in treating diabetic wounds. Molecular docking showed that 22 active compounds in FH ointment could enter the active pocket of PIK3CA. Molecular dynamics was used to prove the binding stability of the active ingredients and protein targets. We found that PIK3CA/Isobutyryl shikonin and PIK3CA/Isovaleryl shikonin combinations had strong binding energies. An in vivo experiment was conducted on PIK3CA, which was the most significant gene.This study comprehensively elucidated the active compounds, potential targets, and molecular mechanism of FH ointment application in treating DUs, and believed that PIK3CA is a promising target for accelerated healing.
糖尿病足溃疡（DU）是糖尿病的一种严重且难以治愈的并发症，发病率较高。复黄软膏（FH 软膏）是一种治疗慢性难治性伤口的有效方剂，但作用机制尚不清楚。本研究通过公共数据库，鉴定出 FH 软膏中的 154 种活性成分及其 1127 个靶基因。这些靶基因与 DU 中 151 个与疾病相关的靶基因的交集产生了 64 个重叠基因。重叠基因在 PPI 网络和富集分析中被识别。PPI 网络鉴定出 12 个核心靶基因，而京都基因与基因组百科全书（KEGG）分析表明，PI3K/Akt 信号通路的上调参与了 FH 软膏治疗糖尿病创面的作用。分子对接显示，FH 软膏中的 22 种活性化合物可以进入 PIK3CA 的活性口袋。分子动力学用于证明活性成分和蛋白质靶标的结合稳定性。我们发现 PIK3CA/异丁酰基紫草素和 PIK3CA/异戊酰基紫草素组合具有很强的结合能。在 PIK3CA 上进行了体内实验，PIK3CA 是最显著的基因。本研究全面阐明了 FH 软膏治疗 DU 的活性成分、潜在靶点和分子机制，认为 PIK3CA 是加速愈合的有前途的靶点。
