Combined metabolomics and network pharmacology to elucidate the mechanisms of Huiyang Shengji decoction in treating diabetic skin ulcer mice

作者：Jia Chen, Baoquan Qu, Danyang Yang, Yazhuo Wang, Haoyue Zhu, Zhengchun Wang, Xiawei Zhang, Huike Ma, Ning Zhao, Li Zhao, Li Zhou, Xiujuan He, Ping Li · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156569 · 被引用次数：8 · 研究领域：Wound Healing and Treatments、Diabetic Foot Ulcer Assessment and Management、Immune cells in cancer

BACKGROUND: Diabetic skin ulcer is a clinical disorder of glucose metabolism that has a long treatment period and is prone to recurrent episodes. Huiyang Shengji decoction (HYSJD) is an effective traditional Chinese medicine for its clinical treatment, but its metabolic effects in patients with diabetic skin ulcers have not been well studied. PURPOSE: Our study aimed to investigate the mechanism of pharmacological treatment of HYSJD in treating diabetic skin ulcers. METHODS: The potential mechanism underlying diabetic wound treatment by HYSJD was screened using network pharmacology. Ultra-high performance liquid chromatography-MS/MS metabolomics analysis and correlation analysis were performed to investigate potential target pathways and genes. Furthermore, the db/db diabetic wound tissues and RAW264.7 macrophage inflammation model verified the mechanism using molecular biology experiments. RESULTS: In network pharmacology, HYSJD played a mainly therapeutic effect by regulating PI3K/AKT signaling pathway, EGFR tyrosine kinase inhibitor resistance, metabolic pathway, and other related metabolic-related pathways. Metabolomics analysis disclosed that L-lysine content increased, while those of linoleic and deoxycholic acids decreased in plasma between the HYSJD-treated group and the control group, participating in biotin metabolism. Among them, PPARγ played an important role. The experiments conducted in db/db mice indicated that HYSJD facilitates VEGF secretion and PPARγ express...