Discovery and Mechanistic Elucidation of Glycyrrhizic Acid Composite Gel in Promoting Wound Healing: A Modernized Study Based on Shengji Yuhong Ointment

作者：Haixin Liu, Minyu Wang, Ying-Wei Li, Bin Xu, Zi-Xuan Wang, Xiang-Long Meng, Hui-Fang Li, Shiyuan Wen · 发表于：Pharmaceuticals · 年份：2025 · DOI：10.3390/ph18111737 · 被引用次数：4 · 研究领域：Pharmacological Effects of Natural Compounds、Wound Healing and Treatments、Ginseng Biological Effects and Applications

Objectives: Shengji Yuhong Ointment (SJYHO) is a classic Traditional Chinese Medicine prescription used for refractory wounds, yet its systemic pharmacological mechanisms remain unclear. This study aimed to identify its key active compounds and develop a simplified, effective topical formulation. Methods: We employed an integrated approach, combining network pharmacology and machine learning to screen the key constituents and core targets of SJYHO. The lead compound, glycyrrhizic acid, was formulated into a hydrogel (GA-Gel). Its therapeutic efficacy was evaluated in a full-thickness excisional wound model in Sprague-Dawley rats over 21 days, assessing healing kinetics, histology, and pain behavior. The interaction between glycyrrhizic acid and the identified target PPIA, along with its immunomodulatory effects, was validated through molecular docking, molecular dynamics simulation, and RT-qPCR. Results: Our integrated analysis identified PPIA as the core target and glycyrrhizic acid as a key bioactive component of SJYHO. Animal experiments demonstrated that GA-Gel significantly accelerated wound closure, which was driven by its multi-faceted actions: reducing inflammation, promoting collagen deposition, alleviating pain, and modulating late-stage angiogenesis. Mechanistically, we confirmed that glycyrrhizic acid stably binds to PPIA. Furthermore, GA-Gel treatment mediated wound immune infiltration by specifically regulating CD8+ T cells, neutrophils, and memory B cells, an e...