He Xiying, Cui Jieqiong, Li Huayan, Zhou Yang, Wu Xinchen, Jiang Chunrong, Xu Zhichang, Wang Ruirui, Xiong Lei
The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, China.
College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming, China.
J Biomol Struct Dyn. 2025 May;43(8):4183-4200. doi: 10.1080/07391102.2024.2301761. Epub 2024 Jan 10.
Xiangqin Jiere granules (XQJRG) is a proprietary Chinese medicine treating children's colds and fevers, but its mechanism of action is unclear. The aim of this study was to explore the antipyretic mechanisms of XQJRG based on pharmacodynamics, non-targeted metabolomics, network pharmacology, molecular biology experiments, molecular docking, and molecular dynamics (MD) simulation. Firstly, the yeast-induced fever model was constructed in young rats to study antipyretic effect of XQJRG. Metabolomics and network pharmacology studies were performed to identify the key compounds, targets and pathways involved in the antipyretic of XQJRG. Subsequently, MetScape was used to jointly analyze targets from network pharmacology and metabolites from metabolomics. Finally, the key targets were validated by enzyme-linked immunosorbent assay (ELISA), and the affinity and stability of key ingredient and targets were evaluated by molecular docking and MD simulation. The animal experimental results showed that after XQJRG treatment, body temperature of febrile rats was significantly reduced, 13 metabolites were significantly modulated, and pathways of differential metabolite enrichment were mainly related to amino acid and lipid metabolism. Network pharmacology results indicated that quercetin and kaempferol were the key active components of XQJRG, , , , and were core targets. ELISA confirmed that XQJRG significantly reduced the plasma concentrations of IL-1β, IL-6, and TNF-α, and the hypothalamic concentrations of COX-2 and PGE2. Molecular docking demonstrated that the binding energies of kaempferol to the core targets were all below -5.0 kcal/mol. MD simulation results showed that the binding free energies of TNF-kaempferol, IL6-kaempferol, IL1B-kaempferol and PTGS2-kaempferol were -87.86 kcal/mol, -70.41 kcal/mol, -69.95 kcal/mol and -106.67 kcal/mol, respectively. In conclusion, XQJRG has antipyretic effects on yeast-induced fever in young rats, and its antipyretic mechanisms may be related to the inhibition of peripheral pyrogenic cytokines release by constituents such as kaempferol, the reduction of hypothalamic fever mediator production, and the amelioration of disturbances in amino acid and lipid metabolism.
香芩解热颗粒（XQJRG）是一种治疗儿童感冒发热的中成药，但其作用机制尚不清楚。本研究旨在基于药效学、非靶向代谢组学、网络药理学、分子生物学实验、分子对接和分子动力学（MD）模拟，探索香芩解热颗粒的解热机制。首先，在幼鼠中构建酵母诱导的发热模型，以研究香芩解热颗粒的解热作用。进行代谢组学和网络药理学研究，以确定参与香芩解热颗粒解热作用的关键化合物、靶点和途径。随后，使用MetScape对网络药理学的靶点和代谢组学的代谢物进行联合分析。最后，通过酶联免疫吸附测定（ELISA）验证关键靶点，并通过分子对接和MD模拟评估关键成分与靶点的亲和力和稳定性。动物实验结果表明，香芩解热颗粒治疗后，发热大鼠的体温显著降低，13种代谢物受到显著调节，差异代谢物富集途径主要与氨基酸和脂质代谢有关。网络药理学结果表明，槲皮素和山奈酚是香芩解热颗粒的关键活性成分，[此处可能缺失部分靶点信息未翻译完整]是核心靶点。ELISA证实，香芩解热颗粒显著降低血浆中IL-1β、IL-6和TNF-α的浓度，以及下丘脑COX-2和PGE2的浓度。分子对接表明，山奈酚与核心靶点的结合能均低于-5.0 kcal/mol。MD模拟结果表明，TNF-山奈酚、IL6-山奈酚、IL1B-山奈酚和PTGS2-山奈酚的结合自由能分别为-87.86 kcal/mol、-70.41 kcal/mol、-69.95 kcal/mol和-106.67 kcal/mol。综上所述，香芩解热颗粒对幼鼠酵母诱导的发热有解热作用，其解热机制可能与山奈酚等成分抑制外周致热细胞因子释放、减少下丘脑发热介质产生以及改善氨基酸和脂质代谢紊乱有关。
