Qumu Daermu, Tian Mu, Li Hengxi, Yang Xiujuan, Han Binhui, Wei Lanting, Li Bo, Ma Mengxue, He Junjie, Shao Xiaoni
College of Pharmacy, Southwest Minzu University, Chengdu, Sichuan, China.
College of Food Science and Technology, Southwest Minzu University, Chengdu, Sichuan, China.
Mol Nutr Food Res. 2025 May;69(9):e70029. doi: 10.1002/mnfr.70029. Epub 2025 Mar 27.
Galangin (GAL), a flavonol found in Alpinia officinarum and propolis, is a promising functional food. This study investigated the therapeutic effects and mechanisms of GAL in mice with hyperuricemic nephropathy (HN) by focusing on renal metabolomics and network pharmacology. In this study, we conducted untargeted metabolomic analysis and network pharmacology prediction. Subsequently, a compound-reaction-enzyme-gene network was constructed based on the results of metabolomics and network pharmacology to elucidate potential connections. The results demonstrated that GAL can improve renal interstitial fibrosis and inflammatory infiltration and reduce serum levels of uric acid (UA), urea nitrogen (UREA), and creatinine (CREA). Metabolome analysis indicated that GAL affected thiamine, pyrimidine, nicotinate, nicotinamide, pyruvate, glyoxylate, and dicarboxylate metabolism. Network pharmacology and experimental results showed that GAL reduced the key target expression of the tumor protein P53 (TP53), tumor necrosis factor (TNF), signal transducer and activator of transcription 3 (STAT3), heat shock protein 90 alpha family class A member 1 (HSP90aa1), albumin (ALB), and caspase-3 (CASP3). GAL also downregulated the expression of Janus kinase 2 (JAK2), phospho-JAK2 (P-JAK2), and phospho-STAT3 (P-STAT3). Furthermore, a joint analysis of the metabolome and network pharmacology showed that GAL can reverse HN through amino acid metabolism, nucleotide metabolism, energy metabolism, and endocrine system pathways. GAL can alleviate HN effectively and might play synergistic therapeutic roles through regulating metabolic profiles and the JAK2/STAT3 signaling pathway.
高良姜素（GAL）是一种存在于高良姜和蜂胶中的黄酮醇，是一种很有前景的功能性食品。本研究通过关注肾脏代谢组学和网络药理学，探讨了GAL对高尿酸血症肾病（HN）小鼠的治疗作用及机制。在本研究中，我们进行了非靶向代谢组学分析和网络药理学预测。随后，基于代谢组学和网络药理学的结果构建了化合物-反应-酶-基因网络，以阐明潜在的联系。结果表明，GAL可以改善肾间质纤维化和炎性浸润，并降低血清尿酸（UA）、尿素氮（UREA）和肌酐（CREA）水平。代谢组分析表明，GAL影响硫胺素、嘧啶、烟酸、烟酰胺、丙酮酸、乙醛酸和二羧酸代谢。网络药理学和实验结果表明，GAL降低了肿瘤蛋白P53（TP53）、肿瘤坏死因子（TNF）、信号转导和转录激活因子3（STAT3）、热休克蛋白90α家族A类成员1（HSP90aa1）、白蛋白（ALB）和半胱天冬酶-3（CASP3）的关键靶点表达。GAL还下调了Janus激酶2（JAK2）、磷酸化JAK2（P-JAK2）和磷酸化STAT3（P-STAT3）的表达。此外，代谢组学和网络药理学的联合分析表明，GAL可以通过氨基酸代谢、核苷酸代谢、能量代谢和内分泌系统途径逆转HN。GAL可以有效缓解HN，并可能通过调节代谢谱和JAK2/STAT3信号通路发挥协同治疗作用。
