Jia Nini, Li Jing, Cui Mengyao, Li Yaqing, Jiang Dayuan, Chu Xiaoqin
School of Pharmacy, Anhui University of Chinese Medicine, No. 1, QianJiang Road, Hefei, 230012, Anhui, P. R. China.
Anhui Medical College, No. 632, Furong Road, Hefei, 230601, Anhui, P. R. China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 17. doi: 10.1007/s00210-025-04011-3.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease. Clinical studies have shown that the incidence and prevalence of T2DM has been on the rise globally in recent years, and the mortality rate is also increasing. Chinese herbs is multiple target for disease. Guizhi Gegen decoction (GZGGD) is one of the most alternative treatment for T2DM. However, the treatment mechanism is unclear. The composition of the GZGGD was determined by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The key targets and pathways were predicted by network pharmacology and molecular docking. In vivo experiments were performed to further verify and reveal the potential mechanism of action. We identified 44 active components of GZGGD (genistein, 26-hydroxyporicoic acid DM, puerarin, eugenol, and gentiobiose). Network pharmacology predicted key targets such as TNF, AKT1, TP53, EGFR, and STAT3, and AGE-RAGE, IL-17 signaling pathways were enriched. Molecular docking showed that the active components of GZGGD have good binding activity with the potential targets of T2DM. In vivo animal experiments showed improvement in white blood, fasting blood glucose, and inflammatory factor levels (INS, TC, TNF-α, and IL-6). This study clarifies the potential role of GZGGD in T2DM, which can help in the study of T2DM.
2型糖尿病（T2DM）是一种慢性代谢性疾病。临床研究表明，近年来T2DM的发病率和患病率在全球范围内呈上升趋势，死亡率也在增加。中药对疾病具有多靶点作用。桂枝葛根汤（GZGGD）是治疗T2DM最具替代作用的方剂之一。然而，其治疗机制尚不清楚。采用超高效液相色谱-四极杆飞行时间质谱法测定了GZGGD的成分。通过网络药理学和分子对接预测了关键靶点和通路。进行体内实验以进一步验证并揭示其潜在作用机制。我们鉴定出了GZGGD的44种活性成分（染料木黄酮、26-羟基茯苓酸DM、葛根素、丁香酚和龙胆二糖）。网络药理学预测了关键靶点如肿瘤坏死因子（TNF）、蛋白激酶B1（AKT1）、肿瘤蛋白53（TP53）、表皮生长因子受体（EGFR）和信号转导和转录激活因子3（STAT3），并富集了晚期糖基化终末产物受体（AGE-RAGE）、白细胞介素17（IL-17）信号通路。分子对接表明，GZGGD的活性成分与T2DM的潜在靶点具有良好的结合活性。体内动物实验表明，白细胞、空腹血糖及炎症因子水平（胰岛素、总胆固醇、TNF-α和IL-6）有所改善。本研究阐明了GZGGD在T2DM中的潜在作用，有助于T2DM的研究。
