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生脉散通过调节PI3K/AKT/GSK3B信号通路对2型糖尿病发挥治疗作用。

The Shengmai San Exerts Therapeutic Effects on Type 2 Diabetes by Modulating the PI3K/AKT/GSK3B Signaling Pathway.

作者信息

Shang Hongchao, Wang Tianyu, Pang Daoran, Qi Yue, Liu Lu, Wang Yifei, Gao Yan

机构信息

Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2025 Apr 2;18:985-1004. doi: 10.2147/DMSO.S507953. eCollection 2025.

DOI:10.2147/DMSO.S507953
PMID:40191827
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11972573/
Abstract

CONTEXT

Shengmai San (SMS) is a traditional Classic Recipes made with Panax ginseng, Ophiopogon, and Schisandra. The precise mechanism of action of SMS remains unclear, despite its noteworthy therapeutic advantages for type 2 diabetes mellitus (T2DM).

OBJECTIVE

The objective of this study was to confirm the mechanism of SMS in the treatment of T2DM.

MATERIALS AND METHODS

UPLC-MS/MS was employed to identify the active components in SMS. Using network pharmacology, the intervention pathways of SMS in T2DM rats were investigated. A high-sugar, high-fat diet and intrabitoneal injection of streptozotocin were used to create a T2DM rat model. The serum parameters of each group were assessed following the completion of the experiment. The mRNA and protein expression levels of genes related to the PI3K/AKT/GSK3B pathway were analyzed using qRT-PCR and Western blot.

RESULTS

There were 39 components found in SMS San by UPLC-Q-Orbitrap/MS. Network pharmacology and molecular docking study indicate that the PI3K/AKT/GSK3B pathway may be a part of SMS's therapeutic mechanism for the treatment of T2DM. Rats' serum levels of TC, TG, LDL-C, MDA, TNF-α, and IL-6 dramatically dropped after taking SMS, whereas SOD and HDL-C levels rose. The improvement of these parameters may be relate to SMS activation of downstream target proteins, PI3K, and AKT.

CONCLUSION

SMS can help cure T2DM mellitus by regulating the PI3K/AKT/GSK3B pathway, improving islet tissue injury, reducing oxidative stress, and easing lipid metabolism issues. This study not only revealed the unique therapeutic mechanism of SMS by regulating the PI3K/AKT/GSK3β signaling pathway, but also provided new theoretical support for multi-target and personalized treatment of diabetes. Its novelty lies in the first exploration of the mechanism of action of traditional Chinese medicine prescriptions through the lens of modern molecular biology, emphasizing the potential of natural medicines in diabetes treatment.

摘要

背景

生脉散（SMS）是一种由人参、麦冬和五味子制成的传统经典方剂。尽管生脉散对2型糖尿病（T2DM）具有显著的治疗优势，但其确切作用机制仍不清楚。

目的

本研究旨在证实生脉散治疗T2DM的机制。

材料与方法

采用超高效液相色谱-串联质谱法（UPLC-MS/MS）鉴定生脉散中的活性成分。运用网络药理学研究生脉散对T2DM大鼠的干预途径。采用高糖高脂饮食联合腹腔注射链脲佐菌素建立T2DM大鼠模型。实验结束后评估各组的血清参数。采用实时荧光定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法（Western blot）分析PI3K/AKT/GSK3B通路相关基因的mRNA和蛋白表达水平。

结果

通过UPLC-Q-Orbitrap/MS在生脉散中发现了39种成分。网络药理学和分子对接研究表明，PI3K/AKT/GSK3B通路可能是生脉散治疗T2DM的作用机制之一。服用生脉散后，大鼠血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平显著下降，而超氧化物歧化酶（SOD）和高密度脂蛋白胆固醇（HDL-C）水平升高。这些参数的改善可能与生脉散激活下游靶蛋白PI3K和AKT有关。

结论

生脉散可通过调节PI3K/AKT/GSK3B通路、改善胰岛组织损伤、减轻氧化应激和缓解脂质代谢问题来帮助治疗T2DM。本研究不仅揭示了生脉散通过调节PI3K/AKT/GSK3β信号通路独特的治疗机制，还为糖尿病的多靶点和个性化治疗提供了新的理论支持。其新颖之处在于首次从现代分子生物学角度探索中药方剂的作用机制，强调了天然药物在糖尿病治疗中的潜力。

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