Banerjee Subhadip, Jaidee Wuttichai, Rujanapun Narawadee, Duangyod Thidarat, Maneerat Tharakorn, Phuneerub Pravaree, Malee Kulwadee, Popluechai Siam, Suthiphasilp Virayu, Puttarak Panupong, Hiransai Poonsit, Laphookhieo Surat, Ramli Salfarina, Vanden Berghe Wim, Cordell Geoffrey A, Charoensup Rawiwan
Medicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang University, Chiang Rai, 57100, Thailand.
School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, 57100, Thailand.
Sci Rep. 2025 Aug 17;15(1):30078. doi: 10.1038/s41598-025-15556-x.
Traditional herbal formulations offer promising avenues for diabetes management by targeting multiple molecular pathways. Mathurameha (MT), a polyherbal preparation, has been historically used for its antidiabetic potential. However, its molecular mechanisms remain largely unexplored. FrE exhibited potent α-glucosidase inhibition (IC₅₀ 0.3 µg/mL) and significantly enhanced glucose uptake in L6 myotubes (3.67 ± 0.23-fold) and 3T3-L1 adipocytes (IC₅₀ 6.78 µg/mL). It also stimulated insulin secretion (1.42-fold), comparable to metformin (1.46-fold), and protected INS-1 pancreatic β-cells from H₂O₂-induced apoptosis (30.65 ± 3.54%) through partial caspase-3 inhibition. LC-MS-QTOF analysis identified 73 metabolites, including ellagic acid, kushenol A, gallic acid, arctiin, neoandrographolide, astilbin, paenol, muricatacin, coumarrayin, and zingerone. Network pharmacology and pathway enrichment analyses revealed key targets (GSK3β, GLUT4, PPARG, INSR, AKT2, CASP3, and MMP9) and highlighted the involvement of PI3K-AKT, AMPK, and GLUT4 signaling pathways. Gene expression analysis confirmed the upregulation of GLUT4, AMPK, IRS, PI3K, and AKT genes in L6 myotubes treated with FrE. These findings suggest that MT exerts antidiabetic effects via the PI3K-AKT/AMPK/GLUT4 signaling axis, promoting glucose uptake, insulin secretion, and β-cell protection. Future studies will focus on in vivo validation, standardization of bioactive fractions, and omics-based approaches to establish a well-defined, effective formulation for diabetes management.
传统草药配方通过靶向多种分子途径为糖尿病管理提供了有前景的途径。Mathurameha（MT）是一种多草药制剂，长期以来因其抗糖尿病潜力而被使用。然而，其分子机制在很大程度上仍未被探索。FrE表现出强大的α-葡萄糖苷酶抑制作用（IC₅₀为0.3μg/mL），并显著增强了L6肌管（3.67±0.23倍）和3T3-L1脂肪细胞（IC₅₀为6.78μg/mL）对葡萄糖的摄取。它还刺激胰岛素分泌（1.42倍），与二甲双胍（1.46倍）相当，并通过部分抑制半胱天冬酶-3保护INS-1胰腺β细胞免受H₂O₂诱导的凋亡（30.65±3.54%）。液相色谱-质谱-四极杆飞行时间分析鉴定出73种代谢物，包括鞣花酸、苦参醇A、没食子酸、牛蒡子苷、新穿心莲内酯、落新妇苷、丹皮酚、异长春花苷内酰胺、香豆素和姜辣素。网络药理学和通路富集分析揭示了关键靶点（GSK3β、GLUT4、PPARG、INSR、AKT2、CASP3和MMP9），并突出了PI3K-AKT、AMPK和GLUT4信号通路的参与。基因表达分析证实了用FrE处理的L6肌管中GLUT4、AMPK、IRS、PI3K和AKT基因的上调。这些发现表明，MT通过PI3K-AKT/AMPK/GLUT4信号轴发挥抗糖尿病作用，促进葡萄糖摄取、胰岛素分泌和β细胞保护。未来的研究将集中在体内验证、生物活性成分的标准化以及基于组学的方法，以建立一种明确有效的糖尿病管理配方。
