Network pharmacology and metabolomics reveal mathurameha, a Thai traditional Anti-Diabetic formula, enhances glucose metabolism through PI3K-AKT/AMPK/GLUT4 pathway modulation
Abstract 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 e...
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Nature Portfolio
2025-08-01
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| author | Subhadip Banerjee Wuttichai Jaidee Narawadee Rujanapun Thidarat Duangyod Tharakorn Maneerat Pravaree Phuneerub Kulwadee Malee Siam Popluechai Virayu Suthiphasilp Panupong Puttarak Poonsit Hiransai Surat Laphookhieo Salfarina Ramli Wim Vanden Berghe Geoffrey A. Cordell Rawiwan Charoensup |
| author_facet | Subhadip Banerjee Wuttichai Jaidee Narawadee Rujanapun Thidarat Duangyod Tharakorn Maneerat Pravaree Phuneerub Kulwadee Malee Siam Popluechai Virayu Suthiphasilp Panupong Puttarak Poonsit Hiransai Surat Laphookhieo Salfarina Ramli Wim Vanden Berghe Geoffrey A. Cordell Rawiwan Charoensup |
| author_sort | Subhadip Banerjee |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-34539a715bb44260aa6ac2e4a71f5334 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-34539a715bb44260aa6ac2e4a71f53342025-08-20T03:07:24ZengNature PortfolioScientific Reports2045-23222025-08-0115112010.1038/s41598-025-15556-xNetwork pharmacology and metabolomics reveal mathurameha, a Thai traditional Anti-Diabetic formula, enhances glucose metabolism through PI3K-AKT/AMPK/GLUT4 pathway modulationSubhadip Banerjee0Wuttichai Jaidee1Narawadee Rujanapun2Thidarat Duangyod3Tharakorn Maneerat4Pravaree Phuneerub5Kulwadee Malee6Siam Popluechai7Virayu Suthiphasilp8Panupong Puttarak9Poonsit Hiransai10Surat Laphookhieo11Salfarina Ramli12Wim Vanden Berghe13Geoffrey A. Cordell14Rawiwan Charoensup15Medicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang UniversityMedicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang UniversityMedicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang UniversityMedicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang UniversityMedicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang UniversityMedicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang UniversityMedicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang UniversitySchool of Science, Mae Fah Luang UniversityDepartment of Industrial Technology and Innovation Management, Faculty of Science and Technology, Pathumwan Institute of TechnologyPhytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla UniversityCenter of Excellence in Marijuana, Hemp, and Kratom, Walailak UniversityCenter of Chemical Innovation for Sustainability (CIS) and School of Science, Mae Fah Luang UniversityFaculty of Pharmacy, Universiti Teknologi MARA Cawangan SelangorLaboratory for Protein Chemistry, Proteomics & Epigenetic Signalling (PPES), Department of Biomedical Sciences, University of AntwerpNatural Products Inc.Medicinal Plant Innovation Center of Mae Fah Luang University, Mae Fah Luang UniversityAbstract 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.https://doi.org/10.1038/s41598-025-15556-xMathuramehaThai traditional medicineTwenty-six medicinal plant mixtureAntidiabetic activityGlucose transportLC-MS/MS-QTOF analysis |
| spellingShingle | Subhadip Banerjee Wuttichai Jaidee Narawadee Rujanapun Thidarat Duangyod Tharakorn Maneerat Pravaree Phuneerub Kulwadee Malee Siam Popluechai Virayu Suthiphasilp Panupong Puttarak Poonsit Hiransai Surat Laphookhieo Salfarina Ramli Wim Vanden Berghe Geoffrey A. Cordell Rawiwan Charoensup Network pharmacology and metabolomics reveal mathurameha, a Thai traditional Anti-Diabetic formula, enhances glucose metabolism through PI3K-AKT/AMPK/GLUT4 pathway modulation Scientific Reports Mathurameha Thai traditional medicine Twenty-six medicinal plant mixture Antidiabetic activity Glucose transport LC-MS/MS-QTOF analysis |
| title | Network pharmacology and metabolomics reveal mathurameha, a Thai traditional Anti-Diabetic formula, enhances glucose metabolism through PI3K-AKT/AMPK/GLUT4 pathway modulation |
| title_full | Network pharmacology and metabolomics reveal mathurameha, a Thai traditional Anti-Diabetic formula, enhances glucose metabolism through PI3K-AKT/AMPK/GLUT4 pathway modulation |
| title_fullStr | Network pharmacology and metabolomics reveal mathurameha, a Thai traditional Anti-Diabetic formula, enhances glucose metabolism through PI3K-AKT/AMPK/GLUT4 pathway modulation |
| title_full_unstemmed | Network pharmacology and metabolomics reveal mathurameha, a Thai traditional Anti-Diabetic formula, enhances glucose metabolism through PI3K-AKT/AMPK/GLUT4 pathway modulation |
| title_short | Network pharmacology and metabolomics reveal mathurameha, a Thai traditional Anti-Diabetic formula, enhances glucose metabolism through PI3K-AKT/AMPK/GLUT4 pathway modulation |
| title_sort | network pharmacology and metabolomics reveal mathurameha a thai traditional anti diabetic formula enhances glucose metabolism through pi3k akt ampk glut4 pathway modulation |
| topic | Mathurameha Thai traditional medicine Twenty-six medicinal plant mixture Antidiabetic activity Glucose transport LC-MS/MS-QTOF analysis |
| url | https://doi.org/10.1038/s41598-025-15556-x |
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