The effects of <i>Gymnema sylvestre</i> extract supplementation on expression of gene associated with glucose homeostasis in diabetic mouse model

Duc Quan Nguyen; Thi Kim Anh  Tran; Thi Trang Do; Thi Huong Giang Tran; Thi Thanh Trung Do; Tat Thanh Le; Huy Hoang Nguyen

doi:10.15625/vjbt-23222

Author affiliations

Authors

Duc Quan Nguyen \(^1\) Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do, Hanoi, Vietnam https://orcid.org/0000-0002-8152-5700
Thi Kim Anh Tran \(^2\) School of Life and Environmental Sciences & Sydney Institute of Agriculture, The University of Sydney, 1 Central Avenue, Eveleigh, NSW, Australia, 2015 https://orcid.org/0000-0002-6689-9077
Thi Trang Do \(^1\) Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do, Hanoi, Vietnam
\(^3\) Publishing House for Science Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do, Hanoi, Vietnam
Thi Huong Giang Tran \(^1\) Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do, Hanoi, Vietnam
Thi Thanh Trung Do Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do, Hanoi, Vietnam
Tat Thanh Le \(^1\) Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do, Hanoi, Vietnam
Huy Hoang Nguyen \(^1\) Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do, Hanoi, Vietnam
\(^4\) Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do, Hanoi, Vietnam

DOI:

https://doi.org/10.15625/vjbt-23222

Keywords:

Diabetes mellitus, Gymnema sylvestre, gymnemic acid, Mus musculus, RT-qPCR analysis.

Abstract

Gymnema sylvestre, a traditional medicinal herb known for its anti-diabetic properties, has been widely used to manage hyperglycemia by various mechanisms, including the inhibition of glucose absorption, stimulation of insulin secretion, and enhancement of pancreatic beta-cell regeneration. In the context of the increasing prevalence of diabetes, particularly in Vietnam, this study investigates the molecular effects of G. sylvestre extract (gymnemic acid) on gene expression associated with glucose homeostasis in diabetic mouse models induced by streptozotocin. The expression levels of key regulators involved in glucose transport, insulin production, and inflammatory responses, such as GLUT2, MAFA, INS2, PDX1, NFKB, and GCK, were evaluated using RT-qPCR analysis. Our findings indicated that diabetic mice, receiving 250 mg of G. sylvestre extract per kg of body weight daily for 6 weeks, exhibited significant improvements in glucose regulation when compared to their counterparts on a high-fat diet. This result was evidenced by increased gene expression related to insulin secretion and glucose uptake, alongside a decrease in body weight and blood glucose levels in diabetic mice. These beneficial outcomes can be attributed to the role of gymnemic acid in supporting various processes, including competitive inhibition of glucose absorption, enhancement of insulin secretion, protection and regeneration of pancreatic beta-cells, and improvement of lipid metabolism. Collectively, these findings highlight the potential of G. sylvestre as a nutrigenomic intervention in diabetes management through its regulation of key metabolic pathways.

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References

Abu Aqel Y., Alnesf A., Aigha I. I., Islam Z., Kolatkar P. R., Teo A., et al. (2024). Glucokinase (GCK) in diabetes: from molecular mechanisms to disease pathogenesis. Cellular & Molecular Biology Letters, 29(1), 120-147. http://doi.org/10.1186/s11658-024-00640-3

Ahamad J., Amin S., and Mir S. R. (2014). Optimization of ultrasonic-assisted extraction of gymnemic acid from Gymnema sylvestre leaves using response surface methodology. Analytical Chemistry Letters, 4, 104-112 http://doi.org/10.1080/22297928.2014.905754

Akinlade O. M., Owoyele B. V., and Soladoye A. O. (2021). Streptozotocin-induced type 1 and 2 diabetes in rodents: a model for studying diabetic cardiac autonomic neuropathy. African Health Sciences, 21(2), 719-727. http://doi.org/10.4314/ahs.v21i2.30

Bensellam M., Laybutt D. R., and Jonas J. C. (2012). The molecular mechanisms of pancreatic β-cell glucotoxicity: Recent findings and future research directions. Molecular and Cellular Endocrinology, 364(1), 1-27. https://doi.org/10.1016/j.mce.2012.08.003

Briscoe V. (2006). Hypoglycemia in type 1 and type 2 diabetes: physiology, pathophysiology, and management. Clinical Diabetes, 24, 115-121. https://doi.org/10.2337/diaclin.24.3.115

Chen G., Xu Y., Zhang H., Muema F. W., and Guo M. (2023). Gymnema sylvestre extract ameliorated streptozotocin-induced hyperglycemia in T2DM rats via gut microbiota. Food Frontiers, 4(3), 1426-1439. https://doi.org/10.1002/fft2.238

Chhabra N. F., Amend A. L., Bastidas-Ponce A., Sabrautzki S., Tarquis-Medina M., Sachs S., et al. (2021). A point mutation in the Pdia6 gene results in loss of pancreatic β-cell identity causing overt diabetes. Molecular Metabolism, 54, 101334. https://doi.org/10.1016/j.molmet.2021.101334

Dludla P. V., Mabhida S. E., Ziqubu K., Nkambule B. B., Mazibuko-Mbeje S. E., Hanser S., et al. (2023). Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress. World Journal of Diabetes, 14(3), 130-146. https://doi.org/10.4239/wjd.v14.i3.130

Eldor R., Yeffet A., Baum K., Doviner V., Amar D., Ben-Neriah Y., et al. (2006). Conditional and specific NF-κB blockade protects pancreatic beta cells from diabetogenic agents. Proceedings of the National Academy of Sciences, 103(13), 5072-5077. https://doi.org/10.1073/pnas.0508166103

Halilu E. (2023). Characterization of crude saponins from stem bark extract of Parinari curatellifolia and evaluation of its antioxidant and antibacterial activities. Physical Sciences Reviews, 9, 1-20. https://doi.org/10.1515/psr-2022-0271

He M. Q., Wang J. Y., Wang Y., Sui J., Zhang M., Ding X., et al. (2020). High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice. Chronic Diseases and Translational Medicine, 6(3), 198-207. https://doi.org/10.1016/j.cdtm.2020.06.003

Heydemann A. (2016). An overview of murine high fat diet as a model for type 2 diabetes mellitus. Journal of Diabetes Research, 2016, 2902351. https://doi.org/10.1155/2016/2902351

Hrovatin K., Bastidas-Ponce A., Bakhti M., Zappia L., Büttner M., Salinno C., et al. (2023). Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas. Nature Metabolism, 5(9), 1615-1637. https://doi.org/10.1038/s42255-023-00876-x

Imam M. U., Azmi N. H., Bhanger M. I., Ismail N., and Ismail M. (2012). Antidiabetic properties of germinated brown rice: a systematic review. Evidence-Based Complementary and Alternative Medicine, 2012, 816501. https://doi.org/10.1155/2012/816501

Kannan P., Karthikeyan P., Subramaniam N., Mohan T., Gopinath B., Chakrapani L. N., et al. (2022). Gymnemic acid protects murine pancreatic β-cells by moderating hyperglycemic stress-induced inflammation and apoptosis in type 1 diabetic rats. Journal of Biochemical and Molecular Toxicology, 36(7), e23050. https://doi.org/10.1002/jbt.23050

Li Y., Xiao Y., Gao W., Pan J., Zhao Q., and Zhang Z. (2019). Gymnemic acid alleviates inflammation and insulin resistance via PPARδ- and NFκB-mediated pathways in db/db mice. Food & Function, 10(9), 5853-5862. https://doi.org/10.1039/C9FO01419E

Liang J., Chirikjian M., Pajvani U. B., and Bartolomé A. (2022). MafA Regulation in β-Cells: From Transcriptional to Post-Translational Mechanisms. Biomolecules, 12(4), 1-14. https://doi.org/10.3390/biom12040535

Livak K. J., and Schmittgen T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods, 25(4), 402-408. https://doi.org/10.1006/meth.2001.1262

Low B. S. J., Lim C. S., Ding S. S. L., Tan Y. S., Ng N. H. J., Krishnan V. G., et al. (2021). Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant β cells. Nature Communications, 12(1), 3133-3153. https://doi.org/10.1038/s41467-021-22843-4

Lu B., Kurmi K., Munoz-Gomez M., Jacobus Ambuludi E. J., Tonne J. M., Rakshit K., et al. (2018). Impaired β-cell glucokinase as an underlying mechanism in diet-induced diabetes. Disease Models & Mechanisms, 11(6), 1-12. https://doi.org/10.1242/dmm.033316

Meyerovich K., Ortis F., and Cardozo A. K. (2018). The non-canonical NF-κB pathway and its contribution to β-cell failure in diabetes. Journal of Molecular Endocrinology, 61(2), 1-6. https://doi.org/10.1530/jme-16-0183

Ngoc N. B., Lin Z. L., and Ahmed W. (2020). Diabetes: What challenges lie ahead for Vietnam? Annals Global Health, 86(1), 1-9. https://doi.org/10.5334/aogh.2526

Nguyen D. Q., Dieu Linh N., Thi Huong Giang T., Kim Thoa N., Tien Nga L., Thi Thanh Trung D., et al. (2024). Investigation of the effects of Huyet Rong germinated red rice on gene expression in diabetic mouse. Vietnam Journal of Biotechnology, 22(4), 530-542. https://doi.org/10.15625/vjbt-21736

Nunta R., Khemacheewakul J., Sommanee S., Mahakuntha C., Chompoo M., Phimolsiripol Y., et al. (2023). Extraction of gymnemic acid from Gymnema inodorum (Lour.) Decne. leaves and production of dry powder extract using maltodextrin. Scientific Reports, 13(1), 11193. https://doi.org/10.1038/s41598-023-38305-4

Ono Y., and Kataoka K. (2021). MafA, NeuroD1, and HNF1β synergistically activate the Slc2a2 (Glut2) gene in β-cells. Journal of Molecular Endocrinology, 67(3), 71-82. https://doi.org/10.1530/JME-20-0339

Pothuraju R., Sharma R. K., Chagalamarri J., Jangra S., and Kumar Kavadi P. (2014). A systematic review of Gymnema sylvestre in obesity and diabetes management. Journal of the Science of Food and Agriculture, 94(5), 834-840. https://doi.org/10.1002/jsfa.6458

Rai S., Kafle A., Devkota H. P., and Bhattarai A. (2023). Characterization of saponins from the leaves and stem bark of Jatropha curcas L. for surface-active properties. Heliyon, 9(5), e15807. https://doi.org/10.1016/j.heliyon.2023.e15807

Saeed R., Ahmed D., and Mushtaq M. (2022). Ultrasound-aided enzyme-assisted efficient extraction of bioactive compounds from Gymnema sylvestre and optimization as per response surface methodology. Sustainable Chemistry and Pharmacy, 29, 100818. https://doi.org/10.1016/j.scp.2022.100818

Skovsø S. (2014). Modeling type 2 diabetes in rats using high fat diet and streptozotocin. Journal of Diabetes Investigation, 5(4), 349-358. https://doi.org/10.1111/jdi.12235

Srinivasan K., and Perumal K. (2020). Extraction and purification of gymnemic acid from Gymnema sylvestre R.Br. Medicinal Plants: Biodiversity, Sustainable Utilization and Conservation. Springer, Singapore (521-529). https://doi.org/10.1007/978-981-15-1636-8_29

Tiwari P., Mishra B. N., and Sangwan N. S. (2014). Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. BioMed Research International, 2014, 830285. https://doi.org/10.1155/2014/830285

Weng X., Sun M., Gao H., Liu Z., Huang J., Liao X., et al. (2019). Germinated brown rice, a whole grain with health benefits for common chronic diseases. Food Science & Nutrition, 2, 119-136. https://scientificliterature.org/Nutrition/Nutrition-19-119.pdf

Yan Z., Gao J., Lv X., Yang W., Wen S., Tong H., et al. (2016). Quantitative evaluation and selection of reference genes for quantitative RT-PCR in mouse acute pancreatitis. BioMed Research International, 2016, 8367063. https://doi.org/10.1155/2016/8367063