Study of Antidiabetic Activities of Carvacrol and Thymol with Structure-Based Method
Keywords:
type 2 diabetes mellitus, obesity, oleuropein, hydroxytyrosolAbstract
Background: The role of natural ingredients such as carvacrol and thymol in walnut leaves (Juglans regia L) could be a breakthrough for treating hyperglycemia and obesity.
Objective: To determine the potential carvacrol and thymol isolates of walnut oil (Juglans regia) in silico, which act on enzyme 11 dehydrogenase 1, fructose receptor 1,6 bisphosphatase, and PPRγ in the treatment of type DM 2.
Methods: Investigate carvacrol, thymol, and their amino acid interactions in silico using Biovia and Autodocks Tool software. Molecular docking between the ligand and the receptor was performed using Autodock 4 version 1.56 using a generic evolutionary algorithm (rigid docking method).
Future research: Computational modeling is the initial research that can be carried out before conducting in vivo and in vitro, further studies to investigate the potential of carvacrol and thymol in overcoming insulin resistance.
Results: The results showed the potential energy produced by the four compounds for each protein in kcal/mol (11βHSD1, F1.6BP1, PPRγ), which are oleuropein (-7.94, -6.83, -8.99), hydroxytyrosol (-3.80, - 5.52, -5.15).
Conclusion: The study results found that these four isolates could be potential anti-diabetic agents.
Downloads
References
H. M. Lawler, C. M. Underkofler, P. A. Kern, C. Erickson, B. Bredbeck, and N. Rasouli, “Adipose Tissue Hypoxia, Inflammation, and Fibrosis in Obese Insulin-Sensitive and Obese Insulin-Resistant Subjects,” J Clin Endocrinol Metab, vol. 101, no. 4, pp. 1422–1428, Apr. 2016, doi: 10.1210/jc.2015-4125.
H. Kahleova, S. Dort, R. Holubkov, and N. Barnard, “A Plant-Based High-Carbohydrate, Low-Fat Diet in Overweight Individuals in a 16-Week Randomized Clinical Trial: The Role of Carbohydrates,” Nutrients, vol. 10, no. 9, p. 1302, Sep. 2018, doi: 10.3390/nu10091302.
P. Morigny, J. Boucher, P. Arner, and D. Langin, “Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics,” Nat Rev Endocrinol, vol. 17, no. 5, pp. 276–295, May 2021, doi: 10.1038/s41574-021-00471-8.
J. Miranda, I. Eseberri, A. Lasa, and M. P. Portillo, “Lipid metabolism in adipose tissue and liver from diet-induced obese rats: a comparison between Wistar and Sprague-Dawley strains,” J Physiol Biochem, vol. 74, no. 4, pp. 655–666, Nov. 2018, doi: 10.1007/s13105-018-0654-9.
J.-E. Lee, H. Schmidt, B. Lai, and K. Ge, “Transcriptional and Epigenomic Regulation of Adipogenesis,” Mol Cell Biol, vol. 39, no. 11, Jun. 2019, doi: 10.1128/MCB.00601-18.
J. Joseph, R. D. Shamburek, E. K. Cochran, P. Gorden, and R. J. Brown, “Lipid Regulation in Lipodystrophy Versus the Obesity-Associated Metabolic Syndrome: The Dissociation of HDL-C and Triglycerides,” J Clin Endocrinol Metab, vol. 99, no. 9, pp. E1676–E1680, Sep. 2014, doi: 10.1210/jc.2014-1878.
R. H. Oakley and J. A. Cidlowski, “The biology of the glucocorticoid receptor: New signaling mechanisms in health and disease,” Journal of Allergy and Clinical Immunology, vol. 132, no. 5, pp. 1033–1044, Nov. 2013, doi: 10.1016/j.jaci.2013.09.007.
M. Bekhbat, E. R. Glasper, S. A. Rowson, S. D. Kelly, and G. N. Neigh, “Measuring corticosterone concentrations over a physiological dynamic range in female rats,” Physiol Behav, vol. 194, pp. 73–76, Oct. 2018, doi: 10.1016/j.physbeh.2018.04.033.
A. Stomby, J. Otten, M. Ryberg, R. Andrew, B. R. Walker, and T. Olsson, “Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus,” Eur J Endocrinol, vol. 182, no. 4, pp. 447–457, Apr. 2020, doi: 10.1530/EJE-19-0901.
K. Peng et al., “11β-Hydroxysteroid Dehydrogenase Type 1(11β-HSD1) mediates insulin resistance through JNK activation in adipocytes,” Sci Rep, vol. 6, no. 1, p. 37160, Dec. 2016, doi: 10.1038/srep37160.
X. Zhang, S. Yang, J. Chen, and Z. Su, “Unraveling the Regulation of Hepatic Gluconeogenesis,” Front Endocrinol (Lausanne), vol. 9, Jan. 2019, doi: 10.3389/fendo.2018.00802.
D. J. Timson, “Fructose 1,6- bis phosphatase: getting the message across,” Biosci Rep, vol. 39, no. 3, Mar. 2019, doi: 10.1042/BSR20190124.
A. Pinto et al., “International practices in the dietary management of fructose 1-6 biphosphatase deficiency,” Orphanet J Rare Dis, vol. 13, no. 1, p. 21, Dec. 2018, doi: 10.1186/s13023-018-0760-3.
N. Waseda, H. Satoh, C. Yoshida, F. Ikeda, A. Kanazawa, and H. Watada, “Effects of SGLT2 Inhibitors on Insulin Secretion and Insulin Resistance—Results from a Cross-Sectional Study,” Diabetes, vol. 67, no. Supplement 1, pp. 1187-P, Jul. 2018, doi: 10.2337/db18-1187-P.
H. Moravej et al., “Chemical Composition and the Effect of Walnut Hydrosol on Glycemic Control of Patients with Type 1 Diabetes,” Int J Endocrinol Metab, vol. 14, no. 1, Jan. 2016, doi: 10.5812/ijem.34726.
