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. 2024 Sep 30;33(3):261-269.
doi: 10.7570/jomes23080. Epub 2024 Aug 5.

Combination of Metformin and Epigallocatechin-3-Gallate Lowers Cortisol, 11β-Hydroxysteroid Dehydrogenase Type 1, and Blood Glucose Levels in Sprague Dawley Rats with Obesity and Diabetes

Diana Mazaya Atsarina  1 , Nyoman Suci Widyastiti  2 , Muflihatul Muniroh  3 , Neni Susilaningsih  4 , Nani Maharani  5
Affiliations

Combination of Metformin and Epigallocatechin-3-Gallate Lowers Cortisol, 11β-Hydroxysteroid Dehydrogenase Type 1, and Blood Glucose Levels in Sprague Dawley Rats with Obesity and Diabetes

Diana Mazaya Atsarina et al. J Obes Metab Syndr. .

Abstract

Background: The combined effects of metformin and epigallocatechin-3-gallate (EGCG) on cortisol, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), and blood glucose levels have not been investigated. This study evaluated the effectiveness of combining EGCG with metformin in regulating those levels in a rat model of diet-induced diabetes and obesity.

Methods: Thirty diabetic and obese rats on a high-fat diet were treated daily for 28 days with EGCG (100 mg/kg of body weight/day), metformin (200 mg/kg of body weight/day), or both. Control groups comprised lean rats, untreated obese diabetic rats, and metformin-only-treated rats. Blood samples were collected to measure cortisol and fasting blood glucose (FBG) levels and liver tissue samples were examined for 11β-HSD1 levels.

Results: Rats receiving combination therapy had significantly reduced cortisol levels (from 36.70±15.13 to 31.25±7.10 ng/mL) compared with the untreated obese diabetic rats but not the rats receiving monotherapy. Rats receiving combination therapy and EGCG monotherapy had significantly lower 11β-HSD1 levels compared with the untreated obese diabetic rats (92.68±10.82 and 93.74±18.11 ng/L vs. 120.66±14.00 ng/L). Combination therapy and metformin monotherapy significantly reduced FBG levels (440.83±133.30 to 140.50±7.36 mg/dL and 480.67±86.32 to 214.17±102.78 mg/dL, respectively) by approximately 68.1% and 55.4% compared with rats receiving EGCG monotherapy and untreated obese diabetic rats.

Conclusion: Combining EGCG with metformin exhibited synergistic effects compared with monotherapy for managing diabetes, leading to improved outcomes in reduction of baseline cortisol levels along with reduction in 11β-HSD1 and blood glucose levels.

Keywords: 11-Beta-hydroxysteroid dehydrogenase type 1; Blood glucose; Diabetes mellitus; Epigallocatechin gallate; Hydrocortisone; Obesity.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mean cortisol level. (A) The mean cortisol levels before and after the test are reported as mean±2 standard deviation (SD; n=6 rats). (B) The mean difference in cortisol levels between pre- and post-test without outliers is presented as mean±2 SD (n=6 rats; except for n in the positive control group=5 rats). *P<0.05; †P<0.01. NC, negative control; PC, positive control; EGCG, epigallocatechin-3-gallate.
Figure 2
Figure 2
Mean 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) level. The mean 11β-HSD1 levels were analyzed and presented as mean±2 standard deviation (n=6 rats). *P<0.05; †P<0.001. NC, negative control; PC, positive control; EGCG, epigallocatechin-3-gallate.
Figure 3
Figure 3
Mean fasting blood glucose (FBG) level. (A) Mean FBG levels were compared pre- and post-test in each group. The values are presented as mean±2 standard deviation (SD; n=6 rats). (B) The mean difference in FBG levels pre- and post-test was analyzed. The values are presented as mean±2 SD (n=6 rats). *P<0.05; †P<0.01; ‡P<0.001. NC, negative control; PC, positive control; EGCG, epigallocatechin-3-gallate.
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References

    1. Ganesan N, Priya J, Devi G. Estimation of cortisol in type II diabetes mellitus among South Indian population. Drug Invent Today. 2019;12:2074.
    1. Almeida C, Monteiro C, Silvestre S. Inhibitors of 11β-hydroxy-steroid dehydrogenase type 1 as potential drugs for type 2 diabetes mellitus: a systematic review of clinical and in vivo preclinical studies. Sci Pharm. 2021;89:5. doi: 10.3390/scipharm89010005. - DOI
    1. Dias JP, Joseph JJ, Kluwe B, Zhao S, Shardell M, Seeman T, et al. The longitudinal association of changes in diurnal cortisol features with fasting glucose: MESA. Psychoneuroendocrinology. 2020;119:104698. doi: 10.1016/j.psyneuen.2020.104698. - DOI - PMC - PubMed
    1. Dammann C, Stapelfeld C, Maser E. Expression and activity of the cortisol-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 is tissue and species-specific. Chem Biol Interact. 2019;303:57–61. doi: 10.1016/j.cbi.2019.02.018. - DOI - PubMed
    1. Scheen AJ. Targeting the metabolic pathway of cortisol as a potential therapy of type 2 diabetes. Med Mal Metab. 2016;10:725–31. doi: 10.1016/S1957-2557(16)30211-5. - DOI

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