Effect of glibenclamide, catechin and ethanolic neem leaf extract on pacreatic beta cell regeneration in alloxan-induced diabetic rat

Olusoji Oyesola; Oluwaseye Olayemi; Solomon Adebanjo; Temitope Ogungbenle; Eunice Ojo-Adebayo

doi:10.20883/medical.e1286

Authors

Oyesola Olusoji Adebusoye Department of Physiology, Olabisi Onabanjo University
Oluwaseye Olayemi Department of Physiology, Olabisi Onabanjo University https://orcid.org/0009-0009-1764-608X
Solomon Adebanjo
Temitope Ogungbenle
Eunice Ojo-Adebayo

DOI:

https://doi.org/10.20883/medical.e1286

Keywords:

Diabetes mellitus, glibenclamide, catechin, neem leaf, β-cell regeneration

Abstract

Background. Type 1 diabetes mellitus is characterized by the destruction of pancreatic β-cells, leading to insulin deficiency and persistent hyperglycemia. This study investigates the regenerative potential of glibenclamide, catechin, and ethanolic neem leaf extract on β-cell function and architecture in alloxan-induced diabetic rats.

Material and methods. Thirty-five male Sprague-Dawley rats were divided into five groups: normal control (Group A), diabetic control (Group B), glibenclamide-treated (Group C), catechin-treated (Group D), and ethanolic neem leaf extract -treated (Group E). Diabetes was induced using alloxan monohydrate (150 mg/kg, i.p.), and treatments were administered orally for 14 days.

Results and conclusions. Biochemical analysis revealed marked hyperglycemia and hypoinsulinemia in diabetic controls, alongside elevated oxidative stress (↑MDA, ↓GSH, SOD, CAT, TAC, TP) and inflammatory markers (NF-κB, IL-6). Treatment with glibenclamide, catechin, and ethanolic neem leaf extract significantly ameliorated these disturbances, with neem producing the most notable improvements. Ethanolic neem leaf extract -treated rats showed near-normal insulin levels, enhanced antioxidant status, and suppressed inflammatory responses. Furthermore, key regenerative markers (IGF-1, GLP-1, EGF, HGF, and betatrophin) were favorably modulated, particularly in the neem group, indicating stimulation of β-cell neogenesis and survival pathways. Histological examination supported the biochemical findings: ethanolic neem leaf extract-treated pancreases exhibited well-preserved islets and restored tissue architecture, contrasting with the degenerative features seen in diabetic controls. These findings suggest that ethanolic neem leaf extract, beyond its hypoglycemic and antioxidant effects, promotes β-cell regeneration through anti-inflammatory and growth factor-mediated mechanisms. This positions neem as a promising phytotherapeutic agent for diabetes management and β-cell restoration.

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References

American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S17-S38. doi: 10.2337/dc22-S002. PMID: 34964875.

Weir GC, Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes. 2004 Dec;53 Suppl 3:S16-21. doi: 10.2337/diabetes.53.suppl_3.s16. PMID: 15561905.

Eguchi, N., Vaziri, N. D., Dafoe, D. C., & Ichii, H. The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes. International journal of molecular sciences, 2021;22(4), 1509. https://doi.org/10.3390/ijms22041509

Wang J, Wang H. Oxidative Stress in Pancreatic Beta Cell Regeneration. Oxid Med Cell Longev. 2017;2017:1930261. doi: 10.1155/2017/1930261. Epub 2017 Aug 3. PMID: 28845211; PMCID: PMC5560096.

Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science. 2001 Aug 31;293(5535):1673-7. doi: 10.1126/science.1061620. Erratum in: Science 2002 Jan 11;295(5553):277. PMID: 11533494.

Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z. W., Long, J. M., et al. IKK-beta links inflammation to obesity-induced insulin resistance. Nature medicine, 2005;11(2), 191–198. https://doi.org/10.1038/nm1185

Assmann, A., Hinault, C., & Kulkarni, R. N. Growth factor control of pancreatic islet regeneration and function. Pediatric diabetes, 2009;10(1), 14–32. https://doi.org/10.1111/j.1399-5448.2008.00468.x

Lee YS, Lee C, Choung JS, Jung HS, Jun HS. Glucagon-Like Peptide 1 Increases β-Cell Regeneration by Promoting α- to β-Cell Transdifferentiation. Diabetes. 2018 Dec;67(12):2601-2614. doi: 10.2337/db18-0155. Epub 2018 Sep 26. PMID: 30257975.

Agudo J, Ayuso E, Jimenez V, Salavert A, Casellas A, Tafuro S, Haurigot V, Ruberte J, Segovia JC, Bueren J, Bosch F. IGF-I mediates regeneration of endocrine pancreas by increasing beta cell replication through cell cycle protein modulation in mice. Diabetologia. 2008 Oct;51(10):1862-72. doi: 10.1007/s00125-008-1087-8. Epub 2008 Jul 29. PMID: 18663428.

Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50(6):537-46. PMID: 11829314.

Rorsman P, Ashcroft FM. Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men. Physiol Rev. 2018 Jan 1;98(1):117-214. doi: 10.1152/physrev.00008.2017. PMID: 29212789; PMCID: PMC5866358.

Khan N, Mukhtar H. Tea Polyphenols in Promotion of Human Health. Nutrients. 2018 Dec 25;11(1):39. doi: 10.3390/nu11010039. PMID: 30585192; PMCID: PMC6356332.

Lan Chi NT, Narayanan M, Chinnathambi A, Govindasamy C, Subramani B, Brindhadevi K, Pimpimon T, Pikulkaew S. Fabrication, characterization, anti-inflammatory, and anti-diabetic activity of silver nanoparticles synthesized from Azadirachta indica kernel aqueous extract. Environ Res. 2022 May 15;208:112684. doi: 10.1016/j.envres.2022.112684. Epub 2022 Jan 5. PMID: 34995544.

Chattopadhyay RR. A comparative evaluation of some blood sugar lowering agents of plant origin. J Ethnopharmacol. 1999 Nov 30;67(3):367-72. doi: 10.1016/s0378-8741(99)00095-1. PMID: 10617074.

Yakubu TM, Salau AK, Oloyede OB, Akanji MA. Effect of aqueous leaf extract of Ficusexasperata in alloxan-induced diabetic Wistar rats. Cam J Exp Biol. 2014;10(01):35-43.

Shah NA, Khan MR. Antidiabetic effect of Sidacordata in alloxan induced diabetic rats. Biomed Res Int. 2014;2014:671294. doi: 10.1155/2014/671294. Epub 2014 Jul 9. PMID: 25114914; PMCID: PMC4119905.

Nazir N, Zahoor M, Ullah R, Ezzeldin E, Mostafa GAE. Curative Effect of Catechin Isolated from ElaeagnusUmbellataThunb. Berries for Diabetes and Related Complications in Streptozotocin-Induced Diabetic Rats Model. Molecules. 2020 Dec 30;26(1):137. doi: 10.3390/molecules26010137. PMID: 33396845; PMCID: PMC7794731.

Dholi SK, Raparla R, Mankala SK, Nagappan K. Invivo Antidiabetic evaluation of Neem leaf extract in alloxan induced rats. Journal of applied Pharmaceutical science. 2011 Jun 30(Issue):100-5.

Nazir S, Wani IA, Masoodi FA. Extraction optimization of mucilage from Basil (Ocimumbasilicum L.) seeds using response surface methodology. J Adv Res. 2017 May;8(3):235-244. doi: 10.1016/j.jare.2017.01.003. Epub 2017 Feb 2. PMID: 28239494; PMCID: PMC5315439.

Diehl, K. H., Hull, R., Morton, D., Pfister, R., Rabemampianina, Y., Smith, D., et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes. Journal of applied toxicology : JAT, 2001;21(1), 15–23. https://doi.org/10.1002/jat.727

Gribble FM, Reimann F. Sulphonylurea action revisited: the post-cloning era. Diabetologia. 2003 Jul;46(7):875-91. doi: 10.1007/s00125-003-1143-3. Epub 2003 Jun 18. PMID: 12819907.

Khan N, Mukhtar H. Tea and health: studies in humans. Curr Pharm Des. 2013;19(34):6141-7. doi: 10.2174/1381612811319340008. PMID: 23448443; PMCID: PMC4055352.

Chattopadhyay RR. Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: part II. J Ethnopharmacol. 2003 Dec;89(2-3):217-9. doi: 10.1016/j.jep.2003.08.006. PMID: 14611885.

Hybertson BM, Gao B. Role of the Nrf2 signaling system in health and disease. Clin Genet. 2014 Nov;86(5):447-52. doi: 10.1111/cge.12474. Epub 2014 Sep 16. PMID: 25099075.

Biswas K, Chattopadhyay I, Banerjee RK, Bandyopadhyay U. Biological activities and medicinal properties of neem (Azadirachta indica). Current science. 2002 Jun 10:1336-45.

Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic β cell proliferation. Cell. 2013 May 9;153(4):747-58. doi: 10.1016/j.cell.2013.04.008. Epub 2013 Apr 25. Retraction in: Cell. 2017 Jan 12;168(1-2):326. doi: 10.1016/j.cell.2016.12.017. PMID: 23623304; PMCID: PMC3756510.

Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013 Jun 4;17(6):819-837. doi: 10.1016/j.cmet.2013.04.008. Epub 2013 May 16. PMID: 23684623.