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

Olusoji Adebusoye Oyesola; Oluwaseye Emmanuel Olayemi; Solomon Olawale Adebanjo; Temitope Esther Ogungbenle; Eunice Oluwabunmi Ojo-Adebayo

doi:10.20883/medical.e1286

Authors

Olusoji Adebusoye Oyesola Department of Physiology, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Ogun State, Nigeria https://orcid.org/0000-0002-5072-1696
Oluwaseye Emmanuel Olayemi Department of Physiology, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Ogun State, Nigeria https://orcid.org/0009-0009-1764-608X
Solomon Olawale Adebanjo Department of Physiology, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Ogun State, Nigeria https://orcid.org/0009-0002-3655-3005
Temitope Esther Ogungbenle Department of Physiology, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Ogun State, Nigeria https://orcid.org/0009-0007-9093-5836
Eunice Oluwabunmi Ojo-Adebayo Department of Physiology, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Ogun State, Nigeria https://orcid.org/0009-0005-0167-9056

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;45:S17–38. https://doi.org/10.2337/dc22-S002.

Weir GC, Bonner-Weir S. Five Stages of Evolving Beta-Cell Dysfunction During Progression to Diabetes. Diabetes. 2004;53:S16–21. https://doi.org/10.2337/diabetes.53.suppl_3.S16.

Eguchi N, Vaziri ND, Dafoe DC, Ichii H. The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes. IJMS. 2021;22:1509. https://doi.org/10.3390/ijms22041509.

Wang J, Wang H. Oxidative Stress in Pancreatic Beta Cell Regeneration. Oxidative Medicine and Cellular Longevity. 2017;2017:1930261. https://doi.org/10.1155/2017/1930261.

Yuan M, Konstantopoulos N, Lee J, Hansen L, Li Z-W, Karin M, Shoelson SE. Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of Ikkβ. Science. 2001;293:1673–7. https://doi.org/10.1126/science.1061620.

Arkan MC, Hevener AL, Greten FR, Maeda S, Li Z-W, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M. IKK-β links inflammation to obesity-induced insulin resistance. Nat Med. 2005;11:191–8. https://doi.org/10.1038/nm1185.

Assmann A, Hinault C, Kulkarni RN. Growth factor control of pancreatic islet regeneration and function. Pediatric Diabetes. 2009;10:14–32. https://doi.org/10.1111/j.1399-5448.2008.00468.x.

Lee Y-S, Lee C, Choung J-S, Jung H-S, Jun H-S. Glucagon-Like Peptide 1 Increases β-Cell Regeneration by Promoting α- to β-Cell Transdifferentiation. Diabetes. 2018;67:2601–14. https://doi.org/10.2337/db18-0155.

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;51:1862–72. https://doi.org/10.1007/s00125-008-1087-8.

Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50:537–46.

Rorsman P, Ashcroft FM. Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men. Physiological Reviews. 2018;98:117–214. https://doi.org/10.1152/physrev.00008.2017.

Khan N, Mukhtar H. Tea Polyphenols in Promotion of Human Health. Nutrients. 2018;11:39. https://doi.org/10.3390/nu11010039.

Lan Chi NT, Narayanan M, Chinnathambi A, Govindasamy C, Subramani B, Brindhadevi K, Pimpimon T, Pikulkaew S. RETRACTED: Fabrication, characterization, anti-inflammatory, and anti-diabetic activity of silver nanoparticles synthesized from Azadirachta indica kernel aqueous extract. Environmental Research. 2022;208:112684. https://doi.org/10.1016/j.envres.2022.112684.

Chattopadhyay RR. A comparative evaluation of some blood sugar lowering agents of plant origin. Journal of Ethnopharmacology. 1999;67:367–72. https://doi.org/10.1016/S0378-8741(99)00095-1.

Yakubu TM, Salau AK, Oloyede OB., Akanji MA. Effect of aqueous leaf extract of Ficus exasperata in alloxan-induced diabetic Wistar rats. Cam J Exp Bio. 2019;10:36. https://doi.org/10.4314/cajeb.v10i1.5.

Shah NA, Khan MR. Antidiabetic Effect of Sida cordata in Alloxan Induced Diabetic Rats. BioMed Research International. 2014;2014:1–15. https://doi.org/10.1155/2014/671294.

Nazir N, Zahoor M, Ullah R, Ezzeldin E, Mostafa GAE. Curative Effect of Catechin Isolated from Elaeagnus Umbellata Thunb. Berries for Diabetes and Related Complications in Streptozotocin-Induced Diabetic Rats Model. Molecules. 2020;26:137. https://doi.org/10.3390/molecules26010137.

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 ( Ocimum basilicum L.) seeds using response surface methodology. Journal of Advanced Research. 2017;8:235–44. https://doi.org/10.1016/j.jare.2017.01.003.

Diehl K, Hull R, Morton D, Pfister R, Rabemampianina Y, Smith D, Vidal J, Vorstenbosch CVD. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J of Applied Toxicology. 2001;21:15–23. https://doi.org/10.1002/jat.727.

Gribble FM, Reimann F. Sulphonylurea action revisited: the post-cloning era. Diabetologia. 2003;46:875–91. https://doi.org/10.1007/s00125-003-1143-3.

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

Chattopadhyay RR. Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: Part II. Journal of Ethnopharmacology. 2003;89:217–9. https://doi.org/10.1016/j.jep.2003.08.006.

Hybertson BM, Gao B. Role of the Nrf2 signaling system in health and disease. Clinical Genetics. 2014;86:447–52. https://doi.org/10.1111/cge.12474.

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 J-S, Melton DA. RETRACTED: Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation. Cell. 2013;153:747–58. https://doi.org/10.1016/j.cell.2013.04.008.

Campbell JE, Drucker DJ. Pharmacology, Physiology, and Mechanisms of Incretin Hormone Action. Cell Metabolism. 2013;17:819–37. https://doi.org/10.1016/j.cmet.2013.04.008.