Kersen (Muntingia calabura L.) Leaf Extract Reduces Blood Glucose Levels and Restores Pancreatic Islets in Alloxan-Induced Mice
DOI:
https://doi.org/10.29313/bcsms.v5i3.21661Keywords:
antidiabetic, hyperglycemia, Muntingia calabura L, kersen leaf extractAbstract
Abstract. Medicinal plants with hypoglycemic properties have long been used in traditional medicine for managing diabetes mellitus, although scientific evidence regarding their efficacy and mechanisms of action remains limited. Muntingia calabura L. (kersen) is a medicinal plant known to contain bioactive compounds with antioxidant and glucose-lowering potential. This study aimed to evaluate the antihyperglycemic effect of M. calabura leaf extract and its ability to repair damage to the pancreatic islets of Langerhans in hyperglycemic mice. A total of 24 male white mice (Mus musculus L.) were randomly divided into six groups: a normal control group, an alloxan-induced hyperglycemic control group, an alloxan plus glibenclamide group, and three treatment groups receiving kersen leaf extract at doses of 200, 400, and 800 mg/kg body weight, respectively. Hyperglycemia was induced using alloxan at a dose of 160 mg/kg body weight, and the extract was administered orally for 14 consecutive days. Blood glucose levels were measured, and pancreatic tissues were examined histologically to assess morphological changes in the islets of Langerhans. The results showed that mice treated with kersen leaf extract exhibited a significant reduction in blood glucose levels compared with the hyperglycemic control group (p<0.05). Histological analysis revealed substantial restoration of pancreatic architecture, characterized by increased islet size and β-cell density resembling those of normal mice. These findings suggest that kersen leaf extract possesses potent antihyperglycemic and β-cell regenerative properties, supporting its potential as a natural candidate for antidiabetic therapy.
References
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29. Krawinkel MB, Ludwig C, Swai ME, Yang RY, Chun KP, Habicht SD. Bitter gourd reduces elevated fasting plasma glucose levels in an intervention study among prediabetics in Tanzania. J Ethnopharmacol. 2018;216:1–7. doi:10.1016/j.jep.2018.01.016.
30. Fuangchan A, Sonthisombat P, Seubnukarn T, Chanouan P, Chotchaisuwat P, Sirigulsatien V, et al. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol.2011;134(2):422–428. doi:10.1016/j.jep.2010.12.045.
31. White PE, Król E, Szwengiel A, Tubacka M, Szczepankiewicz D, Staniek H, et al. Effects of bitter melon and a chromium propionate complex on symptoms of insulin resistance and type 2 diabetes in rat models. Biol Trace Elem Res. 2021;199:1013–1026. doi:10.1007/s12011-020-02202-y.
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33. Guillam MT, Hümmler E, Schaerer E, Wu JY, Birnbaum MJ, Beermann F, et al. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking GLUT-2. Nat Genet. 1997;17:327–330. doi:10.1038/ng1197-327.
34. Mahrosh HS, Mehmood R, Bukhari SA, Afzal G, Arif R. Investigation of hypoglycemic peptides derived from conserved regions of adMc1 to reveal their antidiabetic activities. Biomed Res Int. 2021;2021:5550180. doi:10.1155/2021/5550180.
2. Roglic G, Unwin N, Bennett H, Mathers C, Tuomilehto J, Nag S, et al. The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care. 2005;28(9):2130–2135. doi:10.2337/diacare.28.9.2130.
3. Xiao JB, Högger P. Dietary polyphenols and type 2 diabetes: current insights and future perspectives. Curr Med Chem. 2015;22(1):23–38. doi:10.2174/0929867321666140706130807.
4. Zhao Y, Liu YJ, Yi FZ, Zhang J, Xu ZH, Liu YH, et al. Type 2 diabetes mellitus impairs nasal immunity and increases the risk of hyposmia in COVID-19 mild pneumonia patients. Int Immunopharmacol. 2021;93:107406. doi:10.1016/j.intimp.2021.107406.
5. Salamone D, Rivellese AA, Vetrani C. The relationship between gut microbiota, short-chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre. Acta Diabetol. 2021;58(9):1131–1138. doi:10.1007/s00592-021-01727-5.
6. Karagöz IK, Karagöz A, Özkalaycı F, Doğan C, Kocabay G, Elbay A. Relation between platelet reactivity levels and diabetic retinopathy stage in patients with type 2 diabetes mellitus using multiplate whole blood aggregometry. Semin Ophthalmol. 2021;36(6):392–399. doi:10.1080/08820538.2021.1893759.
7. Hazarika R, Parida P, Neog B, Yadav RN. Binding energy calculation of GSK-3 protein of humans against some anti-diabetic compounds of Momordica charantia Linn (bitter melon). Bioinformation. 2012;8(6):251–254. doi:10.6026/97320630008251.
8. Bunyatyan ND, Bukhtiyarova IP, Drogovoz SZ, Kononenko AV, Olefir YV, Prokof’ev AB, et al. Influence of human biorhythms on blood glucose level and efficacy of hypoglycemic drugs: a review. Pharm Chem J.2017;51(5):399–401. doi:10.1007/s11094-017-1621-4.
9. Lee SH, Min KH, Han JS, Lee DH, Park DB, Jung WK, et al. Effects of brown alga Ecklonia cava on glucose and lipid metabolism in C57BL/KsJ-db/db mice, a model of type 2 diabetes mellitus. Food Chem Toxicol.2012;50(2):575–582. doi:10.1016/j.fct.2011.12.032.
10. Zhao C, Yang CF, Liu B, Lin L, Sarker SD, Nahar L, et al. Bioactive compounds from marine macroalgae and their hypoglycemic benefits. Trends Food Sci Technol. 2018;72:1–12. doi:10.1016/j.tifs.2017.12.001.
11. Fauchier L, Fauchier G, Bisson A, Bodin A, Herbert J, Angoulvant D, et al. Antidiabetic drug use and new-onset atrial fibrillation in patients with diabetes mellitus. Eur Heart J. 2021;42(Suppl 1):ehab724.0457. doi:10.1093/eurheartj/ehab724.0457.
12. Bays HJ. Sodium-glucose co-transporter type 2 (SGLT2) inhibitors: targeting the kidney to improve glycemic control in diabetes mellitus. Diabetes Ther. 2013;4(2):195–220.
13. Panigrahy SK, Bhatt R, Kumar AJ. Reactive oxygen species: sources, consequences and targeted therapy in type 2 diabetes. J Diabetes Ther. 2017;25(2):93–101.
14. Chaudhury A, Duvoor C, Reddy Dendi VS, Kraleti S, Chada A, Ravilla R, et al. Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Front Endocrinol (Lausanne). 2017;8:6.
15. Jung M, Park M, Lee HC, Kang YH, Kang ES, Kim SK. Antidiabetic agents from medicinal plants. Curr Med Chem. 2006;13(10):1203–1218. doi:10.2174/092986706776360860.
16. Khan V, Najmi AK, Akhtar M, Aqil M, Mujeed M, Pillai KK. A pharmacological appraisal of medicinal plants with antidiabetic potential. J Pharm Bioallied Sci. 2012;4(1):27–42.
17. Lee SH, Kang N, Kim EA, Heo SJ, Moon SH, Jeon BT, et al. Antidiabetogenic and antioxidative effects of octaphlorethol A isolated from the brown algae Ishige foliacea in streptozotocin-induced diabetic mice. Food Sci Biotechnol. 2014;23(4):1261–1266. doi:10.1007/s10068-014-0173-6.
18. Vinayagam R, Xiao JB, Xu BJ. An insight into anti-diabetic properties of dietary phytochemicals. Phytochem Rev.2017;16(3):535–553. doi:10.1007/s11101-017-9496-2.
19. Mar K, Fassnacht M, Führer-Sakel D, Honegger JB, Weber MM, Kroiss M. The diagnosis and management of endocrine side effects of immune checkpoint inhibitors. Dtsch Arztebl Int. 2021;118(19):33724917.
20. Murei A, Pillay K, Samie AJ. Syntheses, characterization, and antibacterial evaluation of P. grandiflora extracts conjugated with gold nanoparticles. J Nanomater. 2021;2021:1–10.
21. Sur S, Steele R, Aurora R, Varvares M, Schwetye KE, Ray RB. Bitter melon prevents the development of 4-NQO-induced oral squamous cell carcinoma in an immunocompetent mouse model by modulating immune signaling. Cancer Prev Res. 2018;11(4):191–201. doi:10.1158/1940-6207.CAPR-17-0237.
22. Alexander A, Agrawal M, Uddin A, Siddique S, Shehata AM, Shaker MA, et al. Recent expansions of novel strategies towards drug targeting into the brain. Int J Nanomedicine. 2019;14:5895–5909.
23. Agrawal M, Saraf S, Saraf S, Dubey SK, Puri A, Patel RJ, et al. Recent strategies and advances in the fabrication of nanolipid carriers and their application towards brain targeting. J Control Release. 2020;321:372–415.
24. Preiato VL, Salvagni S, Ricci C, Ardizzoni A, Pelusi C. Diabetes mellitus induced by immune checkpoint inhibitors: type 1 diabetes variant or new clinical entity? Rev Endocr Metab Disord. 2021;22(2):337–349. doi:10.1007/s11154-020-09618-w.
25. Khanna P, Jain SC, Panagariya A, Dixit VP. Hypoglycemic activity of polypeptide-P from a plant source. J Nat Prod. 1981;44(5):648–655. doi:10.1021/np50018a002.
26. Iseli TJ, Nigel T, Zeng XY, Cooney GJ, Kraegen EW, Yao S, et al. Activation of AMPK by bitter melon triterpenoids involves CaMKKβ. PLoS One. 2013;8(4):e62309. doi:10.1371/journal.pone.0062309.
27. Jirousek MR, Johnson TO, Jacques E. Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat Rev Drug Discov. 2002;1(9):696–709.
28. Singh N, Gupta M. Regeneration of beta cells in the islets of Langerhans of the pancreas of alloxan diabetic rats by acetone extract of Momordica charantia (Linn.) fruits. Indian J Exp Biol. 2007;45:1055–1062.
29. Krawinkel MB, Ludwig C, Swai ME, Yang RY, Chun KP, Habicht SD. Bitter gourd reduces elevated fasting plasma glucose levels in an intervention study among prediabetics in Tanzania. J Ethnopharmacol. 2018;216:1–7. doi:10.1016/j.jep.2018.01.016.
30. Fuangchan A, Sonthisombat P, Seubnukarn T, Chanouan P, Chotchaisuwat P, Sirigulsatien V, et al. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol.2011;134(2):422–428. doi:10.1016/j.jep.2010.12.045.
31. White PE, Król E, Szwengiel A, Tubacka M, Szczepankiewicz D, Staniek H, et al. Effects of bitter melon and a chromium propionate complex on symptoms of insulin resistance and type 2 diabetes in rat models. Biol Trace Elem Res. 2021;199:1013–1026. doi:10.1007/s12011-020-02202-y.
32. Duddela S, Nataraj Sekhar P, Padmavati GV, Banerjee AK, Murty USN. Probing the structure of human glucose transporter 2 and analysis of protein–ligand interactions. Med Chem Res. 2010;19:836–853. doi:10.1007/s00044-009-9234-4.
33. Guillam MT, Hümmler E, Schaerer E, Wu JY, Birnbaum MJ, Beermann F, et al. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking GLUT-2. Nat Genet. 1997;17:327–330. doi:10.1038/ng1197-327.
34. Mahrosh HS, Mehmood R, Bukhari SA, Afzal G, Arif R. Investigation of hypoglycemic peptides derived from conserved regions of adMc1 to reveal their antidiabetic activities. Biomed Res Int. 2021;2021:5550180. doi:10.1155/2021/5550180.
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