Effects of Napoleonae imperialis leaf extract and fractions on metabolic signaling and glycemic control in streptozotocin-induced diabetic rats
Napoleonaea imperialis has been investigated for its potential antidiabetic effects due to its reported bioactive phytochemicals, although the underlying molecular mechanisms remain incompletely understood. The current study evaluated the effects of crude extract and fractions from N. imperialis leaves on G-protein-coupled receptors (GPCRs), AMP-activated protein kinase (AMPK), cyclic AMP (cAMP), insulin, glucagon, and glycated hemoglobin (HbA1c) in streptozotocin-induced diabetic rats. In phase one, 42 male albino rats of mean weight 140 g were divided into seven groups (n = 6/group): Group 1 (normal control), Group 2 (diabetic control), Group 3 (drug control), Groups 4, 5, and 6 were the test groups administered 250, 500, and 1,000 mg/kg of the crude extract, respectively, and Group 7 was normal rats receiving 500 mg/kg of the extract only. There was a significant (p < 0.05) decrease in cAMP, glucagon, blood glucose, and HbA1c, as well as a significant (p < 0.05) increase in GPCR, insulin, and AMPK, in Groups 3–7 compared with Group 2. In phase two, 54 animals (mean weight, 140 g) were divided into nine groups (n = 6/group): Group 1 (normal control), Group 2 (diabetic control), Group 3 (drug control), and Groups 4–9 received Fractions 1–6, respectively, for 28 days. The results showed that Fractions 2, 5, and 6 (Groups 5, 8, and 9) significantly reduced cAMP, glucagon, blood glucose, and HbA1c, and increased GPCR, insulin, and AMPK, compared with Group 2. These findings suggest that the crude extract and fractions of N. imperialis ameliorated the studied indicators of diabetes and its complications in streptozotocin-induced diabetic rats. The possible synergistic action of the bioactive agents present in the leaves can account for these effects.
- Adewole S, Ojewole J. Protective effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats. Afr J Tradit Complement Altern Med. 2008;6(1):30-41. doi: 10.4314/ajtcam.v6i1.57071
- Lanjhiyana S, Garabadu D, Ahirwar D, et al. Hypoglycemic activity studies on root extracts of Murraya koenigii root in Alloxan-induced diabetic rats. J Nat Prod Plant Resour. 2011;1(2):91-104.
- Liu B, Wang Y, Zhang Y, Yan B. Mechanisms of protective effects of SGLT2 inhibitors in cardiovascular disease and renal dysfunction. Curr Top Med Chem. 2019;19(20):1818-1849. doi: 10.2174/1568026619666190828161409
- Brantner A, Al-Ajlani M, Zhou Y, Zhao H, Bian B. Screening for biological activities of the traditional Chinese medicine Fang Feng Tong Shen San. Int J Pharm Sci Res. 2017;8(8):3278-3286.
- Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047-1053. doi: 10.2337/diacare.27.5.1047
- Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine. 2019;47(1):22-27. doi: 10.1016/j.mpmed.2018.10.004
- Sudasinghe HP, Peiris DC. Hypoglycemic and hypolipidemic activity of aqueous leaf extract of Passiflora suberosa L. PeerJ. 2018;6:e4389. doi: 10.7717/peerj.4389
- Chaudhury A, Duvoor C, Reddy VS, et al. Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management. Front Endocrinol. 2017;8:6. doi: 10.3389/fendo.2017.00006
- Usman B, Sharma N, Satija S, et al. Recent developments in alpha-glucosidase inhibitors for management of type-2 diabetes: An update. Curr Pharm Des. 2019;25(23):2510-2525. doi: 10.2174/1381612825666190717104547
- Lankatillake C, Huynh T, Dias DA. Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants. Plant Methods. 2019;15:105. doi: 10.1186/s13007-019-0487-8
- Aloh GS, Obeagu EI, Odo CE, Kanu UG, Mba OJ. Effect of methanol extract of Napoleonae imperialis on free radical scavengers and lipid profile of Wistar albino rats. Eur J Pharm Med Res. 2015;2(2):140-154.
- Mba OJ, Omodamiro OD, Aja OA, Azubuike NJ, Okafor PN. Antidiabetic and antioxidant potentials of methanol leaf extract of Napoleonae imperialis in streptozotocin induced diabetic albino rats. J Biol Sci Mol Res. 2023;1(4):194-203.
- Mba OJ, Omodamiro OD, Okafor PN, Maduagwu EN. Hepatoprotective effects of methanol leaf extract of Napoleonae imperialis in streptozotocin induced diabetic albino rats. World J Pharm Sci Res. 2023;12(5):85-99.
- Nayak SS, Pattabiraman TN. A new colorimetric method for the estimation of glycosylated haemoglobin. Clin Chim Acta. 1981;109(3):267-274. doi: 10.1016/0009-8981(81)90312-0
- Kavalali G, Tuncel H, Goksel S, Hatemi HH. Hypoglycemic activity of Urtica pilurifera in streptozotocin-diabetic rats. J Ethnopharmacol. 2003;84(2-3):241-245. doi: 10.1016/s0378-8741(02)00315-x
- Sellamuthu PS, Muniappan BP, Perumal SM, Kandasamy M. Antihyperglycemic effect of mangiterin in streptozotocin induced diabetic rats. J Health Sci. 2009;55(2):206-214. doi: 10.1248/jhs.55.206
- Courtois P, Jijakli H, Ladriere L, Oguzhan B, Sener A, Malaisses W. Pharmacodynamics, insulinotropic action and hypoglycemic effect of nateglinide and glibenclamide in normal and diabetic rats. Int J Mol Med. 2003;11(1):105-109. doi: 10.3892/ijmm.11.1.105
- Mba OJ, Aloh GS, Nwachukwu KC, Michael PO. Phytochemical Characterization, Acute Toxicity Studies of the Methanol Extract of Napoleonae imperialis Leaves. J Genet Cell Biol. 2020;3(3):194-198.
- Kondeti VK, Badri KR, Maddirala DR, Thur SM, Fatima SS, Kasetti RB. Effect of Plerocampus santalinus bark, on blood glucose, serum lipids, plasma insulin and hepatic carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats. Food Chem Toxicol. 2010;48(5):1281-1287. doi: 10.1016/j.fct.2010.02.023
- International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32(7):1327-1334. doi: 10.2337/dc09-9033
- Luangpiom A, Kourjampa W, Junaimaung T. Anti-hyperglycemic properties of Moringa oleifera Lam. Aqueous leaf extract in normal and mildly diabetic mice. Br J Pharmacol Toxicol. 2013;4(3):106-109. doi: 10.19026/bjpt.4.5371
- Gandi RG, Sasikumar PO. Antidiabetic effect of Merremia emarginata Burm. F. in streptozotocin induced diabetic rats. Asian Pac J Trop Biomed. 2012;2(4):281-286. doi: 10.1016/s2221-1691(12)60023-9
- Sharma M, Siddique MW, Shamim AM, Gyanesh S, Pillai KK. Evaluation of antidiabetic and antioxidant effects of Seabuckthorn (Hippophae rhamnoides L.) in streptozotocin-nicotinamide induced diabetic rats. Open Conf Proc J. 2011;2:53-58. doi: 10.2174/2210289201102010053
- Kondeti VK, Badri KR, Maddirala DR, et al. Effect of Pterocarpus santalinus bark, on blood glucose, serum lipids, plasma insulin and hepatic carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats. Food Chem Toxicol. 2010;48(5):1281-1287. doi: 10.1016/j.fct.2010.02.023
- Gopinathan S, Naveenray D. Antidiabetic activity of Clerodendrum phlomdis Linn and Gymnema sylvestre Linn in alloxan induced diabetic rats - a comparative preclinical study. World J Pharm Res. 2014;3(6):1640-1675.
- Jung EJ, Kwon SW, Jung BH, Oh SH, Lee BH. Role of the AMPK/SREBP-1 pathway in the development of orotic acid-induced fatty liver. J Lipid Res. 2011;52(9):1617-1625. doi: 10.1194/jlr.M015263
- Viollet B, Lantier L, Devin-Leclerc J, et al. Targeting the AMPK pathway for the treatment of type 2 diabetes. Front Biosci. 2009;14(9):3380-3400. doi: 10.2741/3460
- Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108(8):1167-1174. doi: 10.1172/JCI13505
- Garcia D, Shaw RJ. AMPK: Mechanism of cellular energy sensing and restoration of metabolic balance. Mol Cell. 2017;66(6):789-800. doi: 10.1016/j.molcel.2017.05.032
- Kuo YH, Lin CH, Shih CC. Antidiabetic and Antihyperlipidemic properties of a triterpenoid compound, dehydroeburicoic acid, from Antrodia camphorata in vitro and in streptozotocin-induced mice. J Agric Food Chem. 2015;63(46):10140-10151. doi: 10.1021/acs.jafc.5b04400
- Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48(7):e245. doi: 10.1038/emm.2016.81
- Shen Y, Fukushima M, Ito Y, et al. Verification of the antidiabetic effects of cinnamon (Cinnamomum zeylanicum) using insulin-uncontrolled type 1 diabetic rats and cultured adipocytes. Biosci Biotechnol Biochem. 2010;74(12):2418-2425. doi: 10.1271/bbb.100453
- Voet D, Voet JG. Biochemistry. 4th ed. Hoboken, USA: Wiley; 2011.
- Reece J, Campbell N. Biology. San Francisco: Benjamin Cummings; 2002.
- Habegger KM, Heppner KM, Geary N, Bartness TJ, DiMarchi R, Tschöp MH. The metabolic actions of glucagon revisited. Nat Rev Endocrinol. 2010;6(12):689-697. doi: 10.1038/nrendo.2010.187
- Bos JL. Epac proteins: multi-purpose cAMP targets. Trends Biochem Sci. 2006;31(12):680-686. doi: 10.1016/j.tibs.2006.10.002
- Bang J, Zippin JH. Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis. Pigment Cell Melanoma Res. 2021;34(1):28-43. doi: 10.1111/pcmr.12920
- Cahill TJ 3rd, Thomsen AR, Tarrasch JT, et al. Distinct conformations of GPCR-β-arrestin complexes mediate desensitization, signaling, and endocytosis. Proc Natl Acad Sci USA. 2017;114(10):2562-2567. doi: 10.1073/pnas.1701529114
