1*Mba, O.J, 1Ajaghaku, D.L, 2Ogbonna, B.O, 3Obila M.U, 4Azubuike, N.J, 4Okafor, P.N, 5Omodamiro, O.D.
1Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria
2Department of Clinical Pharmacy and Pharmacy Management, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria
3Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria
4Department of Biochemistry, College of Natural Sciences, Michael Okpara University of Agriculture Umudike, Abia State, Nigeria
5Department of Pharmacology and Toxicology, School of Pharmacy, Kampala International University, Kampala, Uganda
ABSTRACT:
Background: Peroxisome proliferator activated receptor gamma (PPAR-γ) agonists are beneficial in the treatment of diabetes by stimulating insulin sensitivity and antagonizing hepatic gluconeogenesis.
Objective: The aim of this study was to investigate the antidiabetic effect of phytocompounds synthesized from crude extract and fraction of Napoleonae imperialis, using GC-MS analysis and molecular docking studies.
Methods: Crude extract and fraction from N. imperialis were subjected to gas chromatography mass spectrometry (GC-MS) for identification of bioactive compounds in the plant and molecular docking of Napoleonae imperialis on human PPAR-γ protein was determined by Auto/Vina in Pymol 4.2 and compared with Glibenclamide, a known agonist of PPAR-γ.
Results: Our present study reports the phytochemical analysis of the crude extract and fraction from the leaves of Napoleonae imperialis. Sixty one (61) and eighty four (84) compounds were revealed through GC-MS analysis of the crude extract and fraction of N. imperialis. Molecular docking revealed that Dibutyl phthalate, 7,9-ditert-butyl-1-oxaspiro (4,5) deca,6,9-diene,2,8-dione and Guaiol bound favourably to the target receptor involved in glucose metabolism with a binding score of -7.3 kcal/mol and -7.5 kcal/mol against PPAR-γ.
Conclusions: N. imperialis methanol leaf extract and its bioactive compounds Dibutyl phthalate, 7,9-ditert-butyl-1-oxaspiro (4,5) deca,6,9-diene,2,8-dione and Guaiol had a significant antidiabetic activity against PPAR-γ. The molecular binding interaction of an in-silico data demonstrated that Guaiol has more specificity towards the PPAR-γ binding site and could be a potent antidiabetic compound.
KEYWORDS:
Diabetes mellitus, Napoleonae imperialis, Guaiol, Molecular docking, Gas chromatography mass spectrometry, Peroxisome proliferator activated receptor gamma.
REFERENCES :
1) Kumar, P.J.; Clark, M. Textbook of clinical medicine Pub: Saunders (London); 2002. p. 1099 121.
2) World Health Organization. Global report on diabetes. International Journal of Noncommunicable Disease. 2016; 1(1):3 – 8.
3) International Federation of Diabetes. Simple treatment to curb diabetes. Diabetes Res Clin Pract. 2014; 94:465 – 476.
4) Elbrecht, A.; Chen, Y.; Cullinan, C.A. Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2. Biochem Biophys Res Commun. 1996; 224:431 – 437.
5) Moller, D.E. New drug targets for type 2 diabetes and the metabolic syndrome. Nature. 2001; 414:821 – 827.
6) Guan, H.P.; Yong, L.; Jensen, M.V.; Newgard, C.B. A futile metabolic cycle activated in
adipocytes by anti-diabetic agents. Nat Med. 2002; 8:1122 – 1128.
7) Marx, N.; Froehlich, J.; Siam, L.; Ittner, J. Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2003; 23:283 – 288.
8) Groop, L.C.; Groop, P.H.; Stenman, S. Comparison of pharmacokinetics, metabolic effects and mechanisms of action of glyburide and glipizide during long-term treatment. Diabetes Care. 1987; 10:671 – 678.
9) Mba, O.J.; Aloh, G.S.; Nwachukwu, K.C.; Michael, P.O. Phytochemical Characterization,Acute Toxicity Studies of the Methanol Extract of Napoleonae imperialis Leaves. Journal of Genetics and Cell Biology. 2020; 3(3): 194 – 198.
10) Bilgin, H.M.; Atmaca, M.; Obay, B.D.; Ozekinci, S.; Tasdemir, E.; Ketani, A. Protective effects of coumarin and coumarin derivatives against carbon tetrachloride induced acute hepatotoxicity in rats. Experimental Toxicology and Pharmacology. 2011; 63: 325 – 334.
11) Onyegbule, A.F.; Anowi, C.F.; Gugu, T.H.; Uto-Nedosa, A.U. Evaluation of antimicrobial properties of ethyl acetate extract of the leaves of Napoleonae imperialis family. International Journal of Drug Research and Technology. 2011; 1(1): 45 – 51.
12) Mba, O.J.; Omodamiro, O.D.; Aja, O.A.; Azubuike, N.J.; Okafor, P.N. Antidiabetic and antioxidant potentials of methanol leaf extract of Napoleonae imperialis in streptozotocin induced diabetic albino rats. International Journal of Biological Sciences and Molecular Research. 2023; 1(4):154 – 163.
13) Dogulas, P.J.; Chitti, S.; Ajay, B.P. Virtual screening and molecular docking analysis of Zap- 70 kinase inhibitors. Int J Chem Anal Sci. 2011;2(9):1208–1211.
14) Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J. Comput Chem. 2010; 31: 455 –461.
15) Bugge, A.; Holst, D. PPAR agonists, could tissue targeting pave the way? Biochimie. 2017; 136: 100 – 104.
16) Massaro, M.; Scoditti, E.; Pellegrino, M.; Carluccio, M.A.; Calabriso, N.; Wabitsch, M.; Storelli, C.; Wright, M.; De-Caterina, R. Therapeutic potential of the dual peroxisome proliferator activated receptor (PPAR)alpha/gamma agonist aleglitazar in attenuating TNF-alpha-mediated inflammation and insulin resistance in human adipocytes. Pharmacological Research. 2016; 107: 125 – 136.
17) Himaja, M.; Abdulla, M.D. Synthesis, Docking studies and antioxidant activity of tetra peptide FGVY. International Journal of Research in Ayurveda Pharmacy. 2011; 2(3):905 910.
18) Swain, S.S.; Paidestty, S.K.; Padhy, R.N. Antibacterial activity, computational analysis, and host toxicity study of thymol sulfonamide conjugates. Biomedicine Pharmacotherapy. 2007; 88: 181 – 193.
