In Silico Profiling of Pharmacokinetic Properties and Inhibitory Potentials of Chromolaena odorata aqueous leaf extract against Type-2 Diabetes Protein Targets, Neprilysin and Alpha Amylase
Abstract
Chronic type 2 diabetes interferes with the body's ability to use insulin as intended. Two protein targets, neprilysin and alpha amylase have been reported to contribute to the emergence of type 2 diabetes. Type 2 diabetes medications are ineffective and have unfavorable side effects. The objective of this study was to discover novel chemical agents of Chromolaena odorata aqueous leaf extract that can precisely inhibit the proteins, neprilysin and alpha amylase in type 2 diabetes to restrict the proteins' actions and so covertly induce anti-diabetic effects. Using GC-MS analysis, the phytoconstituents of Chromolaena odorata's aqueous leaf extract were identified. Ten (10) of the twenty-one (21) identified compounds complied with Lipinski rule of five. Swiss-ADME (Absorption, Distribution, Metabolism & Excretion) was used to analyze the pharmacokinetic properties of the compounds that did not violate the Lipinski rule. ADME analysis revealed that the selected compounds displayed suitable pharmacokinetic properties. Molecular docking was employed using PyRx and Biovia Discovery Studio software to predict potential selected bioactive antagonists and non-covalent interactions between the selected ligands, standard drugs and the target proteins. The findings from this study revealed that the identified ligand (carbamic acid) had the highest binding affinity against the target protein neprilysin and alpha amylase when compared to the standard drug, and it also has the potential to advance into pre-clinical and clinical research for future development as an antidiabetic medication.
Keywords
Diabetes, Chromolaena odorata, Neprilysin, Alpha-amylase, Molecular docking
Supporting Institution
Lagos State University
Project Number
1
Thanks
Thank you to the editorial team
References
- Afolabi CA, EO I and IA D-O (2007) Phytochemical constituents and antioxidant properties of extracts from the leaves of Chromolaena odorata. Scientific research and essays 2:191-194.
- Aziz, N.A., Mohamad, M., Mohsin, H.F., Mohamad Nor Hazalin, N.A. and Abdul Hamid, K., (2020). The pharmacological properties and medicinal potential of Chromolaena odorata: A review. International Journal of Pharmaceuticals, Nutraceuticals and Cosmetic Science (IJPNaCS), 2, pp.30-41.
- Bavishi C, Messerli FH, Kadosh B, Ruilope LM and Kario K (2015) Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials. European heart journal 36:1967-1973.
- Chakraborty AK, Rambhade S and Patil UK (2011) Chromolaena odorata (L.): An overview. J Pharm Res 4:573-576.
- Chen L, Magliano DJ and Zimmet PZ (2012) The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives. Nature reviews endocrinology 8:228-236.
- Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW and Tang Y (2012) admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties, ACS Publications.
- Colquitt RB, Colquhoun DA and Thiele RH (2011) In silico modelling of physiologic systems. Best practice & research Clinical anaesthesiology 25:499-510.
- Ekins S, Mestres J and Testa B (2007) In silico pharmacology for drug discovery: applications to targets and beyond. British journal of pharmacology 152:21-37.
- Esser N and Zraika S (2019) Neprilysin inhibition: a new therapeutic option for type 2 diabetes? Diabetologia 62:1113-1122.
- Forouhi NG and Wareham NJ (2010) Epidemiology of diabetes. Medicine 38:602-606.