INHIBITION OF α-AMYLASE AND α-GLUCOSIDASE BY (6RS)-22-HYDROXY-23,24,25,26,27-PENTANOR-VITAMIN-D3-6,19-SULFUR DIOXIDE-ADDUCT, MANOALIDE AND 5β-CHOLESTANE-3α,7α,12α,24,25,26-HEXOL ISOLATED FROM ACETONE EXTRACT OF HELIANTHUS ANNUUS L. SEEDS
Keywords:Helianthus annuus L, Nil, Nil, Kinetics study, Molecular docking
Objective: This investigation includes characterization of phytochemicals from acetone extract of Helianthus annuus L. seeds responsible for α-amylase and α-glucosidase inhibition revealed from in vitroand in silico approaches.
Methods: Seed extract was qualitatively and quantitatively analysed for the presence of bioactive molecules. In vitro α-amylase and α-glucosidase inhibition assays and kinetics studies for α-glucosidase were done. Thin layer chromatography (TLC) autography of extract was done to screen potent inhibitors and characterized by high-resolution liquid chromatography-mass spectrometry (HR LC-MS). Characterized molecules were further used for in silico studies.
Results: Qualitative investigation reveals the presence of flavonoids, glycosides, alkaloids, terpenoids, and steroids. Quantitative analysis for total phenolic content and total flavonoid content of the extract was 0.1±0.005 mg/ml GAE and 0.025±0.003 mg/ml QE respectively. Percent inhibition of α-amylase and α-glucosidase ascertained in presence of extract was 60.42±0.6 and 83.22±0.18 at 0.01 mg while 36.24±0.81 and 37.67±0.15 at 0.005 mg of extracts for both enzymes respectively. Kinetics studies of α-glucosidase inhibition illustrated the non-competitive type of inhibition. TLC autography inhibition patterns were characterized by HR LC-MS. Characterized molecules on docking revealed (6RS)-22-hydroxy-23,24,25,26,27-pentanor-vitamin-D3-6,19-sulfurdioxide-adduct, manoalide and 5β-cholestane-3α,7α,12α,24,25,26-hexol as the best docked molecules with lowest binding energies of-12.5,-11 and-10.2 kcal/mol for α-amylase and-14.2,-11 and-11.2 kcal/mol for α-glucosidase respectively.
Conclusion: Results clearly suggested that (6RS)-22-hydroxy-23,24,25,26,27-pentanor-vitamin-D3-6,19-sulfurdioxide-adduct, manoalide and 5β-cholestane-3α,7α,12α,24,25,26-hexol could be considered as lead molecules for the discovery of potent antidiabetic agents.
Ingale S, Shrivastava S. Chemical studies of new varieties of sunflower (Helianthus annuus) LSF-11 and LSF-8 seeds. Agric Biol J North Am 2011;2:1071–81.
Byrareddy K, Uppar DS, Vyakaranahal BS, Hiremath SM, Hunje R. Nadaf HL. Effect of integrated nutrient management on sunflower hybrid (KBSH-I) seed production. Karnataka J Agric Sci 2008;21:171-5.
Anjum FM, Nadeem M, Khan MI, Hussain S. Nutritional and therapeutic potential of sunflower seeds: a review. Br Food J 2012;114:544–52.
Rajakannu S, Sritharan UR. Phytochemical screening, antimicrobial activity and in vitro antioxidant investigation of methanolic extract of seeds from Helianthus annuus L. Chem Sci Rev Lett 2012;1:30–4.
Mikolajczak KL, Cecil Randolph, Smith J, Wolff IA. Phenolic and sugar components of Armavireo variety sunflower (Helianthus annuus) seed meal. J Agric Food Chem 1970;18:27–32.
Dwivedi A, Sharma G. A review on heliotropism plant: Helianthus annuus L. J Phytopharm 2014;3:149–55.
Brahmachari G. Nevadensin: isolation, chemistry and bioactivity. Int J Green Pharm 2010;4:213-9.
Heo JC, Woo SU, Kweon MA, Park JY, Lee HK, Son M, et al. Aqueous extract of the Helianthus annuus seed alleviate asthmatic symptoms in vivo. Int J Mol Med 2008;21:57–61.
Giada MDLR, Mancini Filho J. Antioxidant capacity of the striped sunflower (Helianthus annuus L.) seed extracts evaluated by three in vitro methods. Int J Food Sci Nutr 2009;60:395–401.
Saini S, Sharma S. Antidiabetic effect of Helianthus Annuus L., seeds ethanolic extract in streptozotocin-nicotinamide induced type 2 diabetes mellitus. Int J Pharm Pharm Sci 2013;5:382–7.
D’Archivio M, Filesi C, Di Benedetto R, Gargiulo R, Giovannini C, Masella R. Polyphenols, dietary sources and bioavailability. Ann Ist Super Sanita 2007;43:348–61.
Koleckar V, Kubikova K, Rehakova Z, Kuca K, Jun D, Opletal LJ, et al. Condensed and hydrolysable tannins as antioxidants influencing the health. Mini-Rev Med Chem 2008;8:436–47.
Sonkamble VV, Zore GB, Kamble LH. A simple method to screen amylase inhibitors using thin layer chromatography. Sci Res Report 2014;4:85–8.
Yadav RNS, Agarwala M. Phytochemical analysis of some medicinal plants. J Phytol 2011;3:10–4.
Kavit M, Patel BN, Jain BK. Phytochemical analysis of leaf extract of Phyllanthus fraternus. Res J Recent Sci 2013;2:12–5.
Aiyegoro OA, Okoh AI. Preliminary phytochemical screening and In vitro antioxidant activities of the aqueous extract of Helichrysum longifolium DC. BMC Complement Altern Med 2010;10:21.
Sonkamble VV, Kamble LH. Antidiabetic potential and identification of phytochemicals from Tinospora cordifolia. Am J Phytomed Clin Ther 2015;3:97-110.
Miller G. Use of dinitrosalicylic acid reagent for determination of reducing sugar. Anal Chem 1959;31:426–8.
Zhang J, Zhao S, Yin P, Yan L, Han J, Shi L, et al. the a-Glucosidase inhibitory activity of polyphenols from the burs of castanea mollissima blume. Molecules 2014;19:8373–86.
Kulsoom J, Syed SM, Saima R, Syed TM, Syed N, Itrat F, et al. 2-arylquinazolin-4(3H)-ones: a new class of a-glucosidase inhibitors. Bioorg Med Chem 2015;4:3–7.
Hati S, Madurkar SM, Bathula C, Thulluri C, Agarwal R, Amber F, et al. Design, synthesis and biological evaluation of small molecules as potent glucosidase inhibitors. Eur J Med Chem 2015;100:188–96.
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2009;31:455–61.
Morris GM, Green LG, Radic Z, Taylor P, Olson AJ, Grynszpan F. Automated docking with protein flexibility in the design of femtomolar “Click Chemistry” inhibitors of acetyl-cholinesterase. J Chem Inf Model 2014;53:898–906.
Dallakyan S, Olson A. Small-molecule library screening by docking with PyRx. Chem Biol 2015;19:243–50.
Pence HE, Williams AJ. ChemSpider: an online chemical information resource. J Chem Edu 2010;87:1123-4.
O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open babel: an open chemical toolbox. J Cheminform 2011;3:33.
Lipinski C. Lead profiling Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today Technol 2004;1:337–41.
Mamgain S, Sharma P, Pathak RK, Baunthiyal M. Computer-aided screening of natural compounds targeting the E6 protein of HPV using molecular docking. Bioinformation 2015;11:236-42.
Wass MN, Kelley LA, Sternberg MJE. 3DLigand site: predicting ligand-binding sites using similar structures. Nucleic Acids Res 2010;38:W469–W73.
Poroikov VV, Filimonov DA, Ihlenfeldt W, Gloriozova TA, Lagunin AA, Borodina YV, et al. PASS biological activity spectrum predictions in the enhanced open NCI database browser. J Chem Inf Comput Sci 2003;43:228–36.
Paramashivam S, Elayaperumal K, Natarajan B, Ramamoorthy M, Balasubramanian S, Narayanan K. In silico pharmacokinetic and molecular docking studies of small molecules derived from Indigofera aspalathoides vahl targeting receptor tyrosine kinases. Bioinformation 2015;11:73–84.
Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, et al. admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 2012;52:3099–105.
Kingma PJ, Menheere PPCA, Sels JP, Kruseman ACN. a-glucosidase inhibition by miglitol in NIPPM patients. Diabetes Care 1992;15:478–83.
Campbell LK, Baker DE, Campbell RK. Miglitol: assessment of its role in the treatment of patients with diabetes mellitus. Ann Pharmacother 2000;34:1291–301.
Madeswaran A, Asokkumar K, Umamaheswari M, Sivashanmugam T, Subhadradevi V, Jagannath P. In silico docking evaluation of α-Amylase inhibitory activity of Butein and Tricetin. J Comput Methods Mol Des 2014;4:51–6.
Dirar A, Waddad A, Mohamed M, Mohamed M, Wadah O, Mohammed M, et al. In silico pharmacokinetics and molecular docking of three leads isolated from Tarconanthus camphoratus L. Int J Pharm Pharm Sci 2016;8:71–7.
Hsu Y, Hung Y, Hu L, Lee Y, Yin M. Anti-diabetic effects of made classic acid and rotundic acid. Nutrients 2015;7:10065–75.
Matsubara K, Matsuzawa Y, Jiao S, Kihara S, Takama T, Nakamura T, et al. Cholesterol-lowering effect of N-(a-methylbenzyl) linoleamide (melinamide) in cholesterol-fed diabetic rats. Atherosclerosis 1988;72:199–204.
Tanwer BS, Vijayvergia R. Biological evaluation of Alangium salviifolium (L. F.) wangerin. J Chem Pharm Res 2014;6:611–8.
Abdel-aziz SA, Hussein MA, Abdel Raheem IT. Design, synthesis and antidiabetic activity of some new 4-amino (or 6-oxo)-2-methyl/benzylthio (or substituted amino) pyrimidine derivatives. Bull Pharm Sci Assiut Univ 2011;34:149–58.
Somani Z, Bhattacharjee R, Chodankar MNA. In vitro antioxidant, anti-inflammatory, inovo antiangiogenic activities and virtual screening of phytoconstituents of Chromolena odorata. Int J Curr Res 2014;6:7766–71.
Rohini K, Srikumar P. In silico approach of anticancer activity of phytochemical coumarins against cancer target JNKS. Int J Pharm Pharm Sci 2013;5:741–2.
Dhanalakshmi R, Manavalan R. In silico docking approach for the antiatherosclerotic activity of phytoconstituents of Corchorus aestuans and ADMET prediction. Asian J Pharm Clin Res 2015;8:350–3.
Chaluveelaveedu N, Kumar A, Nair P, Gupta N, Silakari C, Tripathi T, et al. Molecular docking and in silico ADMET study reveals Acylguanidine 7a as a potential inhibitor of β-secretase. Adv Bioinformatics 2016:1–6. http://dx.doi.org/10.1155/ 2016/9258578.