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Citrus flavonoids collectively dominate the α-amylase and α-glucosidase inhibitions

  • Mouna Sahnoun EMAIL logo , Sahar Trabelsi and Samir Bejar
Published/Copyright: July 31, 2017
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Abstract

A series of citrus flavonoids were evaluated for α-amylase and α-glucosidase inhibitory activities in vitro. The inhibitory capacities of flavanone glycosides were greater than those of polymethoxy flavones for α-amylase. Naringin exhibited the most potent α-glucosidase inhibitory activity with IC50 0.55 μM and was about 196.83 times more active than acarbose. Poncirin led to a 43-fold improvement in α-amylase inhibition over acarbose. The double-reciprocal (Lineweaver-Burk) plot confirms a competitive inhibition mode towards α-amylase and α-glucosidase activities. The inhibition activity was significantly lowered when citrus flavonoids were pre-incubated with starch. The binding site for naringin, poncirin, hesperidin, tangeretin in α-amylase showed a polar contact numbers, respectively, of 47, 54, 51, and 44 more than that involving acarbose. The hydrogen bonds formed between nobilitin and the key residue of Lys506 of α-glucosidase, namely Asn475:N-A:Lys506:O, might provide its extra affinity when compared to tangeritin. These findings provided a strong and rational reason to establish the selected citrus flavonoids capability as a therapeutic target for postprandial hyperglycaemia modulation.

Acknowledgements

This work was supported in part by a grant from the Tunisian Ministry of Higher Education and Scientific Research contract program CBS-LMBEE/code: LR15CBS06_2015-2018.

References

Benavente-Garcia O. & Castillo J. 2008. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J. Agric. Food Chem. 56: 6185–6205.10.1021/jf8006568Search in Google Scholar PubMed

Bharti S., Rani N., Krishnamurthy B. & Arya D.S. 2014. Preclinical evidence for the pharmacological actions of naringin: a review. Planta Med. 80: 437–451.10.1055/s-0034-1368351Search in Google Scholar PubMed

Brayer G.D., Luo Y. & Withers S.G. 1995. The structure of human pancreatic α-amylase at 1.8 Å solution and comparisons with related enzymes. Protein Sci. 4: 1730–1742.10.1002/pro.5560040908Search in Google Scholar PubMed PubMed Central

Cantarel B.L., Coutinho P.M., Rancurel C., Bernard T., Lombard V. & Henrissat B. 2009. The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res. 37: D233–D238.10.1093/nar/gkn663Search in Google Scholar PubMed PubMed Central

Chethan S., Sreerama Y.N. & Malleshi N.G. 2008. Mode of inhibition of finger millet malt amylases by the millet phenolics. Food Chem. 111: 187–191.10.1016/j.foodchem.2008.03.063Search in Google Scholar

De Sales P.M., de Souza P.M., Simeoni L.A., Magalhăes P. de-O. & Silveira D. 2012. α-Amylase inhibitors: a review of raw material and isolated compounds from plant source. J. Pharm. Sci. 15: 141–183.10.18433/J35S3KSearch in Google Scholar

Ebrahim-Habibi A. 2008. Flavonoids as potential antihyperglycemics: an in silico study of their α-amylase inhibitory mode. Drug Future 33 (Suppl. A): 306–307.Search in Google Scholar

Forester S.C., Gu Y.Y. & Lambert J.D. 2012. Inhibition of starch digestion by the green tea polyphenol, (-)-epigallocatechin-3-gallate. Mol. Nutr. Food Res. 56: 1647–1654.10.1002/mnfr.201200206Search in Google Scholar PubMed PubMed Central

Gopinath K., Prakash D. & Sudhandiran G. 2011. Neuroprotective effect of naringin, a dietary flavonoid against 3-nitropropionic acid-induced neuronal apoptosis. Neurochem. Int. 59: 1066–1073.10.1016/j.neuint.2011.08.022Search in Google Scholar PubMed

Han K., Li Y., Zhang Y., Teng Y., Ma Y., Wang M., Wang R., Xu W., Yao Q., Zhang Y., Qin, H., Sun H. & Yu P. 2015. Design, synthesis and docking study of novel tetracyclic oxindole derivatives as α-glucosidase inhibitors. Bioorg. Med. Chem. Lett. 25: 1471–1475.10.1016/j.bmcl.2015.02.031Search in Google Scholar PubMed

Janecek S. 2002. How many conserved sequence regions are there in the α-amylase family? Biologia 57 (Suppl. 11): 29–41.Search in Google Scholar

Janecek S. & Blesak K. 2011. Sequence-structural features and evolutionary relationships of family GH57 α-amylases and their putative α-amylase-like homologues. Protein J. 30: 429–435.10.1007/s10930-011-9348-7Search in Google Scholar PubMed

Janecek S., Svensson B. & MacGregor E.A. 2014. α-Amylase: an enzyme specificity found in various families of glycoside hydrolases. Cell. Mol. Life Sci. 71: 1149–1170.10.1007/s00018-013-1388-zSearch in Google Scholar PubMed

Kawakami K., Aketa S., Nakanami M., Iizuka S. & Hirayama M. 2010. Major water-soluble polyphenols, proanthocyanidins, in leaves of persimmon (Diospyros kaki) and their α-amylase inhibitory activity. Biosci. Biotechnol. Biochem. 74: 1380–1385.10.1271/bbb.100056Search in Google Scholar PubMed

Kim J.B., Han A.R., Park E.Y., Kim J.Y., Cho W., Lee J., Seo E.K. & Lee K.T. 2007. Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-κB inactivation in raw 264.7 macrophage cells. Biol. Pharm. Bul. 30: 2345–2351.10.1248/bpb.30.2345Search in Google Scholar PubMed

Koh L.W., Wong L.L., Loo Y.Y., Kasapis S. & Huang D. 2010. Evaluation of different teas against starch digestibility by mammalian glycosidases. J. Agric. Food Chem. 58: 148–154.10.1021/jf903011gSearch in Google Scholar PubMed

Kufareva I. & Abagyan R. 2012. Methods of protein structure comparison. Methods Mol. Biol. 857: 231–257.10.1007/978-1-61779-588-6_10Search in Google Scholar PubMed PubMed Central

Lobanov M.Y., Bogatyreva N. & Galzitskaya O. 2008. Radius of gyration as an indicator of protein structure compactness. Mol. Biol. 42: 623–628.10.1134/S0026893308040195Search in Google Scholar

Lee J.H., Lee S.H., Kim Y.S. & Jeong C.S. 2009. Protective effects of neohesperidin and poncirin isolated from the fruits of Poncirus trifoliata on potential gastric disease. Phytother. Res. 23: 1748–1753.10.1002/ptr.2840Search in Google Scholar PubMed

Liu J., Wang M.Z., Peng S.L. & Zhang G.Y. 2011. Effect of green tea catechins on the postprandial glycemic response to starches differing in amylose content. J. Agr. Food Chem. 59: 4582–4588.10.1021/jf200355qSearch in Google Scholar PubMed

Lo Piparo E., Scheib H., Frei N., Williamson G., Grigorov M. & Chou C.J. 2008. Flavonoids for controlling starch digestion: structural requirements for inhibiting human alpha-amylase. J. Med. Chem. 51: 3555–3561.10.1021/jm800115xSearch in Google Scholar PubMed

Manaharan T., Appleton D., Cheng H.M. & Palanisamy U.D. 2012. Flavonoids isolated from Syzygium aqueum leaf extract as potential antihyperglycaemic agents. Food Chem. 132: 1802–1807.10.1016/j.foodchem.2011.11.147Search in Google Scholar

McCue P.P. & Shetty K. 2004. Inhibitory effects of rosmarinic acid extracts on porcine pancreatic amylase in vitro. Asia Pac. J. Clin. Nutr. 13: 101–106.Search in Google Scholar

Miao M., Jiang B., Jiang H., Zhang T. & Li X. 2015. Interaction mechanism between green tea extract and human a-amylase for reducing starch digestion. Food Chem. 186: 20–25.10.1016/j.foodchem.2015.02.049Search in Google Scholar PubMed

Miller G.L. 1959. Use of dinitrosalicylic acid reagent for determination of reducing sugar. Anal. Chem. 31: 426–428.10.1021/ac60147a030Search in Google Scholar

Najafian M., Ebrahim-Habibi A., Hezareh N., Yaghmaei P., Parivar K. & Larijani B. 2011. Trans-chalcone: a novel small molecule inhibitor of mammalian a-amylase. Mol. Biol. Rep. 38: 1617–1620.10.1007/s11033-010-0271-3Search in Google Scholar PubMed

Nakajima A., Yamakuni T., Haraguchi M., Omae N., Song S.Y., Kato C., Nakagawasai O., Tadano T., Yokosuka A., Mimaki Y., Sashida Y. & Ohizumi Y. 2007. Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice. J. Pharmacol. Sci. 105: 122–126.10.1254/jphs.SC0070155Search in Google Scholar PubMed

Okuyama M., Saburi W., Mori H. & Kimura A. 2016. α-Glucosidases and α-1,4-glucan lyases: structures, functions, and physiological actions. Cell. Mol. Life Sci. 73: 2727–2751.10.1007/s00018-016-2247-5Search in Google Scholar PubMed

Oz H.S., Chen T. & de Villiers W.J. 2013. Green tea polyphenols and sulfasalazine have parallel anti-inflammatory properties in colitis models. Front. Immunol. 4: 132.10.3389/fimmu.2013.00132Search in Google Scholar PubMed PubMed Central

Ramasubbu N., Ragunath C., Mishra P.J., Thomas L.M., Gyemant G. & Kandra L. 2004. Human salivary α-amylase Trp58 situated at subsite -2 is critical for enzyme activity. Eur. J. Biochem. 271: 2517–2529.10.1111/j.1432-1033.2004.04182.xSearch in Google Scholar PubMed

Roy M.C., Anguenot R., Fillion C., Beaulieu M., Bérubé J. & Richhard D. 2011. Effect of a commercially-available algal phlorotannins extract on digestive enzymes and carbohydrate absorption in vivo. Food Res. Int. 44: 3026–3029.10.1016/j.foodres.2011.07.023Search in Google Scholar

Rtveladze K., Marsh T., Barquera S., Sanchez Romero L.M., Levy D., Melendez G. & Brown M. 2014. Obesity prevalence in Mexico: impact on health and economic burden. Public Health Nutr. 17: 233–239.10.1017/S1368980013000086Search in Google Scholar PubMed

Sun H., Zhang Y., Ding W., Zhao X., Song X., Wang D., Li, Y., Han K., Yang Y., Ma Y., Wang R., Wang D. & Yu P. 2016. Inhibitory activity evaluation and mechanistic studies of tetracyclic oxindole derivatives as α-glucosidase inhibitors. Eur. J. Med. Chem. 123: 365–378.10.1016/j.ejmech.2016.07.044Search in Google Scholar PubMed

Tabernero M., Sarria B., Largo C., Martinez-Lopez S., Madrona A., Espartero J.L. & Mateos R. 2014. Comparative evaluation of the metabolic effects of hydroxytyrosol and its lipophilic derivatives (hydroxytyrosyl acetate and ethyl hydroxytyrosyl ether) in hypercholesterolemic rats. Food Funct. 5: 1556–1563.10.1039/C3FO60677ESearch in Google Scholar PubMed

Tadera K., Minami Y., Takamatsu K. & Matsuoka T. 2006. Inhibition of α-glucosidase and α-amylase by flavonoids. J. Nutr. Sci. Vitaminol. 52: 149–153.10.3177/jnsv.52.149Search in Google Scholar PubMed

Tagami T., Yamashita K., Okuyama M., Mori H., Yao M. & Kimura A. 2013. Molecular basis for the recognition of long-chain substrates by plant α-glucosidases. J. Biol. Chem. 288: 19296–192303.10.1074/jbc.M113.465211Search in Google Scholar PubMed PubMed Central

Tarling C.A., Woods K., Zhang R., Brastianos H.C., Brayer G.D., Andersen R.J & Withers S.G. 2008. The search for novel human pancreatic α-amylase inhibitors: high-throughput screening of terrestrial and marine natural product extracts. Chembiochem 9: 433–438.10.1002/cbic.200700470Search in Google Scholar PubMed

Tripoli E., La Guardia M., Giammanco S., Majo Di D. & Giammanco M. 2007. Citrus flavonoids: molecular structure, biological activity and nutritional properties: a review. Food Chem. 104: 466–479.10.1016/j.foodchem.2006.11.054Search in Google Scholar

Trott O. & Olson A.J. 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J. Comput. Chem. 31: 455–461.10.1002/jcc.21334Search in Google Scholar PubMed PubMed Central

Whitman S.C., Kurowska E.M., Manthey J.A. & Daugherty A. 2005. Nobiletin, a citrus flavonoid isolated from tangerines, selectively inhibits class A scavenger receptor-mediated metabolism of acetylated LDL by mouse macrophages. Atherosclerosis 178: 25–32.10.1016/j.atherosclerosis.2004.07.034Search in Google Scholar PubMed

Worsztynowicz P., Napierała M., Białas W., Grajek W. & Olkowicz M. 2014. Pancreatic α-amylase and lipase inhibitory activity of polyphenolic compounds present in the extract of black chokeberry (Aronia melanocarpa L.). Process Biochem. 49: 1457–1463.10.1016/j.procbio.2014.06.002Search in Google Scholar

Xiao H.X., Lin Q.L., Liu G.Q., Wu Y., Wei W. & Fu X. 2013. Inhibitory effects of green tea polyphenols on the retrogradation of starches from different botanical sources. Food Bioprocess Technol. 6: 2177–2181.10.1007/s11947-011-0739-8Search in Google Scholar

Yoon H.Y., Won Y.Y. & Chung Y.S. 2012. Poncirin prevents bone loss in glucocorticoid induced osteoporosis in vivo and in vitro. J. Bone Miner. Metab. 30: 509–516.10.1007/s00774-012-0350-8Search in Google Scholar PubMed

Zhang G. & Ma Y. 2013. Mechanistic and conformational studies on the interaction of food dye amaranth with human serum albumin by multispectroscopic methods. Food Chem. 136: 442–449.10.1016/j.foodchem.2012.09.026Search in Google Scholar PubMed

Zhang L., Tu Z.C., Yuan T., Wang H., Xie X. & Fu Z.F. 2016. Antioxidants and a-glucosidase inhibitors from Ipomoea batatas leaves identified by bioassay-guided approach and structure-activity relationships. Food Chem. 208: 61–67.10.1016/j.foodchem.2016.03.079Search in Google Scholar PubMed

Zhu X., Luo F., Zheng Y., Zhang J., Huang J., Sun C., Li X. & Chen K. 2013. Characterization, purification of poncirin from edible citrus Ougan (Citrus reticulate cv. Suavissima) and its growth inhibitory effect on human gastric cancer cells SGC-7901. Int. J. Mol. Sci. 14: 8684–8697.10.3390/ijms14058684Search in Google Scholar PubMed PubMed Central

Abbreviations

DMSO

dimethyl sulfoxide

DNSA

3,5-dinitrosalicylic acid

GH

glycoside hydrolase

IC50

the half maximal inhibitory concentration

Rg

radius of gyration

RMSD

root mean square deviation

Received: 2017-6-7
Accepted: 2017-7-19
Published Online: 2017-7-31
Published in Print: 2017-7-26

© 2017 Institute of Molecular Biology, Slovak Academy of Sciences

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