In Silico Analysis of Interaction between Seaweed-Derived Bioactive Compounds and Selected Diabetes-Related Targets

  • T.H. Ogunwa Centre for Bio-computing and Drug Development, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria; Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria
  • T.T. Adeyelu Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria
  • R.Y. Fasimoye Department of Animal and Environmental Biology, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria
  • F.C. Ayenitaju Department of Biochemistry, University of Ibadan, Ibadan, Oyo State, Nigeria
Keywords: protein tyrosine phosphatase 1B; seaweed components; diabetes, docking; a-glucosidase

Abstract

Seaweeds are known for their beneficial health effects in the management of diabetes mellitus (DM). Numerous bioactive metabolites of diverse chemical structures have been found in the marine algae with attributed potent pharmacological effects. The current study was carried out to gain insights into the precise interaction and the inhibitory mechanism of bioactive components, obtained from seaweed, against protein tyrosine phosphatase 1B (PTP1B), the enzyme with a crucial role in insulin insensitivity, and α-glucosidase, which performs the key function in postprandial carbohydrate hydrolysis. Inhibitors of these proteins might be suitable for the management of DM type 2. Molecular docking experiments have shown that the antidiabetic compounds preferably bind to the allosteric site of PTP1B, sandwiched between α3, α6 and α7 helices, with a lesser ΔG value in comparison to the active site. Interacting orientation of eckol, dieckol, 7-phloroeckol, and phlorofucofuroeckol-A was comparable to that of the reference compound. In contrast, the compounds interacted with a-glucosidase at the active site with appreciable affinity. Phlorofucofuroeckol-A, dieckol, and eckol demonstrated high inhibitory potential against the protein as compared to acarbose possibly due to the relatively large molecular size and the presence of numerous OH groups, and additional hydrophobic and π-π interactions that are missing in the acarbose-α-glucosidase complex. The estimated affinity of the compounds showed good correlations with experimental results for both enzymes. The described interaction patterns are essential for understanding the mechanisms responsible for the antidiabetic effects of marine algae.

References

  1. Blair, M. (2016) Diabetes Mellitus Review. Urol Nurs. 36(1), 27-36. DOI

  2. Kharroubi, A.T. & Darwish. H.M. (2015) Diabetes mellitus: The epidemic of the century. World J Diabetes. 6(6), 850-67. DOI

  3. Lee, J.Y., Jung, K.W., Woo, E.R. & Kim, Y. (2008) Docking study of biflavonoids, allosteric inhibitors of protein tyrosine phosphatase 1B. Bull. Korean Chem. Soc. 29, 1479-1484. DOI

  4. Shinde, R.N., Kumar, G.S., Eqbal, S. & Sobhia, M.E. (2018) Screening and identification of potential PTP1B allosteric inhibitors using in silico and in vitro approaches. PLoS One. 18, 13(6), e0199020. DOI

  5. Reddy, M.V., Ghadiyaram, C., Panigrahi, S.K., Krishnamurthy, N.R., Hosahalli, S., Chandrasekharappa, A.P., Manna, D., Badiger, S.E., Dubey, P.K. & Mangamoori, L.N. (2014) X-ray structure of PTP1B in complex with a new PTP1B inhibitor. Protein Pept Lett. 21(1), 90-3. DOI

  6. Iversen, L.F., Andersen, H.S., Branner, S., Mortensen, S.B., Peters, G.H., Norris, K., Olsen, O.H., Jeppesen, C.B., Lundt, B.F., Ripka, W., Møller, K.B. & Møller, N.P. (2000) Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B. J Biol Chem. 275(14), 10300-7. DOI

  7. Wiesmann, C., Barr, K.J., Kung, J., Zhu, J., Erlanson, D.A., Shen, W., Fahr, B.J., Zhong, M., Taylor, L., Randal, M., McDowell, R.S. & Hansen, S.K. (2004) Allosteric inhibition of protein tyrosine phosphatase 1B. Nat Struct Mol Biol. 11(8):730-7. DOI

  8. Cai, X., Han, X., Luo, Y. & Ji, L. (2013) Comparisons of the efficacy of alpha glucosidase inhibitors on type 2 diabetes patients between Asian and Caucasian. PLoS One. 8(11):e79421. DOI

  9. Goodman, B.E. (2010) Insights into digestion and absorption of major nutrients in humans. Adv. Physiol. Educ. 34, 44–53, 2010; DOI:10.1152/advan.00094.2009 DOI

  10. Kumar, S., Narwal, S., Kumar, V. & Prakash, O. (2011) α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacogn. Rev.  5(9), 19-29. DOI

  11. Yin, Z., Zhang, W., Feng, F., Zhang, Y. & Kang, W. (2014) α-Glucosidase inhibitors isolated from medicinal plants. Food Sci. Hum. Wellness. 3(3-4), 136-174. DOI

  12. Chapman, V.J. & Champman, D.J. (1980) ‘‘Seaweeds and Their Uses,’’ Champman and Hall, New York, pp. 62–97. DOI

  13. Hoppe, H.A. & Lerving, T. (1982) ‘‘Marine Algae in Pharmaceutical Science’’. Vol 2 Walter de Gruyter, Berlin, pp. 3–48. DOI

  14. Majee, S.B., Avlani, D. & Biswas, G.R. (2017). Pharmacological, pharmaceutical, cosmetic and diagnostic applications of sulfated polysaccharides from marine algae and bacteria. Afr. J. Pharm. Pharmacol. 11(5), 68-77. DOI

  15. Cardoso, S.M., Pereira, O.R., Seca, A.M., Pinto, D.C. & Silva, A. (2015) Seaweeds as preventive agents for cardiovascular diseases: From nutrients to functional foods. Mar Drugs, 13, 6838-6865. DOI

  16. Albertus, J.S. (2004) Medicinal and pharmaceutical uses of seaweed natural products: A review. J. Applied Phycol. 16, 245-262. DOI

  17. Hwang, E.K., Amano, H. & Park, C.S. (2008) Assessment of the nutritional value of Capsosiphon fulvescens (Chlorophyta): developing a new species of marine macroalgae for cultivation in Korea. J. Appl. Phycol., 20(2), 147-151. DOI

  18. Brown, E.S., Allsopp, P.J., Magee, P.J., Gill, C.I., Nitecki, S., Strain, C.R. & McSorley, E.M. (2014) Seaweed and human health. Nutr Rev.  72(3), 205-16. DOI

  19. Sharifuddin, Y., Chin, Y., Lim P., Phang, S. (2015) Potential bioactive compounds from seaweed for diabetes management. Mar. Drugs. 13, 5447-5491. DOI

  20. Kwon, M.J. & Nam, T.J. (2006) Effects of mesangi (Capsosiphon fulvescens) powder on lipid metabolism in high cholesterol fed rats. J. Korean Soc. Food Sci. Nutr. 35(5), 530-535. DOI

  21. Cho, M., Kang, I.J., Won, M.H., Lee, H.S. & You, S. (2010) The antioxidant properties of ethanol extracts and their solvent-partitioned fractions from various green seaweeds. J Med Food. 13(5), 1232-9. DOI

  22. Kim, Y.M., Kim, I.H. & Nam, T.J. (2012) Induction of apoptosis signaling by glycoprotein of Capsosiphon fulvescens in human gastric cancer (AGS) cells. Nutr. Cancer. 64, 761-769. DOI

  23. Moon, H.E., Islam, N., Ahn, B.R., Chowdhury, S.S., Sohn, H.S., Jung, H.A. & Choi, J.S. (2011) Protein tyrosine phosphatase 1B and α-glucosidase inhibitory phlorotannins from edible brown algae, Ecklonia stolonifera and Eisenia bicyclis. Biosci Biotechnol Biochem. 75(8), 1472-80. DOI

  24. Unnikrishnan, P.S., Suthindhiran, K. & Jayasri, M.A. (2015) Antidiabetic potential of marine algae by inhibiting key metabolic enzymes. Frontiers in Life Science, 8(2), 148-159, DOI

  25. Lee, S.H., Li, Y., Karadeniz, F., Kim, M.M. & Kim, S.K. (2008). α-glucosidase and α-amylase inhibitory activities of phloroglucinol derivatives from edible marine brown alga, Ecklonia cava. J. Sci. Food Agric. 89:1552–1558. DOI

  26. Chin, Y.X., Lim, P.E., Maggs, C.A., Phang, S.M., Sharifuddin, Y. & Green, B.D. (2014) Anti-diabetic potential of selected Malaysian seaweeds. J. Appl. Phycol. DOI

  27. Noda, H., Amano, H., Arashima, K., Hashimoto, S. & Nisizawa, K. (1989) Studies on the antitumour activity of marine algae. Nippon Suisan Gakkaishi. 55, 1259-1264. DOI

  28. Okada, Y., Ishimaru, A., Suzuki, R. & Okuyama, T. (2004) A new phloro­glucinol derivative from the brown alga Eisenia bicyclis: potential for the effective treatment of diabetic complications. J Nat Prod., 67, 103-105. DOI

  29. Shibata, T., Fujimoto, K., Nagayama, K., Yamaguchi, K. & Nakamura, T. (2002) Inhibitory activity of brown algal phlorotannins against hyaluronidase. Int J Food Sci Technol. 37, 703-709. DOI

  30. Shibata, T., Nagayama, K., Tanaka, R., Yamaguchi, K. & Nakamura, T. (2003) Inhibitory effects of brown algal phlorotannins on secretory phospholipase A2s, lipoxygenases and cyclooxygenases. J Appl Phycol. 15, 61-66. DOI

  31. Wijesekara, I., Yoon, N.Y. & Kim, S. (2010) Phlorotannins from Ecklonia cava (Phaeophyceae): Biological activities and potential health benefits. BioFactors. 36(6):408-414. doi: 10.1002/biof.114. DOI

  32. Li, Y., Qian, Z.J., Ryu, B.M., Lee, S.H., Kim, M.M. & Kim, S.K. (2009) Chemical components and its antioxidant properties in vitro: An edible marine brown alga, Ecklonia cava. Bioorg. Med. Chem. 17, 1963-1973. DOI

  33. Kong, C.S., Kim, J.A., Yoon, N.Y., Kim, S.K. (2009) Induction of apoptosis by phloroglucinol derivative from Ecklonia cava in MCF-7 human breast cancer cells. Food Chem. Toxicol. 47, 1653-1658. DOI

  34. Athukorala, Y. & Jeon, Y.J. (2005) Screening for Angiotensin 1-converting enzyme inhibitory activity of Ecklonia cava. J. Food Sci. Nutr. 10, 134-139. DOI

  35. Lee, S.H., Li, Y., Karadeniz, F., Kim, M.M., Kim, S.K. (2009) α–Glycosidase and α–amylase inhibitory activities of phloroglucinal derivatives from edible marine brown alga, Ecklonia cava. J. Sci. Food Agric. 89, 1552-1558. DOI

  36. Ogunwa, T.H. (2018) Binding model of antidiabetic constituents from capsosiphon fulvescens with human aldose reductase. Op Acc J Bio Eng & Bio Sci 1(2), 1-7. OAJBEB.MS.ID.000110 DOI

  37. Ogunwa, T.H. & Ayenitaju, F.C. (2017) An insight into the precise molecular interaction and inhibitory potential of amentoflavone and its substituted derivatives on human α-amylase. Arch. Curr. Res. Int. 10(1), 1-14. DOI

  38. 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. DOI

  39. Seelinger, D. & de Groot, B.L. Ligand docking and binding site analysis with PYMOL and Autodock/Vina. J. Comput. Aided Mol. Des. 24, 417-422. DOI

  40. Laskowski, R.A. & Swindells, M.B. (2011) LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 51(10), 2778-86. DOI

  41. Fricker, P., Gastreich, M. & Rarey, M. (2004) Automated generation of structural molecular formulas under constraints. J. Chem. Info. Comput. Sci. 44(3), 1065-1078. DOI

  42. Hevener, K.E., Zhao, W., Ball, D.M., Babaoglu, K., Qi, J., White, S.W. & Lee, R.E. (2009) Validation of molecular docking programs for virtual screening against dihydropteroate synthase. J. Chem. Inf. Model. 49(2), 444-60. DOI

  43. Nisha, C.M., Kumar, A., Vimal, A., Bai, B.M., Pal, D. & Kumar, A. (2016) Docking and ADMET prediction of few GSK-3 inhibitors divulges 6-bromoindirubin-3-oxime as a potential inhibitor. J. Mol. Graph. Model. 65, 100-107. DOI

  44. Kang, S.M., Heo, S.J., Kim, K.N., Lee, S.H., Yang, H.M., Kim, A.D., Jeon, Y.J. (2012) Molecular docking studies of a phlorotannin, dieckol isolated from Ecklonia cava with tyrosinase inhibitory activity. Bioorg Med Chem. 20(1), 311-6. DOI

  45. Lopes, G., Andrade, P.B. & Valentão, P. (2016) Phlorotannins: Towards New Pharmacological Interventions for Diabetes Mellitus Type 2. Molecules. 22(1). pii: E56. DOI

  46. Bischoff, H. (1995) The mechanism of α--glucosidase inhibition in the management of diabetes. Clin. Invest. Med. 18(4), 303-311. DOI

  47. Luthra, T., Agarwal, R., Estari, M., Adepally, U. & Sen, S. (2017) A novel library of α-arylketones as potential inhibitors of α-glucosidase: their design, synthesis, in vitro and in vivo studies. Sci. Rep. 7, 13246−13426. DOI

  48. Yashihito, O., Akiko, I., Ryuichiro, S., & Toru, O, (2004) A new phloroglucinol derivative from the brown alga Eisenia bicyclis: Potential for the effective treatment of diabetic complications. J. Nat. Prod., 67, 103-105. DOI

  49. Lee, S.H., Park, M.H., Heo, S.J., Kang, S.M., Ko, S.C., Han, J.S. & Jeon, Y.J. (2010) Dieckol isolated from Ecklonia cava inhibits α-glucosidase and α-amylase in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Food Chem. Toxicol. 48, 2633-2637. DOI

  50. Lee, S.H., Park, M.H., Kang, S.M., Ko, S.C., Kang, M.C., Cho, S., Park, P.J., Jeon, B.T., Kim, S.K., Han, J.S. & Jeon, Y.J. (2012) Dieckol isolated from Ecklonia cava protects against high-glucose induced damage to rat insulinoma cells by reducing oxidative stress and apoptosis. Biosci Biotechnol Biochem. 76(8), 1445-51. DOI

  51. Eom, S.H., Lee, S.H., Yoon, N.Y., Jung, W.K., Jeon, Y.J., Kim, S.K., Lee, M.S. & Kim, Y.M. (2012) α-Glucosidase- and α-amylase-inhibitory activities of phlorotannins from Eisenia bicyclis. J Sci Food Agric. 92(10), 2084-90. DOI

  52. Barde, S.R., Sakhare, R.S., Kanthale, S.B., Chandak, P.G. & Jamkhande, P.G. (2015) Marine bioactive agents: A short review on new marine antidiabetic compounds. Asian Pac. J. Trop. Dis. 5, 209-213. DOI

Published
2018-11-15
Section
Experimental Research