DOCKING STUDIES OF PLANT POLYPHENOLS WITH AΒ FRAGMENTS SUGGESTS DETERMINANTS THAT ENABLE DESIGN OF INHIBITORS TOWARDS PREVENTING AGGREGATION EVENTS DURING ALZHEIMER’S
Abstract
The aggregation of Amyloid beta peptides is considered as one of the causative events in the pathogenesis of Alzheimer’s disease (AD). Polyphenols present in different plant sources, which have acclaimed therapeutic values, are known to inhibit the formation of Amyloid fibrils. Hence, docking studies with different polyphenols were carried out to appreciate their binding modes and plausible molecular interactions. The results reveal a consensus pattern of association, exhibiting that all the ligands preferentially dock to the metal coordinating residues in the peptide fragments. In fact, the metal interacting geometries in the Aβ segments are known to be implicated in aggregation events. Further, due to non-specific binding, these polyphenols are expected to have a competitive inhibitory efficacy over a range of amyloid peptide fragments. Thus, these findings suggest that the polyphenolic compounds could become promising lead molecules that aid in the development of inhibitors and neuroprotectors towards prevention of amyloid fibril formations and AD.
Keywords:
Alzheimer’s disease, Amyloid fibrils, Amyloid peptide, Neuroprotectors, PolyphenolsDOI
https://doi.org/10.25004/IJPSDR.2013.050407References
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8. Tartaglia G.G., Cavalli A., Pellarin R., Caflisch A. The role of aromaticity, exposed surface, and dipole moment in determining protein aggregation rates. Protein. Sci. 2004; 3:1939-1941.
9. Gazit E. A possible role for p-stacking in self-assembly of amyloid fibrils. FASEB. J . 2002; 16:77-83.
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11. Gao X, Zheng CY, Yang L, Tang XC, Zhang HY. Huperzine A protects isolated rat brain mitochondria against beta-amyloid peptide. Free. Radic .Biol .Med. 2009; 46:11: 1454–1462.
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13. Amalesh Samanta, Gouranga Das, Sanjoy Kumar Das. Roles of Flavonoids In Plants. Int.J. Pharm. Sci. Tech. 2011; 6: 12-135.
14. Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: A review of their intracellular targets. European Journal of Pharmacology. 2006; 545:1: 51–64.
15. Luan H, Kan Z, Xu Y, Lv C, Jiang W. Rosmarinic acid protects against experimental diabetes with cerebral ischemia: relation toinflammation response. J.Neuroinflammation 2013; 10:28: 10-28.
16. Teresa Iuvone, Daniele De Filippis, Giuseppe Esposito, Alessandra D’Amico, and Angelo A. Izzo. The Spice Sage and Its Active Ingredient Rosmarinic Acid Protect PC12 Cells from Amyloid Peptide-Induced Neurotoxicity. J.P.E.T. 2006; 317:3: 1143–1149.
17. Yair Porat, Adel Abramowitz and Ehud Gazit. Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism. Chem.Biol. Drug. Des. 2006; 67:1: 27–37.
18. Antoni Camins , Felix Junyent , Ester Verdaguer , Carlos Beas-Zarate , Argelia E. Rojas-Mayorquín , Daniel Ortuño-Sahagún and Mercè Pallàs. Resveratrol: An Anti-aging Drug with Potential Therapeutic Applications in Treating Diseases. Pharmaceuticals. 2009; 2:3: 194-205.
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21. Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Multifunction of myricetin on A beta: neuroprotection via a conformational change of A beta and reduction of A beta via the interference of secretases. J Neurosci Res. 2008; 86:2: 368-377.
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23. Sabu M Chacko, Priya T Thambi, Ramadasan Kuttan, Ikuo Nishigaki Chacko et al. Beneficial effects of green tea: A literature review . Chinese Medicine 2010; 5:13.
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25. Melissa A. Moss, Nicholas H. Varvel,1 Michael R. Nichols, Dana Kim Reed, Terrone L. Rosenberry. Nordihydroguaiaretic Acid Does Not Disaggregate-Amyloid(1–40) Protofibrils but Does Inhibit Growth Arising from Direct Protofibril Association. Mol Pharmacol. 2004; 66:3: 592–600.
26. Jae Kyeom Kim, Soo Jung Choi, Hong Yon Cho, Han-Joon Hwang, Young Jun Kim, Seung Taik Lim, Chang-Ju Kim, Hye Kyung Kim, Sabrina Peterson, Dong Hoon Shin. Protective effects of kaempferol against amyloid beta peptide induced neurotoxicity in ICR mice. Biosci. Biotechnol.Biochem. 2010; 74:2: 397-401.
27. Jason Pitt a,, William Roth a, Pascale Lacor a, Amos B. Smith III b,c, Matthew Blankenship d, Pauline Velasco a, Fernanda De Felice e, Paul Breslin b,f,, William L. Klein a. Alzheimer's-associated Aβ oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicology and Applied Pharmacology 2009; 240:2: 189-197.
28. Alaa H. Abuznait, Hisham Qosa, Belnaser A. Busnena, Khalid A. El Sayed, and Amal Kaddoumi. Olive-Oil-Derived Oleocanthal Enhances β Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s disease: In Vistro and in Vivo Studies. ACS.Chem.Neurosci 2013; 4:6: 973-982.
29. Wang Y, XIa Z, Xu JR, Wang YX, Hou LN, Qiu Y,Chen HZ . α-mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates β-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation. Neuropharmacology 2012; 62:2: 871-81.
30. Reyes-Fermín LM, González-Reyes S, Tarco-Álvarez NG, Hernández-Nava M, Orozco-Ibarra M, Pedraza-Chaverri J. Neuroprotective effect of α-mangostin and curcumin against iodoacetate-induced cell death. Nutr Neurosci. 2012; 15:5: 34-41.
31. Shrikant Mishra and Kalpana Palanivelu.The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Ann Indian Acad Neurol. 2008; 11:1: 13-19.
32. Fusheng Yang, Giselle P. Lim, Aynun N. Begum, Oliver J. Ubeda, Mychica R. Simmons, Surendra S. Ambegaokar, Pingping Chen, Rakez Kayed, Charles G. Glabe, Salley A. Frautschy, and Gregory M. Cole. Curcumin Inhibits Formation of Amyloid Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo. J.Biol. Chem 2005; 280:7: 5892-5901.
33. Wang Q, Xu J, Rottinghaus GE, Simonyi A, Lubahn D, Sun GY, Sun AY. Resveratrol protects against global cerebral ischemic injury in gerbils. Brain.Res 2002; 958:2: 439-447.
34. Mario Caruana , Tobias Högen , Johannes Levin , Andreas Hillmer , Armin Giese , Neville Vassallo. Inhibition and disaggregation of a-synuclein oligomers by natural polyphenolic compounds. FEBS Letters 2011; 585:8: 1113-1120.
35. Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ. Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004; 36:5: 592-604.
36. Guedj F, Se´brie´ C, Rivals I, Ledru A, Paly E, et al. Green Tea Polyphenols Rescue of Brain Defects Induced by Overexpression of DYRK1A. PLoS. ONE. 2009; 4:2: e4606
37. Young Jin Jang, Jiyoung Kim, Jaesung Shim, Jaekyoon Kim, Sanguine Byun, Min-Ho Oak, Ki Won Lee, and Hyong Joo Lee. Kaempferol Attenuates 4-Hydroxynonenal-Induced Apoptosis in PC12 Cells by Directly Inhibiting NADPH Oxidase. JPET. 2011; 337:3: 747-754.
38. Narayan P, Krishnarjuna B, Vishwanathan V, Jagadeesh Kumar D, Babu S, Ramanathan KV, K Easwaran KR, Nagendra H G, Raghothama S.Does Aluminium bind to Histidine? An NMR investigation of Amyloid β12 and Amyloid β16 fragments. Chem. Biol. Drug. Des. 2013; 82:1: 48-59.
39. Kramer B, Rarey M, Lengauer T. Evaluation of the FLEXX Incremental Construction Algorithm for Protein–Ligand Docking. Proteins: Structure, Function, and Genetics 1999; 37:2: 228-241.
2. Finder V H. Alzheimer's disease: a general introduction and pathomechanism. Journal of Alzheimer's disease 2010; 22:3: 5-19.
3. Yankner BA., Duffy L. and Kirschner D. Neurotrophic and neurotoxic effects of amyloid-β protein: reversal by tachykinin neuropeptides. Science 1990; 250:279-282.
4. Terzi E., Holzemann G. and Seelig J. Reversible random coil beta-sheet transition of the Alzheimer beta-amyloid fragment (25–35). Biochemistry 1994; 33:1345-1350.
5. Anthony W. Fitzpatrick, Tuomas P. J. Knowles, Christopher A.Waudby, Michele Vendruscolo, Christopher M. Dobson. Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation. PLoS. Comput. Biol. 2011; 7:e1002169.
6. Shen C. and Murphy R. M. Solvent effects on self-assembly of beta-amyloid peptide.Biophys. J. 1995; 69:640-651.
7. Snyder S. W., Ladror U. S., Wade W. S., Wang G. T., Barrett L. W., Matayoshi E. D., Huffaker H. J., Krafft G. A. and Holzman T. F. Amyloid- β aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths. Biophys. J. 1994; 67:1216-1228.
8. Tartaglia G.G., Cavalli A., Pellarin R., Caflisch A. The role of aromaticity, exposed surface, and dipole moment in determining protein aggregation rates. Protein. Sci. 2004; 3:1939-1941.
9. Gazit E. A possible role for p-stacking in self-assembly of amyloid fibrils. FASEB. J . 2002; 16:77-83.
10. Francesca Mangialasche, Alina Solomon, Bengt Winblad, Patrizia Mecocci, Miia Kivipelto. Alzheimer’s disease: clinical trials and drug development. Lancet.Neurol. 2010; 9:7: 702–716.
11. Gao X, Zheng CY, Yang L, Tang XC, Zhang HY. Huperzine A protects isolated rat brain mitochondria against beta-amyloid peptide. Free. Radic .Biol .Med. 2009; 46:11: 1454–1462.
12. Claudine Manach, Andrzej Mazur, Augustin Scalbert. Polyphenols and prevention of cardiovascular diseases. Lippincott Williams & Wilkins 2005; 16:1:77-84.
13. Amalesh Samanta, Gouranga Das, Sanjoy Kumar Das. Roles of Flavonoids In Plants. Int.J. Pharm. Sci. Tech. 2011; 6: 12-135.
14. Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: A review of their intracellular targets. European Journal of Pharmacology. 2006; 545:1: 51–64.
15. Luan H, Kan Z, Xu Y, Lv C, Jiang W. Rosmarinic acid protects against experimental diabetes with cerebral ischemia: relation toinflammation response. J.Neuroinflammation 2013; 10:28: 10-28.
16. Teresa Iuvone, Daniele De Filippis, Giuseppe Esposito, Alessandra D’Amico, and Angelo A. Izzo. The Spice Sage and Its Active Ingredient Rosmarinic Acid Protect PC12 Cells from Amyloid Peptide-Induced Neurotoxicity. J.P.E.T. 2006; 317:3: 1143–1149.
17. Yair Porat, Adel Abramowitz and Ehud Gazit. Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism. Chem.Biol. Drug. Des. 2006; 67:1: 27–37.
18. Antoni Camins , Felix Junyent , Ester Verdaguer , Carlos Beas-Zarate , Argelia E. Rojas-Mayorquín , Daniel Ortuño-Sahagún and Mercè Pallàs. Resveratrol: An Anti-aging Drug with Potential Therapeutic Applications in Treating Diseases. Pharmaceuticals. 2009; 2:3: 194-205.
19. Valérie Vingtdeux, Ute Dreses-Werringloer, Haitian Zhao, Peter Davies and Philippe Marambaud. Therapeutic potential of resveratrol in Alzheimer's disease. BMC. Neuroscience 2008; 9:2: S6.
20. Gonzales AM, OrlandoRA. Sensitive Aβ Oligomerization Assay for Identification of Small Molecule Inhibitors. The Open Biotechnology Journal 2009; 3:1: 108-116.
21. Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Multifunction of myricetin on A beta: neuroprotection via a conformational change of A beta and reduction of A beta via the interference of secretases. J Neurosci Res. 2008; 86:2: 368-377.
22. Mubeen Ahmed Ansari, Hafiz Mohammed Abdul, Gururaj Joshi, Wycliffe O.Opii, D.Allan Butterfield. Protective Effect of Quercetin in Primary Neurons against Aβ (1-42): Relevance to Alzheimer's Disease. J. Nutr. Biochem. 2009; 20:4: 269–275.
23. Sabu M Chacko, Priya T Thambi, Ramadasan Kuttan, Ikuo Nishigaki Chacko et al. Beneficial effects of green tea: A literature review . Chinese Medicine 2010; 5:13.
24. Silvia Mandel, Orly Weinreb, Tamar Amit and Moussa B. H. Youdim. Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: implications for neurodegenerative diseases. Journal of Neurochemistry 2004; 88:6: 1555-1569.
25. Melissa A. Moss, Nicholas H. Varvel,1 Michael R. Nichols, Dana Kim Reed, Terrone L. Rosenberry. Nordihydroguaiaretic Acid Does Not Disaggregate-Amyloid(1–40) Protofibrils but Does Inhibit Growth Arising from Direct Protofibril Association. Mol Pharmacol. 2004; 66:3: 592–600.
26. Jae Kyeom Kim, Soo Jung Choi, Hong Yon Cho, Han-Joon Hwang, Young Jun Kim, Seung Taik Lim, Chang-Ju Kim, Hye Kyung Kim, Sabrina Peterson, Dong Hoon Shin. Protective effects of kaempferol against amyloid beta peptide induced neurotoxicity in ICR mice. Biosci. Biotechnol.Biochem. 2010; 74:2: 397-401.
27. Jason Pitt a,, William Roth a, Pascale Lacor a, Amos B. Smith III b,c, Matthew Blankenship d, Pauline Velasco a, Fernanda De Felice e, Paul Breslin b,f,, William L. Klein a. Alzheimer's-associated Aβ oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicology and Applied Pharmacology 2009; 240:2: 189-197.
28. Alaa H. Abuznait, Hisham Qosa, Belnaser A. Busnena, Khalid A. El Sayed, and Amal Kaddoumi. Olive-Oil-Derived Oleocanthal Enhances β Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s disease: In Vistro and in Vivo Studies. ACS.Chem.Neurosci 2013; 4:6: 973-982.
29. Wang Y, XIa Z, Xu JR, Wang YX, Hou LN, Qiu Y,Chen HZ . α-mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates β-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation. Neuropharmacology 2012; 62:2: 871-81.
30. Reyes-Fermín LM, González-Reyes S, Tarco-Álvarez NG, Hernández-Nava M, Orozco-Ibarra M, Pedraza-Chaverri J. Neuroprotective effect of α-mangostin and curcumin against iodoacetate-induced cell death. Nutr Neurosci. 2012; 15:5: 34-41.
31. Shrikant Mishra and Kalpana Palanivelu.The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Ann Indian Acad Neurol. 2008; 11:1: 13-19.
32. Fusheng Yang, Giselle P. Lim, Aynun N. Begum, Oliver J. Ubeda, Mychica R. Simmons, Surendra S. Ambegaokar, Pingping Chen, Rakez Kayed, Charles G. Glabe, Salley A. Frautschy, and Gregory M. Cole. Curcumin Inhibits Formation of Amyloid Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo. J.Biol. Chem 2005; 280:7: 5892-5901.
33. Wang Q, Xu J, Rottinghaus GE, Simonyi A, Lubahn D, Sun GY, Sun AY. Resveratrol protects against global cerebral ischemic injury in gerbils. Brain.Res 2002; 958:2: 439-447.
34. Mario Caruana , Tobias Högen , Johannes Levin , Andreas Hillmer , Armin Giese , Neville Vassallo. Inhibition and disaggregation of a-synuclein oligomers by natural polyphenolic compounds. FEBS Letters 2011; 585:8: 1113-1120.
35. Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ. Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004; 36:5: 592-604.
36. Guedj F, Se´brie´ C, Rivals I, Ledru A, Paly E, et al. Green Tea Polyphenols Rescue of Brain Defects Induced by Overexpression of DYRK1A. PLoS. ONE. 2009; 4:2: e4606
37. Young Jin Jang, Jiyoung Kim, Jaesung Shim, Jaekyoon Kim, Sanguine Byun, Min-Ho Oak, Ki Won Lee, and Hyong Joo Lee. Kaempferol Attenuates 4-Hydroxynonenal-Induced Apoptosis in PC12 Cells by Directly Inhibiting NADPH Oxidase. JPET. 2011; 337:3: 747-754.
38. Narayan P, Krishnarjuna B, Vishwanathan V, Jagadeesh Kumar D, Babu S, Ramanathan KV, K Easwaran KR, Nagendra H G, Raghothama S.Does Aluminium bind to Histidine? An NMR investigation of Amyloid β12 and Amyloid β16 fragments. Chem. Biol. Drug. Des. 2013; 82:1: 48-59.
39. Kramer B, Rarey M, Lengauer T. Evaluation of the FLEXX Incremental Construction Algorithm for Protein–Ligand Docking. Proteins: Structure, Function, and Genetics 1999; 37:2: 228-241.
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01-10-2013
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“DOCKING STUDIES OF PLANT POLYPHENOLS WITH AΒ FRAGMENTS SUGGESTS DETERMINANTS THAT ENABLE DESIGN OF INHIBITORS TOWARDS PREVENTING AGGREGATION EVENTS DURING ALZHEIMER’S”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 5, no. 4, Oct. 2013, pp. 170-4, https://doi.org/10.25004/IJPSDR.2013.050407.
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How to Cite
“DOCKING STUDIES OF PLANT POLYPHENOLS WITH AΒ FRAGMENTS SUGGESTS DETERMINANTS THAT ENABLE DESIGN OF INHIBITORS TOWARDS PREVENTING AGGREGATION EVENTS DURING ALZHEIMER’S”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 5, no. 4, Oct. 2013, pp. 170-4, https://doi.org/10.25004/IJPSDR.2013.050407.
