Focus on Polydatin Interaction with Sirtuins Family: a Comparative Computational Analysis

Ivan Vito Ferrari¹ , Alex De Gregorio² , Maria Pia Fuggetta³ , Giampietro Ravagnan⁴ , Wafa Ali⁵ , Fulvio Perrella⁶ , Federico Coppola⁷ , Mauro Di Mario⁸ , Paolo Patrizio⁹ , Mohnad Abdalla¹⁰

Section:Research Paper, Product Type: Journal-Paper
Vol.10 , Issue.3 , pp.1-8, Jun-2023

Online published on Jun 30, 2023

Copyright © Ivan Vito Ferrari, Alex De Gregorio, Maria Pia Fuggetta, Giampietro Ravagnan, Wafa Ali, Fulvio Perrella, Federico Coppola, Mauro Di Mario, Paolo Patrizio, Mohnad Abdalla . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 

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Abstract :
Sirtuins (SIRTs), a family of NAD+-dependent deacetylases, are involved in the regulation of physiological functions such as aging and inflammation. They are able to catalyze metabolic reactions, thus regulating several cellular processes, such as energy metabolism, stress response, cell survival and apoptosis, DNA repair, tissue regeneration and neuronal signaling. The present article examines the interaction of three polyphenols, as Resveratrol, Polydatin and Curcumin, with Sirtuins family. The data obtained through a computational analysis, by Molecular Docking and Molecular Dynamics approaches, shows that these natural compounds are able to bind the active site of Sirtuins involved in numerous biochemical signaling. Moreover, the results highlight that Polydatin bind all the considered SIRT proteins showing an excellent docking capability in terms of Binding Energies scores and estimation of Inhibition Constant Ki. Moreover, by the study of Dynamic Simulation (RMSF, RMSD, protein-ligand interactions, timeline simulation in the range of 100 ns) and Repeatability Docking tests, Polydatin appear more stable than Curcumin when binds SIRT-3 rather than SIRT-5 protein.

Key-Words / Index Term :
Polydatin, Curcumin, Docking analysis and Sirtuins proteins

References :
[1]Alqarni, M. H., Foudah, A. I., Muharram, M. M., and Labrou, N. E.,”The pleiotropic function of human sirtuins as modulators of metabolic pathways and viral infections”,Cells, Vol.10,pp.460,2021.
[2] Carafa, V., Altucci, L., and Nebbioso, A. “ Dual tumor suppressor and tumor promoter action of sirtuins in determining malignant phenotype,”Frontiers in pharmacology, Vol.10, pp.38,2019.
[3] Imai, S. I., and Guarente, L”NAD+ and sirtuins in aging and disease,”Trends in cell biology, Vol.24, Issue.8,pp. 464-471,2014.
[4] Pukhalskaia, A. E., Diatlova, A. S., Linkova, N. S., and Kvetnoy, I. M.,” Sirtuins: role in the regulation of oxidative stress and the pathogenesis of neurodegenerative diseases.,”Neuroscience and Behavioral Physiology,pp. 1-11,2022.
[5] Kratz, E. M., So?kiewicz, K., Kubis-Kubiak, and A., Piwowar, “ Sirtuins as important factors in pathological states and the role of their molecular activity modulators”, International journal of molecular sciences,Vol.22,pp.630,2021.
[6] Verdin, E., Hirschey, M. D., Finley, L. W.,and Haigis, M. C,” Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling”,Trends in biochemical sciences ,Vol.35,pp.669-675,2010.
[7] Michan, S., and Sinclair, D.,“Sirtuins in mmals: insights into their biological function,”iochemical Journal,Vol.404,pp.1-13,2007.
[8] Sebastián, C., Satterstrom, F. K., Haigis, M. C., and Mostoslavsky, R.,”From sirtuin biology to human diseases: an update. Journal of Biological Chemistry, Vol.287,p.42444-42452.
[9] Denu, J. M., and Gottesfeld, J. M;”Minireview series on sirtuins: from biochemistry to health and disease”,Journal of Biological Chemistry,Vol. 287,pp.42417-42418,2012.
[10] Sauve, A. A., Wolberger, C., Schramm, V. L., Boeke, J. D.” The biochemistry of sirtuins”,Annu. Rev. Biochem,Vol.75,pp.435-465,2006.
[11] Guarente, L.,” Sirtuins, aging, and medicine”,New England Journal of Medicine, Vol.364,pp. 2235-2244,2011.
[12] Chen, C., Zhou, M., Ge, Y., and Wang, X,”SIRT1 and aging related signaling pathways,” Mechanisms of ageing and development,Vol. 187,pp.111215,2020.
[13] Picard, F., Kurtev, M., Chung, N.,and Topark-Ngarm, A., Senawong, T., Machado de Oliveira, R., Guarente, L,” Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-?”,Nature,Vol. 429,pp. 771-776,2004.
[14] Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., and Sinclair, D. A,”Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan”,Nature,Vol.425,pp.191-196,2003.
[15] Sundaresan, N. R., Vasudevan, P., Zhong, L., Kim, G., Samant, S., Parekh, V., and Gupta, M. P,” The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun”,Nature medicine,Vol. 18,pp.1643-1650,2012.
[16] Kuang, J., Chen, L., Tang, Q., Zhang, J., Li, Y., and He, J,”The role of Sirt6 in obesity and diabetes”,Frontiers in physiology, Vol.9, pp.135,2018.
[17] Vakhrusheva, O., Smolka, C., Gajawada, P., Kostin, S., Boettger, T., Kubin, T., Bober, E,” Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice”,Circulation research,Vol.102,pp. 703-710,2008.
[18] Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., and Verdin, E,”SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation,”Nature , Vol.464,pp. 121-125,2010.
[19] Mathias, R. A., Greco, T. M., Oberstein, A., Budayeva, H. G., Chakrabarti, R., Rowland, E. A., and Cristea, I. M,” Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity”,Cell,Vol. 159,pp. 1615-1625,2014.
[20] Guedouari, H., Daigle, T., Scorrano, L.and Hebert-Chatelain, E.,” Sirtuin 5 protects mitochondria from fragmentation and degradation during starvation”,Biochimica et Biophysica Acta (BBA)-Molecular Cell Research,Vol. 864,pp. 169-176,2017.
[21] De Oliveira, R. M., Vicente Miranda, H., Francelle, L., Pinho, R., Szegö, É. M., Martinho, R., and Outeiro, T. F,” The mechanism of sirtuin 2–mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease”, PLoS biology,Vol.15,pp.e2000374,2017.
[22] Chalkiadaki, A., and Guarente, L,” The multifaceted functions of Sirtuins in cancer”,Nature Reviews Cancer,Vol. 15,pp.608-624,2015.
[23] Saunders, L. R., Verdin, E,” Sirtuins: critical regulators at the crossroads between cancer and aging,”Oncogene,Vol. 26,pp. 5489-5504,2007.
[24] Min, S. W., Sohn, P. D., Cho, S. H., Swanson, R. A., Gan, L.,”Sirtuins in neurodegenerative diseases: an update on potential mechanisms”, Frontiers in aging neuroscience,Vol. 5,pp.53,2013.
[25] J??ko, H., Wencel, P., Strosznajder, R. P., and Strosznajder, J. B.,”Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders”,Neurochemical research,Vol. 42,pp. 876-890,2017.
[26] Zhang, F., Wang, S., Gan, L., Vosler, P. S., Gao, Y., Zigmond, and M. J., Chen, J.” Protective effects and mechanisms of sirtuins in the nervous system”,Progress in neurobiology,Vol. 95,pp.373-395,2011.
[27] Donmez, G., and Outeiro, T. F”SIRT1 and SIRT2: emerging targets in neurodegeneration”,EMBO molecular medicine,Vol. 5,pp. 344-352,2013.
[28] Lipska, K., Filip, A. A., Gumieniczek, A,”Post?py w badaniach nad inhibitorami deacetylaz histonów jako lekami przeciwnowotworowymi”, Advances in Hygiene Experimental Medicine/Postepy Higieny i Medycyny Doswiadczalnej , Vol.72,2018.
[29] Peredo-Escárcega, A. E., Guarner-Lans, V., Pérez-Torres, I., Ortega-Ocampo, S., Carreón-Torres, E., Castrejón-Tellez, V., and Rubio-Ruiz, M. E.,” The combination of resveratrol and quercetin attenuates metabolic syndrome in rats by modifying the serum fatty acid composition and by upregulating SIRT 1 and SIRT 2 expression in white adipose tissue.,”Evidence-Based Complementary and Alternative Medicine, Vol.2015,2015.
[30] Sinha, D., Sarkar, N., Biswas, J., and Bishayee, A,” Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms,”In Seminars in cancer biology,Vol.40,pp.209-232. Academic Press,2016.
[31] Soleas, G. J., Diamandis, E. P., and Goldberg, D. M,”Resveratrol: a molecule whose time has come? And gone?”, Clinical biochemistry,Vol.30,pp. 91-113,1997.
[32] Soleas, G. J., Diamandis, E. P., and Goldberg, D. M,”Wine as a biological fluid: history, production, and role in disease prevention,”Journal of clinical laboratory analysis,Vol.11,pp.287-313,1997.
[33] Fuggetta, M. P., Bordignon, V., Cottarelli, A., Macchi, B., Frezza, C., Cordiali-Fei, P., and Ravagnan, G,”Downregulation of proinflammatory cytokines in HTLV-1-infected T cells by Resveratrol”,Jurnal of Experimental Clinical Cancer Research,Vol.35,pp. 1-9,2016.
[34] Fuggetta, M. P., D`Atri, S., Lanzilli, G., Tricarico, M., Cannavò, E., Zambruno, G., and Ravagnan, G,” In vitro antitumour activity of resveratrol in human melanoma cells sensitive or resistant to temozolomide,”Melanoma Research,Vol.14,pp.189-196,2004.
[35] Waterhouse, A. L., and Lamuela-Raventós, R. M,” The occurrence of piceid, a stilbene glucoside, in grape berries”, Phytochemistry,Vol. 37,pp. 571-573,1994.
36] Ravagnan, G., De Filippis, A., Cartenì, M., De Maria, S., Cozza, V., Petrazzuolo, M., and Donnarumma, G,”Polydatin, a natural precursor of resveratrol, induces ?-defensin production and reduces inflammatory response”, Inflammation,Vol.36,pp.26-34,2013.
[37] Di Benedetto, A., Posa, F., De Maria, S., Ravagnan, G., Ballini, A., Porro, C., and Mori, G,” Polydatin, natural precursor of resveratrol, promotes osteogenic differentiation of mesenchymal stem cells,”International Journal of Medical Sciences,Vol. 15,pp. 944,2018.
[38] De Maria, S., Scognamiglio, I., Lombardi, A., Amodio, N., Caraglia, M., Cartenì, M., and Stiuso, P,” Polydatin, a natural precursor of resveratrol, induces cell cycle arrest and differentiation of human colorectal Caco-2 cell,” Journal of translational medicine,Vol. 11,pp.1-11,2013.
[39] Perrella, F., Coppola, F., Petrone, A., Platella, C., Montesarchio, D., Stringaro, A., and Musumeci, D,”Interference of polydatin/resveratrol in the ACE2: spike recognition during COVID-19 infection. A focus on their potential mechanism of action through computational and biochemical assays,”Biomolecules, Vol. 11,Issue.7, pp.1048,2021.
[40] Wang, H. L., Gao, J. P., Han, Y. L., Xu, X., Wu, R., Gao, Y., Cui, X. H.” Comparative studies of polydatin and resveratrol on mutual transformation and antioxidative effect in vivo” ,Phytomedicine,Vol. 22,pp.553-559,2015.
[41] Yang, F., Lim, G. P., Begum, A. N., and Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Cole, G. M,”Curcumin inhibits formation of amyloid ? oligomers and fibrils, binds plaques, and reduces amyloid in vivo; Journal of Biological Chemistry ,Vol. 280,pp.5892-5901,2005.
[42] Aggarwal, B. B., Kumar, A., and Bharti, A. C,”Anticancer potential of curcumin: preclinical and clinical studies,Anticancer research,Vol. 23,pp. 363-398,2003.
[43] Anand, P., Kunnumakkara, A. B., Newman, R. A., Aggarwal, B. B. Bioavailability of curcumin: problems and promises, Molecular pharmaceutics, Vol.4,Issue.6,pp.807-818,2007.
[44] Hatcher, H., Planalp, R., Cho, J., Torti, F. M., and Torti, S. V,” Curcumin: from ancient medicine to current clinical trials”, Cellular and molecular life sciences,Vol. 65,pp.1631-1652,2008.
[45] Maheshwari, R. K., Singh, A. K., Gaddipati, J., and Srimal, R. C,” Multiple biological activities of curcumin: a short review. Life sciences”,Vol. 78,pp. 2081-2087,2006.
[46] Ammon, H. P.,and Wahl, M. A,” Pharmacology of Curcuma longa”,Planta medica,Vol. 57,pp.1-7,1991.
[47] Catherine, R. E., Nicholas, M., and George, P,” Antioxidant properties of phenolic compounds”,Trends in plant science ,Vol. 2,pp.152-159,1997.
[48] Manach, C., Scalbert, A., Morand, C., Rémésy, C.,and Jiménez, L,” Polyphenols: food sources and bioavailability”,The American journal of clinical nutrition,Vol. 79,pp.727-747,2004.
[49] Rice-Evans, C. A., Miller, N. J., and Paganga, G,” Structure-antioxidant activity relationships of flavonoids and phenolic acids,”Free radical biology and medicine,Vol. 20,pp. 933-956,1996.
50] Ozdal, T., Sela, D. A., Xiao, J., Boyacioglu, D., and Chen, F., Capanoglu, E,”The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility”, Nutrients,Vol. 8,pp.78,2016.
[51] Zhao, L., Cen, F., Tian, F., Li, M. J., Zhang, Q., Shen, H. Y., and Du, J.,” Combination treatment with quercetin and resveratrol attenuates high fat diet induced obesity and associated inflammation in rats via the AMPK?1/SIRT1 signaling pathway”, Experimental and therapeutic medicine,Vol. 14,pp. 5942-5948,2017.
[52] Davis, J. M., Murphy, E. A., Carmichael, M. D., Davis, B,” Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance”,American Journal of Physiology-Regulatory, Integrative and Comparative Physiology,Vol. 296,pp.R1071-R1077,2009.
[53] Yao, H., Rahman, I,” Perspectives on translational and therapeutic aspects of SIRT1 in inflammaging and senescence”,Biochemical pharmacology,Vol. 84,pp.1332-1339,2012.
[54] Chen, T., Li, J., Liu, J., Li, N., Wang, S., Liu, H., Bu, P.,” Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-?/Smad3 pathway”, American Journal of Physiology-Heart and Circulatory Physiology,Vol. 308,pp.H424-H434,2015.
[55] Rahnasto-Rilla, M., Tyni, J., Huovinen, M., Jarho, E., Kulikowicz, T., Ravichandran, S., Moaddel, R,”Natural polyphenols as sirtuin 6 modulators”,Scientific reports,Vol. 8,pp.1-11,2018.
[56] Margie, T. B., Brian, C. S., and John, M. D,” Mechanism of human SIRT1 activation by resveratrol” ,Journal of Biological Chemistry,Vol. 280,pp.17187-17195,2005.
[57] Li, L., Tan, H. P., Liu, C. Y., Yu, L. T., Wei, D. N., Zhang, Z. C., and Gu, Z. T,” Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria.,”Neural Regeneration Research,Vol. 14,pp.1573,2019.
[58] Zeng, Z., Chen, Z., Xu, S., Zhang, Q., Wang, X., Gao, Y., and Zhao, K. S.,” Polydatin protecting kidneys against hemorrhagic shock-induced mitochondrial dysfunction via SIRT1 activation and p53 deacetylation,”Oxidative Medicine and Cellular Longevity Vol. 2016,2016.
[59] Yang, Y., Duan, W., Lin, Y., Yi, W., Liang, Z., Yan, J., and Jin, Z.,” SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury,” Free Radical Biology and Medicine,Vol. 5,pp.667-679,2013.
[60] Seeliger, D., de Groot, B. L.”Ligand docking and binding site analysis with PyMOL and Autodock/Vina”,Journal of computer-aided molecular design,Vol. 24,pp. 417-422,2010.
[61] Dallakyan, S., and Olson, A.J,” Small-molecule library screening by docking with PyRx. Chemical biology: methods and protocols”,pp. 243-250,2015.
[62] Choudhary, M. I., Shaikh, M., tul-Wahab, A., and ur-Rahman, A,” In silico identification of potential inhibitors of key SARS-CoV-2 3CL hydrolase (Mpro) via molecular docking, MMGBSA predictive binding energy calculations, and molecular dynamics simulation.,”Plos one, Vol. 15,Issue.7, pp.e0235030,2020.
[63] Trott, O., and Olson, A. J,” AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading”,Journal of computational chemistry,Vol. 31,pp.455-461,2010.
[64] Forli, S., Huey, R., Pique, M. E., Sanner, M. F., Goodsell, D.and S.,Olson, A. J,” Computational protein–ligand docking and virtual drug screening with the AutoDock suite”,Nature protocols,Vol. 11,pp. 905-919,2016.
[65] Wallace, A. C., Laskowski, R. A., and Thornton, J. M,”LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions”,Protein engineering, design and selection,Vol. 8,pp.127-134,1995.
[66] Zeng, Z., Yang, Y., Dai, X., Xu, S., Li, T., Zhang, Q., and Chen, Z., Polydatin ameliorates injury to the small intestine induced by hemorrhagic shock via SIRT3 activation-mediated mitochondrial protection”,Expert Opinion on Therapeutic Targets,Vol. 20,pp. 645-652,2016.eserved