RESVERATROLUL
ANTIOXIDANTUL TINEREŢII
În ultimele decenii, modificările stilului de viață, în special a obiceiurile alimentare, au fost considerate tot mai mult ca un mijloc util de prevenire și tratare a bolilor cronice.
În acest context, polifenolii au apărut ca o alternativă naturală cu efecte benefice pe scară largă împotriva bolilor cardiovasculare, iniţial. Polifenolii sunt metabolizați de intestin, celule hepatice sau microbiote intestinale.
Printre numeroșii compuşi fitochimici, s-a raportat că fitoestrogenii conțin cele mai multe molecule bioactive şi care, se găsesc în soia, legume și fructe. Acești compuși pot fi clasificați în patru grupe principale, cum ar fi izoflavonoizi, flavonoizi, stilbeni și lignani. Dintre aceștia, stilbenele, în special trans-resveratrolul și glucozidul său, sunt raportate pe scară largă ca fiind benefice pentru sănătatea umană, chiar dovedind că posedă activitate antioxidantă, anticarcinogenă, antitumorală și estrogenică / antiestrogenică.
Resveratrolul este astfel un polifenol natural (trans-3,4 ′, 5-trihidroxistilben), care posedă proprietăți antiinflamatorii, antitumorigene și antioxidante, iar principalele surse includ strugurii (Vitis vinifera L.), o varietate de fructe de pădure, arahide, plante medicinale și vinul roșu.
Activitate antioxidantă şi antiinflamatoare
Activitate anticancer
ACTIVITATE DE PROTECŢIE CARDIOVASCULARĂ
EFECTE NEUROPROTECTOARE
REFERINŢE ŞTIINŢIFICE
- Kalantari H., Das Dipak K. Physiological effects of resveratrol. BioFactors. 2010;36:401–406. doi: 10.1002/biof.100.
- Renaud S., de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet. 1992;339:1523–1526. doi: 10.1016/0140-6736(92)91277-F.
- Keylor M.H., Matsuura B.S., Stephenson C.R.J. Chemistry and biology of resveratrol-derived natural products. Chem. Rev. 2015;115:8976–9027. doi: 10.1021/cr500689b.
- Nawaz W., Zhou Z., Deng S., Ma X., Ma X., Li C., Shu X. Therapeutic versatility of resveratrol derivatives. Nutrients. 2017;9:1188. doi: 10.3390/nu9111188.
- Li M., Kildegaard K.R., Chen Y., Rodriguez A., Borodina I., Nielsen J. De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae. Metab. Eng. 2015;32:1–11. doi: 10.1016/j.ymben.2015.08.007.
- Wang Y., Halls C., Zhang J., Matsuno M., Zhang Y., Yu O. Stepwise increase of resveratrol biosynthesis in yeast Saccharomyces cerevisiaeby metabolic engineering. Metab. Eng. 2011;13:455–463. doi: 10.1016/j.ymben.2011.04.005
- Li M., Schneider K., Kristensen M., Borodina I., Nielsen J. Engineering yeast for high-level production of stilbenoid antioxidants. Sci. Rep. 2016;6:36827. doi: 10.1038/srep36827
- Beekwilder J., Wolswinkel R., Jonker H., Hall R., de Vos C.H., Bovy A. Production of resveratrol in recombinant microorganisms. Appl. Environ. Microbiol. 2006;72:5670–5672. doi: 10.1128/AEM.00609-06.
- Burns J., Yokota T., Ashihara H., Lean M.E.J., Crozier A. Plant foods and herbal sources of resveratrol. J. Agric. Food Chem. 2002;50:3337–3340. doi: 10.1021/jf0112973
- Marques F.Z., Markus M.A., Morris B.J. Resveratrol: Cellular actions of a potent natural chemical that confers a diversity of health benefits. Int. J. Biochem. Cell Biol. 2009;41:2125–2128. doi: 10.1016/j.biocel.2009.06.003.
- Aschemann-Witzel J., Grunert K.G. Resveratrol food supplements: A survey on the role of individual consumer characteristics in predicting the attitudes and adoption intentions of us American and Danish respondents. BMC Public Health. 2015;15:110. doi: 10.1186/s12889-015-1348-7.
- Risuleo G. Chapter 33—Resveratrol: Multiple activities on the biological functionality of the cell. In: Gupta R.C., editor. Nutraceuticals.Academic Press; Boston, MA, USA: 2016. pp. 453–464.
- Akinwumi B.C., Bordun K.M., Anderson H.D. Biological activities of stilbenoids. Int. J. Mol. Sci. 2018;19:792. doi: 10.3390/ijms19030792
- Anisimova N.Y., Kiselevsky M.V., Sosnov A.V., Sadovnikov S.V., Stankov I.N., Gakh A.A. Trans-, cis-, and dihydro-resveratrol: A comparative study. Chem. Cen. J. 2011;5:88. doi: 10.1186/1752-153X-5-88.
- Orallo F. Comparative studies of the antioxidant effects of cis– and trans-resveratrol. Curr. Med. Chem. 2006;13:87–98. doi: 10.2174/092986706775197962.
- Park E.-J., Pezzuto J.M. The pharmacology of resveratrol in animals and humans. Biochim. Biophys. Acta. 2015;1852:1071–1113. doi: 10.1016/j.bbadis.2015.01.014
- Cichewicz R.H., Kouzi S.A. Resveratrol oligomers: Structure, chemistry, and biological activity. In: Atta ur R., editor. Studies in Natural Products Chemistry.Volume 26. Elsevier; Amsterdam, The Netherlands: 2002. pp. 507–579.
- Walle T. Bioavailability of resveratrol. Ann. N. Y. Acad. Sci. 2011;1215:9–15. doi: 10.1111/j.1749-6632.2010.05842.x
- Fan P., Marston A., Hay A.-E., Hostettmann K. Rapid separation of three glucosylated resveratrol analogues from the invasive plant Polygonum cuspidatumby high-speed countercurrent chromatography. J. Sep. Sci. 2009;32:2979–2984. doi: 10.1002/jssc.200900057.
- Shan B., Cai Y.-Z., Brooks J.D., Corke H. Antibacterial properties of Polygonum cuspidatumroots and their major bioactive constituents. Food Chem. 2008;109:530–537. doi: 10.1016/j.foodchem.2007.12.064.
- Jacob C., Kirsch G., Slusarenko A., Winyard P.G., Burkholz T. Recent Advances in Redox Active Plant and Microbial Products: From Basic Chemistry to Widespread Applications in Medicine and Agriculture.Springer; Manhattan, NJ, USA: 2014.
- Su D., Cheng Y., Liu M., Liu D., Cui H., Zhang B., Zhou S., Yang T., Mei Q. Comparision of piceid and resveratrol in antioxidation and antiproliferation activities in vitro. PLoS ONE. 2013;8:e54505. doi: 10.1371/journal.pone.0054505
- Fabris S., Momo F., Ravagnan G., Stevanato R. Antioxidant properties of resveratrol and piceid on lipid peroxidation in micelles and monolamellar liposomes. Biophys. Chem. 2008;135:76–83. doi: 10.1016/j.bpc.2008.03.005.
- Cheynier V., Sarni-Manchado P., Quideau S. Recent Advances in Polyphenol Research.Wiley; Hoboken, NJ, USA: 2012. p. 158.
- Park S., Lim J., Kim J.R., Cho S. Inhibitory effects of resveratrol on hepatitis B virus X protein-induced hepatocellular carcinoma. J. Vet. Sci. 2017;18:419–429. doi: 10.4142/jvs.2017.18.4.419.
- Lee P.-S., Chiou Y.-S., Ho C.-T., Pan M.-H. Chemoprevention by resveratrol and pterostilbene: Targeting on epigenetic regulation. BioFactors. 2018;44:26–35. doi: 10.1002/biof.1401
- Yeo S.C., Ho P.C., Lin H.S. Pharmacokinetics of pterostilbene in sprague-dawley rats: The impacts of aqueous solubility, fasting, dose escalation, and dosing route on bioavailability. Mol. Nutr. Food Res. 2013;57:1015–1025. doi: 10.1002/mnfr.201200651
- Pei-Sheng L., Yi-Shiou C., Chi-Tang H., Min-Hsiung P. Chemoprevention by resveratrol and pterostilbene: Targeting on epigenetic regulation. BioFactors. 2018;44:26–35.
- De Vries K., Strydom M., Steenkamp V. Bioavailability of resveratrol: Possibilities for enhancement. J. Herb. Med. 2018;11:71–77. doi: 10.1016/j.hermed.2017.09.002.
- Rimando A.M., Suh N. Biological/chemopreventive activity of stilbenes and their effect on colon cancer. Planta Med. 2008;74:1635–1643. doi: 10.1055/s-0028-1088301.
- Kuršvietienė L., Stanevičienė I., Mongirdienė A., Bernatonienė J. Multiplicity of effects and health benefits of resveratrol. Medicina. 2016;52:148–155. doi: 10.1016/j.medici.2016.03.003.
- Yang S.-C., Tseng C.-H., Wang P.-W., Lu P.-L., Weng Y.-H., Yen F.-L., Fang J.-Y. Pterostilbene, a methoxylated resveratrol derivative, efficiently eradicates planktonic, biofilm, and intracellular MRSA by topical application. Front. Microbiol. 2017;8:1103. doi: 10.3389/fmicb.2017.01103.
- Yang T., Wang L., Zhu M., Zhang L., Yan L. Properties and molecular mechanisms of resveratrol: A review. Pharmazie. 2015;70:501–506.
- Moyano-Mendez J.R., Fabbrocini G., de Stefano D., Mazzella C., Mayol L., Scognamiglio I., Carnuccio R., Ayala F., La Rotonda M.I., De Rosa G. Enhanced antioxidant effect of trans-resveratrol: Potential of binary systems with polyethylene glycol and cyclodextrin. Drug Dev. Ind. Pharm. 2014;40:1300–1307. doi: 10.3109/03639045.2013.817416.
- Gokce E.H., Korkmaz E., Dellera E., Sandri G., Bonferoni M.C., Ozer O. Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: Evaluation of antioxidant potential for dermal applications. Int. J. Nanomed. 2012;7:1841–1850. doi: 10.2147/IJN.S29710
- Chen J., Wei N., Lopez-Garcia M., Ambrose D., Lee J., Annelin C., Peterson T. Development and evaluation of resveratrol, vitamin e, and epigallocatechin gallate loaded lipid nanoparticles for skin care applications. Eur. J. Pharm. Biopharm. 2017;117:286–291. doi: 10.1016/j.ejpb.2017.04.008.
- Shen J., Zhou Q., Li P., Wang Z., Liu S., He C., Zhang C., Xiao P. Update on phytochemistry and pharmacology of naturally occurring resveratrol oligomers. Molecules. 2017;22:2050. doi: 10.3390/molecules22122050.
- Duarte A., Martinho A., Luís Â., Figueiras A., Oleastro M., Domingues F.C., Silva F. Resveratrol encapsulation with methyl-β-cyclodextrin for antibacterial and antioxidant delivery applications. Food Sci. Technol. 2015;63:1254–1260. doi: 10.1016/j.lwt.2015.04.004
- Malhotra A., Bath S., Elbarbry F. An organ system approach to explore the antioxidative, anti-inflammatory, and cytoprotective actions of resveratrol. Oxid. Med. Cell. Longev. 2015;2015:803971. doi: 10.1155/2015/803971
- Szekeres T., Fritzer-Szekeres M., Saiko P., Jäger W. Resveratrol and resveratrol analogues—structure—activity relationship. Pharm. Res. 2010;27:1042–1048. doi: 10.1007/s11095-010-0090-1.
- Stivala L.A., Savio M., Carafoli F., Perucca P., Bianchi L., Maga G., Forti L., Pagnoni U.M., Albini A., Prosperi E., et al. Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. J. Biol. Chem. 2001;276:22586–22594. doi: 10.1074/jbc.M101846200.
- Iuga C., Alvarez-Idaboy J.R., Russo N. Antioxidant activity of trans-resveratrol toward hydroxyl and hydroperoxyl radicals: A quantum chemical and computational kinetics study. J. Org. Chem. 2012;77:3868–3877. doi: 10.1021/jo3002134.
- Gülçin İ. Antioxidant properties of resveratrol: A structure–activity insight. Innov. Food Sci. Emerg. Technol. 2010;11:210–218. doi: 10.1016/j.ifset.2009.07.002.
- Papuc C., Goran G.V., Predescu C.N., Nicorescu V., Stefan G. Plant polyphenols as antioxidant and antibacterial agents for shelf-life extension of meat and meat products: Classification, structures, sources, and action mechanisms. Compr. Rev. Food Sci. Food Saf. 2017;16:1243–1268. doi: 10.1111/1541-4337.12298.
- Bhullar K.S., Hubbard B.P. Lifespan and healthspan extension by resveratrol. Biochim. Biophys. Acta. 2015;1852:1209–1218. doi: 10.1016/j.bbadis.2015.01.012.
- Konyalioglu S., Armagan G., Yalcin A., Atalayin C., Dagci T. Effects of resveratrol on hydrogen peroxide-induced oxidative stress in embryonic neural stem cells. Neural Regen. Res. 2013;8:485–495.
- Means J.C., Gerdes B.C., Koulen P. Distinct mechanisms underlying resveratrol-mediated protection from types of cellular stress in C6 glioma cells. Int. J. Mol. Sci. 2017;18:1521. doi: 10.3390/ijms18071521.
- Bishayee A. Cancer prevention and treatment with resveratrol: From rodent studies to clinical trials. Cancer Prev. Res. 2009;2:409–418. doi: 10.1158/1940-6207.CAPR-08-0160.
- Zykova T.A., Zhu F., Zhai X., Ma W.Y., Ermakova S.P., Lee K.W., Bode A.M., Dong Z. Resveratrol directly targets COX-2 to inhibit carcinogenesis. Mol. Carcinog. 2008;47:797–805. doi: 10.1002/mc.20437.
- Varoni E.M., Lo Faro A.F., Sharifi-Rad J., Iriti M. Anticancer molecular mechanisms of resveratrol. Front. Nutr. 2016;3:8. doi: 10.3389/fnut.2016.00008
- Pezzuto J.M. Resveratrol as an inhibitor of carcinogenesis. Pharm. Biol. 2008;46:443–573. doi: 10.1080/13880200802116610.
- Van Ginkel P.R., Sareen D., Subramanian L., Walker Q., Darjatmoko S.R., Lindstrom M.J., Kulkarni A., Albert D.M., Polans A.S. Resveratrol inhibits tumor growth of human neuroblastoma and mediates apoptosis by directly targeting mitochondria. Clin. Cancer Res. 2007;13:5162–5169. doi: 10.1158/1078-0432.CCR-07-0347
- Kundu J.K., Surh Y.J. Cancer chemopreventive and therapeutic potential of resveratrol: Mechanistic perspectives. Cancer Lett. 2008;269:243–261. doi: 10.1016/j.canlet.2008.03.057.
- Li L., Qiu R.L., Lin Y., Cai Y., Bian Y., Fan Y., Gao X.J. Resveratrol suppresses human cervical carcinoma cell proliferation and elevates apoptosis via the mitochondrial and p53 signaling pathways. Oncol. Lett. 2018;15:9845–9851. doi: 10.3892/ol.2018.8571
- Cheng L., Yan B., Chen K., Jiang Z., Zhou C., Cao J., Qian W., Li J., Sun L., Ma J., et al. Resveratrol-induced downregulation of NAF-1 enhances the sensitivity of pancreatic cancer cells to gemcitabine via the ROS/Nrf2 signaling pathways. Oxid. Med. Cell. Longev. 2018;2018:9482018. doi: 10.1155/2018/9482018
- Singh A., Bishayee A., Pandey A. Targeting histone deacetylases with natural and synthetic agents: An emerging anticancer strategy. Nutrients. 2018;10:731. doi: 10.3390/nu10060731.
- Brisdelli F., D′Andrea G., Bozzi A. Resveratrol: A natural polyphenol with multiple chemopreventive properties (Review) Curr. Drug Metab. 2009;10:530–546. doi: 10.2174/138920009789375423.
- Shukla Y., Singh R. Resveratrol and cellular mechanisms of cancer prevention. Ann. N. Y. Acad. Sci. 2011;1215:1–8. doi: 10.1111/j.1749-6632.2010.05870.x.
- Roccaro A.M., Leleu X., Sacco A., Moreau A.S., Hatjiharissi E., Jia X., Xu L., Ciccarelli B., Patterson C.J., Ngo H.T., et al. Resveratrol exerts antiproliferative activity and induces apoptosis in waldenstrom′s macroglobulinemia. Clin. Cancer Res. 2008;14:1849–1858. doi: 10.1158/1078-0432.CCR-07-1750
- De Sá Coutinho D., Pacheco M., Frozza R., Bernardi A. Anti-inflammatory effects of resveratrol: Mechanistic insights. Int. J. Mol. Sci. 2018;19:1812. doi: 10.3390/ijms19061812.
- Sinha D., Sarkar N., Biswas J., Bishayee A. Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms. Semin. Cancer Biol. 2016;40–41:209–232. doi: 10.1016/j.semcancer.2015.11.001.
- Alamolhodaei N.S., Tsatsakis A.M., Ramezani M., Hayes A.W., Karimi G. Resveratrol as MDR reversion molecule in breast cancer: An overview. Food Chem. Toxicol. 2017;103:223–232. doi: 10.1016/j.fct.2017.03.024.
- Valentovic M.A. Evaluation of resveratrol in cancer patients and experimental models. Adv. Cancer Res. 2018;137:171–188
- Zulueta A., Caretti A., Signorelli P., Ghidoni R. Resveratrol: A potential challenger against gastric cancer. World J. Gastroenterol. 2015;21:10636–10643. doi: 10.3748/wjg.v21.i37.10636.
- Aluyen J.K., Ton Q.N., Tran T., Yang A.E., Gottlieb H.B., Bellanger R.A. Resveratrol: Potential as anticancer agent. J. Diet. Suppl. 2012;9:45–56. doi: 10.3109/19390211.2011.650842.
- Colin D., Limagne E., Jeanningros S., Jacquel A., Lizard G., Athias A., Gambert P., Hichami A., Latruffe N., Solary E., et al. Endocytosis of resveratrol via lipid rafts and activation of downstream signaling pathways in cancer cells. Cancer Prev. Res. (Phila) 2011;4:1095–1106. doi: 10.1158/1940-6207.CAPR-10-0274.
- Fulda S., Debatin K.M. Resveratrol modulation of signal transduction in apoptosis and cell survival: A mini-review. Cancer Detect. Prev. 2006;30:217–223. doi: 10.1016/j.cdp.2006.03.007.
- Lin H.Y., Tang H.Y., Davis F.B., Davis P.J. Resveratrol and apoptosis. Ann. N. Y. Acad. Sci. 2011;1215:79–88. doi: 10.1111/j.1749-6632.2010.05846.x.
- Whitlock N.C., Baek S.J. The anticancer effects of resveratrol: Modulation of transcription factors. Nutr. Cancer. 2012;64:493–502. doi: 10.1080/01635581.2012.667862.
- Mitra S., Dash R. Natural products for the management and prevention of breast cancer. Evid. Based Complement. Alternat. Med. 2018;2018:23. doi: 10.1155/2018/8324696.
- Mut-Salud N., Alvarez P.J., Garrido J.M., Carrasco E., Aranega A., Rodriguez-Serrano F. Antioxidant intake and antitumor therapy: Toward nutritional recommendations for optimal results. Oxid. Med. Cell. Longev. 2016;2016:6719534. doi: 10.1155/2016/6719534.
- Jiang Z., Chen K., Cheng L., Yan B., Qian W., Cao J., Li J., Wu E., Ma Q., Yang W. Resveratrol and cancer treatment: Updates. Ann. N. Y. Acad. Sci. 2017;1403:59–69. doi: 10.1111/nyas.13466.
- Yan F., Sun X., Xu C. Protective effects of resveratrol improve cardiovascular function in rats with diabetes. Exp. Ther. Med. 2018;15:1728–1734. doi: 10.3892/etm.2017.5537.
- Delucchi F., Berni R., Frati C., Cavalli S., Graiani G., Sala R., Chaponnier C., Gabbiani G., Calani L., Rio D.D., et al. Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats. PLoS ONE. 2012;7:e39836. doi: 10.1371/journal.pone.0039836.
- Riba A., Deres L., Sumegi B., Toth K., Szabados E., Halmosi R. Cardioprotective effect of resveratrol in a postinfarction heart failure model. Oxid. Med. Cell. Longev. 2017;2017:6819281. doi: 10.1155/2017/6819281.
- Öztürk E., Arslan A.K.K., Yerer M.B., Bishayee A. Resveratrol and diabetes: A critical review of clinical studies. Biomed. Pharm. 2017;95:230–234. doi: 10.1016/j.biopha.2017.08.070.
- Bishayee A., Barnes K.F., Bhatia D., Darvesh A.S., Carroll R.T. Resveratrol suppresses oxidative stress and inflammatory response in diethylnitrosamine-initiated rat hepatocarcinogenesis. Cancer Prev. Res. 2010;3:753–763. doi: 10.1158/1940-6207.CAPR-09-0171.
- Hung L.-M., Chen J.-K., Huang S.-S., Lee R.-S., Su M.-J. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc. Res. 2000;47:549–555. doi: 10.1016/S0008-6363(00)00102-4.
- Das S., Santani D.D., Dhalla N.S. Experimental evidence for the cardioprotective effects of red wine. Exp. Clin. Cardiol. 2007;12:5–10.
- Zahedi H.S., Jazayeri S., Ghiasvand R., Djalali M., Eshraghian M.R. Effects of Polygonum cuspidatumcontaining resveratrol on inflammation in male professional basketball players. Int. J. Prev. Med. 2013;4:S1.
- Zhang H., Li C., Kwok S.-T., Zhang Q.-W., Chan S.-W. A review of the pharmacological effects of the dried root of Polygonum cuspidatum(Hu Zhang) and its constituents. Evid. Based Complement. Alternat. Med. 2013;2013:13. doi: 10.1155/2013/208349
- Kurita S., Kashiwagi T., Ebisu T., Shimamura T., Ukeda H. Content of resveratrol and glycoside and its contribution to the antioxidative capacity of Polygonum cuspidatum(Itadori) harvested in Kochi. Biosci. Biotechnol. Biochem. 2014;78:499–502. doi: 10.1080/09168451.2014.890032.
- Rauf A., Imran M., Suleria H.A.R., Ahmad B., Peters D.G., Mubarak M.S. A comprehensive review of the health perspectives of resveratrol. Food Funct. 2017;8:4284–4305. doi: 10.1039/C7FO01300K
- Wahab A., Gao K., Jia C., Zhang F., Tian G., Murtaza G., Chen J. Significance of resveratrol in clinical management of chronic diseases. Molecules. 2017;22:1329. doi: 10.3390/molecules22081329.
- Sun A.Y., Wang Q., Simonyi A., Sun G.Y. Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol. Neurobiol. 2010;41:375–383. doi: 10.1007/s12035-010-8111-y.
- Tellone E., Galtieri A., Russo A., Giardina B., Ficarra S. Resveratrol: A focus on several neurodegenerative diseases. Oxid. Med. Cell. Longev. 2015;2015:14. doi: 10.1155/2015/392169.
- Bastianetto S., Ménard C., Quirion R. Neuroprotective action of resveratrol. Biochim. Biophys. Acta. 2015;1852:1195–1201. doi: 10.1016/j.bbadis.2014.09.011
- Rege S.D., Geetha T., Griffin G.D., Broderick T.L., Babu J.R. Neuroprotective effects of resveratrol in alzheimer disease pathology. Front. Aging Neurosci. 2014;6:218. doi: 10.3389/fnagi.2014.00218.
- Farzaei M.H., Rahimi R., Nikfar S., Abdollahi M. Effect of resveratrol on cognitive and memory performance and mood: A meta-analysis of 225 patients. Pharmacol. Res. 2018;128:338–344. doi: 10.1016/j.phrs.2017.08.009.
- Cai J.C., Liu W., Lu F., Kong W.B., Zhou X.X., Miao P., Lei C.X., Wang Y. Resveratrol attenuates neurological deficit and neuroinflammation following intracerebral hemorrhage. Exp. Ther. Med. 2018;15:4131–4138. doi: 10.3892/etm.2018.5938.
91. Singh N., Bansal Y., Bhandari R., Marwaha L., Singh R., Chopra K., Kuhad A. Resveratrol protects against ICV collagenase-induced neurobehavioral and biochemical deficits. J. Inflamm. (Lond.) 2017;14:14. doi: 10.1186/s12950-017-0158-3.