Abstract
Inflammatory bowel disease is a debilitating idiopathic inflammatory condition of the gastrointestinal tract. Generally, this illness contains two chief subtypes: ulcerative colitis and Crohn’s disease. As a consequence of drug tolerance and insufficient efficacy of available conventional therapies, applying natural products such as resveratrol and its derivatives is of high interest. In the present manuscript, we specified the pivotal effects of resveratrol in inflammatory bowel disease by putting our emphasis on cellular and molecular signaling pathways. This perceptive approach gives researchers a bright way which represents the participation of oxidative stress, adhesion molecules, kinases, nuclear factor erythroid 2–related factor 2, NLRP3 (NOD–, LRR–, and pyrin domain–containing protein 3 inflammasome, peroxisome proliferator–activated receptor, nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase, inflammatory responses, inducible nitric oxide synthase, tumor necrosis factor α, interleukins, small ubiquitin-like modifier 1, nicotinamide adenine dinucleotide, autophagy, xenophagy, and gut-microbiome composition in putative therapeutic influences of resveratrol in inflammatory bowel disease. To overwhelm the challenges encountered in resveratrol delivery, nanoformulations with colon-specific drug delivery systems are described.
Graphical Abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
All data are available in the manuscript.
References
Abdallah DM, Ismael NR (2011) Resveratrol abrogates adhesion molecules and protects against TNBS-induced ulcerative colitis in rats. Can J Physiol Pharmacol 89:811–818. https://doi.org/10.1139/Y11-080
Abdin AA (2013) Targeting sphingosine kinase 1 (SphK1) and apoptosis by colon-specific delivery formula of resveratrol in treatment of experimental ulcerative colitis in rats. Eur J Pharmacol 718:145–153. https://doi.org/10.1016/j.ejphar.2013.08.040
Abdolghaffari AH, Nikfar S, Rahimi H, Abdollahi M (2012) A comprehensive review of antibiotics in clinical trials for inflammatory bowel disease. Int J Pharmacol 8:596–613. https://doi.org/10.3923/ijp.2012.596.613
Al Azzaz J, Rieu A, Aires V, Delmas D, Chluba J, Winckler P, Bringer M-A, Lamarche J, Vervandier-Fasseur D, Dalle F, Lapaquette P, Guzzo J (2019) Resveratrol-induced xenophagy promotes intracellular bacteria clearance in intestinal epithelial cells and macrophages. Front Immunol 9:3149. https://doi.org/10.3389/fimmu.2018.03149
Alrafas HR, Busbee PB, Nagarkatti M, Nagarkatti PS (2019) Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of tregs and suppression of Th17 cells. J Leukoc Biol 106:467–480. https://doi.org/10.1002/jlb.3a1218-476rr
Alrafas HR, Busbee PB, Chitrala KN, Nagarkatti M, Nagarkatti P (2020a) Alterations in the gut microbiome and suppression of histone deacetylases by resveratrol are associated with attenuation of colonic inflammation and protection against colorectal cancer. J Clin Med 9:1796. https://doi.org/10.3390/jcm9061796
Alrafas HR, Busbee PB, Nagarkatti M, Nagarkatti PS (2020b) Resveratrol downregulates miR-31 to promote T regulatory cells during prevention of TNBS-induced colitis. Mol Nutr Food Res 64:1900633. https://doi.org/10.1002/mnfr.201900633
Antonioli L, Colucci R, Pellegrini C, Giustarini G, Sacco D, Tirotta E, Caputi V, Marsilio I, Giron MC, Németh ZH, Blandizzi C, Fornai M (2016) The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders. Expert Opin Ther Targets 20:179–191. https://doi.org/10.1517/14728222.2016.1086752
Argollo M, Gilardi D, Peyrin-Biroulet C, Chabot JF, Peyrin-Biroulet L, Danese S (2019) Comorbidities in inflammatory bowel disease: a call for action. Lancet Gastroenterol Hepatol 4:643–654. https://doi.org/10.1016/S2468-1253(19)30173-6
Ashrafizadeh M, Ahmadi Z, Mohammadinejad R, Farkhondeh T, Samarghandian S (2020) Curcumin activates the Nrf2 pathway and induces cellular protection against oxidative injury. Curr Mol Med 20:116–133. https://doi.org/10.2174/1566524019666191016150757
Ashrafizadeh M, Fekri HS, Ahmadi Z, Farkhondeh T, Samarghandian S (2020) Therapeutic and biological activities of berberine: the involvement of Nrf2 signaling pathway. J Cell Biochem 12:1575–1585. https://doi.org/10.1002/jcb.29392
Atanasov AG, Zotchev SB, Dirsch VM, International Natural Product Sciences Taskforce, Supuran CT (2021) Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 20:200–216. https://doi.org/10.1038/s41573-020-00114-z
Atreya R, Neurath MF (2018) Mechanisms of molecular resistance and predictors of response to biological therapy in inflammatory bowel disease. Lancet Gastroenterol Hepatol 3:790–802. https://doi.org/10.1016/S2468-1253(18)30265-6
Augustin MA, Sanguansri L, Lockett T (2013) Nano- and micro-encapsulated systems for enhancing the delivery of resveratrol. Ann N Y Acad Sci 1290:107–112. https://doi.org/10.1111/nyas.12130
Aziz I, Simrén M (2021) The overlap between irritable bowel syndrome and organic gastrointestinal diseases. Lancet Gastroenterol Hepatol 6:139–148. https://doi.org/10.1016/S2468-1253(20)30212-0
Barberio B, Zamani M, Black CJ, Savarino EV, Ford AC (2021) Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 6:359–370. https://doi.org/10.1016/S2468-1253(21)00014-5
Baxter R (2008) Anti-aging properties of resveratrol: review and report of a potent new antioxidant skin care formulation. J Cosmet Dermatol 7:2–7. https://doi.org/10.1111/j.1473-2165.2008.00354.x
Berman AY, Motechin RA, Wiesenfeld MY, Holz MK (2017) The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol 1:35. https://doi.org/10.1038/s41698-017-0038-6
Biagi M, Bertelli AA (2015) Wine, alcohol and pills: what future for the French paradox? Life Sci 131:19–22. https://doi.org/10.1016/j.lfs.2015.02.024
Bird JK, Raederstorff D, Weber P, Steinert RE (2017) Cardiovascular and antiobesity effects of resveratrol mediated through the gut microbiota. Adv Nutr 8:839–849. https://doi.org/10.3945/an.117.016568
Boskabady MH, Karimi GR, Samarghandian S, Farkhondeh T (2012) Tracheal responsiveness to methacholine and ovalbumin; and lung inflammation in guinea pigs exposed to inhaled lead after sensitization. Ecotoxicol Environ Saf 86:233–8. https://doi.org/10.1016/j.ecoenv.2012.09.025
Boyd M, Thodberg M, Vitezic M, Bornholdt J, Vitting-Seerup K, Chen Y, Coskun M, Li Y, Lo BZS, Klausen P, Schweiger PJ, Pedersen AG, Rapin N, Skovgaard K, Dahlgaard K, Andersson R, Terkelsen TB, Lilje B, Troelsen JT et al (2018) Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies. Nat Commun 9:1661. https://doi.org/10.1038/s41467-018-03766-z
Breuss JM, Atanasov AG, Uhrin P (2019) Resveratrol and its effects on the vascular system. Int J Mol Sci 20:1523. https://doi.org/10.3390/ijms20071523
Carrera-Quintanar L, López Roa RI, Quintero-Fabián S, Sánchez-Sánchez MA, Vizmanos B, Ortuño-Sahagún D (2018) Phytochemicals that influence gut microbiota as prophylactics and for the treatment of obesity and inflammatory diseases. Mediat Inflamm 2018:9734845. https://doi.org/10.1155/2018/9734845
Carrizzo A, Forte M, Damato A, Trimarco V, Salzano F, Bartolo M, Maciag A, Puca AA, Vecchione C (2013) Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases. Food Chem Toxicol 61:215–226. https://doi.org/10.1016/j.fct.2013.07.021
Carter AB, Misyak SA, Hontecillas R, Bassaganya-Riera J (2009) Dietary modulation of inflammation-induced colorectal cancer through PPARγ. PPAR Res 2009:498352. https://doi.org/10.1155/2009/498352
Chen Y, Zheng Z, Li C, Pan Y, Tang X, Wang XJ (2019) Synthetic imine resveratrol analog 2-methoxyl-3,6-dihydroxyl-IRA ameliorates colitis by activating protective Nrf2 pathway and inhibiting NLRP3 expression. Oxidative Med Cell Longev 2019:7180284. https://doi.org/10.1155/2019/7180284
Chen L, Collij V, Jaeger M, van den Munckhof ICL, Vich Vila A, Kurilshikov A, Gacesa R, Sinha T, Oosting M, Joosten LAB, Rutten JHW, Riksen NP, Xavier RJ, Kuipers F, Wijmenga C, Zhernakova A, Netea MG, Weersma RK, Fu J (2020) Gut microbial co-abundance networks show specificity in inflammatory bowel disease and obesity. Nat Commun 11:4018. https://doi.org/10.1038/s41467-020-17840-y
Chen G, Yang Z, Wen D, Guo J, Xiong Q, Li P, Zhao L, Wang J, Wu C, Dong L (2021) Polydatin has anti-inflammatory and antioxidant effects in LPS-induced macrophages and improves DSS-induced mice colitis. Immun Inflamm Dis 9:959–970. https://doi.org/10.1002/iid3.455
Chimento A, De Amicis F, Sirianni R, Sinicropi MS, Puoci F, Casaburi I, Saturnino C, Pezzi V (2019) Progress to improve oral bioavailability and beneficial effects of resveratrol. Int J Mol Sci 20:1381. https://doi.org/10.3390/ijms20061381
Chiu HF, Venkatakrishnan K, Golovinskaia O, Wang CK (2021) Gastroprotective effects of polyphenols against various gastro-intestinal disorders: a mini-review with special focus on clinical evidence. Molecules 26:2090. https://doi.org/10.3390/molecules26072090
Cho S, Namkoong K, Shin M, Park J, Yang E, Ihm J, Thu VT, Kim HK, Han J (2017) Cardiovascular protective effects and clinical applications of resveratrol. J Med Food 20:323–334. https://doi.org/10.1089/jmf.2016.3856
Chung JY, Jeong JH, Song J (2020) Resveratrol modulates the gut-brain axis: focus on glucagon-like peptide-1, 5-HT, and gut microbiota. Front Aging Neurosci 12:588044. https://doi.org/10.3389/fnagi.2020.588044
Clarke JO, Mullin GE (2008) A review of complementary and alternative approaches to immunomodulation. Nutr Clin Pract 23:49–62. https://doi.org/10.1177/011542650802300149
Colica C, Milanović M, Milic N, Aiello V, De Lorenzo A, Abenavoli L (2018) A systematic review on natural antioxidant properties of resveratrol. Nat Prod Commun 13:1195–1203. https://doi.org/10.1177/1934578X1801300923
Contado C, Caselotto L, Mello P, Maietti A, Marvelli L, Marchetti N, Dalpiaz A (2020) Design and formulation of eudragit-coated zein/pectin nanoparticles for the colon delivery of resveratrol. Eur Food Res Technol 246:2427–2441. https://doi.org/10.1007/s00217-020-03586-w
Cui X, Jin Y, Hofseth AB, Pena E, Habiger J, Chumanevich A, Poudyal D, Nagarkatti M, Nagarkatti PS, Singh UP, Hofseth LJ (2010) Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer Prev Res 3:549–559. https://doi.org/10.1158/1940-6207.CAPR-09-0117
Devi A, Dwibedi V, Khan ZA (2021) Natural antioxidants in new age-related diseases. Rev Bras 31:387–407. https://doi.org/10.1007/s43450-021-00175-0
Direito R, Rocha J, Sepodes B, Eduardo-Figueira M (2021) Phenolic compounds impact on rheumatoid arthritis, inflammatory bowel disease and microbiota modulation. Pharmaceutics 13:145. https://doi.org/10.3390/pharmaceutics13020145
Faghihzadeh F, Adibi P, Hekmatdoost A (2014) Effects of dietary resveratrol supplementation on liver enzymes, hs-CRP, and hepatic steatosis in patients with nonalcoholic fatty liver disease. Iran J Nutr Sci Food Technol 8:40–49 http://nsft.sbmu.ac.ir/article-1-1495-en.html
Fairbrass KM, Costantino SJ, Gracie DJ, Ford AC (2020) Prevalence of irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease in remission: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 5:1053–1062. https://doi.org/10.1016/S2468-1253(20)30300-9
Farkhondeh T, Samarghandian S, Pourbagher-Shahri AM, Sedaghat M (2019) The impact of curcumin and its modified formulations on Alzheimer’s disease. J Cell Physiol 234:16953–16965. https://doi.org/10.1002/jcp.28411
Farkhondeh T, Folgado SL, Pourbagher-Shahri AM, Ashrafizadeh M, Samarghandian S (2020a) The therapeutic effect of resveratrol: focusing on the Nrf2 signaling pathway. Biomed Pharmacother 127:110234. https://doi.org/10.1016/j.biopha.2020.110234
Farzaei MH, Rahimi R, Abdollahi M (2015) The role of dietary polyphenols in the management of inflammatory bowel disease. Curr Pharm Biotechnol 16:196–210. https://doi.org/10.2174/1389201016666150118131704
Fazel Nabavi S, Li H, Daglia M, Mohammad Nabavi S (2014) Resveratrol and stroke: from chemistry to medicine. Curr Neurovasc Res 11:390–397. https://doi.org/10.2174/1567202611666140912114833
Fereidoni M, Jahanbakhshi S (2015) A review of resveratrol effects on longevity. SJIMU 23:54–72
Figueiras TS, Neves-Petersen MT, Petersen SB (2011) Activation energy of light induced isomerization of resveratrol. J Fluoresc 21:1897–1906. https://doi.org/10.1007/s10895-011-0886-3
Frombaum M, Le Clanche S, Bonnefont-Rousselot D, Borderie D (2012) Antioxidant effects of resveratrol and other stilbene derivatives on oxidative stress and NO bioavailability: potential benefits to cardiovascular diseases. Biochimie 94:269–276. https://doi.org/10.1016/j.biochi.2011.11.001
Fürst R, Zündorf I (2014) Plant-derived anti-inflammatory compounds: hopes and disappointments regarding the translation of preclinical knowledge into clinical progress. Mediat Inflamm 2014:146832. https://doi.org/10.1155/2014/146832
Gambini J, Inglés M, Olaso G, Lopez-Grueso R, Bonet-Costa V, Gimeno-Mallench L, Mas-Bargues C, Abdelaziz KM, Gomez-Cabrera MC, Vina J, Borras C (2015) Properties of resveratrol: in vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxidative Med Cell Longev 2015:837042. https://doi.org/10.1155/2015/837042
Gandhi H, Rathore C, Dua K, Vihal S, Tambuwala MM, Negi P (2020) Efficacy of resveratrol encapsulated microsponges delivered by pectin based matrix tablets in rats with acetic acid-induced ulcerative colitis. Drug Dev Ind Pharm 46:365–375. https://doi.org/10.1080/03639045.2020.1724127
GBD 2017 Inflammatory Bowel Disease Collaborators (2020) The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 5:17–30. https://doi.org/10.1016/S2468-1253(19)30333-4
Gianchecchi E, Fierabracci A (2020) Insights on the effects of resveratrol and some of its derivatives in cancer and autoimmunity: a molecule with a dual activity. Antioxidants 9:91. https://doi.org/10.3390/antiox9020091
Giang J, Lan X, Crichton M, Marx W, Marshall S (2021) Efficacy and safety of biophenol-rich nutraceuticals in adults with inflammatory gastrointestinal diseases or irritable bowel syndrome: a systematic literature review and meta-analysis. Nutr Diet 79:76–93. https://doi.org/10.1111/1747-0080.12672
González R, Ballester I, López-Posadas R, Suárez MD, Zarzuelo A, Martínez-Augustin O, Sánchez de Medina F (2011) Effects of flavonoids and other polyphenols on inflammation. Crit Rev Food Sci Nutr 51:331–362. https://doi.org/10.1080/10408390903584094
Graham B, Xavier RJ (2020) Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature 578:527–539. https://doi.org/10.1038/s41586-020-2025-2
Griñán-Ferré C, Bellver-Sanchis A, Izquierdo V, Corpas R, Roig-Soriano J, Chillón M, Andres-Lacueva C, Somogyvári M, Sőti C, Sanfeliu C, Pallàs M (2021) The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer’s disease pathology: from antioxidant to epigenetic therapy. Ageing Res Rev 67:101271. https://doi.org/10.1016/j.arr.2021.101271
Gupta SC, Tyagi AK, Deshmukh-Taskar P, Hinojosa M, Prasad S, Aggarwal BB (2014) Downregulation of tumor necrosis factor and other proinflammatory biomarkers by polyphenols. Arch Biochem Biophys 559:91–99. https://doi.org/10.1016/j.abb.2014.06.006
Hodson R (2016) Inflammatory bowel disease. Nature 540:97. https://doi.org/10.1038/540S97a
Hsieh T, Juan G, Darzynkiewicz Z, Wu JM (1999) Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21 WAF1/CIP1, and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G. Cancer Res 59:2596–2601 https://cancerres.aacrjournals.org/content/59/11/2596.long
Hu Y, Chen D, Zheng P, Yu J, He J, Mao X, Yu B (2019) The bidirectional interactions between resveratrol and gut microbiota: an insight into oxidative stress and inflammatory bowel disease therapy. Biomed Res Int 2019:5403761. https://doi.org/10.1155/2019/5403761
Hu S, Venema WT, Westra HJ, Vila AV, Barbieri R, Voskuil MD, Blokzijl T, Jansen BH, Li Y, Daly MJ, Xavier RJ (2021) Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease. Nat Commun 12:1122. https://doi.org/10.1038/s41467-021-21458-z
Hubbard BP, Sinclair DA (2014) Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci 35:146–154. https://doi.org/10.1016/j.tips.2013.12.004
Hwang D, Jo H, Ma SH, Lim YH (2018) Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells. Food Chem Toxicol 118:880–888. https://doi.org/10.1016/j.fct.2018.06.039
Iglesias N, Galbis E, Díaz-Blanco MJ, Lucas R, Benito E, De-Paz MV (2019) Nanostructured chitosan-based biomaterials for sustained and colon-specific resveratrol release. Int J Mol Med Sci 20:398. https://doi.org/10.3390/ijms20020398
Irrazabal T, Thakur BK, Croitoru K, Martin A (2021) Preventing colitis-associated colon cancer with antioxidants: a systematic review. Cell Mol Gastroenterol Hepatol 11:1177–1197. https://doi.org/10.1016/j.jcmgh.2020.12.013
Jo H, Hwang D, Kim JK, Lim YH (2017) Oxyresveratrol improves tight junction integrity through the PKC and MAPK signaling pathways in Caco-2 cells. Food Chem Toxicol 108:203–213. https://doi.org/10.1016/j.fct.2017.08.002
Kamalian A, Sohrabi Asl M, Dolatshahi M, Afshari K, Shamshiri S, Momeni Roudsari N, Momtaz S, Rahimi R, Abdollahi M, Abdolghaffari AH (2020) Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways. World J Gastroenterol 26:3365–3400. https://doi.org/10.3748/wjg.v26.i24.3365
Khare V, Krnjic A, Frick A, Gmainer C, Asboth M, Jimenez K, Lang M, Baumgartner M, Evstatiev R, Gasche C (2019) Mesalamine and azathioprine modulate junctional complexes and restore epithelial barrier function in intestinal inflammation. Sci Rep 9:2842. https://doi.org/10.1038/s41598-019-39401-0
Khare T, Palakurthi SS, Shah BM, Palakurthi S, Khare S (2020) Natural product-based nanomedicine in treatment of inflammatory bowel disease. Int J Mol Med Sci 21:3956. https://doi.org/10.3390/ijms21113956
Khor B, Gardet A, Xavier RJ (2011) Genetics and pathogenesis of inflammatory bowel disease. Nature 474:307–317. https://doi.org/10.1038/nature10209
Kim WS, Song HY, Mushtaq S, Kim JM, Byun EH, Yuk JM, Byun EB (2019) Therapeutic potential of gamma-irradiated resveratrol in ulcerative colitis via the anti-inflammatory activity and differentiation of tolerogenic dendritic cells. Cell Physiol Biochem 52:1117–1138. https://doi.org/10.33594/000000076
Kim SW, Kim S, Son M, Cheon JH, Park YS (2020a) Melatonin controls microbiota in colitis by goblet cell differentiation and antimicrobial peptide production through Toll-like receptor 4 signalling. Sci Rep 10:2232. https://doi.org/10.1038/s41598-020-59314-7
Kim WS, Kim K, Byun EB, Song HY, Han JM, Park WY, Yuk JM, Byun EH (2020b) RM, a novel resveratrol derivative, attenuates inflammatory responses induced by lipopolysaccharide via selectively increasing the Tollip protein in macrophages: a partial mechanism with therapeutic potential in an inflammatory setting. Int Immunopharmacol 78:106072. https://doi.org/10.1016/j.intimp.2019.106072
Korzenik J, Koch AK, Langhorst J (2017) Complementary and integrative gastroenterology. Med Clin North Am 101:943–954. https://doi.org/10.1016/j.mcna.2017.04.009
Kuršvietienė L, Stanevičienė I, Mongirdienė A, Bernatonienė J (2016) Multiplicity of effects and health benefits of resveratrol. Medicina 52:148–155. https://doi.org/10.1016/j.medici.2016.03.003
Lange KW, Li S (2018) Resveratrol, pterostilbene, and dementia. BioFactors 44:83–90. https://doi.org/10.1002/biof.1396
Lanzilli G, Cottarelli A, Nicotera G, Guida S, Ravagnan G, Fuggetta MP (2011) Anti-inflammatory effect of resveratrol and polydatin by in vitro IL-17 modulation. Inflammation 35:240–248. https://doi.org/10.1007/s10753-011-9310-z
Larrosa M, Tomé-Carneiro J, Yáñez-Gascón MJ, Alcántara D, Selma MV, Beltrán D, García-Conesa MT, Urbán C, Lucas R, Tomás-Barberán F, Morales JC, Espín JC (2010) Preventive oral treatment with resveratrol pro-prodrugs drastically reduce colon inflammation in rodents. J Med Chem 53:7365–7376. https://doi.org/10.1021/jm1007006
Lastra D, Fernández-Ginés R, Manda G, Cuadrado A (2021) Perspectives on the clinical development of NRF2-targeting drugs. In: Schmidt HHHW, Ghezzi P, Cuadrado A (eds) Reactive oxygen species. Handbook of Experimental Pharmacology, vol 264. Springer, Cham. pp. 93-141. https://doi.org/10.1007/164_2020_381
Li M, Li P, Tang R, Lu H (2022) Resveratrol and its derivates improve inflammatory bowel disease by targeting gut microbiota and inflammatory signaling pathways. Food Sci Human Wellness 11:22–31. https://doi.org/10.1016/j.fshw.2021.07.003
Likhitwitayawuid K (2021) Oxyresveratrol: sources, productions, biological activities, pharmacokinetics, and delivery systems. Molecules 26:4212. https://doi.org/10.3390/molecules26144212
Liu B, Li S, Sui X, Guo L, Liu X, Li H, Gao L, Cai S, Li Y, Wang T, Piao X (2018) Root extract of Polygonum cuspidatum Siebold & Zucc. ameliorates DSS-induced ulcerative colitis by affecting NF-kappaB signaling pathway in a mouse model via synergistic effects of polydatin, resveratrol, and emodin. Front Pharmacol 9:347. https://doi.org/10.3389/fphar.2018.00347
Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, Andrews E, Ajami NJ, Bonham KS, Brislawn CJ, Casero D, Courtney H, Gonzalez A, Graeber TG, Hall AB, Lake K, Landers CJ, Mallick H, Plichta DR et al (2019) Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569:655–662. https://doi.org/10.1038/s41586-019-1237-9
Lotfi K, Nouri M, Askari G (2020) The effect of resveratrol supplementation on improving non-alcoholic fatty liver: a review on randomized clinical trials. J Clin Excellence 9:11-22.
Lozano-Pérez AA, Rodriguez-Nogales A, Ortiz-Cullera V, Algieri F, Garrido-Mesa J, Zorrilla P, Rodriguez-Cabezas ME, Garrido-Mesa N, Utrilla MP, De Matteis L, de la Fuente JM, Cenis JL, Gálvez J (2014) Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats. Int J Nanomedicine 9:4507–4520. https://doi.org/10.2147/IJN.S68526
Malayeri SR, Azadniya A, Rasaee MJ (2019) Effect of eight-week high intensity interval training and resveratrol intake on serum adiponectin and resistin in type 2 diabetic rats. IJOGI 18:1–8
Malinowski B, Wiciński M, Sokołowska MM, Hill NA, Szambelan M (2020) The rundown of dietary supplements and their effects on inflammatory bowel disease-a review. Nutrients 12:1423. https://doi.org/10.3390/nu12051423
Martín AR, Villegas I, La Casa C, Alarcón De La Lastra C (2004) Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. Biochem Pharmacol 67:1399–1410. https://doi.org/10.1016/j.bcp.2003.12.024
Mousavi T, Nikfar S, Abdollahi M (2021) Comprehensive study on the administrative, economic, regional, and regulatory prospects of complementary and alternative medicine (CAM) in inflammatory bowel disease (IBD). Expert Rev Clin Pharmacol 14:865–888. https://doi.org/10.1080/17512433.2021.1925108
Mozaffari S, Nikfar S, Abdolghaffari AH, Abdollahi M (2014) New biologic therapeutics for ulcerative colitis and Crohn’s disease. Expert Opin Biol Ther 14:583–600. https://doi.org/10.1517/14712598.2014.885945
Naserifar M, Hosseinzadeh H, Abnous K, Mohammadi M, Taghdisi SM, Ramezani M, Alibolandi M (2020) Oral delivery of folate-targeted resveratrol-loaded nanoparticles for inflammatory bowel disease therapy in rats. Life Sci 262:118555. https://doi.org/10.1016/j.lfs.2020.118555
Neves AR, Lúcio M, Lima J, Reis S (2012) Resveratrol in medicinal chemistry: a critical review of its pharmacokinetics, drug-delivery, and membrane interactions. Curr Med Chem 19:1663–1681. https://doi.org/10.2174/092986712799945085
Peritore AF, D'Amico R, Cordaro M, Siracusa R, Fusco R, Gugliandolo E, Genovese T, Crupi R, Di Paola R, Cuzzocrea S, Impellizzeri D (2021) PEA/Polydatin: anti-inflammatory and antioxidant approach to counteract DNBS-induced colitis. Antioxidants 10:464. https://doi.org/10.3390/antiox10030464
Pujara N, Wong KY, Qu Z, Wang R, Moniruzzaman M, Rewatkar P, Kumeria T, Ross BP, McGuckin M, Popat A (2021) Oral delivery of β-lactoglobulin-nanosphere-encapsulated resveratrol alleviates inflammation in winnie mice with spontaneous ulcerative colitis. Mol Pharm 18:627–640. https://doi.org/10.1021/acs.molpharmaceut.0c00048
Rahal K, Schmiedlin-Ren P, Adler J, Dhanani M, Sultani V, Rittershaus AC, Reingold L, Zhu J, McKenna BJ, Christman GM, Zimmermann EM (2012) Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan-polysaccharide rat model of Crohn’s disease. Inflamm Bowel Dis 18:613–623. https://doi.org/10.1002/ibd.21843
Rahimi R, Nikfar S, Abdollahi M (2013) Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines: a meta-analysis. World J Gastroenterol 19:5738–5749. https://doi.org/10.3748/wjg.v19.i34.5738
Ramírez-Garza SL, Laveriano-Santos EP, Marhuenda-Muñoz M, Storniolo CE, Tresserra-Rimbau A, Vallverdú-Queralt A, Lamuela-Raventós RM (2018) Health effects of resveratrol: results from human intervention trials. Nutrients 10:1892. https://doi.org/10.3390/nu10121892
Robinson K, Mock C, Liang D (2015) Pre-formulation studies of resveratrol. Drug Dev Ind Pharm 41:1464–1469. https://doi.org/10.3109/03639045.2014.958753
Ryan FJ, Ahern AM, Fitzgerald RS, Laserna-Mendieta EJ, Power EM, Clooney AG, O'Donoghue KW, McMurdie PJ, Iwai S, Crits-Christoph A, Sheehan D, Moran C, Flemer B, Zomer AL, Fanning A, O'Callaghan J, Walton J, Temko A, Stack W et al (2020) Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease. Nat Commun 11:1512. https://doi.org/10.1038/s41467-020-15342-5
de Sá Coutinho D, Pacheco MT, Frozza RL, Bernardi A (2018) Anti-inflammatory effects of resveratrol: mechanistic insights. Int J Mol Sci 19:1812. https://doi.org/10.3390/ijms19061812
Sabzevary-Ghahfarokhi M, Soltani A, Luzza F, Larussa T, Rahimian G, Shirzad H, Bagheri N (2020) The protective effects of resveratrol on ulcerative colitis via changing the profile of Nrf2 and IL-1β protein. Mol Biol Rep 47:6941–6947. https://doi.org/10.1007/s11033-020-05753-4
Salehi B, Mishra AP, Nigam M, Sener B, Kilic M, Sharifi-Rad M, Fokou PVT, Martins N, Sharifi-Rad J (2018) Resveratrol: a double-edged sword in health benefits. Biomedicines 6:91. https://doi.org/10.3390/biomedicines6030091
Samarghandian S, Borji A, Afshari R, Delkhosh MB, Gholami A (2013) The effect of lead acetate on oxidative stress and antioxidant status in rat bronchoalveolar lavage fluid and lung tissue. Toxicol Mech Methods 23:432–436. https://doi.org/10.3109/15376516.2013.777136
Samarghandian S, Azimi-Nezhad M, Mehrad-Majd H, Mirhafez SR (2015) Thymoquinone ameliorates acute renal failure in gentamicintreated adult male rats. Pharmacology 96(3-4):112-7. https://doi.org/10.1159/000436975
Samarghandian S, Azimi-Nezhad M, Farkhondeh T (2019) Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells. J Cell Physiol 234:10421–10431. https://doi.org/10.1002/jcp.27710
Samsami M, Ebrahimi Daryani N, Rezanejad P, Hekmatdoost A (2014) Effects of oral resveratrol supplementation on inflammation and quality of life in patients with ulcerative colitis. Iran J Nutr Sci Food Technol 9:93–102 https://www.sid.ir/en/journal/ViewPaper.aspx?id = 442793
Samsamikor M, Daryani NE, Asl PR, Hekmatdoost A (2016) Resveratrol supplementation and oxidative/anti-oxidative status in patients with ulcerative colitis: a randomized, double-blind, placebo-controlled pilot study. Arch Med Res 47:304–309. https://doi.org/10.1016/j.arcmed.2016.07.003
Sánchez-Fidalgo S, Cárdeno A, Villegas I, Talero E, de la Lastra CA (2010) Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice. Eur J Pharmacol 633:78–84. https://doi.org/10.1016/j.ejphar.2010.01.025
Serra D, Almeida LM, Dinis TC (2016) Anti-inflammatory protection afforded by cyanidin-3-glucoside and resveratrol in human intestinal cells via Nrf2 and PPAR-γ: Comparison with 5-aminosalicylic acid. Chem Biol Interact 260:102–109. https://doi.org/10.1016/j.cbi.2016.11.003
Sethi G, Sung B, Kunnumakkara AB, Aggarwal BB (2009) Targeting TNF for treatment of cancer and autoimmunity. In: Grewal IS (ed) Therapeutic targets of the TNF superfamily. Advances in experimental medicine and biology, vol 647. Springer, New York, NY, pp. 37-51. https://doi.org/10.1007/978-0-387-89520-8_3
Seyyedebrahimi S, Khodabandehloo H, Nasli Esfahani E, Meshkani R (2018) The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. Acta Diabetol 55:341–353. https://doi.org/10.1007/s00592-017-1098-3
Shah BM, Palakurthi SS, Khare T, Khare S, Palakurthi S (2020) Natural proteins and polysaccharides in the development of micro/nano delivery systems for the treatment of inflammatory bowel disease. Int J Biol Macromol 165:722–737. https://doi.org/10.1016/j.ijbiomac.2020.09.214
Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C (2015) NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol 6:262. https://doi.org/10.3389/fphar.2015.00262
Shaoul R, Day AS (2019) Nutritional regulators of intestinal inflammation. Curr Opin Gastroenterol 35:486–490. https://doi.org/10.1097/MOG.0000000000000585
Sharma M, Mohapatra J, Wagh A, Patel HM, Pandey D, Kadam S, Argade A, Deshpande SS, Shah GB, Chatterjee A, Jain MR (2014) Involvement of TACE in colon inflammation: a novel mechanism of regulation via SIRT-1 activation. Cytokine 66:30–39. https://doi.org/10.1016/j.cyto.2013.12.010
Shaterzadeh-Yazdi H, Noorbakhsh MF, Hayati F, Samarghandian S, Farkhondeh T (2018) Immunomodulatory and anti-inflammatory effects of thymoquinone. Cardiovasc Hematol Disord Drug Targets 18:52–60. https://doi.org/10.2174/1871529X18666180212114816
Shayganfard M (2020) Molecular and biological functions of resveratrol in psychiatric disorders: a review of recent evidence. Cell Biosci 10:128. https://doi.org/10.1186/s13578-020-00491-3
Shen J, Zhou Q, Li P, Wang Z, Liu S, He C, Zhang C, Xiao P (2017) Update on phytochemistry and pharmacology of naturally occurring resveratrol oligomers. Molecules 22:2050. https://doi.org/10.3390/molecules22122050
Singh UP, Singh NP, Singh B, Hofseth LJ, Taub DD, Price RL, Nagarkatti M, Nagarkatti PS (2010) Resveratrol (trans-3,5,4′-trihydroxystilbene) induces silent mating type information regulation-1 and down-regulates nuclear transcription factor-κB activation to abrogate dextran sulfate sodium-induced colitis. J Pharmacol Exp Ther 332:829–839. https://doi.org/10.1124/jpet.109.160838
Singh UP, Singh NP, Singh B, Hofseth LJ, Taub DD, Price RL, Nagarkatti M, Nagarkatti PS (2012) Role of resveratrol-induced CD11b+Gr-1+myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3+ T cells and amelioration of chronic colitis in IL-10 -/- mice. Brain Behav Immun 26:72–82. https://doi.org/10.1016/j.bbi.2011.07.236
Smolig JM, Baur JA, Hausenblas HA (2011) Resveratrol and health--a comprehensive review of human clinical trials. Mol Nutr Food Res 55:1129–1141. https://doi.org/10.1002/mnfr.201100143
Springer M, Moco S (2019) Resveratrol and its human metabolites-effects on metabolic health and obesity. Nutrients 11:143. https://doi.org/10.3390/nu11010143
Stojanov S, Kreft S (2020) Gut microbiota and the metabolism of phytoestrogens. Rev Bras 30:145–154. https://doi.org/10.1007/s43450-020-00049-x
Sun H, Cai H, Fu Y, Wang Q, Ji K, Du L, Xu C, Tian L, He N, Wang J, Zhang M, Liu Y, Wang Y, Li J, Liu Q (2020) The protection effect of resveratrol against radiation-induced inflammatory bowel disease via NLRP-3 inflammasome repression in mice. Dose-Response 18:1559325820931292. https://doi.org/10.1177/1559325820931292
Taghipour YD, Bahramsoltani R, Marques AM, Naseri R, Rahimi R, Haratipour P, Iranpanah A, Panah AI, Farzaei MH, Abdollahi M (2018) A systematic review of nano formulation of natural products for the treatment of inflammatory bowel disease: drug delivery and pharmacological targets. Daru J Pharm Sci 26:229–239. https://doi.org/10.1007/s40199-018-0222-4
Tain YL, Hsu CN (2018) Developmental programming of the metabolic syndrome: can we reprogram with resveratrol? Int J Mol Sci 19:2584. https://doi.org/10.3390/ijms19092584
Talebi M, Talebi M, Farkhondeh T, Samarghandian S (2020a) Molecular mechanism-based therapeutic properties of honey. Biomed Pharmacother 130:110590. https://doi.org/10.1016/j.biopha.2020.110590
Talebi M, Zarshenas MM, Yazdani E, Moein M (2020b) Preparation and evaluation of possible antioxidant activities of Rose traditional tablet"[Qurs-e-Vard]" a selected Traditional Persian Medicine [TPM] formulation via various procedures. Curr Drug Discov Technol 18:e28092020186381. https://doi.org/10.2174/1570163817666200929114517
Talebi M, Talebi M, Farkhondeh T, Kopustinskiene DM, Simal-Gandara J, Bernatoniene J, Samarghandian S (2021a) An updated review on the versatile role of chrysin in neurological diseases: chemistry, pharmacology, and drug delivery approaches. Biomed Pharmacother 141:111906. https://doi.org/10.1016/j.biopha.2021.111906
Talebi M, İlgün S, Ebrahimi V, Talebi M, Farkhondeh T, Ebrahimi H, Samarghandian S (2021b) Zingiber officinale ameliorates Alzheimer’s disease and cognitive impairments: lessons from preclinical studies. Biomed Pharmacother 133:111088. https://doi.org/10.1016/j.biopha.2020.111088
Talebi M, Kakouri E, Talebi M, Tarantilis PA, Farkhondeh T, İlgün S, Pourbagher-Shahri AM, Samarghandian S (2021c) Nutraceuticals-based therapeutic approach: recent advances to combat pathogenesis of Alzheimer’s disease. Expert Rev Neurother 21:625–642. https://doi.org/10.1080/14737175.2021.1923479
Talebi M, Talebi M, Farkhondeh T, Mishra G, İlgün S, Samarghandian S (2021d) New insights into the role of the Nrf2 signaling pathway in green tea catechin applications. Phytother Res 35:3078–3112. https://doi.org/10.1002/ptr.7033
Talebi M, Talebi M, Farkhondeh T, Samarghandian S (2021e) Biological and therapeutic activities of thymoquinone: focus on the Nrf2 signaling pathway. Phytother Res 35:1739–1753. https://doi.org/10.1002/ptr.6905
Tye H, Yu CH, Simms LA, de Zoete MR, Kim ML, Zakrzewski M, Penington JS, Harapas CR, Souza-Fonseca-Guimaraes F, Wockner LF, Preaudet A, Mielke LA, Wilcox SA, Ogura Y, Corr SC, Kanojia K, Kouremenos KA, De Souza DP, McConville MJ et al (2018) NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease. Nat Commun 9:3728. https://doi.org/10.1038/s41467-018-06125-0
Venkataraman B, Ojha S, Belur PD, Bhongade B, Raj V, Collin PD, Adrian TE, Subramanya SB (2020) Phytochemical drug candidates for the modulation of peroxisome proliferator-activated receptor γ in inflammatory bowel diseases. Phytother Res 34:1530–1549. https://doi.org/10.1002/ptr.6625
Ventham NT, Kennedy NA, Adams AT, Kalla R, Heath S, O'Leary KR, Drummond H, IBD BIOM consortium; IBD CHARACTER consortium, Wilson DC, Gut IG, Nimmo ER, Satsangi J (2016) Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease. Nat Commun 7:13507. https://doi.org/10.1038/ncomms13507
Verhoog S, Taneri PE, Roa Díaz ZM, Marques-Vidal P, Troup JP, Bally L, Franco OH, Glisic M, Muka T (2019) Dietary factors and modulation of bacteria strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: a systematic review. Nutrients 11:1565. https://doi.org/10.3390/nu11071565
Wagnerova A, Babickova J, Liptak R, Vlkova B, Celec P, Gardlik R (2017) Sex differences in the effect of resveratrol on DSS-induced colitis in mice. Gastroenterol Res Pract 2017:8051870. https://doi.org/10.1155/2017/8051870
Walle T (2011) Bioavailability of resveratrol. Ann N Y Acad Sci 1215:9–15. https://doi.org/10.1111/j.1749-6632.2010.05842.x
Wang J, Zhang Z, Fang A, Wu K, Chen X, Wang G, Mao F (2020) Resveratrol attenuates inflammatory bowel disease in mice by regulating SUMO1. Biol Pharm Bull 43:450–457. https://doi.org/10.1248/bpb.b19-00786
Wenzel E, Somoza V (2005) Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res 49:472–481. https://doi.org/10.1002/mnfr.200500010
Wortley C (2021) Crohn’s warrior. Lancet Gastroenterol Hepatol 6:168. https://doi.org/10.1016/S2468-1253(21)00030-3
Xiao Q, Zhu W, Feng W, Lee SS, Leung AW, Shen J, Gao L, Xu C (2019) A review of resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy. Front Pharmacol 9:1534. https://doi.org/10.3389/fphar.2018.01534
Xu Q, Si LY (2012) Resveratrol role in cardiovascular and metabolic health and potential mechanisms of action. Nutr Res 32:648–658. https://doi.org/10.1016/j.nutres.2012.07.002
Xue YQ, Di JM, Luo Y, Cheng KJ, Wei X, Shi Z (2014) Resveratrol oligomers for the prevention and treatment of cancers. Oxidative Med Cell Longev 2014:765832. https://doi.org/10.1155/2014/765832
Yanaka A (2018) Role of NRF2 in protection of the gastrointestinal tract against oxidative stress. J Clin Biochem Nutr 63:18–25. https://doi.org/10.3164/jcbn.17-139
Yao J, Wang JY, Liu L, Li YX, Xun AY, Zeng WS, Jia CH, Wei XX, Feng JL, Zhao L, Wang LS (2010a) Anti-oxidant effects of resveratrol on mice with DSS-induced ulcerative colitis. Arch Med Res 41:288–294. https://doi.org/10.1016/j.arcmed.2010.05.002
Yao J, Wang LS, Li YX, Wang JY, Sun LP, Mo J, Shao CW (2010b) Resveratrol increases the percentages of CD4+CD25+Foxp3+ regulatory T cells in peripheral blood and mesenteric lymph nodes of mice with ulcerative colitis. World Chin J Dig 18:2905-2908. https://doi.org/10.11569/wcjd.v18.i27.2905
Yao J, Wang JY, Liu L, Zeng WS, Li YX, Xun AY, Zhao L, Jia CH, Feng JL, Wei XX, Wang LS (2011) Polydatin ameliorates DSS-induced colitis in mice through inhibition of nuclear factor-kappaB activation. Planta Med 77:421–427. https://doi.org/10.1055/s-0030-1250462
Yao J, Wei C, Wang JY, Zhang R, Li YX, Wang LS (2015) Effect of resveratrol on Treg/Th17 signaling and ulcerative colitis treatment in mice. World J Gastroenterol 21:6572–6581. https://doi.org/10.3748/wjg.v21.i21.6572
Yashiro T, Yura S, Tobita A, Toyoda Y, Kasakura K, Nishiyama C (2020) Pterostilbene reduces colonic inflammation by suppressing dendritic cell activation and promoting regulatory T cell development. FASEB J 34:14810–14819. https://doi.org/10.1096/fj.202001502R
Yasutomi E, Inokuchi T, Hiraoka S, Takei K, Igawa S, Yamamoto S, Ohmori M, Oka S, Yamasaki Y, Kinugasa H, Takahara M, Harada K, Furukawa M, Itoshima K, Okada K, Otsuka F, Tanaka T, Mitsuhashi T, Kato J, Okada H (2021) Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease. Sci Rep 11:11086. https://doi.org/10.1038/s41598-021-90441-x
Yazdani E, Talebi M, Zarshenas MM, Moein M (2019) Evaluation of possible antioxidant activities of barberry solid formulation, a selected formulation from traditional Persian medicine (TPM) via various procedures. Biointerface Res Appl Chem 9:4517–1521. https://doi.org/10.33263/BRIAC96.517521
Yildiz G, Yildiz Y, Ulutas PA, Yaylali A, Ural M (2015) Resveratrol pretreatment ameliorates TNBS colitis in rats. Recent Pat Endocr Metab Immune Drug Discov 9:134–140. https://doi.org/10.2174/1872214809666150806105737
Youn J, Lee JS, Na HK, Kundu JK, Surh YJ (2009) Resveratrol and piceatannol inhibit iNOS expression and NF-kappaB activation in dextran sulfate sodium-induced mouse colitis. Nutr Cancer 61:847–854. https://doi.org/10.1080/01635580903285072
Yu B, Xie R, Jin L, Tian X, Niu Y, Ma T, Yang H (2019) Trans-δ-viniferin inhibits Ca2+-activated Cl− channels and improves diarrhea symptoms. Fitoterapia 139:104367. https://doi.org/10.1016/j.fitote.2019.104367
Zhang X, Deeke SA, Ning Z, Starr AE, Butcher J, Li J, Mayne J, Cheng K, Liao B, Li L, Singleton R, Mack D, Stintzi A, Figeys D (2018) Metaproteomics reveals associations between microbiome and intestinal extracellular vesicle proteins in pediatric inflammatory bowel disease. Nat Commun 9:2873. https://doi.org/10.1038/s41467-018-05357-4
Zhang L, Hui XUE, Zhao G, Qiao C, Xiaomei SUN, Pang C, Zhang D (2019) Curcumin and resveratrol suppress dextran sulfate sodium-induced colitis in mice. Mol Med Rep 19:3053–3060. https://doi.org/10.3892/mmr.2019.9974
Zobeiri M, Momtaz S, Parvizi F, Tewari D, Farzaei MH, Nabavi SM (2020) Targeting mitogen-activated protein kinases by natural products: a novel therapeutic approach for inflammatory bowel diseases. Curr Pharm Biotechnol 21:1342–1353. https://doi.org/10.2174/1389201021666191216122555
Acknowledgements
The figures are created by https://smart.servier.com.
Author information
Authors and Affiliations
Contributions
MT and SS: conceptualization, validation of resources, and data extraction; MT, MT, and TF: writing of the manuscript; SS: revision and edition of the final version. All of the authors have read and approved the final submission.
Corresponding author
Ethics declarations
Ethics Approval and Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Competing Interests
The authors declare no competing of interests.
Supplementary Information
ESM 1
(PDF 149 kb)
Rights and permissions
About this article
Cite this article
Talebi, M., Talebi, M., Farkhondeh, T. et al. Therapeutic Effects of Resveratrol in Inflammatory Bowel Diseases: Shedding Light on the Role of Cellular and Molecular Pathways. Rev. Bras. Farmacogn. 32, 160–173 (2022). https://doi.org/10.1007/s43450-022-00247-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s43450-022-00247-9