The Effects of Resveratrol in Chronic Diseases

Abstract

Resveratrol is a nutraceutical with various therapeutic benefits in the body. It is known to be found in many plants. It is found in different concentrations in plants such as grape, mulberry, strawberry and peanut etc. It is a secondary metabolite synthesized by exposure of plants to conditions such as ultraviolet, injury and fungi in order to synthesize resveratrol. A lot of research made on resveratrol has shown that it regulates the immune system and provides benefits against chronic diseases. It has also shown that it protects the body against oxidative stress in cardiovascular diseases and neurodegenerative diseases, thus preventing the formation of oxidative stress and preventing the formation and development of inflammation. Furthermore resveratrol intake has an effect on glucose metabolism and fat metabolism. Thus, it is thought that it can form a defense against the development of obesity. Resveratrol also has effects on apoptosis, mitochondrial biogenesis, anti-oxidant system and enzymes, glucose and lipid metabolism, and inflammatory cytokines that play a role in cellular processes. In addition, it has been observed that it has anti-tumor properties, regulates blood sugar, protects heart and nerve cells, and has anti-adiggienic activity. According to information obtained in experiments, glucose and lipid metabolism, blood pressure, fat mass, inflammation and oxidative stress associated with metabolic syndrome are regulated by resveratrol intake. To conclude, in this rewiev, it was aimed to evaluate the studies on potential effects of resveratrol on health and its role in the prevention and treatment of chronic diseases.

Keywords

• antiinflammatories
• antioxidants
• dietary supplement
• 3.5,4'-Trihydroxystilben

Resveratrolün Kronik Hastalıklar Üzerindeki Etkileri

Abstract

Resveratrol, vücutta çeşitli terapötik faydaları bulunan bir nutrasötiktir. Çok sayıda bitkide bulunduğu bilinmektedir. Özellikle üzüm, dut, çilek ve yer fıstığı gibi besinlerde farklı konsantrasyonlarda olduğu görülmüştür. Resveratrol bitkilerin ultraviyole, yaralanma ve mantar gibi durumlara maruz kalması sonucu, sentezlenen ikincil metabolittir. Resveratrol üzerine yapılan araştırmaların sonucunda; immun sistemi düzenlediği, kronik hastalıklara karşı fayda sağladığı gözlenmiştir. Kardiyovasküler hastalıklar ve nörodejeneratif hastalıklarda vücudu oksijen stresine karşı koruduğu, oksidatif stres oluşumunu engellediği, inflamasyon oluşumunu ve gelişimini engellediği gözlenmiştir. Resveratrol alımının, glikoz metabolizması ve yağ metabolizması üzerinde etkili olduğu gözlenmiştir. Bu nedenle obezite gelişimine karşı vücutta etkili olabileceği düşünülmektedir. Resveratrolün hücresel süreçlerde rol oynayan apoptoz, mitokondriyal biyogenez, anti-oksidan sistem ve enzimler, glikoz ve lipit metabolizması ve inflamatuvar sitokinler üzerine de etkileri bulunmaktadır. Bunların yanında anti-tümör özellik gösterdiği, kan şekerini regüle ettiği, kalp ve sinir hücrelerini koruduğu, anti-adipojenik faaliyet gösterdiği yapılan araştırmalarda gözlenmiştir. Metabolik sendromla ilişkili glikoz ve lipit metabolizması, kan basıncı, yağ kütlesi, inflamasyon ve oksidatif stresin resveratrol alımıyla regüle edildiği yapılan deneylerde elde edilmiştir. Bu derlemede, resveratrolün sağlık üzerine potansiyel etki mekanizmaları ile kronik hastalıkların önlenmesi ve tedavisindeki rolü üzerine yapılan araştırmaların değerlendirilmesi amaçlanmıştır.

Keywords

• antienflamatuarlar
• antioksidanlar
• besin takviyesi
• 3.5,4'-Trihidroksistilben

References

1. Aronson JK. Defining 'nutraceuticals': Neither nutritious nor pharmaceutical. Br J Clin Pharmacol. 2017;83(1):8-19.
2. Ronis MJJ, Pedersen KB, Watt J. Adverse effects of nutraceuticals and dietary supplements. Annu Rev Pharmacol Toxicol. 2018;58:583-601.
3. Karaman S, Özcan T. Fonksiyonel Süt ürünlerinin geliştirilmesinde nutrasötik bileşenler. Gıda ve Yem Bilimi Teknolojisi Dergisi. 2018;20:30-45.
4. Shaito A, Posadino AM, Younes N, Hasan H, Halabi S, Alhababi D, et al. Potential adverse effects of resveratrol: A literature review. Int J Mol Sci. 2020;21(6):2084.
5. Pannu N, Bhatnagar A. Resveratrol: from enhanced biosynthesis and bioavailability to multitargeting chronic diseases. Biomed Pharmacother. 2019;109:2237-2251.
6. Ronis MJJ, Pedersen KB, Watt J. Adverse effects of nutraceuticals and dietary supplements. Annu Rev Pharmacol Toxicol. 2018;58:583-601.
7. Yang AJT, Bagit A, MacPherson REK. Resveratrol, metabolic dysregulation, and Alzheimer’s disease: Considerations for neurogenerative disease. Int J Mol Sci. 2021;22(9):4628.
8. Tain YL, Hsu CN. Developmental programming of the metabolic syndrome: Can we reprogram with resveratrol?. Int J Mol Sci. 2018;19(9):2584.

9. Zhang LX, Li CX, Kakar MU, Khan MS, Wu PF, Amir RM, et al. Resveratrol (RV): A pharmacological review and call for further research. Biomed Pharmacother. 2021;143:112164.
10. Barber TM, Kabisch S, Randeva HS, Pfeiffer AFH, Weickert MO. Implications of resveratrol in obesity and ınsulin resistance: A State-of-the-Art review. Nutrients. 2022;14(14):2870.
11. Chaplin A, Carpéné C, Mercader J. Resveratrol, metabolic syndrome, and gut microbiota. Nutrients. 2018;10(11):1651.
12. Hu Y, Chen D, Zheng P, Yu J, He J, Mao X, et al. The bidirectional interactions between resveratrol and gut microbiota: An insight into oxidative stress and inflammatory bowel disease therapy. Biomed Res Int. 2019; 2019: 5403761.
13. Berman AY, Motechin RA, Wiesenfeld MY, Holz MK. The therapeutic potential of resveratrol: A review of clinical trials. NPJ Precision Oncology. 2017;1(1): 1-9.
14. Biesinger S, Michaels HA, Quadros AS, Qian Y, Rabovsky AB, Badger RS, et al. A combination of isolated phytochemicals and botanical extracts lowers diastolic blood pressure in a randomized controlled trial of hypertensive subjects. Eur J Clin Nutr. 2016;70(1):10-16.
15. Göçmen AY, Burgucu D, Gümüşlü S. Effect of resveratrol on platelet activation in hypercholesterolemic rats: CD40-CD40L system as a potential target. Appl Physiol Nutr Metab. 2011;36(3):323-330.
16. Lin YC, Chen LH, Varadharajan T, Tsai MJ, Chia YC, Yuan TC, et al. Resveratrol inhibits glucose-induced migration of vascular smooth muscle cells mediated by focal adhesion kinase. Mol Nutr Food Res. 2014;58(7):1389-1401.
17. Bonnefont-Rousselot D. Resveratrol and cardiovascular diseases. Nutrients. 2016; 8(5):250.
18. Breuss JM, Atanasov AG, Uhrin P. Resveratrol and its effects on the vascular system. Int J Mol Sci. 2019;20(7):1523.
19. Dolinsky VW, Chakrabarti S, Pereira TJ, Oka T, Levasseur J, Beker D, et al. Resveratrol prevents hypertension and cardiac hypertrophy in hypertensive rats and mice. Biochim Biophys Acta. 2013;1832(10):1723-1733.
20. Dyck GJB, Raj P, Zieroth S, Dyck JRB, Ezekowitz JA. The effects of resveratrol in patients with cardiovascular disease and heart failure: A narrative review. Int J Mol Sci. 2019;20(4):904.
21. Sung MM, Das SK, Levasseur J, Byrne NJ, Fung D, Kim TT, et al. Resveratrol treatment of mice with pressure-overload-induced heart failure improves diastolic function and cardiac energy metabolism. Circ Heart Fail. 2015;8(1):128-137.
22. Kung HC, Lin KJ, Kung CT, Lin TK. Oxidative stress, mitochondrial dysfunction, and neuroprotection of polyphenols with respect to resveratrol in Parkinson’s disease. Biomedicines. 2021;9(8):918.
23. Brites D, Fernandes A. Neuroinflammation and depression: Microglia activation, extracellular microvesicles and microRNA dysregulation. Front Cell Neurosci. 2015;9:476.
24. Zortea K, Franco VC, Francesconi LP, Cereser KM, Lobato MI, Belmonte-de-Abreu PS. Resveratrol supplementation in schizophrenia patients: A randomized clinical trial evaluating serum glucose and cardiovascular risk factors. Nutrients. 2016;8(2):73.
25. Alayev A, Berger SM, Holz MK. Resveratrol as a novel treatment for diseases with mTOR pathway hyperactivation. Ann N Y Acad Sci. 2015;1348(1):116-123.
26. McCubrey JA, Lertpiriyapong K, Steelman LS, Abrams SL, Yang LV, Murata RM, et al. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging (Albany NY). 2017;9(6):1477-1536.
27. Majumdar AP, Banerjee S, Nautiyal J, Patel BB, Patel V, Du J, et al. Curcumin synergizes with resveratrol to inhibit colon cancer. Nutr Cancer. 2009;61(4):544-553.
28. Carter LG, D'Orazio JA, Pearson KJ. Resveratrol and cancer: Focus on in vivo evidence. Endocr Relat Cancer. 2014;21(3):R209-R225.
29. Ko JH, Sethi G, Um JY, Shanmugam MK, Arfuso F, Kumar AP, et al. The role of resveratrol in cancer therapy. J Mol Sci. 2017;18(12):2589.
30. Hausenblas HA, Schoulda JA, Smoliga JM. Resveratrol treatment as an adjunct to pharmacological management in type 2 diabetes mellitus--systematic review and meta-analysis. Mol Nutr Food Res. 2015;59(1):147-159.
31. Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012;32(7):537-541.
32. Thazhath SS, Wu T, Bound MJ, Checklin HL, Standfield S, Jones KL, et al. Administration of resveratrol for 5 wk has no effect on glucagon-like peptide 1 secretion, gastric emptying, or glycemic control in type 2 diabetes: A randomized controlled trial. Am J Clin Nutr. 2016;103(1):66-70.
33. Novelle MG, Wahl D, Diéguez C, Bernier M, de Cabo R. Resveratrol supplementation: Where are we now and where should we go?. Ageing Res Rev. 2015;21:1-15.
34. Jimenez-Gomez Y, Mattison JA, Pearson KJ, Martin-Montalvo A, Palacios HH, Sossong AM, et al. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet. Cell Metab. 2013;18(4):533-545.
35. Konings E, Timmers S, Boekschoten MV, Goossens GH, Jocken JW, Afman LA, et al. The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men. Int J Obes (Lond). 2014;38(3):470-473.
36. Springer M, Moco S. Resveratrol and ıts human metabolites-effects on metabolic health and obesity. Nutrients. 2019;11(1):143.
37. Szkudelska K, Nogowski L, Szkudelski T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol. 2009;113(1-2):17-24.
38. Gomez-Zorita S, Tréguer K, Mercader J, Carpéné C. Resveratrol directly affects in vitro lipolysis and glucose transport in human fat cells. J Physiol Biochem. 2013;69(3):585-593.
39. Zhao Y, Chen B, Shen J, Wan L, Zhu Y, Yi T, et al. The beneficial effects of quercetin, curcumin, and resveratrol in obesity. Oxid Med Cell Longev. 2017;2017:1459497.
40. Wang S, Moustaid-Moussa N, Chen L, Mo H, Shastri A, Su R, et al. Novel insights of dietary polyphenols and obesity. J Nutr Biochem. 2014;25(1):1-18.
41. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127(6):1109-1122.
42. Szkudelska K, Szkudelski T. Resveratrol, obesity and diabetes. Eur J Pharmacol. 2010;635(1-3):1-8.
43. Heebøll S, Kreuzfeldt M, Hamilton-Dutoit S, Kjær PM, Stødkilde-Jørgensen H, Møller HJ, et al. Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease. Scand J Gastroenterol. 2016;51(4):456-464.
44. Chen S, Zhao X, Ran L, Wan J, Wang X, Qin Y, et al. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial. Dig Liver Dis. 2015;47(3):226-232.
45. Chachay VS, Macdonald GA, Martin JH, Whitehead JP, O'Moore-Sullivan TM, Lee P, et al. Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014;12(12):2092-103.e1036.
46. Chen XX, Xu YY, Wu R, Chen Z, Fang K, Han YX, et al. Resveratrol reduces glucolipid metabolic dysfunction and learning and memory ımpairment in a NAFLD rat model: Involvement in regulating the ımbalance of nesfatin-1 abundance and copine 6 expression. Front Endocrinol (Lausanne). 2019;10:434.
47. Alberdi G, Rodríguez VM, Macarulla MT, Miranda J, Churruca I, Portillo MP. Hepatic lipid metabolic pathways modified by resveratrol in rats fed an obesogenic diet. Nutrition. 2013;29(3):562-567.
48. Abenavoli L, Larussa T, Corea A, Procopio AC, Boccuto L, Dallio M, et al. Dietary polyphenols and non-alcoholic fatty liver disease. Nutrients. 2021;13(2):494.
49. Poulsen MM, Vestergaard PF, Clasen BF, Radko Y, Christensen LP, Stødkilde-Jørgensen H, et al. High-dose resveratrol supplementation in obese men: An investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes. 2013;62(4):1186-1195.
50. Heebøll S, Thomsen KL, Pedersen SB, Vilstrup H, George J, Grønbæk H. Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease. World J Hepatol. 2014;6(4):188-198.
51. Benvenga S, Feldt-Rasmussen U, Bonofiglio D, Asamoah E. Nutraceutical supplements in the thyroid setting: Health benefits beyond basic nutrition. Nutrients. 2019;11(9):2214.
52. Giuliani C, Iezzi M, Ciolli L, Hysi A, Bucci I, Santo DS, et al. Resveratrol has anti-thyroid effects both in vitro and in vivo. Food Chem Toxicol. 2017;107(Pt A):237-247.
53. Lervolino M, Lepore E, Forte G, Laganà AS, Buzzaccarini G, Unfer V. Natural molecules in the management of polycystic ovary syndrome (PCOS): An analytical review. Nutrients. 2021;13(5):1677.
54. Furat Rencber S, Kurnaz Ozbek S, Eraldemır C, Sezer Z, Kum T, Ceylan S, et al. Effect of resveratrol and metformin on ovarian reserve and ultrastructure in PCOS: An experimental study. J Ovarian Res. 2018;11(1):55.
55. Mansour A, Samadi M, Sanginabadi M, Gerami H, Karimi S, Hosseini S, et al. Effect of resveratrol on menstrual cyclicity, hyperandrogenism and metabolic profile in women with PCOS. Clin Nutr. 2021;40(6):4106-4112.
56. Malvasi A, Tinelli A, Lupica G, Vimercati A, Spyropoulou K, Dellino M, et al. Effects of a combination of resveratrol and alpha-lipoic acid on body weight and adipose composition in women with PCOS: A preliminary pilot study. Eur Rev Med Pharmacol Sci. 2022;26(18):6578-6582.
57. Bahramrezaie M, Amidi F, Aleyasin A, Saremi A, Aghahoseini M, Brenjian S, et al. Effects of resveratrol on VEGF & HIF1 genes expression in granulosa cells in the angiogenesis pathway and laboratory parameters of polycystic ovary syndrome: A triple-blind randomized clinical trial. J Assist Reprod Genet. 2019;36(8):1701-1712.
58. Ali Fadlalmola H, Elhusein AM, Al-Sayaghi KM, Albadrani MS, Swamy DV, Mamanao DM, et al. Efficacy of resveratrol in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized clinical trials. Pan Afr Med J. 2023;44:134.
59. Hao J, Chen C, Huang K, Huang J, Li J, Liu P, et al. Polydatin improves glucose and lipid metabolism in experimental diabetes through activating the Akt signaling pathway. Eur J Pharmacol. 2014;745:152-165.
60. Kershaw J, Kim KH. The therapeutic potential of piceatannol, a natural stilbene, in metabolic diseases: A Review. J Med Food. 2017;20(5):427-438.
61. Hou CY, Tain YL, Yu HR, Huang LT. The effects of resveratrol in the treatment of metabolic syndrome. Int J Mol Sci. 2019;20(3):535.
62. Méndez-del Villar M, González-Ortiz M, Martínez-Abundis E, Pérez-Rubio KG, Lizárraga-Valdez R. Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. 2014;12(10):497-501.
63. Zeraattalab-Motlagh S, Jayedi A, Shab-Bidar S. The effects of resveratrol supplementation in patients with type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease: an umbrella review of meta-analyses of randomized controlled trials. Am J Clin Nutr. 2021;114(5):1675-1685.
64. Rubio-Ruiz ME, Guarner-Lans V, Cano-Martínez A, Díaz-Díaz E, Manzano-Pech L, Gamas-Magaña A, et al. Resveratrol and quercetin administration ımproves antioxidant defenses and reduces fatty liver in metabolic syndrome rats. Molecules. 2019;24(7):1297.
65. Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14(5):612-622.