RESVERATROLÜN BULUNDUĞU KAYNAKLAR VE TIBBİ ÖNEMİ

Yıl 2021, , 652 - 673, 27.09.2021

Seren Gündoğdu , Ümmügülsüm Uçar , Ayşe Uz

https://doi.org/10.33483/jfpau.903916

Cited By: 1

Öz

Amaç: Resveratrol (trans-3,5,4’-trihidroksi-stilben) üzüm, asma, yer fıstığı, kızılcık, yaban mersini gibi birçok bitkisel kaynakta bulunan polifenolik bir bileşiktir. Resveratrol ile ilgili daha önceki araştırmalar kardiyovasküler sistemler, inflamasyon ve karsinogenez/kanser gelişimi ile ilgili farmakolojik etkileri üzerine odaklıyken son zamanlarda araştırmaların büyük çoğunluğu yaşlanma süreci, diyabet, alzheimer ve diğer nörodejeneratif hastalıklar üzerinde potansiyel etkileri keşfedilerek genişletilmiştir. Bu derleme kapsamında resveratrol hakkında genel bilgilerin, bulunduğu kaynakların ve özellikle son yıllarda üzerinde çalışılan biyolojik etkilerinin (in vitro, in vivo) derlenmesi amaçlanmıştır.

Sonuç ve Tartışma: Resveratrolün yapısal olarak trans- formu baskındır. Bitkilerde daha stabil ve oksidatif bozunmaya karşı dayanıklı olan glikozitleri halinde bulunmaktadır. Resveratrol eldesinde sıklıkla kullanılan Polygonum cuspidatum bitkisinin çeşitli ekstreleri, ticari önemi olan ürünlerin ortaya çıkmasını sağlamıştır. Resveratrol başlıca antienflamatuvar, antioksidan, antikanser ve kardiyoprotektif etkilere sahip bir moleküldür. Yapılan farmakokinetik çalışmalarda resveratrolün iyi absorbe edildiği, ilk geçiş etkisi nedeniyle sülfat ve glukuronit konjugatları şeklinde hızla metabolize edildiği ve idrarla elimine edildiği bildirilmiştir. Ayrıca resveratrolün iyi tolere edildiği ve belirgin bir toksisite göstermediği rapor edilmiştir. Gıda/nutrasötik veya ilaç şeklinde alınabilen resveratrolün insan sağlığı üzerine olan çeşitli etkilerinden faydalanmak amacıyla biyoyararlanımı göz önüne alındığında iyi formüle edilmiş resveratrol taşıyan tablet, kapsül, nanopartikül formülasyonlarının hazırlanması ve kullanılması gerektiği sonucuna varılmıştır.

Anahtar Kelimeler

Resveratrol, tıbbi bitki, antioksidan, kardiyoprotektif, nöroprotektif

Destekleyen Kurum

-

Proje Numarası

-

Teşekkür

-

SOURCES OF RESVERATROL AND ITS MEDICINAL SIGNIFICANCE

Öz

Objective: Resveratrol (trans-3,5,4'-trihydroxy-stilbene) is a polyphenolic compound found in many plant sources such as grapes, vine, peanuts, cranberries, blueberries. While previous research on resveratrol has focused on its pharmacological effects on cardiovascular systems, inflammation, and carcinogenesis/cancer development, most of the research has recently been expanded by exploring its potential effects on the aging process, diabetes, Alzheimer's, and other neurodegenerative diseases. Within the scope of this review, it is aimed to compile general information about resveratrol, its sources, and especially its biological effects (in vitro, in vivo) studied in recent years.

Result and Discussion: Resveratrol is structurally dominated by the trans- form. It is found in plants as glycosides that are more stable and resistant to oxidative degradation. Various extracts of the Polygonum cuspidatum plant, which are frequently used in the production of resveratrol, have led to the emergence of commercially important products. Resveratrol is a molecule that has mainly anti-inflammatory, antioxidant, anticancer, and cardioprotective effects. In pharmacokinetic studies, it has been reported that resveratrol is well absorbed, rapidly metabolized in the form of sulfate and glucuronide conjugates due to its first-pass effect, and eliminated in the urine. Besides, resveratrol has been reported to be well-tolerated and to show no apparent toxicity. Considering the bioavailability of resveratrol, which can be taken as food/nutraceutical or as a medicine, to benefit from the various effects on human health, it was concluded that tablet, capsule, and nanoparticle formulations containing well-formulated resveratrol should be prepared and used.

Anahtar Kelimeler

Resveratrol, medicinal plant, antioxidant, cardioprotective, neuroprotective

Proje Numarası

-

Kaynakça

• 1. Érsek, T., Király, Z. (1986). Phytoalexins: Warding‐off compounds in plants?. Physiologia Plantarum, 68(2), 343-346. [CrossRef]
• 2. Hasan, M., Bae, H. (2017). An overview of stress-induced resveratrol synthesis in grapes: perspectives for resveratrol-enriched grape products. Molecules, 22(2), 294. [CrossRef]
• 3. Takaoka, M.J. (1940). Of the phenolic substances of white hellebore (Veratrum grandiflorum Loes. fil.). Journal Faculty Science Hokkaido Imperial University, 3, 1-16.
• 4. Goldberg, D.M., Ng, E., Yan, J., Karumanchiri, A., Soleas, G.J., Diamandis, E.P. (1996). Regional differences in resveratrol isomer concentrations of wines from various cultivars. Journal of Wine Research, 7(1), 13-24. [CrossRef]
• 5. Park, E.J., Pezzuto, J.M. (2015). The pharmacology of resveratrol in animals and humans. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1852(6), 1071-1113. [CrossRef]
• 6. Colica, C., Milanović, M., Milić, N., Aiello, V., De Lorenzo, A., Abenavoli, L. (2018). A systematic review on natural antioxidant properties of resveratrol. Natural Product Communications, 13(9), 1195-1203. [CrossRef]
• 7. Tian, B., Liu, J. (2019). Resveratrol: A review of plant sources, synthesis, stability, modification and food application. Journal of the Science of Food and Agriculture. [CrossRef]
• 8. Sanders, T.H., McMichael, R.W., Hendrix, K.W. (2000). Occurrence of resveratrol in edible peanuts. Journal of Agricultural and Food Chemistry, 48(4), 1243-1246. [CrossRef]
• 9. Burns, J., Yokota, T., Ashihara, H., Lean, M.E., Crozier, A. (2002). Plant foods and herbal sources of resveratrol. Journal of Agricultural and Food Chemistry, 50(11), 3337-3340. [CrossRef]
• 10. Sparvoli, F., Martin, C., Scienza, A., Gavazzi, G., Tonelli, C. (1994). Cloning and molecular analysis of structural genes involved in flavonoid and stilbene biosynthesis in grape (Vitis vinifera L.). Plant Molecular Biology, 24(5), 743-755. [CrossRef]
• 11. Giovinazzo, G., Ingrosso, I., Paradiso, A., De Gara, L., Santino, A. (2012). Resveratrol biosynthesis: plant metabolic engineering for nutritional improvement of food. Plant Foods for Human Nutrition, 67(3), 191-199. [CrossRef]
• 12. Vrhovsek, U., Wendelin, S., Eder, R. (1997). Effects of various vinification techniques on the concentration of cis-and trans-resveratrol and resveratrol glucoside isomers in wine. American Journal of Enology and Viticulture, 48(2), 214-219.
• 13. Versari, A., Parpinello, G.P., Tornielli, G.B., Ferrarini, R., Giulivo, C. (2001). Stilbene compounds and stilbene synthase expression during ripening, wilting, and UV treatment in grape cv. Corvina. Journal of Agricultural and Food Chemistry, 49(11), 5531-5536. [CrossRef]
• 14. Mattivi, F., Reniero, F., Korhammer, S. (1995). Isolation, characterization, and evolution in red wine vinification of resveratrol monomers. Journal of Agricultural and Food Chemistry, 43(7), 1820-1823.
• 15. Lamuela-Raventos, R.M., Romero-Perez, A.I., Waterhouse, A.L., De La Torre-Boronat, M.C. (1995). Direct HPLC analysis of cis-and trans-resveratrol and piceid isomers in Spanish red Vitis vinifera wines. Journal of Agricultural and Food Chemistry, 43(2), 281-283.
• 16. Jeandet, P., Bessis, R., Maume, B.F., Sbaghi, M. (1993). Analysis of resveratrol in Burgundy wines. Journal of Wine Research, 4(2), 79-85. [CrossRef]
• 17. Athar, M., Back, J.H., Tang, X., Kim, K.H., Kopelovich, L., Bickers, D.R., Kim, A.L. (2007). Resveratrol: a review of preclinical studies for human cancer prevention. Toxicology and Applied Pharmacology, 224(3), 274-283. [CrossRef]
• 18. Cui, X., Jin, Y., Hofseth, A.B., Pena, E., Habiger, J., Chumanevich, A., Poudyal, D., Nagarkatti, M., Nagarkatti, P.S., Singh, U.P., Hofseth, L.J. (2010). Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer Prevention Research, 3(4), 549-559. [CrossRef]
• 19. Bhullar, K.S., Hubbard, B.P. (2015). Lifespan and healthspan extension by resveratrol. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1852(6), 1209-1218. [CrossRef]
• 20. Lin, S.C., Ho, C.T., Chuo, W.H., Li, S., Wang, T.T., Lin, C.C. (2017). Effective inhibition of MERS-CoV infection by resveratrol. BMC Infectious Diseases, 17(1), 144. [CrossRef]
• 21. Bola, C., Bartlett, H., Eperjesi, F.(2014). Resveratrol and the eye: activity and molecular mechanisms. Graefes Arch Clin Exp Ophthalmol, 252, 699–713. [CrossRef]
• 22. Liu, B.L., Zhang, X., Zhang, W., Zhen, H.N. (2007). New enlightenment of French Paradox: resveratrol's potential for cancer chemoprevention and anti-cancer therapy. Cancer Biology & Therapy, 6(12), 1833-1836. [CrossRef]
• 23. Udenigwe, C.C., Ramprasath, V.R., Aluko, R.E., Jones, P.J. (2008). Potential of resveratrol in anticancer and anti-inflammatory therapy. Nutrition Reviews, 66(8), 445-454. [CrossRef]
• 24. Ergin, K., Yaylalı, A. (2013). Resveratrol ve etkileri üzerine bir gözden geçirme. Medical Journal of Suleyman Demirel University, 20(3), 115-120.
• 25. Romero-Pérez, A.I., Ibern-Gómez, M., Lamuela-Raventós, R.M., de la Torre-Boronat, M.C. (1999). Piceid, the major resveratrol derivative in grape juices. Journal of Agricultural and Food Chemistry, 47(4), 1533-1536. [CrossRef]
• 26. Baur, J.A., Sinclair, D.A. (2006). Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews Drug Discovery, 5(6), 493-506. [CrossRef]
• 27. Cheynier, V., Schneider, R., Salmon, J.M., Fulcrand, H. (2010). Chemistry of wine. Elsevier, Oxford,, 3, p. 1119-1172.
• 28. Frémont, L. (2000). Biological effects of resveratrol. Life Sciences, 66(8), 663-673. [CrossRef]
• 29. Venugopal, R., Liu, R.H. (2012). Phytochemicals in diets for breast cancer prevention: The importance of resveratrol and ursolic acid. Food Science and Human Wellness, 1(1), 1-13. [CrossRef]
• 30. Kuhnle, G., Spencer, J.P., Chowrimootoo, G., Schroeter, H., Debnam, E.S., Srai, S.K.S., Rice-Evans, C., Hahn, U. (2000). Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochemical and Biophysical Research Communications, 272(1), 212-217. [CrossRef]
• 31. Chukwumah, Y., Walker, L., Vogler, B., Verghese, M. (2011). In vitro absorption of dietary trans-resveratrol from boiled and roasted peanuts in Caco-2 cells. Journal of Agricultural and Food Chemistry, 59(23), 12323-12329. [CrossRef]
• 32. Wang, W.X., Qian, J.Y., Wang, X.J., Jiang, A.P., Jia, A.Q. (2014). Anti-HIV-1 activities of extracts and phenolics from Smilax china L. Pakistan Journal of Pharmaceutical Sciences, 27, 147-151.
• 33. Menezes, J.C., Diederich, M.F. (2019). Natural dimers of coumarin, chalcones, and resveratrol and the link between structure and pharmacology. European Journal of Medicinal Chemistry, 182, 111637. [CrossRef]
• 34. Huang, X.T., Li, X., Xie, M.L., Huang, Z., Huang, Y.X., Wu, G.X., Peng, Z.R., Sun, Y.N., Ming, Q.L., Liu, Y.X., Chen, J.P., Xu, S.N. (2019). Resveratrol: Review on its discovery, anti-leukemia effects and pharmacokinetics. Chemico-biological İnteractions, 306, 29-38. [CrossRef]
• 35. Polonini, H. C., de Almeida Bastos, C., de Oliveira, M.A.L., da Silva, C.G.A., Collins, C.H., Brandão, M.A. F., Raposo, N.R.B. (2014). In vitro drug release and ex vivo percutaneous absorption of resveratrol cream using HPLC with zirconized silica stationary phase. Journal of Chromatography B, 947, 23-31. [CrossRef]
• 36. Andres-Lacueva, C., Macarulla, M.T., Rotches-Ribalta, M., Boto-Ordóñez, M., Urpi-Sarda, M., Rodríguez, V.M., Portillo, M.P. (2012). Distribution of resveratrol metabolites in liver, adipose tissue, and skeletal muscle in rats fed different doses of this polyphenol. Journal of Agricultural and Food Chemistry, 60(19), 4833-4840. [CrossRef]
• 37. Lastra, C., Villegas, I. (2005). Resveratrol as an anti‐inflammatory and anti‐aging agent: Mechanisms and clinical implications. Molecular Nutrition & Food Research, 49(5), 405-430. [CrossRef]
• 38. Wang, P., Sang, S. (2018). Metabolism and pharmacokinetics of resveratrol and pterostilbene. BioFactors, 44(1), 16-25. [CrossRef]
• 39. Crowell, J.A., Korytko, P.J., Morrissey, R.L., Booth, T.D., Levine, B.S. (2004). Resveratrol-associated renal toxicity. Toxicological Sciences, 82(2), 614-619. [CrossRef]
• 40. Williams, L.D., Burdock, G.A., Edwards, J.A., Beck, M., Bausch, J. (2009). Safety studies conducted on high-purity trans-resveratrol in experimental animals. Food and Chemical Toxicology, 47(9), 2170-2182. [CrossRef]
• 41. Keskin, N., Noyan, T., Kunter, B. (2009). Resveratrol ile Üzümden Gelen Sağlık. Türkiye Klinikleri Journal of Medical Science, 29(5), 1273-1279.
• 42. Hurst, W.J., Glinski, J.A., Miller, K.B., Apgar, J., Davey, M.H., Stuart, D.A. (2008). Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products. Journal of Agricultural and Food Chemistry, 56(18), 8374-8378. [CrossRef]
• 43. Shrikanta, A., Kumar, A., Govindaswamy, V. (2015). Resveratrol content and antioxidant properties of underutilized fruits. Journal of Food Science and Technology, 52(1), 383-390. [CrossRef]
• 44. Sobolev, V.S., Cole, R.J. (1999). trans-Resveratrol content in commercial peanuts and peanut products. Journal of Agricultural and Food Chemistry, 47(4), 1435-1439. [CrossRef]
• 45. Ibern-Gómez, M., Roig-Perez, S., Lamuela-Raventós, R. M., de la Torre-Boronat, M. C. (2000). Resveratrol and piceid levels in natural and blended peanut butters. Journal of Agricultural and Food Chemistry, 48(12), 6352-6354. [CrossRef]
• 46. Tokuşoǧlu, Ö., Ünal, M.K., Yemiş, F. (2005). Determination of the phytoalexin resveratrol (3, 5, 4 ‘-trihydroxystilbene) in peanuts and pistachios by high-performance liquid chromatographic diode array (HPLC-DAD) and gas chromatography− mass spectrometry (GC-MS). Journal of Agricultural and Food Chemistry, 53(12), 5003-5009. [CrossRef]
• 47. Soleas, G.J., Diamandis, E.P., Goldberg, D.M. (1997). Resveratrol: a molecule whose time has come? And gone?. Clinical Biochemistry, 30(2), 91-113. [CrossRef]
• 48. Tzanova, M., Peeva, P. (2018). Rapid HPLC method for simultaneous quantification of trans-resveratrol and quercetin in the skin of red grapes. Food Analytical Methods, 11(2), 514-521. [CrossRef]
• 49. Sebastià, N., Montoro, A., León, Z., Soriano, J.M. (2017). Searching trans-resveratrol in fruits and vegetables: a preliminary screening. Journal of Food Science and Technology, 54(3), 842-845. [CrossRef]
• 50. Wang, Y., Catana, F., Yang, Y., Roderick, R., van Breemen, R.B. (2002). An LC-MS method for analyzing total resveratrol in grape juice, cranberry juice, and in wine. Journal of Agricultural and Food Chemistry, 50(3), 431-435. [CrossRef]
• 51. Lyons, M.M., Yu, C., Toma, R.B., Cho, S.Y., Reiboldt, W., Lee, J., van Breemen, R.B. (2003). Resveratrol in raw and baked blueberries and bilberries. Journal of Agricultural and Food Chemistry, 51(20), 5867-5870. [CrossRef]
• 52. Rimando, A.M., Kalt, W., Magee, J.B., Dewey, J., Ballington, J.R. (2004). Resveratrol, pterostilbene, and piceatannol in vaccinium berries. Journal of Agricultural and Food Chemistry, 52(15), 4713-4719. [CrossRef]
• 53. Callemien, D., Jerkovic, V., Rozenberg, R., Collin, S. (2005). Hop as an interesting source of resveratrol for brewers: optimization of the extraction and quantitative study by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry. Journal of Agricultural and Food Chemistry, 53(2), 424-429. [CrossRef]
• 54. Jerkovic, V., Callemien, D., Collin, S. (2005). Determination of stilbenes in hop pellets from different cultivars. Journal of Agricultural and Food Chemistry, 53(10), 4202-4206. [CrossRef]
• 55. Counet, C., Callemien, D., Collin, S. (2006). Chocolate and cocoa: New sources of trans-resveratrol and trans-piceid. Food Chemistry, 98(4), 649-657. [CrossRef]
• 56. Mark, L., Nikfardjam, M.S.P., Avar, P., Ohmacht, R. (2005). A validated HPLC method for the quantitative analysis of trans-resveratrol and trans-piceid in Hungarian wines. Journal of Chromatographic Science, 43(9), 445-449. [CrossRef]
• 57. Yaman, Ü.R., Yıldırım, H.K., Adıgüzel, B., Yücel, U. (2013). Farklı Bölgelere Ait Ticari Şarapların Resveratrol İçerikleri. Academic Food Journal/Akademik GIDA, 11(3-4), 40-46.
• 58. Tatarczak-Michalewska, M., Blicharska, E., Flieger, J. (2017). Correlation of metal and trans-resveratrol concentrations in red wine. Analytical Letters, 50(12), 2023-2029. [CrossRef]
• 59. Šćepanović, R.P., Wendelin, S., Raičević, D., Eder, R. (2019). Characterization of the phenolic profile of commercial Montenegrin red and white wines. European Food Research and Technology, 245(10), 2233-2245. [CrossRef]
• 60. Goldberg, D.M., Yan, J., Ng, E., Diamandis, E.P., Karumanchiri, A., Soleas, G., Waterhouse, A.L. (1995). A global survey of trans-resveratrol concentrations in commercial wines. American Journal of Enology and Viticulture, 46(2), 159-165.
• 61. Sautter, C.K., Denardin, S., Alves, A.O., Mallmann, C.A., Penna, N.G., Hecktheuer, L.H. (2005). Determinação de resveratrol em sucos de uva no Brasil. Food Science and Technology, 25(3), 437-442. [CrossRef]
• 62. Concenco, F.I., Brotto, G.F., Nora, L. (2019). Grape Wine and Juice: Comparison on Resveratrol Levels. International Journal of Advanced Engineering Research and Science, 6(4), 378-386. [CrossRef]
• 63. Sánchez-Fidalgo, S., Cárdeno, A., Villegas, I., Talero, E., de la Lastra, C.A. (2010). Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice. European Journal of Pharmacology, 633(1-3), 78-84. [CrossRef]
• 64. Yao, L., Wan, J., Li, H., Ding, J., Wang, Y., Wang, X., Li, M. (2015). Resveratrol relieves gestational diabetes mellitus in mice through activating AMPK. Reproductive Biology and Endocrinology, 13(1), 118. [CrossRef]
• 65. Chang C.C., Lin K.Y., Peng K.Y., Day Y.J., Hung L.M. (2015). Resveratrol exerts anti-obesity effects in high-fat diet obese mice and displays differential dosage effects on cytotoxicity, differentiation, and lipolysis in 3T3-L1 cells. Endocrine Journal, 63, 169-178. [CrossRef]
• 66. Sayın, O., Arslanand, N., Güner, G. (2008). Resveratrol ve kardiyovasküler sistem. Turkish Journal of Biochemistry, 33(3), 117-121.
• 67. Leonard, S.S., Xia, C., Jiang, B.H., Stinefelt, B., Klandorf, H., Harris, G.K., Shi, X. (2003). Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochemical and Biophysical Research Communications, 309(4), 1017-1026. [CrossRef]
• 68. Uysal M. (2006). Serbest radikaller ve oksidatif stres. Biyokimya, Nobel Tıp Kitabevleri, İstanbul, p. 829-835.
• 69. Vlachogianni, I.C., Fragopoulou, E., Kostakis, I.K., Antonopoulou, S. (2015). In vitro assessment of antioxidant activity of tyrosol, resveratrol and their acetylated derivatives. Food Chemistry, 177, 165-173. [CrossRef]
• 70. Zunino, S.J.,Storms, D.H., Stephensen, C.B. (2007). Diets rich in polyphenols and vitamin A inhibit the development of type I autoimmune diabetes in nonobese diabetic mice. The Journal of Nutrition, 137(5), 1216-1221. [CrossRef]
• 71. Lee, J.A., Ha, S.K., Cho, E., Choi, I. (2015). Resveratrol as a bioenhancer to improve anti-inflammatory activities of apigenin. Nutrients, 7(11), 9650-9661. [CrossRef]
• 72. Ray, P.S., Maulik, G., Cordis, G.A., Bertelli, A.A., Bertelli, A., Das, D.K. (1999). The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radical Biology and Medicine, 27(1-2), 160-169. [CrossRef]
• 73. Carrizzo, A., Puca, A., Damato, A., Marino, M., Franco, E., Pompeo, F., Traficante, A., Civitillo, F., Santini, L., Trimarco, V., Vecchione, C. (2013). Resveratrol improves vascular function in patients with hypertension and dyslipidemia by modulating NO metabolism. Hypertension, 62(2), 359-366. [CrossRef]
• 74. Miura, D., Miura, Y., Yagasaki, K. (2003). Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats. Life Sciences, 73(11), 1393-1400. [CrossRef]
• 75. Wang, Z., Zou, J., Cao, K., Hsieh, T.C., Huang, Y., Wu, J.M. (2005). Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. International Journal of Molecular Medicine, 16(4), 533-540. [CrossRef]
• 76. Lanzilli, G., Fuggetta, M.P., Tricarico, M., Cottarelli, A., Serafino, A., Falchetti, R., Ravagnan, G., Turriziani, M., Adamo, R., Franzese, O., Bonmassar, E. (2006). Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro. International Journal of Oncology, 28(3), 641-648. [CrossRef]
• 77. Schneider, Y., Vincent, F., Duranton, B., Badolo, L., Gossé, F., Bergmann, C., Seiler, N., Raul, F. (2000). Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Letters, 158(1), 85-91. [CrossRef]
• 78. Sheth, S., Jajoo, S., Kaur, T., Mukherjea, D., Sheehan, K., Rybak, L.P., Ramkumar, V. (2012). Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21pathway. PloS One, 7(12). [CrossRef]
• 79. Selvaraj, S., Sun, Y., Sukumaran, P., Singh, B.B. (2016). Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway. Molecular Carcinogenesis, 55(5), 818-831. [CrossRef]
• 80. Gomes, L., Sorgine, M., Passos, C.L.A., Ferreira, C., de Andrade, I.R., Silva, J.L., Atella, G.C., Mermelstein, C.S., Fialho, E. (2019). Increase in fatty acids and flotillins upon resveratrol treatment of human breast cancer cells. Scientific Reports, 9(1), 1-11. [CrossRef]
• 81. Schmitt, E., Lehmann, L., Metzler, M., Stopper, H. (2002). Hormonal and genotoxic activity of resveratrol. Toxicology Letters, 136(2), 133-142. [CrossRef]
• 82. Gündoğdu, S., Uz, A. (2021). Resveratrol’ün kanser hücreleri üzerine etkisi. Literatür Eczacılık Bilimleri Dergisi (yayına gönderildi).
• 83. Fuggetta, M.,Mattivi, F. (2011). The immunomodulating activities of resveratrol glucosides in humans. Recent Patents on Food, Nutrition & Agriculture, 3(2), 81-90. [CrossRef]
• 84. Abba, Y., Hassim, H., Hamzah, H., Noordin, M.M. (2015). Antiviral activity of resveratrol against human and animal viruses. Advances in Virology. [CrossRef]
• 85. Yücel, Ç., Karatoprak, G.Ş., Atmar, A. (2018). Novel resveratrol-loaded nanocochleates and effectiveness in the treatment of diabetes. FABAD Journal of Pharmaceutical Sciences, 43(2), 35-44.
• 86. Do, G.M., Jung, U.J., Park, H.J., Kwon, E.Y., Jeon, S.M., McGregor, R.A., Choi, M.S. (2012). Resveratrol ameliorates diabetes‐related metabolic changes via activation of AMP‐activated protein kinase and its downstream targets in db/db mice. Molecular Nutrition & Food Research, 56(8), 1282-1291. [CrossRef]
• 87. Yang, D.K., Kang, H.S. (2018). Anti-diabetic effect of cotreatment with quercetin and resveratrol in streptozotocin-induced diabetic rats. Biomolecules & Therapeutics, 26(2), 130. [CrossRef]
• 88. Oomen, C.A., Farkas, E., Roman, V., Van Der Beek, E.M., Luiten, P.G., Meerlo, P. (2009). Resveratrol preserves cerebrovascular density and cognitive function in aging mice. Frontiers in Aging Neuroscience, 1, 4. [CrossRef]
• 89. Quincozes-Santos, A., Gottfried, C. (2011). Resveratrol modulates astroglial functions: neuroprotective hypothesis. Annals of the New York Academy of Sciences, 1215(1), 72-78. [CrossRef]
• 90. Robb, E.L., Stuart, J.A. (2010). trans-Resveratrol as a neuroprotectant. Molecules, 15(3), 1196-1212. [CrossRef]
• 91. Khan, R.S., Fonseca-Kelly, Z., Callinan, C., Zuo, L., Sachdeva, M.M., Shindler, K.S. (2012). SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells. Frontiers in Cellular Neuroscience, 6, 63. [CrossRef]
• 92. Bournival, J., Quessy, P., Martinoli, M.G. (2009). Protective effects of resveratrol and quercetin against MPP+-induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cellular and Molecular Neurobiology, 29(8), 1169-1180. [CrossRef]
• 93. Bowers, J.L., Tyulmenkov, V.V., Jernigan, S.C., Klinge, C.M. (2000). Resveratrol acts as a mixed agonist/antagonist for estrogen receptors α and β. Endocrinology, 141(10), 3657-3667. [CrossRef]
• 94. Serrero, G., Lu, R. (2001). Effect of resveratrol on the expression of autocrine growth modulators in human breast cancer cells. Antioxidants and Redox Signaling, 3(6), 969-979. [CrossRef]
• 95. Henry, L.A., Witt, D.M. (2002). Resveratrol: phytoestrogen effects on reproductive physiology and behavior in female rats. Hormones and Behavior, 41(2), 220-228. [CrossRef]
• 96. Howitz, K.T., Bitterman, K.J., Cohen, H.Y., Lamming, D.W., Lavu, S., Wood, J.G., Zipkin, R.E., Chung, P., Kisielewski, A., Zhang, L.L., Scherer, B.B., Sinclair, D.A. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature, 425(6954), 191-196. [CrossRef]
• 97. Morselli, E., Maiuri, M.C., Markaki, M., Megalou, E., Pasparaki, A., Palikaras, K., Criollo, A., Galluzzi, L., Malik, S.A., Vitale, I., Michaud, M., Madeo, F., Tavernarakis, N., Kroemer, G. (2010). Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death & Disease, 1(1),e10. [CrossRef]
• 98. Wood, J.G., Rogina, B., Lavu, S., Howitz, K., Helfand, S.L., Tatar, M., Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature, 430(7000), 686-689. [CrossRef]
• 99. Das, D.K., Mukherjee, S., Ray, D. (2010). Erratum to: resveratrol and red wine, healthy heart and longevity. Heart Failure Reviews, 15, 467-477. [CrossRef]
• 100. Rascón, B., Hubbard, B.P., Sinclair, D.A., Amdam, G.V. (2012). The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. Aging (Albany NY), 4(7), 499-508. [CrossRef]
• 101. Hernández‐Hernández, E.M., Serrano‐García, C., Antonio Vázquez‐Roque, R., Díaz, A., Monroy, E., Rodríguez‐Moreno, A., Florán, B., Flores, G. (2016). Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats. Synapse, 70(5), 206-217. [CrossRef]
• 102. Yu, C., Shin, Y.G., Kosmeder, J.W., Pezzuto, J.M., van Breemen, R.B. (2003). Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Communications in Mass Spectrometry, 17(4), 307-313. [CrossRef]
• 103. Kanduja, K.L., Hardwaj, A., Kaushik, G. (2004). Resveratrol inhibits N-nitrosodiethylamine-induced ornithine decarboxylase and cyclooxygenase in mice. Journal of Nutritional Science and Vitaminology, 50(1), 61-65. [CrossRef]
• 104. Soldati, P.P., Polonini, H.C., Paes, C.Q., Restrepob, J.A., Creczynksi-Pasa, T.B., Chaves, M.G., Brandao, M.A.F., Pittella, F., Raposo, N.R. (2018). Controlled release of resveratrol from lipid nanoparticles improves antioxidant effect. IFAC-PapersOnLine, 51(27), 16-21. [CrossRef]
• 105. Nunes, R., Baião, A., Monteiro, D., das Neves, J., Sarmento, B. (2020). Zein nanoparticles as low-cost, safe, and effective carriers to improve the oral bioavailability of resveratrol. Drug Delivery and Translational Research, 10(3), 826-837. [CrossRef]