Molecular and Therapeutic Effects of Fisetin Flavonoid in Diseases

Yıl 2020, Cilt: 4 Sayı: 3, 190 - 196, 01.09.2020

Ezgi Nur Sarı , Yasemin Soysal

Öz

ABSTRACT
Chronic inflammation is defined as a prolonged and impaired immune response leading to a wide range of physiological and pathological
conditions, for instance; abnormalities in nervous system, heart diseases, diabetes, obesity, lung diseases, immunological diseases, and cancer.
In order to suppress chronic inflammatory diseases, inflammation should be prevented and treatments without side effects are needed at this
time.
Traditional medicine and dietary restriction have been used in treatment by people for ages. Today, the WHO (the World Health Organization)
data reveals that approximately 60% of the world’s population and about 80% of the population of the developing countries have turned to
herbal medicines. In this context, nutraceuticals attract attention because of their being safe, economical, easily accessible and in low toxicity,
and their usages are gradually increasing.
Recently, fisetin, a new flavonoid among nutritional supplements, has attracted considerable attention. Fisetin, a bioactive flavonol found in
fruits and vegetables, has chemo-preventive, anti-metastatic, neuroprotective, antioxidant, and anti-inflammatory effects. It is known that the
concentration of fisetin is mainly high in strawberries, apples and dates. Studies conducted in cell culture and animal models have shown that
fisetin has potential healing effects on diseases by affecting various signal pathways.
The effects of fisetin, which is a natural nutritional compound with promising potential, on obesity, cancer, neurological diseases, diabetes and
cardiovascular diseases are presented to the attention of researchers with this review in the light of current studies.
Keywords: fisetin, flavonoid, nutraceuticals, polyphenols, therapeutic effects

Anahtar Kelimeler

fisetin, flavonoid, nutraceuticals, polyphenols

Kaynakça

• 1. Krishnamoorthy S, Honn KV. Inflammation and disease progression. Cancer Metastasis Rev 2006;25:481–491. [CrossRef]
• 2. Lanza FL, Chan FKL, Quigley EMM. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 2009;104:728–738. [CrossRef]
• 3. Pal HC, Pearlman RL, Afaq F. Fisetin and its role in chronic diseases. Adv Exp Med Biol 2016;928:213–244. [CrossRef]
• 4. Prasad S, Aggarwal BB. Chronic diseases caused by chronic inflammation require chronic treatment: anti-inflammatory role of dietary spices. J Clin Cell Immunol 2014;5:238. [CrossRef]
• 5. Gupta SC, Tyagi AK, Deshmukh-Taskar P, Hinojosa M, Prasad S, Aggarwal BB. Downregulation of tumor necrosis factor and other proinflammatory biomarkers by polyphenols. Arch Biochem Biophys 2014;559:91–99. [CrossRef]
• 6. Jin T, Kim OY, Shin MJ, et al. Fisetin up-regulates the expression of adiponectin in 3T3-L1 Adipocytes via the activation of silent mating type information regulation 2 homologue 1(SIRT1) deacetylase and peroxisome proliferator-activated receptors (PPARs). J Agric Food Chem 2014;62:10468–10474. [CrossRef]
• 7. Kimira M, Arai Y, Shimoi K, Watanabe S. Japanese intake of flavonoids and isoflavonoids from foods. J Epidemiol 1998;8:168–175. [CrossRef]
• 8. Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J Nutr 2000;130:2243–2250. [CrossRef]
• 9. Jash SK, Mondal S. Bioactive flavonoid fisetin --A molecule of pharmacological interest. Signpost Open Access J Org Biomol Chem 2014;2:89–128. https://moam.info/bioactive-flavonoid-fisetin-a-amolecule- of-signpost-e-journals_5b728a57097c47b61f8b4673.html
• 10. Kim A, Lee W, Yun JM. Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions. Nutr Res Pract 2017;11:430–434. [CrossRef ]
• 11. Kashyap D, Garg VK, Tuli HS, et al. Fisetin and quercetin: Promising flavonoids with chemopreventive potential. Biomolecules 2019;9:174. [CrossRef]
• 12. Bhui K, Prasad S, George J, Shukla Y. Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Lett 2009;282:167–176. [CrossRef]
• 13. Union for International Cancer Control (UICC). New Global Cancer Data: GLOBOCAN, 2018. https://www.uicc.org/news/new-globalcancer- data-globocan-2018
• 14. American Cancer Society. Cancer Facts & Figures 2016. https://www. cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/ cancer-facts-figures-2016.html
• 15. Soto AM, Sonnenschein C. Environmental causes of cancer: endocrine disruptors as carcinogens. Nat Rev Endocrinol 2010;6:363–370. [CrossRef]
• 16. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359–E386. [CrossRef]
• 17. Gündoğdu T, Akbulut G. Bromelain and Cancer. Turkiye Klin J Health Sci 2019;4:79–84. [CrossRef]
• 18. Mehta P, Pawar A, Mahadik K, Bothiraja C. Emerging novel drug delivery strategies for bioactive flavonol fisetin in biomedicine. Biomed Pharmacother 2018;106:1282–1291. [CrossRef]
• 19. Suh Y, Afaq F, Khan N, Johnson JJ, Khusro FH, Mukhtar H. Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells. Carcinogenesis 2010;31:1424–1433. [CrossRef]
• 20. Fisetin. ScienceDirect Topics. https://www.sciencedirect.com/topics/ neuroscience/fisetin
• 21. Prasath GS, Subramanian SP. Modulatory effects of fisetin, a bioflavonoid, on hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in hepatic and renal tissues in streptozotocin-induced diabetic rats. Eur J Pharmacol 2011;668:492– 496. [CrossRef]
• 22. Touil YS, Auzeil N, Boulinguez F, et al. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite. Biochem Pharmacol 2011;82:1731–1739. [CrossRef]
• 23. Currais A, Prior M, Dargusch R, et al. Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice. Aging Cell 2014;13:379–390. [CrossRef]
• 24. Kashyap D, Sharma A, Sak K, Tuli HS, Buttar HS, Bishayee A,. Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy. Life Sci 2018;194:75–87. [CrossRef]
• 25. Touil YS, Seguin J, Scherman D, Chabot GG. Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice. Cancer Chemother Pharmacol 2011;68:445–455. [CrossRef]
• 26. Ravichandran N, Suresh G, Ramesh B, Siva GV. Fisetin, a novel flavonol attenuates benzo (a) pyrene-induced lung carcinogenesis in Swiss albino mice. Food Chem Toxicol 2011;49:1141–1147. [CrossRef]
• 27. Lall RK, Adhami VM, Mukhtar H. Dietary flavonoid fisetin for cancer prevention and treatment. Mol Nutr Food Res 2016;60:1396–1405. [CrossRef]
• 28. Suh Y, Afaq F, Johnson JJ, Mukhtar H. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/ NF-kappaB-signaling pathways. Carcinogenesis 2009;30:300–307. [CrossRef]
• 29. Lu X, Jung J in, Cho HJ, et al. Fisetin inhibits the activities of cyclindependent kinases leading to cell cycle arrest in HT-29 human colon cancer cells. J Nutr 2005;135:2884–2890. [CrossRef]
• 30. Chen Y, Wu Q, Song L, et al. Polymeric micelles encapsulating fisetin improve the therapeutic effect in colon cancer. ACS Appl Mater Interfaces 2015;7:534–542. [CrossRef]
• 31. Chou R-H, Hsieh S-C, Yu Y-L, Huang M-H, Huang Y-C, Hsieh Y-H. Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway. PLoS One 2013;8:e71983. [CrossRef]
• 32. Lin M-T, Lin C-L, Lin T-Y, et al. Synergistic effect of fisetin combined with sorafenib in human cervical cancer HeLa cells through activation of death receptor-5 mediated caspase-8/caspase-3 and the mitochondria-dependent apoptotic pathway. Tumor Biol 2016;37:6987–6996. [CrossRef]
• 33. Adan A, Baran Y. The pleiotropic effects of fisetin and hesperetin on human acute promyelocytic leukemia cells are mediated through apoptosis, cell cycle arrest, and alterations in signaling networks. Tumor Biol 2015;36:8973–8984. [CrossRef]
• 34. Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 2018;36:18–28. [CrossRef]
• 35. Ishige K, Schubert D, Sagara Y. Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radic Biol Med 2001;30:433–446. [CrossRef]
• 36. Maher P. Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin. Genes Nutr 2009;4:297–307. [CrossRef]
• 37. Zhen L, Zhu J, Zhao X, et al. The antidepressant-like effect of fisetin involves the serotonergic and noradrenergic system. Behav Brain Res 2012;228:359–366. [CrossRef]
• 38. Renoudet VV, Costa-Mallen P, Hopkins E. A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson’s disease. J Med Food 2012;15:758–761. [CrossRef]
• 39. Alikatte K, Palle S, Kumar RJ, Pathakala N. Fisetin improved iotenoneinduced behavioral deficits, oxidative changes, and mitochondrial dysfunctions in rat model of Parkinson’s Disease. J Diet Suppl 2020;29:1–15. [CrossRef]
• 40. Sagara Y, Vanhnasy J, Maher P. Induction of PC12 cell differentiation by flavonoids is dependent upon extracellular signal-regulated kinase activation. J Neurochem 2004;90:1144–1155. [CrossRef]
• 41. Prasath GS, Subramanian SP. Antihyperlipidemic effect of fisetin, a bioflavonoid of strawberries, studied in streptozotocin-induced diabetic rats. J Biochem Mol Toxicol 2014;28:442–449. [CrossRef]
• 42. Kim HJ, Kim SH, Yun JM. Fisetin inhibits hyperglycemia-induced proinflammatory cytokine production by epigenetic mechanisms. Evid Based Complement Alternat Med 2012;2012:639469. [CrossRef]
• 43. Kwak S, Ku SK, Bae JS. Fisetin inhibits high-glucose-induced vascular inflammation in vitro and in vivo. Inflamm Res 2014;63:779–787. [CrossRef]
• 44. Jung CH, Kim H, Ahn J, Jeon T-I, Lee D-H, Ha T-Y. Fisetin regulates obesity by targeting mTORC1 signaling. J Nutr Biochem 2013;24:1547– 1554. [CrossRef]
• 45. Lee Y, Bae EJ. Inhibition of mitotic clonal expansion mediates fisetinexerted prevention of adipocyte differentiation in 3T3-L1 cells. Arch Pharm Res 2013;36:1377–1384. [CrossRef]
• 46. Hu LF, Feng J, Dai X, et al. Oral flavonoid fisetin treatment protects against prolonged high-fat-diet-induced cardiac dysfunction by regulation of multicombined signaling. J Nutr Biochem 2020;77:108253. [CrossRef]
• 47. Althunibat OY, Al Hroob AM, Abukhalil MH, Germoush MO, Jumah MB, Mahmoud AM. Fisetin ameliorates oxidative stress, inflammation and apoptosis in diabetic cardiomyopathy. Life Sci 2019;221:83–92. [CrossRef]
• 48. Farsad-Naeimi A, Alizadeh M, Esfahani A, Aminabad ED. Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients. Food Funct 2018;9:2025–2031. [CrossRef]
• 49. National Institutes of Health (NIH). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/ results?cond=fisetin&term=&cntry=&state=&city=&dist=