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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Therapeutic Potential and Molecular Mechanisms of the Multitargeted Flavonoid Fisetin

Author(s): Abdur Rauf, Tareq Abu-Izneid, Muhammad Imran, Hassan A. Hemeg, Kashif Bashir, Abdullah S.M. Aljohani, Mona S.M. Aljohani, Fahad A. Alhumaydhi, Ishaq N. Khan, Talha Bin Emran, Tanweer Aslam Gondal, Nikhil Nath, Ishtiaque Ahmad and Muthu Thiruvengadam*

Volume 23, Issue 21, 2023

Published on: 19 July, 2023

Page: [2075 - 2096] Pages: 22

DOI: 10.2174/1568026623666230710162217

Price: $65


Flavonoids effectively treat cancer, inflammatory disorders (cardiovascular and nervous systems), and oxidative stress. Fisetin, derived from fruits and vegetables, suppresses cancer growth by altering cell cycle parameters that lead to cell death and angiogenesis without affecting healthy cells. Clinical trials are needed in humans to prove the effectiveness of this treatment for a wide range of cancers. According to the results of this study, fisetin can be used to prevent and treat a variety of cancers. Despite early detection and treatment advances, cancer is the leading cause of death worldwide. We must take proactive steps to reduce the risk of cancer. The natural flavonoid fisetin has pharmacological properties that suppress cancer growth. This review focuses on the potential drug use of fisetin, which has been extensively explored for its cancer-fighting ability and other pharmacological activities such as diabetes, COVID-19, obesity, allergy, neurological, and bone disorders. Researchers have focused on the molecular function of fisetin. In this review, we have highlighted the biological activities against chronic disorders, including cancer, metabolic illnesses, and degenerative illnesses, of the dietary components of fisetin.

Keywords: Fisetin, Flavonoids, Bioactive compounds, Cancer, Pharmacological activities, COVID-19.

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Kubina, R.; Krzykawski, K.; Kabała-Dzik, A.; Wojtyczka, R.D.; Chodurek, E.; Dziedzic, A. Fisetin, a potent anticancer flavonol exhibiting cytotoxic activity against neoplastic malignant cells and cancerous conditions: A scoping, comprehensive review. Nutrients, 2022, 14(13), 2604.
[] [PMID: 35807785]
Antika, L.; Dewi, R. Pharmacological aspects of fisetin. Asian Pac. J. Trop. Biomed., 2021, 11(1), 1.
Schmid, J. Ueber das fisetin, den farbstoff des fisetholzes. Ber. Dtsch. Chem. Ges., 1886, 19(2), 1734-1749.
Ul-Hassan, S.S.; Samanta, S.; Dash, R.; Karpiński, T.M.; Habibi, E.; Sadiq, A. The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress. Front. Pharmacol., 2022, 13.
Li, Y.; Liu, Y.; Chen, J.; Hu, J. Protective effect of Fisetin on the lipopolysaccharide-induced preeclampsia-like rats. Hypertens. Pregnancy, 2022, 41(1), 23-30.
[] [PMID: 34933650]
Inkielewicz-Stepniak, I.; Radomski, M.W.; Wozniak, M. Fisetin prevents fluoride- and dexamethasone-induced oxidative damage in osteoblast and hippocampal cells. Food Chem. Toxicol., 2012, 50(3-4), 583-589.
[] [PMID: 22198064]
Liao, Y.C.; Shih, Y.W.; Chao, C.H.; Lee, X.Y.; Chiang, T.A. Involvement of the ERK signaling pathway in fisetin reduces invasion and migration in the human lung cancer cell line A549. J. Agric. Food Chem., 2009, 57(19), 8933-8941.
[] [PMID: 19725538]
Slika, H.; Mansour, H.; Wehbe, N.; Nasser, S.A.; Iratni, R.; Nasrallah, G.; Shaito, A.; Ghaddar, T.; Kobeissy, F.; Eid, A.H. Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms. Biomed. Pharmacother., 2022, 146, 112442.
[] [PMID: 35062053]
Liu, X.; Xiao, X.; Han, X.; Yao, L.; Lan, W. Natural flavonoids alleviate glioblastoma multiforme by regulating long non-coding RNA. Biomed. Pharmacother., 2023, 161, 114477.
[] [PMID: 36931030]
Salvamani, S.; Gunasekaran, B.; Shaharuddin, N.A.; Ahmad, S.A.; Shukor, M.Y. Antiartherosclerotic effects of plant flavonoids. Biomed Res Int., 2014, 2014, 480258.
Benavente-García, O.; Castillo, J. Update on uses and properties of citrus flavonoids: New findings in anticancer, cardiovascular, and anti-inflammatory activity. J. Agric. Food Chem., 2008, 56(15), 6185-6205.
[] [PMID: 18593176]
Singh, B.N.; Shankar, S.; Srivastava, R.K. Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochem. Pharmacol., 2011, 82(12), 1807-1821.
[] [PMID: 21827739]
Li, M.; Qian, M.; Jiang, Q.; Tan, B.; Yin, Y.; Han, X. Evidence of flavonoids on disease prevention. Antioxidants, 2023, 12(2), 527.
[] [PMID: 36830086]
Alsamri, H.; Athamneh, K.; Pintus, G.; Eid, A.H.; Iratni, R. Pharmacological and antioxidant activities of Rhus coriaria L. (Sumac). Antioxidants, 2021, 10(1), 73.
[] [PMID: 33430013]
Braidy, N.; Behzad, S.; Habtemariam, S.; Ahmed, T.; Daglia, M.; Nabavi, S.M.; Sobarzo-Sanchez, E.; Nabavi, S.F. Neuroprotective effects of citrus fruit-derived flavonoids, nobiletin and tangeret in in Alzheimer’s and Parkinson’s disease. CNS Neurol. Disord. Drug Targets, 2017, 16(4), 387-397.
[PMID: 28474543]
Minocha, T.; Birla, H.; Obaid, A.A.; Rai, V.; Sushma, P.; Shivamallu, C. Flavonoids as promising neuroprotectants and their therapeutic potential against alzheimer’s disease. Oxidative Med. Cell Longev, 2022, 2022, 6038996.
Zilli, A.M.H.; Zilli, E.M. Review of evidence and perspectives of flavonoids on metabolic syndrome and neurodegenerative disease. Protein Pept. Lett., 2021, 28(7), 725-734.
[] [PMID: 33504293]
Lotfi, N.; Yousefi, Z.; Golabi, M.; Khalilian, P.; Ghezelbash, B.; Montazeri, M.; Shams, M.H.; Baghbadorani, P.Z.; Eskandari, N. The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update. Front. Immunol., 2023, 14, 1077531.
[] [PMID: 36926328]
Maaliki, D.; Shaito, A.A.; Pintus, G.; El-Yazbi, A.; Eid, A.H. Flavonoids in hypertension: A brief review of the underlying mechanisms. Curr. Opin. Pharmacol., 2019, 45, 57-65.
[] [PMID: 31102958]
Fardoun, M.M.; Maaliki, D.; Halabi, N.; Iratni, R.; Bitto, A.; Baydoun, E.; Eid, A.H. Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets. Clin. Sci., 2020, 134(12), 1403-1432.
[] [PMID: 32556180]
Corcoran, M.P.; Lamon-Fava, S.; Fielding, R.A. Skeletal muscle lipid deposition and insulin resistance: Effect of dietary fatty acids and exercise. Am. J. Clin. Nutr., 2007, 85(3), 662-677.
[PMID: 17344486]
Kumar, R.; Yeni, C.M.; Utami, N.A.; Masand, R.; Asrani, R.K.; Patel, S.K.; Kumar, A.; Yatoo, M.I.; Tiwari, R.; Natesan, S.; Vora, K.S.; Nainu, F.; Bilal, M.; Dhawan, M.; Emran, T.B.; Ahmad, T.; Harapan, H.; Dhama, K. SARS-CoV-2 infection during pregnancy and pregnancy-related conditions: Concerns, challenges, management and mitigation strategies–a narrative review. J. Infect. Public Health, 2021, 14(7), 863-875.
[] [PMID: 34118736]
Maher, P. The potential of flavonoids for the treatment of neurodegenerative diseases. Int. J. Mol. Sci., 2019, 20(12), 3056.
[] [PMID: 31234550]
Anusha, C.; Sumathi, T.; Joseph, L.D. Protective role of apigenin on rotenone induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis. Chem. Biol. Interact., 2017, 269, 67-79.
[] [PMID: 28389404]
Tareq, A.M.; Emran, T.B.; Dhama, K.; Dhawan, M.; Tallei, T.E. Impact of SARS-CoV-2 delta variant (B.1.617.2) in surging second wave of COVID-19 and efficacy of vaccines in tackling the ongoing pandemic. Hum. Vaccin. Immunother., 2021, 17(11), 4126-4127.
[] [PMID: 34473593]
Yang, P.M.; Tseng, H.H.; Peng, C.W.; Chen, W.S.; Chiu, S.J. Dietary flavonoid fisetin targets caspase-3-deficient human breast cancer MCF-7 cells by induction of caspase-7-associated apoptosis and inhibition of autophagy. Int. J. Oncol., 2012, 40(2), 469-478.
[PMID: 21922137]
Pak, F.; Oztopcu-Vatan, P. Fisetin effects on cell proliferation and apoptosis in glioma cells. Z. Naturforsch. C J. Biosci., 2019, 74(11-12), 295-302.
[] [PMID: 31421049]
Park, B.S.; Choi, N.E.; Lee, J.H.; Kang, H.M.; Yu, S.B.; Kim, H.J.; Kang, H.K.; Kim, I.R. Crosstalk between fisetin-induced apoptosis and autophagy in human oral squamous cell carcinoma. J. Cancer, 2019, 10(1), 138-146.
[] [PMID: 30662534]
Hossain, M.J.; Ahmmed, F.; Rahman, S.M.A.; Sanam, S.; Emran, T.B.; Mitra, S. Impact of online education on fear of academic delay and psychological distress among university students following one year of COVID-19 outbreak in Bangladesh. Heliyon, 2021, 7(6), e07388.
[] [PMID: 34258456]
Tsai, Y.H.; Lin, J.J.; Ma, Y.S.; Peng, S.F.; Huang, A.C.; Huang, Y.P.; Fan, M.J.; Lien, J.C.; Chung, J.G. Fisetin inhibits cell proliferation through the induction of G0/G1 phase arrest and caspase-3-mediated apoptosis in mouse leukemia cells. Am. J. Chin. Med., 2019, 47(4), 841-863.
[] [PMID: 31096772]
Fu, C.Y.; Chen, M.C.; Tseng, Y.S.; Chen, M.C.; Zhou, Z.; Yang, J.J.; Lin, Y.M.; Viswanadha, V.P.; Wang, G.; Huang, C.Y. Fisetin activates Hippo pathway and JNK/ERK/AP-1 signaling to inhibit proliferation and induce apoptosis of human osteosarcoma cells via ZAK overexpression. Environ. Toxicol., 2019, 34(8), 902-911.
[] [PMID: 31044527]
Chen, J.K.; Peng, S.F.; Lai, K.C.; Liu, H.C.; Huang, Y.P.; Lin, C.C.; Huang, C.; Chueh, F.S.; Chung, J.G. Fistein suppresses human osteosarcoma U-2 OS cell migration and invasion via affecting FAK, uPA and NF-ĸB signaling pathway in vitro. in vivo, 2019, 33(3), 801-810.
[] [PMID: 31028200]
Khan, N.; Jajeh, F.; Eberhardt, E.L.; Miller, D.D.; Albrecht, D.M.; Van Doorn, R.; Hruby, M.D.; Maresh, M.E.; Clipson, L.; Mukhtar, H.; Halberg, R.B. Fisetin and 5-fluorouracil: Effective combination for PIK3CA -mutant colorectal cancer. Int. J. Cancer, 2019, 145(11), 3022-3032.
[] [PMID: 31018249]
Won, D.H.; Chung, S.H.; Shin, J.A.; Hong, K.O.; Yang, I.H.; Yun, J.W.; Cho, S.D. Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines. J. Clin. Biochem. Nutr., 2019, 64(2), 97-105.
[] [PMID: 30936621]
Tabasum, S.; Singh, R.P. Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells via attenuation of epithelial to mesenchymal transition. Chem. Biol. Interact., 2019, 303, 14-21.
[] [PMID: 30802432]
Jia, S.; Xu, X.; Zhou, S.; Chen, Y.; Ding, G.; Cao, L. Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways. Cell Death Dis., 2019, 10(2), 142.
[] [PMID: 30760707]
Syed, D.N.; Chamcheu, J.C.; Khan, M.I.; Sechi, M.; Lall, R.K.; Adhami, V.M.; Mukhtar, H. Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: Findings from 3-D melanoma skin equivalents and computational modeling. Biochem. Pharmacol., 2014, 89(3), 349-360.
[] [PMID: 24675012]
Feng, C.; Yuan, X.; Chu, K.; Zhang, H.; Ji, W.; Rui, M. Preparation and optimization of poly (lactic acid) nanoparticles loaded with fisetin to improve anti-cancer therapy. Int. J. Biol. Macromol., 2019, 125, 700-710.
[] [PMID: 30521927]
Guo, G.; Zhang, W.; Dang, M.; Yan, M.; Chen, Z. Fisetin induces apoptosis in breast cancer MDA-MB-453 cells through degradation of HER2/neu and via the PI3K/Akt pathway. J. Biochem. Mol. Toxicol., 2019, 33(4), e22268.
[] [PMID: 30431692]
Bariar, B.; Vestal, C.G.; Deem, B.; Goodenow, D.; Ughetta, M.; Engledove, R.W.; Sahyouni, M.; Richardson, C. Bioflavonoids promote stable translocations between MLL-AF9 breakpoint cluster regions independent of normal chromosomal context: Model system to screen environmental risks. Environ. Mol. Mutagen., 2019, 60(2), 154-167.
[] [PMID: 30387535]
Pawar, A.; Singh, S.; Rajalakshmi, S.; Shaikh, K.; Bothiraja, C. Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting. Artif. Cells Nanomed. Biotechnol., 2018, 46(sup1), 347-361.
[] [PMID: 29334247]
Si, Y.; Liu, J.; Shen, H.; Zhang, C.; Wu, Y.; Huang, Y.; Gong, Z.; Xue, J.; Liu, T. Fisetin decreases TET1 activity and CCNY/CDK16 promoter 5hmC levels to inhibit the proliferation and invasion of renal cancer stem cell. J. Cell. Mol. Med., 2019, 23(2), 1095-1105.
[] [PMID: 30411496]
Jeng, L.B.; Kumar Velmurugan, B.; Chen, M.C.; Hsu, H.H.; Ho, T.J.; Day, C.H.; Lin, Y.M.; Padma, V.V.; Tu, C.C.; Huang, C.Y. Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo. J. Cell. Physiol., 2018, 233(9), 7134-7142.
[] [PMID: 29574877]
Xiao, X.; Zou, J.; Fang, Y.; Meng, Y.; Xiao, C.; Fu, J.; Liu, S.; Bai, P.; Yao, Y. Fisetin and polymeric micelles encapsulating fisetin exhibit potent cytotoxic effects towards ovarian cancer cells. BMC Complement. Altern. Med., 2018, 18(1), 91.
[] [PMID: 29544480]
Farsad-Naeimi, A.; Alizadeh, M.; Esfahani, A.; Darvish Aminabad, E. Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients. Food Funct., 2018, 9(4), 2025-2031.
[] [PMID: 29541713]
Wang, J.; Huang, S. Fisetin inhibits the growth and migration in the A549 human lung cancer cell line via the ERK1/2 pathway. Exp. Ther. Med., 2018, 15(3), 2667-2673.
[PMID: 29467859]
Ferreira de Oliveira, J.M.P.; Pacheco, A.R.; Coutinho, L.; Oliveira, H.; Pinho, S.; Almeida, L.; Fernandes, E.; Santos, C. Combination of etoposide and fisetin results in anti-cancer efficiency against osteosarcoma cell models. Arch. Toxicol., 2018, 92(3), 1205-1214.
[] [PMID: 29270805]
Kashyap, D.; Sharma, A.; Sak, K.; Tuli, H.S.; Buttar, H.S.; Bishayee, A. Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy. Life Sci., 2018, 194, 75-87.
[] [PMID: 29225112]
Ge, C.; Xu, M.; Qin, Y.; Gu, T.; Lou, D.; Li, Q.; Hu, L.; Nie, X.; Wang, M.; Tan, J. Fisetin supplementation prevents high fat diet-induced diabetic nephropathy by repressing insulin resistance and RIP3-regulated inflammation. Food Funct., 2019, 10(5), 2970-2985.
[] [PMID: 31074472]
Althunibat, O.Y.; Al Hroob, A.M.; Abukhalil, M.H.; Germoush, M.O.; Bin-Jumah, M.; Mahmoud, A.M. Fisetin ameliorates oxidative stress, inflammation and apoptosis in diabetic cardiomyopathy. Life Sci., 2019, 221, 83-92.
[] [PMID: 30742869]
Kim, A.; Yun, J.M. Combination treatments with luteolin and fisetin enhance anti-inflammatory effects in high glucose-treated THP-1 cells through histone acetyltransferase/histone deacetylase regulation. J. Med. Food, 2017, 20(8), 782-789.
[] [PMID: 28650731]
Kim, A.; Lee, W.; Yun, J.M. Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions. Nutr. Res. Pract., 2017, 11(5), 430-434.
[] [PMID: 28989580]
Sandireddy, R.; Yerra, V.G.; Komirishetti, P.; Areti, A.; Kumar, A. Fisetin imparts neuroprotection in experimental diabetic neuropathy by modulating Nrf2 and NF-κB pathways. Cell. Mol. Neurobiol., 2016, 36(6), 883-892.
[] [PMID: 26399251]
Prasath, G.S.; Pillai, S.I.; Subramanian, S.P. Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats. Eur. J. Pharmacol., 2014, 740, 248-254.
[] [PMID: 25064342]
Prasath, G.S.; Subramanian, S.P. Fisetin, a tetra hydroxy flavone recuperates antioxidant status and protects hepatocellular ultrastructure from hyperglycemia mediated oxidative stress in streptozotocin induced experimental diabetes in rats. Food Chem. Toxicol., 2013, 59, 249-255.
[] [PMID: 23791753]
Prasath, G.S.; Sundaram, C.S.; Subramanian, S.P. Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats. Endocrine, 2013, 44(2), 359-368.
[] [PMID: 23277230]
Zhao, X.; Li, X.L.; Liu, X.; Wang, C.; Zhou, D.S.; Ma, Q.; Zhou, W.H.; Hu, Z.Y. Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors. Pharmacol. Res., 2015, 102, 286-297.
[] [PMID: 26520392]
Kan, E.; Kiliçkan, E.; Ayar, A.; Çolak, R. Effects of two antioxidants; α-lipoic acid and fisetin against diabetic cataract in mice. Int. Ophthalmol., 2015, 35(1), 115-120.
[] [PMID: 25488016]
Jin, T.; Kim, O.Y.; Shin, M.J.; Choi, E.Y.; Lee, S.S.; Han, Y.S.; Chung, J.H. 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(43), 10468-10474.
[] [PMID: 25286082]
Watanabe, M.; Hisatake, M.; Fujimori, K. Fisetin suppresses lipid accumulation in mouse adipocytic 3T3-L1 cells by repressing GLUT4-mediated glucose uptake through inhibition of mTOR-C/EBPα signaling. J. Agric. Food Chem., 2015, 63(20), 4979-4987.
[] [PMID: 25945786]
Jeon, T.I.; Park, J.W.; Ahn, J.; Jung, C.H.; Ha, T.Y. Fisetin protects against hepatosteatosis in mice by inhibiting miR-378. Mol. Nutr. Food Res., 2013, 57(11), 1931-1937.
[] [PMID: 23818290]
Cho, Y.; Chung, J.H.; Do, H.J.; Jeon, H.J.; Jin, T.; Shin, M.J. Effects of fisetin supplementation on hepatic lipogenesis and glucose metabolism in Sprague–Dawley rats fed on a high fat diet. Food Chem., 2013, 139(1-4), 720-727.
[] [PMID: 23561166]
Jung, C.H.; 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(8), 1547-1554.
[] [PMID: 23517912]
Minxuan, X.; Sun, Y.; Dai, X.; Zhan, J.; Long, T.; Xiong, M.; Li, H.; Kuang, Q.; Tang, T.; Qin, Y.; Chenxu, G.; Jun, T. Fisetin attenuates high fat diet-triggered hepatic lipid accumulation: A mechanism involving liver inflammation overload associated TACE/TNF-α pathway. J. Funct. Foods, 2019, 53, 7-21.
Xu, M.; Ge, C.; Qin, Y.; Gu, T.; Lv, J.; Wang, S.; Ma, Y.; Lou, D.; Li, Q.; Hu, L.; Nie, X.; Wang, M.; Huang, P.; Tan, J. Activated TNF-α/RIPK3 signaling is involved in prolonged high fat diet-stimulated hepatic inflammation and lipid accumulation: inhibition by dietary fisetin intervention. Food Funct., 2019, 10(3), 1302-1316.
[] [PMID: 30793717]
Garg, S.; Malhotra, R.K.; Khan, S.I.; Sarkar, S.; Susrutha, P.N.; Singh, V.; Goyal, S.; Nag, T.C.; Ray, R.; Bhatia, J.; Arya, D.S. Fisetin attenuates isoproterenol-induced cardiac ischemic injury in vivo by suppressing RAGE/NF-κB mediated oxidative stress, apoptosis and inflammation. Phytomedicine, 2019, 56, 147-155.
[] [PMID: 30668335]
Ma, T.; Kandhare, A.D.; Mukherjee-Kandhare, A.A.; Bodhankar, S.L. Fisetin, a plant flavonoid ameliorates doxorubicin-induced cardiotoxicity in experimental rats: the decisive role of caspase-3, COX-II, cTn-I, iNOs and TNF-α. Mol. Biol. Rep., 2019, 46(1), 105-118.
[] [PMID: 30362071]
Dong, B.; Liu, C.; Xue, R.; Wang, Y.; Sun, Y.; Liang, Z.; Fan, W.; Jiang, J.; Zhao, J.; Su, Q.; Dai, G.; Dong, Y.; Huang, H. Fisetin inhibits cardiac hypertrophy by suppressing oxidative stress. J. Nutr. Biochem., 2018, 62, 221-229.
[] [PMID: 30312797]
Shanmugam, K.; Ravindran, S.; Kurian, G.A.; Rajesh, M. Fisetin confers cardioprotection against myocardial ischemia reperfusion injury by suppressing mitochondrial oxidative stress and mitochondrial dysfunction and inhibiting glycogen synthase kinase 3β activity. Oxidative Med. Cell. Long., 2018, 2018
Chen, Y.P.; Sivalingam, K.; Shibu, M.A.; Peramaiyan, R.; Day, C.H.; Shen, C.Y.; Lai, C.H.; Chen, R.J.; Viswanadha, V.P.; Chen, Y.F.; Huang, C.Y. Protective effect of Fisetin against angiotensin II-induced apoptosis by activation of IGF-IR-PI3K-Akt signaling in H9c2 cells and spontaneous hypertension rats. Phytomedicine, 2019, 57, 1-8.
[] [PMID: 30668312]
Yu, X.; Jiang, X.; Zhang, X.; Chen, Z.; Xu, L.; Chen, L.; Wang, G.; Pan, J. The effects of fisetin on lipopolysaccharide-induced depressive-like behavior in mice. Metab. Brain Dis., 2016, 31(5), 1011-1021.
[] [PMID: 27209403]
ALTamimi, J.Z.; BinMowyna, M.N.; AlFaris, N.A.; Alagal, R.I.; El-kott, A.F.; AL-Farga, A.M. Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R. Saudi Pharm. J., 2021, 29(1), 27-42.
Zhou, P.; Hua, F.; Wang, X.; Huang, J.L. Therapeutic potential of IKK-β inhibitors from natural phenolics for inflammation in cardiovascular diseases. Inflammopharmacology, 2020, 28(1), 19-37.
[] [PMID: 31894515]
Hussain, T.; Al-Attas, O.S.; Alamery, S.; Ahmed, M.; Odeibat, H.A.M.; Alrokayan, S. The plant flavonoid, fisetin alleviates cigarette smoke-induced oxidative stress, and inflammation in Wistar rat lungs. J. Food Biochem., 2019, 43(8), e12962.
[] [PMID: 31368542]
Ahmad, A.; Ali, T.; Rehman, S.U.; Kim, M.O. Phytomedicine-based potent antioxidant, fisetin protects CNS-insult LPS-induced oxidative stress-mediated neurodegeneration and memory impairment. J. Clin. Med., 2019, 8(6), 850.
[] [PMID: 31207963]
Zhang, L.; Wang, H.; Zhou, Y.; Zhu, Y.; Fei, M. Fisetin alleviates oxidative stress after traumatic brain injury via the Nrf2-ARE pathway. Neurochem. Int., 2018, 118, 304-313.
[] [PMID: 29792955]
Hytti, M.; Szabó, D.; Piippo, N.; Korhonen, E.; Honkakoski, P.; Kaarniranta, K.; Petrovski, G.; Kauppinen, A. Two dietary polyphenols, fisetin and luteolin, reduce inflammation but augment DNA damage-induced toxicity in human RPE cells. J. Nutr. Biochem., 2017, 42, 37-42.
[] [PMID: 28113103]
Seo, S.H.; Jeong, G.S. Fisetin inhibits TNF-α-induced inflammatory action and hydrogen peroxide-induced oxidative damage in human keratinocyte HaCaT cells through PI3K/AKT/Nrf-2-mediated heme oxygenase-1 expression. Int. Immunopharmacol., 2015, 29(2), 246-253.
[] [PMID: 26590114]
Annunziata, G.; Sureda, A.; Orhan, I.E.; Battino, M.; Arnone, A.; Jiménez-García, M.; Capó, X.; Cabot, J.; Sanadgol, N.; Giampieri, F.; Tenore, G.C.; Kashani, H.R.K.; Silva, A.S.; Habtemariam, S.; Nabavi, S.F.; Nabavi, S.M. The neuroprotective effects of polyphenols, their role in innate immunity and the interplay with the microbiota. Neurosci. Biobehav. Rev., 2021, 128, 437-453.
[] [PMID: 34245757]
Chen, T.J.; Feng, Y.; Liu, T.; Wu, T.T.; Chen, Y.J.; Li, X.; Li, Q.; Wu, Y.C. Fisetin regulates gut microbiota and exerts neuroprotective effect on mouse model of Parkinson’s disease. Front. Neurosci., 2020, 14, 549037.
[] [PMID: 33381005]
Currais, A.; Farrokhi, C.; Dargusch, R.; Armando, A.; Quehenberger, O.; Schubert, D.; Maher, P. Fisetin reduces the impact of aging on behavior and physiology in the rapidly aging SAMP8 mouse. J. Gerontol. A Biol. Sci. Med. Sci., 2018, 73(3), 299-307.
[] [PMID: 28575152]
Jacob, S.; Thangarajan, S. Fisetin impedes developmental methylmercury neurotoxicity via downregulating apoptotic signalling pathway and upregulating Rho GTPase signalling pathway in hippocampus of F 1 generation rats. Int. J. Dev. Neurosci., 2018, 69(1), 88-96.
[] [PMID: 30009881]
Rajendran, M.; Ramachandran, R. Fisetin protects against rotenone-induced neurotoxicity through signaling pathway. Front. Biosci., 2019, 11(1), 20-28.
[PMID: 30468635]
Li, L.; Qin, J.; Fu, T.; Shen, J. Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma. Doc. Ophthalmol., 2019, 138(2), 125-135.
[] [PMID: 30756213]
Funakoshi-Tago, M.; Nakamura, K.; Tago, K.; Mashino, T.; Kasahara, T. Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin. Int. Immunopharmacol., 2011, 11(9), 1150-1159.
[] [PMID: 21443976]
Zheng, W.; Feng, Z.; You, S.; Zhang, H.; Tao, Z.; Wang, Q.; Chen, H.; Wu, Y. Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice. Int. Immunopharmacol., 2017, 45, 135-147.
[] [PMID: 28213268]
Feng, G.; Jiang, Z.; Sun, B.; Fu, J.; Li, T. Fisetin alleviates lipopolysaccharide-induced acute lung injury via TLR4-mediated NF-κB signaling pathway in rats. Inflammation, 2016, 39(1), 148-157.
[] [PMID: 26272311]
Kim, S.C.; Kang, S.H.; Jeong, S.J.; Kim, S.H.; Ko, H.S.; Kim, S.H. Inhibition of c-Jun N-terminal kinase and nuclear factor κ B pathways mediates fisetin-exerted anti-inflammatory activity in lipopolysccharide-treated RAW264.7 cells. Immunopharmacol. Immunotoxicol., 2012, 34(4), 645-650.
[] [PMID: 22239491]
Zhen, L.; Zhu, J.; Zhao, X.; Huang, W.; An, Y.; Li, S.; Du, X.; Lin, M.; Wang, Q.; Xu, Y.; Pan, J. The antidepressant-like effect of fisetin involves the serotonergic and noradrenergic system. Behav. Brain Res., 2012, 228(2), 359-366.
[] [PMID: 22197297]
Kumar, R.; Khursheed, R.; Kumar, R.; Awasthi, A.; Sharma, N.; Khurana, S.; Kapoor, B.; Khurana, N.; Singh, S.K.; Gowthamarajan, K.; Wadhwani, A. Self-nanoemulsifying drug delivery system of fisetin: Formulation, optimization, characterization and cytotoxicity assessment. J. Drug Deliv. Sci. Technol., 2019, 54, 101252.
Hu, L.F.; Feng, J.; Dai, X.; Sun, Y.; Xiong, M.; Lai, L.; Zhong, S.; Yi, C.; Chen, G.; Li, H.; Yang, Q.; Kuang, Q.; Long, T.; Zhan, J.; Tang, T.; Ge, C.; Tan, J.; Xu, M. Oral flavonoid fisetin treatment protects against prolonged high-fat-diet-induced cardiac dysfunction by regulation of multicombined signaling. J. Nutr. Biochem., 2020, 77, 108253.
[] [PMID: 31835147]
Sun, Q.; Zhang, W.; Zhong, W.; Sun, X.; Zhou, Z. Dietary fisetin supplementation protects against alcohol-induced liver injury in mice. Alcohol. Clin. Exp. Res., 2016, 40(10), 2076-2084.
[] [PMID: 27575873]
Zhang, J.; Zhao, L.; Hu, C.; Wang, T.; Lu, J.; Wu, C.; Chen, L.; Jin, M.; Hu, H.; Ji, G.; Cao, Q.; Jiang, Y. Fisetin prevents acetaminophen-induced liver injury by promoting autophagy. Front. Pharmacol., 2020, 11, 162.
[] [PMID: 32184730]
Elkholy, R.; Balaha, M.; El-Anwar, N.; Kandeel, S.; Hedya, S.; Abd-El Rahman, M.N. Fisetin and telmisartan each alone or in low-dose combination alleviate OVA-induced food allergy in mice. Pharmacol. Rep., 2019, 71(2), 330-337.
[] [PMID: 30826574]
Kim, G.D.; Lee, S.E.; Park, Y.S.; Shin, D.H.; Park, G.G.; Park, C.S. Immunosuppressive effects of fisetin against dinitrofluorobenzene-induced atopic dermatitis-like symptoms in NC/Nga mice. Food Chem. Toxicol., 2014, 66, 341-349.
[] [PMID: 24525099]
Song, B.; Guan, S.; Lu, J.; Chen, Z.; Huang, G.; Li, G.; Xiong, Y.; Zhang, S.; Yue, Z.; Deng, X. Suppressive effects of fisetin on mice T lymphocytes in vitro and in vivo. J. Surg. Res., 2013, 185(1), 399-409.
[] [PMID: 23993202]
Goh, F.Y.; Upton, N.; Guan, S.; Cheng, C.; Shanmugam, M.K.; Sethi, G.; Leung, B.P.; Wong, W.S.F. Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB. Eur. J. Pharmacol., 2012, 679(1-3), 109-116.
[] [PMID: 22290391]
Kim, Y.H.; Kim, J.L.; Lee, E.J.; Park, S.H.; Han, S.Y.; Kang, S.A.; Kang, Y.H. Fisetin antagonizes cell fusion, cytoskeletal organization and bone resorption in RANKL-differentiated murine macrophages. J. Nutr. Biochem., 2014, 25(3), 295-303.
[] [PMID: 24524902]
Léotoing, L.; Wauquier, F.; Guicheux, J.; Miot-Noirault, E.; Wittrant, Y.; Coxam, V. The polyphenol fisetin protects bone by repressing NF-κB and MKP-1-dependent signaling pathways in osteoclasts. PLoS One, 2013, 8(7), e68388.
[] [PMID: 23861901]
Hytti, M.; Piippo, N.; Korhonen, E.; Honkakoski, P.; Kaarniranta, K.; Kauppinen, A. Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation. Sci. Rep., 2015, 5(1), 17645.
[] [PMID: 26619957]
Chen, C.; Yao, L.; Cui, J.; Liu, B. Fisetin protects against intracerebral hemorrhage-induced neuroinflammation in aged mice. Cerebrovasc. Dis., 2018, 45(3-4), 154-161.
[] [PMID: 29587289]
Wang, T.H.; Wang, S.Y.; Wang, X.D.; Jiang, H.Q.; Yang, Y.Q.; Wang, Y.; Cheng, J.L.; Zhang, C.T.; Liang, W.W.; Feng, H.L. Fisetin exerts antioxidant and neuroprotective effects in multiple mutant hSOD1 models of amyotrophic lateral sclerosis by activating ERK. Neuroscience, 2018, 379, 152-166.
[] [PMID: 29559385]
Ahmad, A.; Ali, T.; Park, H.Y.; Badshah, H.; Rehman, S.U.; Kim, M.O. Neuroprotective effect of fisetin against amyloid-beta-induced cognitive/synaptic dysfunction, neuroinflammation, and neurodegeneration in adult mice. Mol. Neurobiol., 2017, 54(3), 2269-2285.
[] [PMID: 26944285]
Fazel Nabavi, S.; Braidy, N.; Habtemariam, S.; Sureda, A.; Manayi, A.; Mohammad Nabavi, S. Neuroprotective effects of fisetin in alzheimer’s and parkinson’s diseases: From chemistry to medicine. Curr. Top. Med. Chem., 2016, 16(17), 1910-1915.
[] [PMID: 26845554]
Krasieva, T.B.; Ehren, J.; O’Sullivan, T.; Tromberg, B.J.; Maher, P. Cell and brain tissue imaging of the flavonoid fisetin using label-free two-photon microscopy. Neurochem. Int., 2015, 89, 243-248.
[] [PMID: 26271433]
Prakash, D.; Sudhandiran, G. Dietary flavonoid fisetin regulates aluminium chloride-induced neuronal apoptosis in cortex and hippocampus of mice brain. J. Nutr. Biochem., 2015, 26(12), 1527-1539.
[] [PMID: 26411262]
Maher, P. Protective effects of fisetin and other berry flavonoids in Parkinson’s disease. Food Funct., 2017, 8(9), 3033-3042.
[] [PMID: 28714503]
Prakash, D.; Gopinath, K.; Sudhandiran, G. Fisetin enhances behavioral performances and attenuates reactive gliosis and inflammation during aluminum chloride-induced neurotoxicity. Neuromolecular Med., 2013, 15(1), 192-208.
[] [PMID: 23315010]
Xu, S.P.; Li, Y.S. Fisetin inhibits pristine-induced systemic lupus erythematosus in a murine model through CXCLs regulation. Int. J. Mol. Med., 2018, 42(6), 3220-3230.
[] [PMID: 30272314]
Kim, J.H.; Kim, M.Y.; Kim, J.H.; Cho, J.Y. Fisetin suppresses macrophage-mediated inflammatory responses by blockade of Src and Syk. Biomol. Ther., 2015, 23(5), 414-420.
[] [PMID: 26336580]
Pal, H.C.; Athar, M.; Elmets, C.A.; Afaq, F. Fisetin inhibits UVB-induced cutaneous inflammation and activation of PI3K/AKT/NFκB signaling pathways in SKH-1 hairless mice. Photochem. Photobiol., 2015, 91(1), 225-234.
[] [PMID: 25169110]
Liu, S.H.; Lin, C.H.; Hung, S.K.; Chou, J.H.; Chi, C.W.; Fu, S.L. Fisetin inhibits lipopolysaccharide-induced macrophage activation and dendritic cell maturation. J. Agric. Food Chem., 2010, 58(20), 10831-10839.
[] [PMID: 20923145]
Gutiérrez-Venegas, G.; Contreras-Sánchez, A.; Ventura-Arroyo, J.A. Anti-inflammatory activity of fisetin in human gingival fibroblasts treated with lipopolysaccharide. J. Asian Nat. Prod. Res., 2014, 16(10), 1009-1017.
[] [PMID: 25263652]
Kwak, S.; Ku, S.K.; Bae, J.S. Fisetin inhibits high-glucose-induced vascular inflammation in vitro and in vivo. Inflamm. Res., 2014, 63(9), 779-787.
[] [PMID: 24923846]
Wang, Y.; Wang, B.; Lu, J.; Shi, H.; Gong, S.; Wang, Y.; Hamdy, R.C.; Chua, B.H.L.; Yang, L.; Xu, X. Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice. J. Neurochem., 2017, 143(5), 561-568.
[] [PMID: 28945929]
Qian, R.; Liang, M.; Fu, P. FP297Anti-Inflammatory Flavonoid Fisetin Attenuates LPS-Induced Acute Kidney Injury via Inhibiting TLR4/NF-kappaB Pathway. Nephrol. Dial. Transplant., 2019, 34(Suppl. 1), gfz106.FP297.
Zhao, L.; Zhang, J.; Pan, L.; Chen, L.; Wang, Y.; Liu, X.; You, L.; Jia, Y.; Hu, C. Protective effect of 7,3′,4′-flavon-3-ol (fisetin) on acetaminophen-induced hepatotoxicity in vitro and in vivo. Phytomedicine, 2019, 58, 152865.
[] [PMID: 30831465]
Prasath, G.S.; Subramanian, S.P. 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(3), 492-496.
[] [PMID: 21816145]
Constantin, R.P.; Constantin, J.; Pagadigorria, C.L.S.; Ishii-Iwamoto, E.L.; Bracht, A.; de Castro, C.V.; Yamamoto, N.S. Prooxidant activity of fisetin: Effects on energy metabolism in the rat liver. J. Biochem. Mol. Toxicol., 2011, 25(2), 117-126.
[] [PMID: 20957679]
Constantin, R.P.; Constantin, J.; Pagadigorria, C.L.S.; Ishii-Iwamoto, E.L.; Bracht, A.; Ono, M.K.C.; Yamamoto, N.S. The actions of fisetin on glucose metabolism in the rat liver. Cell Biochem. Funct., 2010, 28(2), 149-158.
[] [PMID: 20084677]
Sun, X.; Xu, B.; Xue, Y.; Li, H.; Zhang, H.; Zhang, Y.; Kang, L.; Zhang, X.; Zhang, J.; Jia, Z.; Zhang, X. Characterization and structure-activity relationship of natural flavonoids as hERG K + channel modulators. Int. Immunopharmacol., 2017, 45, 187-193.
[] [PMID: 28235721]
Hirano, T.; Higa, S.; Arimitsu, J.; Naka, T.; Shima, Y.; Ohshima, S.; Fujimoto, M.; Yamadori, T.; Kawase, I.; Tanaka, T. Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils. Int. Arch. Allergy Immunol., 2004, 134(2), 135-140.
[] [PMID: 15153793]
Jo, W.R.; Park, H.J. Antiallergic effect of fisetin on IgE-mediated mast cell activation in vitro and on passive cutaneous anaphylaxis (PCA). J. Nutr. Biochem., 2017, 48, 103-111.
[] [PMID: 28797929]
Wu, M.Y.; Hung, S.K.; Fu, S.L. Immunosuppressive effects of fisetin in ovalbumin-induced asthma through inhibition of NF-κB activity. J. Agric. Food Chem., 2011, 59(19), 10496-10504.
[] [PMID: 21899296]
Che, D.N.; Cho, B.O.; Shin, J.Y.; Kang, H.J.; Kim, Y.S.; Jang, S.I. Fisetin inhibits IL-31 production in stimulated human mast cells: Possibilities of fisetin being exploited to treat histamine-independent pruritus. Life Sci., 2018, 201, 121-129.
[] [PMID: 29604269]
Léotoing, L.; Davicco, M.J.; Lebecque, P.; Wittrant, Y.; Coxam, V. The flavonoid fisetin promotes osteoblasts differentiation through Runx2 transcriptional activity. Mol. Nutr. Food Res., 2014, 58(6), 1239-1248.
[] [PMID: 24535991]
Sakai, E.; Shimada-Sugawara, M.; Yamaguchi, Y.; Sakamoto, H.; Fumimoto, R.; Fukuma, Y.; Nishishita, K.; Okamoto, K.; Tsukuba, T. Fisetin inhibits osteoclastogenesis through prevention of RANKL-induced ROS production by Nrf2-mediated up-regulation of phase II antioxidant enzymes. J. Pharmacol. Sci., 2013, 121(4), 288-298.
[] [PMID: 23538677]
Choi, S.W.; Son, Y.J.; Yun, J.M.; Kim, S.H. Fisetin inhibits osteoclast differentiation via downregulation of p38 and c-Fos-NFATc1 signaling pathways Evid-Based Complement. Altern. Med, 2012, 2012
Alzaabi, M.M.; Hamdy, R.; Ashmawy, N.S.; Hamoda, A.M.; Alkhayat, F.; Khademi, N.N.; Al Joud, S.M.A.; El-Keblawy, A.A.; Soliman, S.S.M. Flavonoids are promising safe therapy against COVID-19. Phytochem. Rev., 2022, 21(1), 291-312.
[] [PMID: 34054380]
Mouffouk, C.; Mouffouk, S.; Mouffouk, S.; Hambaba, L.; Haba, H. Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2). Eur. J. Pharmacol., 2021, 891, 173759.
[] [PMID: 33249077]
Chaves, O.A.; Lima, C.R.; Fintelman-Rodrigues, N.; Sacramento, C.Q.; de Freitas, C.S.; Vazquez, L.; Temerozo, J.R.; Rocha, M.E.N.; Dias, S.S.G.; Carels, N.; Bozza, P.T.; Castro-Faria-Neto, H.C.; Souza, T.M.L. Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases. Int. J. Biol. Macromol., 2022, 222(Pt A), 1015-1026.
[] [PMID: 36183752]
Chaves, O.A.; Fintelman-Rodrigues, N.; Wang, X.; Sacramento, C.Q.; Temerozo, J.R.; Ferreira, A.C.; Mattos, M.; Pereira-Dutra, F.; Bozza, P.T.; Castro-Faria-Neto, H.C.; Russo, J.J.; Ju, J.; Souza, T.M.L. Commercially available flavonols are better SARS- CoV-2 inhibitors than isoflavone and flavones. Viruses, 2022, 14(7), 1458.
[] [PMID: 35891437]
Mishra, A.; Kaur, U.; Singh, A. Fisetin 8-C-glucoside as entry inhibitor in SARS CoV-2 infection: Molecular modelling study. J. Biomol. Struct. Dyn., 2022, 40(11), 5128-5137.
[] [PMID: 33382023]
Schmitt, C.A.; Tchkonia, T.; Niedernhofer, L.J.; Robbins, P.D.; Kirkland, J.L.; Lee, S. COVID-19 and cellular senescence. Nat. Rev. Immunol., 2023, 23(4), 251-263.
[] [PMID: 36198912]
Tallei, T.E.; Tumilaar, S.G.; Niode, N.J.; Fatimawali; Kepel, B.J.; Idroes, R.; Effendi, Y.; Sakib, S.A.; Emran, T.B. Potential of plant bioactive compounds as SARS-CoV-2 main protease (M pro) and spike (S) glycoprotein inhibitors: a molecular docking study. Scientifica, 2020, 2020, 1-18.
[] [PMID: 33425427]
Khan, N.; Syed, D.N.; Ahmad, N.; Mukhtar, H. Fisetin: A dietary antioxidant for health promotion. Antioxid. Redox Signal., 2013, 19(2), 151-162.
[] [PMID: 23121441]

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