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2000
Volume 15, Issue 8
  • ISSN: 2210-3155
  • E-ISSN: 2210-3163

Abstract

Background

Liver disease is a common cause of death worldwide.

Objectives

This study aims to investigate the effects and mechanisms of Fisetin on hepatotoxicity, liver injury, and liver fibrosis.

Methods

We adhered to the PRISMA 2020 guidelines in this systematic review. Our search used MeSH keywords encompassed Embase, PubMed, Web of Science, Scopus, and Cochrane Library for articles published before March 2, 2024. Relevant data was extracted from the publications, meticulously recorded in a standard form, and subsequently reviewed for outcomes and mechanisms.

Results

Fisetin protects hepatocytes from oxidative stress by neutralizing free radicals (Oand HO), reduces oxidative stress, prevents lipid peroxidation, and increases endogenous antioxidants. It also reduces inflammation lowering the production of tumor necrosis factor α (TNF-α), interleukins (IL)1, IL-6, IL-18, IL-1β suppressing nuclear factor kappa B (NF-κB) activation, and cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) inhibition, reducing monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), NLR family pyrin domain-containing 3 (NLRP3) inflammasome and interferon-gamma (IFN‐γ). Moreover, it inhibited apoptosis-modulated enzyme activity and detoxification enzymes modulating the activity of cytochrome P450 and Phase II detoxification enzymes. Fisetin prevented fibrosis by inhibiting the activation of hepatic stellate cells (HSCs), attenuating extracellular matrix (ECM) remodeling-associated genes, and suppressing transforming growth factor-β (TGF-β) signaling pathway and attenuating collagen production. It decreased lipid accumulation and liver function tests.

Conclusion

and studies indicated that Fisetin can enhance detoxification, attenuate liver injury, and reduce fibrosis, which helps maintain liver health.

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2024-09-18
2025-10-27
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References

  1. SharmaA. NagalliS. Chronic Liver Disease.StatPearls.Treasure Island, FLStatPearls Publishing2024
    [Google Scholar]
  2. GrønkjærL.L. LauridsenM.M. Quality of life and unmet needs in patients with chronic liver disease: A mixed-method systematic review.JHEP Reports20213610037010.1016/j.jhepr.2021.10037034805816
    [Google Scholar]
  3. TeshomeE. HailuW. AdaneA. Belayneh MeleseE. Abebaw AngawD. TarekegnG.E. Clinical and individual factors of quality of life of chronic liver disease patients at University of Gondar comprehensive specialized hospital, Northwest Ethiopia 2022.Medicine (Baltimore)202310245e3542510.1097/MD.000000000003542537960830
    [Google Scholar]
  4. MessinaA. Duclos-ValléeJ.C. Molecular Mechanisms of Hepatotoxicity.Int. J. Mol. Sci.2023244379110.3390/ijms2404379136835204
    [Google Scholar]
  5. BashirA. HoilatG.J. SarwalP. Liver Toxicity.StatPearls.Treasure Island, FLStatPearls Publishing2024
    [Google Scholar]
  6. ZhangC.Y. YuanW.G. HeP. LeiJ.H. WangC.X. Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets.World J. Gastroenterol.20162248105121052210.3748/wjg.v22.i48.1051228082803
    [Google Scholar]
  7. GarbuzenkoD.V. Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.World J. Clin. Cases202210123662367610.12998/wjcc.v10.i12.366235647163
    [Google Scholar]
  8. JivadN. Heidari-SoureshjaniS. BagheriH. SherwinC.M.T. RostamianS. Anti-seizure Effects and Mechanisms of Berberine: A Systematic Review.Curr. Pharm. Biotechnol.20242510.2174/011389201028323724010712174938385486
    [Google Scholar]
  9. DarvishiM. NouriM. RahimiR. Heidari-SoureshjaniS. Hashemi RafsanjaniS.M.R. A Systematic Review of the Impact of Resveratrol on Viral Hepatitis and Chronic Viral Hepatitis-related Hepatocellular Carcinoma.Curr. Mol. Med.20242410.2174/011566524028434724012507255538375839
    [Google Scholar]
  10. KhosraviM.R. RaeisiE. Heidari-SoureshjaniS. SherwinC.M.T. The survey of antitumor effects of bromelain on neoplastic breast cells: A systematic review.Journal of Herbmed Pharmacology2024131101810.34172/jhp.2024.48078
    [Google Scholar]
  11. ShuklaR. PandeyV. VadnereG.P. LodhiS. Chapter 18 - Role of Flavonoids in Management of Inflammatory Disorders.Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases (Second Edition)Academic Press2019293322
    [Google Scholar]
  12. PalH.C. PearlmanR.L. AfaqF. Fisetin and Its Role in Chronic Diseases.Adv. Exp. Med. Biol.201692821324410.1007/978‑3‑319‑41334‑1_1027671819
    [Google Scholar]
  13. LiS. TanH.Y. WangN. CheungF. HongM. FengY. The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases.Oxid. Med. Cell. Longev.201820181839481810.1155/2018/839481829507653
    [Google Scholar]
  14. Gajender MazumderA. SharmaA. AzadM.A.K. A Comprehensive Review of the Pharmacological Importance of Dietary Flavonoids as Hepatoprotective Agents.Evid. Based Complement. Alternat. Med.202320231413911710.1155/2023/413911737123086
    [Google Scholar]
  15. KimM. JeeS.C. SungJ.S. Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways.Antioxidants202413218010.3390/antiox1302018038397778
    [Google Scholar]
  16. KoneruM. SahuB.D. KumarJ.M. KunchaM. KadariA. KilariE.K. SistlaR. Fisetin protects liver from binge alcohol-induced toxicity by mechanisms including inhibition of matrix metalloproteinases (MMPs) and oxidative stress.J. Funct. Foods20162258860110.1016/j.jff.2016.02.019
    [Google Scholar]
  17. CheemerlaS. BalakrishnanM. Global Epidemiology of Chronic Liver Disease.Clin. Liver Dis. (Hoboken)202117536537010.1002/cld.106134136143
    [Google Scholar]
  18. SchwartzA.G. RateW.R. Inhibition of aflatoxin B1-induced cytotoxicity and binding to DNA in cultured rat liver cells by naturally occurring flavones.J. Environ. Pathol. Toxicol.19792410211028448249
    [Google Scholar]
  19. BueningM.K. ChangR.L. HuangM.T. FortnerJ.G. WoodA.W. ConneyA.H. Activation and inhibition of benzo(a)pyrene and aflatoxin B1 metabolism in human liver microsomes by naturally occurring flavonoids.Cancer Res.198141167727448777
    [Google Scholar]
  20. AdemoyeroA.A. DalviR.R. Efficacy of activated charcoal and other agents in the reduction of hepatotoxic effects of a single dose of aflatoxin b1 in chickens.Toxicol. Lett.1983161-215315710.1016/0378‑4274(83)90024‑36404013
    [Google Scholar]
  21. DalviR.R. AdemoyeroA.A. Toxic effects of aflatoxin B1 in chickens given feed contaminated with Aspergillus flavus and reduction of the toxicity by activated charcoal and some chemical agents.Avian Dis.1984281616910.2307/15901286426455
    [Google Scholar]
  22. SubramanianP. JayakumarM. JayapalanJ.J. HashimO.H. Chronotherapeutic effect of fisetin on expression of urea cycle enzymes and inflammatory markers in hyperammonaemic rats.Pharmacol. Rep.20146661037104210.1016/j.pharep.2014.06.01825443732
    [Google Scholar]
  23. YangQ. LiaoJ. DengX. LiangJ. LongC. XieC. ChenX. ZhangL. SunJ. PengJ. ChuB. GuoG. LuoF. QianZ. Anti-tumor activity and safety evaluation of fisetin-loaded methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) nanoparticles.J. Biomed. Nanotechnol.201410458059110.1166/jbn.2014.174624734510
    [Google Scholar]
  24. HuardC.A. GaoX. Dey HazraM.E. Dey HazraR.O. LebsockK. EasleyJ.T. MillettP.J. HuardJ. Effects of Fisetin Treatment on Cellular Senescence of Various Tissues and Organs of Old Sheep.Antioxidants2023128164610.3390/antiox1208164637627641
    [Google Scholar]
  25. FrancisA.R. ShettyT.K. BhattacharyaR.K. Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of plant flavonoids.Mutat. Res. Genet. Toxicol. Test.1989222439340110.1016/0165‑1218(89)90114‑62495440
    [Google Scholar]
  26. SoučekP. KondrováE. HeřmánekJ. StopkaP. BoumendjelA. UengY.F. GutI. New model system for testing effects of flavonoids on doxorubicin-related formation of hydroxyl radicals.Anticancer Drugs201122217618410.1097/CAD.0b013e328341a17b21218605
    [Google Scholar]
  27. MauryaB.K. TrigunS.K. Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin‐B1 Induced Hepatocellular Carcinoma in Rats.Oxid. Med. Cell. Longev.201620161197279310.1155/2016/197279326682000
    [Google Scholar]
  28. SunQ. ZhangW. ZhongW. SunX. ZhouZ. Dietary Fisetin Supplementation Protects Against Alcohol‐Induced Liver Injury in Mice.Alcohol. Clin. Exp. Res.201640102076208410.1111/acer.1317227575873
    [Google Scholar]
  29. HusseinA. S.; A Ragab, O.; A El Senosi, Y.; A Abdel-Muttalib, S., Biochemical effect of fisetinon experimentally induced liver damage in rats.Benha Vet. Med. J.20183439810710.21608/bvmj.2018.44202
    [Google Scholar]
  30. MauryaB.K. TrigunS.K. Fisetin Attenuates AKT Associated Growth Promoting Events in AflatoxinB1 Induced Hepatocellular Carcinoma.Anticancer. Agents Med. Chem.201918131885189110.2174/187152061866617122922333529298655
    [Google Scholar]
  31. ShiY.S. LiC.B. LiX.Y. WuJ. LiY. FuX. ZhangY. HuW.Z. Fisetin Attenuates Metabolic Dysfunction in Mice Challenged with a High-Fructose Diet.J. Agric. Food Chem.201866318291829810.1021/acs.jafc.8b0214030040414
    [Google Scholar]
  32. ZhaoL. ZhangJ. PanL. ChenL. WangY. LiuX. YouL. JiaY. HuC. Protective effect of 7,3′,4′-flavon-3-ol (fisetin) on acetaminophen-induced hepatotoxicity in vitro and in vivo.Phytomedicine20195815286510.1016/j.phymed.2019.15286530831465
    [Google Scholar]
  33. ChoiM.S. ChoiJ.Y. KwonE.Y. Fisetin Alleviates Hepatic and Adipocyte Fibrosis and Insulin Resistance in Diet-Induced Obese Mice.J. Med. Food202023101019103210.1089/jmf.2019.461932856978
    [Google Scholar]
  34. ZhangH. ZhangH. WuX. GuoY. ChengW. QianF. Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling.Acta Pharmacol. Sin.202041101348135610.1038/s41401‑020‑0462‑y32661350
    [Google Scholar]
  35. ZhangJ. ZhaoL. HuC. WangT. LuJ. WuC. ChenL. JinM. HuH. JiG. CaoQ. JiangY. Fisetin Prevents Acetaminophen-Induced Liver Injury by Promoting Autophagy.Front. Pharmacol.20201116210.3389/fphar.2020.0016232184730
    [Google Scholar]
  36. LiZ. WangY. ZhangY. WangX. GaoB. LiY. LiR. WangJ. Protective Effects of Fisetin on Hepatic Ischemia-reperfusion Injury Through Alleviation of Apoptosis and Oxidative Stress.Arch. Med. Res.202152216317310.1016/j.arcmed.2020.10.00933645502
    [Google Scholar]
  37. PuJ.L. HuangZ.T. LuoY.H. MouT. LiT.T. LiZ.T. WeiX.F. WuZ.J. Fisetin mitigates hepatic ischemia-reperfusion injury by regulating GSK3β/AMPK/NLRP3 inflammasome pathway.Hepatobiliary Pancreat. Dis. Int.202120435236010.1016/j.hbpd.2021.04.01334024736
    [Google Scholar]
  38. YangH. CaoQ. YuanZ. WuX. LiM. Enhanced therapeutic efficacy of a novel self-micellizing nanoformulation-loading fisetin against acetaminophen-induced liver injury.Nanomedicine (Lond.)202116272431244810.2217/nnm‑2021‑023234632809
    [Google Scholar]
  39. El-FadalyA.A. AfifiN.A. El-ErakyW. SalamaA. AbdelhameedM.F. El-RahmanS.S.A. RamadanA. Fisetin alleviates thioacetamide-induced hepatic fibrosis in rats by inhibiting Wnt/β-catenin signaling pathway.Immunopharmacol. Immunotoxicol.202244335536610.1080/08923973.2022.204719835255766
    [Google Scholar]
  40. UmarM. MuzammilS. ZahoorM.A. MustafaS. AshrafA. HayatS. IjazM.U. Fisetin attenuates arsenic-induced hepatic damage by improving biochemical, inflammatory, apoptotic, and histological profile: In vivo and in silico approach.Evid. Based Complement. Alternat. Med.202220221910.1155/2022/100525536310620
    [Google Scholar]
  41. ZhouZ.S. KongC.F. SunJ.R. QuX.K. SunJ.H. SunA.T. Fisetin Ameliorates Alcohol-Induced Liver Injury through Regulating SIRT1 and SphK1 Pathway.Am. J. Chin. Med.20225082171218410.1142/S0192415X2250093836266756
    [Google Scholar]
  42. UganR.A. CadirciE. UnH. CinarI. GurbuzM.A. Fisetin Attenuates Paracetamol-Induced Hepatotoxicity by Regulating CYP2E1 Enzyme.An. Acad. Bras. Cienc.2023952e2020140810.1590/0001‑376520232020140837018834
    [Google Scholar]
  43. PubChem. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004. PubChem Compound Summary for CID 5281614, Fisetin2004Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Fisetin (Accessed on: Dec 13, 2023).
  44. PubChem. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004. PubChem Compound Summary for CID 5281614, Fisetin.2004Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Fisetin (Accessed on: Apr 24, 2024).
  45. AdeliO.A. Heidari-SoureshjaniS. RostamianS. Azadegan-DehkordiZ. KhaghaniA. Effects and Mechanisms of Fisetin against Ischemia-reperfusion Injuries: A Systematic Review.Curr. Pharm. Biotechnol.202425162138215310.2174/011389201028182124010210541538310454
    [Google Scholar]
  46. ElsallabiO. PatrunoA. PesceM. CataldiA. CarradoriS. GalloriniM. Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection.Molecules202227373810.3390/molecules2703073835164003
    [Google Scholar]
  47. SunY. QinH. ZhangH. FengX. YangL. HouD.X. ChenJ. Fisetin inhibits inflammation and induces autophagy by mediating PI3K/AKT/mTOR signaling in LPS-induced RAW264.7 cells.Food Nutr. Res.2021656510.29219/fnr.v65.635533841067
    [Google Scholar]
  48. Abd El HalimH.I. El ShaerD.F. The possible ameliorating role of fisetin on hepatic changes induced by fluoxetine in adult male albino rats: Histological, immunohistochemical, and biochemical study.J. Microsc. Ultrastruct.202311316117110.4103/jmau.jmau_84_2238025186
    [Google Scholar]
  49. LiS. TanH.Y. WangN. ZhangZ.J. LaoL. WongC.W. FengY. The Role of Oxidative Stress and Antioxidants in Liver Diseases.Int. J. Mol. Sci.20151611260872612410.3390/ijms16112594226540040
    [Google Scholar]
  50. BayırH. AnthonymuthuT.S. TyurinaY.Y. PatelS.J. AmoscatoA.A. LamadeA.M. YangQ. VladimirovG.K. PhilpottC.C. KaganV.E. Achieving Life through Death: Redox Biology of Lipid Peroxidation in Ferroptosis.Cell Chem. Biol.202027438740810.1016/j.chembiol.2020.03.01432275865
    [Google Scholar]
  51. AllamehA. Niayesh-MehrR. AliarabA. SebastianiG. PantopoulosK. Oxidative Stress in Liver Pathophysiology and Disease.Antioxidants2023129165310.3390/antiox1209165337759956
    [Google Scholar]
  52. GalarisD. BarboutiA. PantopoulosK. Iron homeostasis and oxidative stress: An intimate relationship.Biochim. Biophys. Acta Mol. Cell Res.201918661211853510.1016/j.bbamcr.2019.11853531446062
    [Google Scholar]
  53. UrtasunR. de la RosaL.C. NietoN. Oxidative and nitrosative stress and fibrogenic response.Clin. Liver Dis.2008124769790, viii10.1016/j.cld.2008.07.00518984466
    [Google Scholar]
  54. LiangS. KisselevaT. BrennerD.A. The Role of NADPH Oxidases (NOXs) in Liver Fibrosis and the Activation of Myofibroblasts.Front. Physiol.201671710.3389/fphys.2016.0001726869935
    [Google Scholar]
  55. ZhouC. HuangY. NieS. ZhouS. GaoX. ChenG. Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent.Eur. J. Med. Res.202328129710.1186/s40001‑023‑01271‑837626424
    [Google Scholar]
  56. BhattiJ.S. BhattiG.K. ReddyP.H. Mitochondrial dysfunction and oxidative stress in metabolic disorders — A step towards mitochondria based therapeutic strategies.Biochim. Biophys. Acta Mol. Basis Dis.2017186351066107710.1016/j.bbadis.2016.11.01027836629
    [Google Scholar]
  57. GaoL. LaudeK. CaiH. Mitochondrial pathophysiology, reactive oxygen species, and cardiovascular diseases.Vet. Clin. North Am. Small Anim. Pract.2008381137155, vi10.1016/j.cvsm.2007.10.00418249246
    [Google Scholar]
  58. BehlT. MakkarR. AnwerM.K. HassaniR. KhuwajaG. KhalidA. MohanS. AlhazmiH.A. SachdevaM. RachamallaM. Mitochondrial Dysfunction: A Cellular and Molecular Hub in Pathology of Metabolic Diseases and Infection.J. Clin. Med.2023128288210.3390/jcm1208288237109219
    [Google Scholar]
  59. NapolitanoG. FascioloG. VendittiP. Mitochondrial Management of Reactive Oxygen Species.Antioxidants20211011182410.3390/antiox1011182434829696
    [Google Scholar]
  60. MittalM. SiddiquiM.R. TranK. ReddyS.P. MalikA.B. Reactive oxygen species in inflammation and tissue injury.Antioxid. Redox Signal.20142071126116710.1089/ars.2012.514923991888
    [Google Scholar]
  61. MazzoliA. CrescenzoR. CiglianoL. SpagnuoloM.S. CancelliereR. GattoC. IossaS. Early Hepatic Oxidative Stress and Mitochondrial Changes Following Western Diet in Middle Aged Rats.Nutrients20191111267010.3390/nu1111267031694213
    [Google Scholar]
  62. GarelnabiM. LitvinovD. MahiniH. Antioxidant and anti-inflammatory role of paraoxonase 1: Implication in arteriosclerosis diseases.N. Am. J. Med. Sci.201241152353210.4103/1947‑2714.10331023181222
    [Google Scholar]
  63. TanwarS. RhodesF. SrivastavaA. TremblingP.M. RosenbergW.M. Inflammation and fibrosis in chronic liver diseases including non-alcoholic fatty liver disease and hepatitis C.World J. Gastroenterol.202026210913310.3748/wjg.v26.i2.10931969775
    [Google Scholar]
  64. BukkeV.N. MoolaA. ServiddioG. VendemialeG. BellantiF. Nuclear factor erythroid 2-related factor 2-mediated signaling and metabolic associated fatty liver disease.World J. Gastroenterol.202228486909692110.3748/wjg.v28.i48.690936632321
    [Google Scholar]
  65. NabizadehZ. NasrollahzadehM. ShabaniA.A. MirmohammadkhaniM. NasrabadiD. Evaluation of the anti-inflammatory activity of fisetin-loaded nanoparticles in an in vitro model of osteoarthritis.Sci. Rep.20231311549410.1038/s41598‑023‑42844‑137726323
    [Google Scholar]
  66. HassanS.S. SamantaS. DashR. KarpińskiT.M. HabibiE. SadiqA. AhmadiA. BungauS. The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress.Front. Pharmacol.202213101583510.3389/fphar.2022.101583536299900
    [Google Scholar]
  67. LiuH. LuQ. Fisetin Alleviates Inflammation and Oxidative Stress in Deep Vein Thrombosis via MAPK and NRF2 Signaling Pathway.Int. J. Mol. Sci.2024257372410.3390/ijms2507372438612535
    [Google Scholar]
  68. WangK. Molecular mechanisms of hepatic apoptosis.Cell Death Dis.201451e99610.1038/cddis.2013.49924434519
    [Google Scholar]
  69. KashyapD. GargV.K. TuliH.S. YererM.B. SakK. SharmaA.K. KumarM. AggarwalV. SandhuS.S. Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential.Biomolecules20199517410.3390/biom905017431064104
    [Google Scholar]
  70. PeiK. GuiT. KanD. FengH. JinY. YangY. ZhangQ. DuZ. GaiZ. WuJ. LiY. An Overview of Lipid Metabolism and Nonalcoholic Fatty Liver Disease.BioMed Res. Int.2020202011210.1155/2020/402024932733940
    [Google Scholar]
  71. LiouC.J. WeiC.H. ChenY.L. ChengC.Y. WangC.L. HuangW.C. Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice.Cell. Physiol. Biochem.20184951870188410.1159/00049365030235452
    [Google Scholar]
  72. JeonT.I. ParkJ.W. AhnJ. JungC.H. HaT.Y. Fisetin protects against hepatosteatosis in mice by inhibiting miR-378.Mol. Nutr. Food Res.201357111931193710.1002/mnfr.20130007123818290
    [Google Scholar]
  73. ShinM.J. ChoY. MoonJ. JeonH.J. LeeS.M. ChungJ.H. Hypocholesterolemic effect of daily fisetin supplementation in high fat fed Sprague–Dawley rats.Food Chem. Toxicol.201357849010.1016/j.fct.2013.03.01023524313
    [Google Scholar]
  74. Ramos-TovarE. MurielP. Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver.Antioxidants2020912127910.3390/antiox912127933333846
    [Google Scholar]
  75. LalaV. ZubairM. MinterD.A. Liver Function Tests.StatPearls.Treasure Island, FLStatPearls Publishing2024
    [Google Scholar]
  76. SahlanM. Rizka Alia HapsariN. Diah PratamiK. Cahya KhayraniA. LischerK. AlhazmiA. MohammedsalehZ.M. ShaterA.F. SalehF.M. AlsanieW.F. SayedS. GaberA. Potential hepatoprotective effects of flavonoids contained in propolis from South Sulawesi against chemotherapy agents.Saudi J. Biol. Sci.202128105461546810.1016/j.sjbs.2021.08.02234588856
    [Google Scholar]
  77. ZhaoB. LiuK. LiuX. LiQ. LiZ. XiJ. XieF. LiX. Plant‐derived flavonoids are a potential source of drugs for the treatment of liver fibrosis.Phytother. Res.20243863122314510.1002/ptr.819338613172
    [Google Scholar]
  78. KoyamaY. BrennerD.A. Liver inflammation and fibrosis.J. Clin. Invest.20171271556410.1172/JCI8888128045404
    [Google Scholar]
  79. Al-KhayriJ.M. SahanaG.R. NagellaP. JosephB.V. AlessaF.M. Al-MssallemM.Q. Flavonoids as Potential Anti-Inflammatory Molecules: A Review.Molecules2022279290110.3390/molecules2709290135566252
    [Google Scholar]
  80. KangK.A. PiaoM.J. Madduma HewageS.R.K. RyuY.S. OhM.C. KwonT.K. ChaeS. HyunJ.W. Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway.Tumour Biol.20163779615962410.1007/s13277‑016‑4864‑x26797785
    [Google Scholar]
  81. OrtizC. SchierwagenR. SchaeferL. KleinS. TrepatX. TrebickaJ. Extracellular Matrix Remodeling in Chronic Liver Disease.Current Tissue Microenvironment Reports202123415210.1007/s43152‑021‑00030‑334337431
    [Google Scholar]
  82. YanY. ZengJ. XingL. LiC. Extra- and Intra-Cellular Mechanisms of Hepatic Stellate Cell Activation.Biomedicines202198101410.3390/biomedicines908101434440218
    [Google Scholar]
  83. JuH.Y. KimJ. HanS.J. The flavonoid fisetin ameliorates renal fibrosis by inhibiting SMAD3 phosphorylation, oxidative damage, and inflammation in ureteral obstructed kidney in mice.Kidney Res. Clin. Pract.202342332533910.23876/j.krcp.22.03437098680
    [Google Scholar]
  84. JinT. KimO.Y. ShinM.J. ChoiE.Y. LeeS.S. HanY.S. ChungJ.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.20146243104681047410.1021/jf502849j25286082
    [Google Scholar]
  85. ArriazuE. Ruiz de GalarretaM. CuberoF.J. Varela-ReyM. Pérez de ObanosM.P. LeungT.M. LopategiA. BenedictoA. Abraham-EnachescuI. NietoN. Extracellular matrix and liver disease.Antioxid. Redox Signal.20142171078109710.1089/ars.2013.569724219114
    [Google Scholar]
  86. DuvalF. Moreno-CuevasJ.E. González-GarzaM.T. Rodríguez-MontalvoC. Cruz-VegaD.E. Protective mechanisms of medicinal plants targeting hepatic stellate cell activation and extracellular matrix deposition in liver fibrosis.Chin. Med.2014912710.1186/s13020‑014‑0027‑425606051
    [Google Scholar]
  87. ChangJ. HuangC. LiS. JiangX. ChangH. LiM. Research Progress Regarding the Effect and Mechanism of Dietary Polyphenols in Liver Fibrosis.Molecules202329112710.3390/molecules2901012738202710
    [Google Scholar]
  88. LiangD. LiuL. ZhaoY. LuoZ. HeY. LiY. TangS. TangJ. ChenN. Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer.Front. Pharmacol.202314118671210.3389/fphar.2023.118671237560476
    [Google Scholar]
  89. VaidyaA. KaleV.P. TGF-β signaling and its role in the regulation of hematopoietic stem cells.Syst. Synth. Biol.201591-211010.1007/s11693‑015‑9161‑225972984
    [Google Scholar]
  90. RenL.L. MiaoH. WangY.N. LiuF. LiP. ZhaoY.Y. TGF-β as A Master Regulator of Aging-Associated Tissue Fibrosis.Aging Dis.20231451633165010.14336/AD.2023.022237196129
    [Google Scholar]
  91. Cabral-PachecoG.A. Garza-VelozI. Castruita-De la RosaC. Ramirez-AcuñaJ.M. Perez-RomeroB.A. Guerrero-RodriguezJ.F. Martinez-AvilaN. Martinez-FierroM.L. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.Int. J. Mol. Sci.20202124973910.3390/ijms2124973933419373
    [Google Scholar]
  92. DharD. BaglieriJ. KisselevaT. BrennerD.A. Mechanisms of liver fibrosis and its role in liver cancer.Exp. Biol. Med. (Maywood)202024529610810.1177/153537021989814131924111
    [Google Scholar]
  93. WightT.N. Potter-PerigoS. The extracellular matrix: an active or passive player in fibrosis?Am. J. Physiol. Gastrointest. Liver Physiol.20113016G950G95510.1152/ajpgi.00132.201121512158
    [Google Scholar]
  94. MishraA. PaulS. SwarnakarS. Downregulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice.Biochimie201193585486610.1016/j.biochi.2011.02.00721354255
    [Google Scholar]
  95. KrishnakumarI.M. Jaja-ChimedzaA. JosephA. BalakrishnanA. MaliakelB. SwickA. Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study.J. Nutr. Sci.202211e7410.1017/jns.2022.7236304817
    [Google Scholar]
  96. BothirajaC. YojanaB.D. PawarA.P. ShaikhK.S. ThoratU.H. Fisetin-loaded nanocochleates: formulation, characterisation, in vitro anticancer testing, bioavailability and biodistribution study.Expert Opin. Drug Deliv.2014111172910.1517/17425247.2013.86013124294925
    [Google Scholar]
  97. BarringtonR. WilliamsonG. BennettR.N. DavisB.D. BrodbeltJ.S. KroonP.A. Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model.J. Funct. Foods200911748710.1016/j.jff.2008.09.01120046888
    [Google Scholar]
  98. GolonkoA. OlichwierA.J. SwislockaR. SzczerbinskiL. LewandowskiW. Why Do Dietary Flavonoids Have a Promising Effect as Enhancers of Anthracyclines? Hydroxyl Substituents, Bioavailability and Biological Activity.Int. J. Mol. Sci.202224139110.3390/ijms2401039136613834
    [Google Scholar]
  99. TengH. DengH. HeY. LvQ. ChenL. The role of dietary flavonoids for modulation of ATP binding cassette transporter mediated multidrug resistance.eFood20212523424610.53365/efood.k/144604
    [Google Scholar]
  100. ZhangJ. JiangK. AnK. RenS.H. XieX. JinY. LinJ. Novel water-soluble fisetin/cyclodextrins inclusion complexes: Preparation, characterization, molecular docking and bioavailability.Carbohydr. Res.2015418202810.1016/j.carres.2015.09.01326531135
    [Google Scholar]
  101. KumarR.M. KumarH. BhattT. JainR. PanchalK. ChaurasiyaA. JainV. Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics.Pharmaceuticals (Basel)202316219610.3390/ph1602019637259344
    [Google Scholar]
  102. KadariA. GudemS. KulhariH. BhandiM.M. BorkarR.M. KolapalliV.R.M. SistlaR. Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles.Drug Deliv.201724122423210.1080/10717544.2016.124536628156161
    [Google Scholar]
  103. GuzzoM.R. UemiM. DonateP.M. NikolaouS. MachadoA.E.H. OkanoL.T. Study of the complexation of fisetin with cyclodextrins.J. Phys. Chem. A200611036105451055110.1021/jp061333716956235
    [Google Scholar]
  104. AboushanabA.R. El-MoslemanyR.M. El-KamelA.H. MehannaR.A. BakrB.A. AshourA.A. Targeted Fisetin-Encapsulated β-Cyclodextrin Nanosponges for Breast Cancer.Pharmaceutics2023155148010.3390/pharmaceutics1505148037242722
    [Google Scholar]
  105. PrasathG.S. SubramanianS.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.2011668349249610.1016/j.ejphar.2011.07.02121816145
    [Google Scholar]
  106. TouilY.S. AuzeilN. BoulinguezF. SaighiH. RegazzettiA. SchermanD. ChabotG.G. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite.Biochem. Pharmacol.201182111731173910.1016/j.bcp.2011.07.09721840301
    [Google Scholar]
  107. QaedE. Al-HamyariB. Al-MaamariA. QaidA. AlademyH. AlmoiliqyM. MunyemanaJ.C. Al-NusaifM. AlafifiJ. AlyafeaiE. SafiM. GengZ. TangZ. MaX. Fisetin’s Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies.Global Medical Genetics202310320522010.1055/s‑0043‑177221937565061
    [Google Scholar]
  108. KhanN. AfaqF. SyedD.N. MukhtarH. Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells.Carcinogenesis20082951049105610.1093/carcin/bgn07818359761
    [Google Scholar]
  109. DeodharM. Al RihaniS.B. ArwoodM.J. DarakjianL. DowP. TurgeonJ. MichaudV. Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice.Pharmaceutics202012984610.3390/pharmaceutics1209084632899642
    [Google Scholar]
  110. JungH. LeeS. Inhibition of Human Cytochrome P450 Enzymes by Allergen Removed Rhus verniciflua Stoke Standardized Extract and Constituents.Evid. Based Complement. Alternat. Med.20142014115035110.1155/2014/15035125061471
    [Google Scholar]
  111. HodginK.S. DonovanE.K. Kekes-SzaboS. LinJ.C. FeickJ. MasseyR.L. NessT.J. YoungerJ.W. Placebo-ControlledA. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea).Int. J. Environ. Res. Public Health2021185248310.3390/ijerph1805248333802381
    [Google Scholar]
  112. SealI. SilS. DasA. RoyS. Assessment of toxicity and genotoxic safety profile of novel fisetin ruthenium-p-cymene complex in mice.Toxicol. Res.202339221322910.1007/s43188‑022‑00158‑w37008693
    [Google Scholar]
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  • Article Type:
    Review Article
Keyword(s): ECM; Fisetin; hepatotoxicity; lipid accumulation; liver fibrosis; liver injury
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