Skip to content
2000
Volume 25, Issue 13
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Luteolin is a naturally occurring flavonoid that exhibits significant potential in mitigating organ fibrosis. This review consolidates evidence from studies demonstrating the antifibrotic effects of luteolin in hepatic, renal, cardiac, pulmonary, dermal, subretinal, and pancreatic fibrosis. Mechanistically, luteolin targets key pathways that drive fibrosis, including the TGF-β/Smad, STAT3, NF-κB, and AMPK signaling pathways, while suppressing oxidative stress, inflammation, and fibroblast activation. In hepatic fibrosis, luteolin inhibits hepatic stellate cell activation, reduces collagen synthesis, and counteracts ferroptosis by modulating the SLC7A11 and GPX4 pathways. Renal fibrosis is alleviated through the regulation of the SIRT1/FOXO3 and AMPK/NLRP3/TGF-β pathways, thereby attenuating ECM accumulation and inflammation. Cardiac benefits arise from luteolin’s modulation of NO-cGMP, AKT/GSK-3, and Nrf2/NF-κB axes, improving myocardial function. Pulmonary fibrosis models highlight the ability of luteolin to inhibit TGF-β1-induced Smad3 phosphorylation and inflammatory cytokine release. Additionally, luteolin demonstrates efficacy in skin and subretinal fibrosis by targeting TGF-β/Smad and YAP/TAZ pathways. Toxicology and pharmacokinetic studies indicate favorable safety profiles. Despite promising preclinical outcomes, clinical data remain scarce. The multi-target engagement, low toxicity, and broad bioactivity of luteolin position it as a compelling candidate for antifibrotic therapy. Further clinical research is warranted to translate these findings into therapeutic applications for fibrotic disorders.

Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575408729250811073556
2025-08-21
2025-12-31
Loading full text...

Full text loading...

References

  1. RockeyD.C. BellP.D. HillJ.A. Fibrosis--a common pathway to organ injury and failure.N. Engl. J. Med.2015372121138114910.1056/NEJMra1300575 25785971
    [Google Scholar]
  2. WeiskirchenR. WeiskirchenS. TackeF. Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications.Mol. Aspects Med.20196521510.1016/j.mam.2018.06.003 29958900
    [Google Scholar]
  3. WynnT.A. Cellular and molecular mechanisms of fibrosis.J. Pathol.2008214219921010.1002/path.2277 18161745
    [Google Scholar]
  4. WynnT.A. RamalingamT.R. Mechanisms of fibrosis: Therapeutic translation for fibrotic disease.Nat. Med.20121871028104010.1038/nm.2807 22772564
    [Google Scholar]
  5. HendersonN.C. RiederF. WynnT.A. Fibrosis: From mechanisms to medicines.Nature2020587783555556610.1038/s41586‑020‑2938‑9 33239795
    [Google Scholar]
  6. FranklinT.J. Therapeutic approaches to organ fibrosis.Int. J. Biochem. Cell Biol.1997291798910.1016/S1357‑2725(96)00121‑5 9076943
    [Google Scholar]
  7. ZhuM. SunY. SuY. GuanW. WangY. HanJ. WangS. YangB. WangQ. KuangH. Luteolin: A promising multifunctional natural flavonoid for human diseases.Phytother. Res.20243873417344310.1002/ptr.8217 38666435
    [Google Scholar]
  8. Batudeligen; Han, Z.; Chen, H.; Narisu; Xu, Y.; Anda; Han, G. Luteolin alleviates liver fibrosis in rat hepatic stellate cell HSC-T6: A proteomic analysis.Drug Des. Devel. Ther.2023171819182910.2147/DDDT.S402864 37360572
    [Google Scholar]
  9. ChenC.Y. PengW.H. WuL.C. WuC.C. HsuS.L. Luteolin ameliorates experimental lung fibrosis both in vivo and in vitro: Implications for therapy of lung fibrosis.J. Agric. Food Chem.20105822116531166110.1021/jf1031668 20958047
    [Google Scholar]
  10. WangT. PanD. ZhangY. LiD. ZhangY. XuT. LuoY. MaY. Luteolin antagonizes angiotensin II-dependent proliferation and collagen synthesis of cultured rat cardiac fibroblasts.Curr. Pharm. Biotechnol.201516543043910.2174/1389201015666141110142402 25382303
    [Google Scholar]
  11. HuangR. ZengJ. YuX. ShiY. SongN. ZhangJ. WangP. LuoM. MaY. XiaoC. WangL. DuG. CaiH. YangW. Luteolin alleviates diabetic nephropathy fibrosis involving AMPK/NLRP3/TGF-β pathway.Diabetes Metab. Syndr. Obes.2024172855286710.2147/DMSO.S450094 39100967
    [Google Scholar]
  12. YangX. LiQ. LiuW. ZongC. WeiL. ShiY. HanZ. Mesenchymal stromal cells in hepatic fibrosis/cirrhosis: From pathogenesis to treatment.Cell. Mol. Immunol.202320658359910.1038/s41423‑023‑00983‑5 36823236
    [Google Scholar]
  13. FriedmanS.L. PinzaniM. Hepatic fibrosis 2022: Unmet needs and a blueprint for the future.Hepatology202275247348810.1002/hep.32285 34923653
    [Google Scholar]
  14. HigashiT. FriedmanS.L. HoshidaY. Hepatic stellate cells as key target in liver fibrosis.Adv. Drug Deliv. Rev.2017121274210.1016/j.addr.2017.05.007 28506744
    [Google Scholar]
  15. ZhangM. Serna-SalasS. DambaT. BorghesanM. DemariaM. MoshageH. Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives.Mech. Ageing Dev.202119911157210.1016/j.mad.2021.111572 34536446
    [Google Scholar]
  16. KwonE.Y. ChoiM.S. Luteolin targets the toll-like receptor signaling pathway in prevention of hepatic and adipocyte fibrosis and insulin resistance in diet-induced obese mice.Nutrients20181010141510.3390/nu10101415 30282902
    [Google Scholar]
  17. ZhaoW. LiangC. ChenZ. PangR. ZhaoB. ChenZ. Luteolin inhibits proliferation and collagen synthesis of hepatic stellate cells.Zhonghua Gan Zang Bing Za Zhi2002103204206 12113680
    [Google Scholar]
  18. LiJ. LiX. XuW. WangS. HuZ. ZhangQ. DengX. WangJ. ZhangJ. GuoC. Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT/mTOR/p70S6K and TGFβ/Smad signalling pathways.Liver Int.20153541222123310.1111/liv.12638 25040634
    [Google Scholar]
  19. ChenJ. GeJ. ChenW. ZhaoY. SongT. FuK. LiX. ZhengY. UPLC-Q-TOF-MS based investigation into the bioactive compounds and molecular mechanisms of lamiophlomis herba against hepatic fibrosis.Phytomedicine202312115508510.1016/j.phymed.2023.155085 37757709
    [Google Scholar]
  20. ZhaoJ. QiY.F. YuY.R. STAT3: A key regulator in liver fibrosis.Ann. Hepatol.20212110022410.1016/j.aohep.2020.06.010 32702499
    [Google Scholar]
  21. CumminsC.B. WangX. Nunez LopezO. GrahamG. TieH.Y. ZhouJ. RadhakrishnanR.S. Luteolin-mediated inhibition of hepatic stellate cell activation via suppression of the STAT3 pathway.Int. J. Mol. Sci.2018196156710.3390/ijms19061567 29795016
    [Google Scholar]
  22. XuF. LiuC. ZhouD. ZhangL. TGF-β/SMAD Pathway and its regulation in hepatic fibrosis.J. Histochem. Cytochem.201664315716710.1369/0022155415627681 26747705
    [Google Scholar]
  23. SiapoushS. RezaeiR. AlavifardH. HatamiB. ZaliM.R. VosoughM. LorzadehS. ŁosM.J. BaghaeiK. GhavamiS. Therapeutic implications of targeting autophagy and TGF-β crosstalk for the treatment of liver fibrosis.Life Sci.202332912189410.1016/j.lfs.2023.121894 37380126
    [Google Scholar]
  24. DomitrovićR. JakovacH. TomacJ. ŠainI. Liver fibrosis in mice induced by carbon tetrachloride and its reversion by luteolin.Toxicol. Appl. Pharmacol.2009241331132110.1016/j.taap.2009.09.001 19747501
    [Google Scholar]
  25. PanQ. LuoY. XiaQ. HeK. Ferroptosis and liver fibrosis.Int. J. Med. Sci.202118153361336610.7150/ijms.62903 34522161
    [Google Scholar]
  26. ChenJ. LiX. GeC. MinJ. WangF. The multifaceted role of ferroptosis in liver disease.Cell Death Differ.202229346748010.1038/s41418‑022‑00941‑0 35075250
    [Google Scholar]
  27. HanZ. Batudeligen; Chen, H; Narisu; Anda; Xu, Y; Xue, L Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11.BMC Complement. Med. Ther.202424119310.1186/s12906‑024‑04486‑2 38755566 PMC11100030
    [Google Scholar]
  28. CzajaA.J. Hepatic inflammation and progressive liver fibrosis in chronic liver disease.World J. Gastroenterol.201420102515253210.3748/wjg.v20.i10.2515 24627588
    [Google Scholar]
  29. KoyamaY. BrennerD.A. Liver inflammation and fibrosis.J. Clin. Invest.20171271556410.1172/JCI88881 28045404
    [Google Scholar]
  30. HammerichL. TackeF. Hepatic inflammatory responses in liver fibrosis.Nat. Rev. Gastroenterol. Hepatol.2023201063364610.1038/s41575‑023‑00807‑x 37400694
    [Google Scholar]
  31. GaoY. ShiW. YaoH. AiY. LiR. WangZ. LiuT. DaiW. XiaoX. ZhaoJ. NiuM. BaiZ. An integrative pharmacology based analysis of refined liuweiwuling against liver injury: A novel component combination and hepaprotective mechanism.Front. Pharmacol.20211274701010.3389/fphar.2021.747010 34630116
    [Google Scholar]
  32. AshourA.A. El-KamelA.H. MehannaR.A. MouradG. HeikalL.A. Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: A promising therapy for liver fibrosis.Drug Deliv.20222913270328010.1080/10717544.2022.2142700 36330597
    [Google Scholar]
  33. SchwabeR.F. TabasI. PajvaniU.B. Mechanisms of fibrosis development in nonalcoholic steatohepatitis.Gastroenterology202015871913192810.1053/j.gastro.2019.11.311 32044315
    [Google Scholar]
  34. SchuppanD. SurabattulaR. WangX.Y. Determinants of fibrosis progression and regression in NASH.J. Hepatol.201868223825010.1016/j.jhep.2017.11.012 29154966
    [Google Scholar]
  35. Naiki-ItoA. The roles of gap junctional intercellular communication in non-alcoholic steatohepatitis (NASH) and liver fibrosis.Nihon Yakurigaku Zasshi2021156315215610.1254/fpj.20100 33952843
    [Google Scholar]
  36. SagawaH. Naiki-ItoA. KatoH. NaikiT. YamashitaY. SuzukiS. SatoS. ShiomiK. KatoA. KunoT. MatsuoY. KimuraM. TakeyamaH. TakahashiS. Connexin 32 and luteolin play protective roles in non-alcoholic steatohepatitis development and its related hepatocarcinogenesis in rats.Carcinogenesis20153612bgv14310.1093/carcin/bgv143 26494227
    [Google Scholar]
  37. LiuB. NguyenP.L. YuH. LiX. WangH. NguyenT.G.B. SahooP.K. SurM. ReddyJ. SillmanS. KachmanS.D. AltartouriB. LuG. NatarajanS.K. PattabiramanM. YuJ. Honey vesicle-like nanoparticles protect aged liver from non-alcoholic steatohepatitis.Acta Pharm. Sin. B20241483661367910.1016/j.apsb.2024.05.002 39220874
    [Google Scholar]
  38. Rayego-MateosS. ValdivielsoJ.M. New therapeutic targets in chronic kidney disease progression and renal fibrosis.Expert Opin. Ther. Targets202024765567010.1080/14728222.2020.1762173 32338087
    [Google Scholar]
  39. NastaseM.V. Zeng-BrouwersJ. WygreckaM. SchaeferL. Targeting renal fibrosis: Mechanisms and drug delivery systems.Adv. Drug Deliv. Rev.201812929530710.1016/j.addr.2017.12.019 29288033
    [Google Scholar]
  40. HumphreysB.D. Mechanisms of renal fibrosis.Annu. Rev. Physiol.20188030932610.1146/annurev‑physiol‑022516‑034227 29068765
    [Google Scholar]
  41. GuY.Y. LiuX.S. HuangX.R. YuX.Q. LanH.Y. TGF-β in renal fibrosis: Triumphs and challenges.Future Med. Chem.202012985386610.4155/fmc‑2020‑0005 32233802
    [Google Scholar]
  42. MengX. Nikolic-PatersonD.J. LanH.Y. TGF-β: The master regulator of fibrosis.Nat. Rev. Nephrol.201612632533810.1038/nrneph.2016.48 27108839
    [Google Scholar]
  43. RahmanM.D.H. BiswasP. DeyD. HannanM.A. SahabuddinM. ArafY. KwonY. EmranT.B. AliM.S. UddinM.J. An in-silico identification of potential flavonoids against kidney fibrosis targeting TGFβR-1.Life20221211176410.3390/life12111764 36362919
    [Google Scholar]
  44. HoffmannN. PetersJ. Functions of the (pro)renin receptor (Atp6ap2) at molecular and system levels: Pathological implications in hypertension, renal and brain development, inflammation, and fibrosis.Pharmacol. Res.202117310592210.1016/j.phrs.2021.105922 34607004
    [Google Scholar]
  45. LvL.L. LiuB.C. Role of non-classical renin-angiotensin system axis in renal fibrosis.Front. Physiol.2015611710.3389/fphys.2015.00117 25954204
    [Google Scholar]
  46. SongN. TuH. LiY. XiongW. ZhangL. LiuH. DingW. LongM. RenD. ZhongJ. Inhibitory potential of shen-shuai-ling formulation on renal interstitial fibrosis via upregulation of PLZF. Evid Based Complement Altern.Med20222022596780410.1155/2022/5967804 35399631
    [Google Scholar]
  47. BlackL.M. LeverJ.M. AgarwalA. Renal inflammation and fibrosis: A double-edged sword.J. Histochem. Cytochem.201967966368110.1369/0022155419852932 31116067
    [Google Scholar]
  48. ZhouW. ShaY. ZengJ. ZhangX. ZhangA. GeX. Computational systems pharmacology, molecular docking and experiments reveal the protective mechanism of li-da-qian mixture in the treatment of glomerulonephritis.J. Inflamm. Res.2021146939695810.2147/JIR.S338055 34949932
    [Google Scholar]
  49. TanakaT. A mechanistic link between renal ischemia and fibrosis.Med. Mol. Morphol.20175011810.1007/s00795‑016‑0146‑3 27438710
    [Google Scholar]
  50. LiF. WeiR. HuangM. ChenJ. LiP. MaY. ChenX. Luteolin can ameliorate renal interstitial fibrosis-induced renal anaemia through the SIRT1/FOXO3 pathway.Food Funct.20221322118961191410.1039/D2FO02477B 36321482
    [Google Scholar]
  51. CalleP. HotterG. Macrophage phenotype and fibrosis in diabetic nephropathy.Int. J. Mol. Sci.2020218280610.3390/ijms21082806 32316547
    [Google Scholar]
  52. MohandesS. DokeT. HuH. MukhiD. DhillonP. SusztakK. Molecular pathways that drive diabetic kidney disease.J. Clin. Invest.20231334e16565410.1172/JCI165654 36787250
    [Google Scholar]
  53. ZhangM. HeL. LiuJ. ZhouL. Luteolin attenuates diabetic nephropathy through suppressing inflammatory response and oxidative stress by inhibiting STAT3 pathway.Exp. Clin. Endocrinol. Diabetes20211291072973910.1055/a‑0998‑7985 31896157
    [Google Scholar]
  54. XiongC. WuQ. FangM. LiH. ChenB. ChiT. Protective effects of luteolin on nephrotoxicity induced by long-term hyperglycaemia in rats.J. Int. Med. Res.2020484030006052090364210.1177/0300060520903642 32242458
    [Google Scholar]
  55. DingJ. WangY. WangZ. HuS. LiZ. LeC. HuangJ. XuX. HuangJ. QiuP. Luteolin ameliorates methamphetamine-induced podocyte pathology by inhibiting tau phosphorylation in mice.Evid. Based Complement. Alternat. Med.20222022590992610.1155/2022/5909926 35368760
    [Google Scholar]
  56. YeZ. YangS. ChenL. YuW. XiaY. LiB. ZhouX. ChengF. Luteolin alleviated calcium oxalate crystal induced kidney injury by inhibiting Nr4a1-mediated ferroptosis.Phytomedicine202513615630210.1016/j.phymed.2024.156302 39662099
    [Google Scholar]
  57. FrangogiannisN.G. Cardiac fibrosis.Cardiovasc. Res.202111761450148810.1093/cvr/cvaa324 33135058
    [Google Scholar]
  58. KongP. ChristiaP. FrangogiannisN.G. The pathogenesis of cardiac fibrosis.Cell. Mol. Life Sci.201471454957410.1007/s00018‑013‑1349‑6 23649149
    [Google Scholar]
  59. MaruyamaK. Imanaka-YoshidaK. The pathogenesis of cardiac fibrosis: A review of recent progress.Int. J. Mol. Sci.2022235261710.3390/ijms23052617 35269759
    [Google Scholar]
  60. PurnomoY. PiccartY. CoenenT. PrihadiJ. LijnenP. Oxidative stress and transforming growth factor-β1-induced cardiac fibrosis.Cardiovasc. Hematol. Disord. Drug Targets201313216517210.2174/1871529X11313020010 23988004
    [Google Scholar]
  61. NakayamaA. MoritaH. NakaoT. YamaguchiT. SumidaT. IkedaY. KumagaiH. MotozawaY. TakahashiT. ImaizumiA. HashimotoT. NagaiR. KomuroI. A food-derived flavonoid luteolin protects against angiotens in ii-induced cardiac remodeling.PLoS One2015109e013710610.1371/journal.pone.0137106 26327560
    [Google Scholar]
  62. GonzálezA. SchelbertE.B. DíezJ. ButlerJ. Myocardial interstitial fibrosis in heart failure.J. Am. Coll. Cardiol.201871151696170610.1016/j.jacc.2018.02.021 29650126
    [Google Scholar]
  63. RavassaS. LópezB. TreibelT.A. San JoséG. Losada-FuentenebroB. TapiaL. Bayés-GenísA. DíezJ. GonzálezA. Cardiac fibrosis in heart failure: Focus on non-invasive diagnosis and emerging therapeutic strategies.Mol. Aspects Med.20239310119410.1016/j.mam.2023.101194 37384998
    [Google Scholar]
  64. HuW. XuT. WuP. PanD. ChenJ. ChenJ. ZhangB. ZhuH. LiD. Luteolin improves cardiac dysfunction in heart failure rats by regulating sarcoplasmic reticulum Ca2+-ATPase 2a.Sci. Rep.201774101710.1038/srep41017 28112209
    [Google Scholar]
  65. WangZ. ShiW. WuT. PengT. WangX. LiuS. YangZ. WangJ. LiP.L. TianR. HongY. YangH. BaiL. HuY. ChengX. LiH. ZhangX.J. SheZ.G. A high-throughput drug screening identifies luteolin as a therapeutic candidate for pathological cardiac hypertrophy and heart failure.Front. Cardiovasc. Med.202310113063510.3389/fcvm.2023.1130635 36998980
    [Google Scholar]
  66. RidwanM. DimiatiH. SyukriM. LesmanaR. Potential molecular mechanism underlying cardiac fibrosis in diabetes mellitus: A narrative review.Egypt. Heart J.20237514610.1186/s43044‑023‑00376‑z 37306727
    [Google Scholar]
  67. RitchieR.H. AbelE.D. Basic mechanisms of diabetic heart disease.Circ. Res.2020126111501152510.1161/CIRCRESAHA.120.315913 32437308
    [Google Scholar]
  68. RussoI. FrangogiannisN.G. Diabetes-associated cardiac fibrosis: Cellular effectors, molecular mechanisms and therapeutic opportunities.J. Mol. Cell. Cardiol.201690849310.1016/j.yjmcc.2015.12.011 26705059
    [Google Scholar]
  69. LiX. RekepM. TianJ. WuQ. ChenM. YangS. ZhangL. ZhangG. QinY. YuX. XueQ. LiuY. Luteolin attenuates diabetic myocardial hypertrophy by inhibiting proteasome activity.Pharmacology20231081476010.1159/000527201 36423586
    [Google Scholar]
  70. XiaoC. ChenM.Y. HanY.P. LiuL.J. YanJ.L. QianL.B. The protection of luteolin against diabetic cardiomyopathy in rats is related to reversing JNK-suppressed autophagy.Food Funct.20231462740274910.1039/D2FO03871D 36852907
    [Google Scholar]
  71. LiL. LuoW. QianY. ZhuW. QianJ. LiJ. JinY. XuX. LiangG. Luteolin protects against diabetic cardiomyopathy by inhibiting NF-κB-mediated inflammation and activating the Nrf2-mediated antioxidant responses.Phytomedicine20195915277410.1016/j.phymed.2018.11.034
    [Google Scholar]
  72. Abu-ElsaadN. El-KarefA. The falconoid luteolin mitigates the myocardial inflammatory response induced by high-carbohydrate/high-fat diet in wistar rats.Inflammation201841122123110.1007/s10753‑017‑0680‑8 29047036
    [Google Scholar]
  73. NobleP.W. BarkauskasC.E. JiangD. Pulmonary fibrosis: Patterns and perpetrators.J. Clin. Invest.201212282756276210.1172/JCI60323 22850886
    [Google Scholar]
  74. KoudstaalT. Funke-ChambourM. KreuterM. MolyneauxP.L. WijsenbeekM.S. Pulmonary fibrosis: From pathogenesis to clinical decision-making.Trends Mol. Med.202329121076108710.1016/j.molmed.2023.08.010 37716906
    [Google Scholar]
  75. ThannickalV.J. ToewsG.B. WhiteE.S. LynchJ.P. MartinezF.J. Mechanisms of pulmonary fibrosis.Annu. Rev. Med.200455139541710.1146/annurev.med.55.091902.103810 14746528
    [Google Scholar]
  76. YanL. JiangM.Y. FanX.S. Research into the anti-pulmonary fibrosis mechanism of Renshen Pingfei formula based on network pharmacology, metabolomics, and verification of AMPK/PPAR-γ pathway of active ingredients.J. Ethnopharmacol.202331711677310.1016/j.jep.2023.116773 37308028
    [Google Scholar]
  77. RenX. YangT. ZhangK. LiuY. WangC. WuL. ZhangJ. Cyclodextrin MOFs modified dry powder inhalers quadruple bioavailability of luteolin to ameliorate fibrosing interstitial lung disease.Int. J. Pharm.202364512340510.1016/j.ijpharm.2023.123405 37703957
    [Google Scholar]
  78. RicheldiL. CollardH.R. JonesM.G. Idiopathic pulmonary fibrosis.Lancet2017389100821941195210.1016/S0140‑6736(17)30866‑8 28365056
    [Google Scholar]
  79. MossB.J. RyterS.W. RosasI.O. Pathogenic mechanisms underlying idiopathic pulmonary fibrosis.Annu. Rev. Pathol.202217151554610.1146/annurev‑pathol‑042320‑030240 34813355
    [Google Scholar]
  80. SpagnoloP. KropskiJ.A. JonesM.G. LeeJ.S. RossiG. KarampitsakosT. MaherT.M. TzouvelekisA. RyersonC.J. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development.Pharmacol. Ther.202122210779810.1016/j.pharmthera.2020.107798 33359599
    [Google Scholar]
  81. PanB. WuF. LuS. LuW. CaoJ. ChengF. OuM. ChenY. ZhangF. WuG. MeiL. Luteolin‐loaded hyaluronidase nanoparticles with deep tissue penetration capability for idiopathic pulmonary fibrosis treatment.Small Methods2024240098010.1002/smtd.202400980 39370583
    [Google Scholar]
  82. FashnerJ. Gastroesophageal reflux disease: A general overview.HCA Healthc. J. Med.20201410.36518/2689‑0216.1042
    [Google Scholar]
  83. AllaixM.E. RebecchiF. MorinoM. SchlottmannF. PattiM.G. Gastroesophageal reflux and idiopathic pulmonary fibrosis.World J. Surg.20174171691169710.1007/s00268‑017‑3956‑0 28258461
    [Google Scholar]
  84. Bédard MéthotD. LeblancÉ. LacasseY. Meta-analysis of gastroesophageal reflux disease and idiopathic pulmonary fibrosis.Chest20191551334310.1016/j.chest.2018.07.038 30120950
    [Google Scholar]
  85. ZhuJ. ZhouD. YuM. LiY. Appraising the causal role of smoking in idiopathic pulmonary fibrosis: A Mendelian randomization study.Thorax202479217918110.1136/thorax‑2023‑220012 37217291
    [Google Scholar]
  86. BellouV. BelbasisL. EvangelouE. Tobacco smoking and risk for pulmonary fibrosis.Chest2021160398399310.1016/j.chest.2021.04.035 33905677
    [Google Scholar]
  87. SudhakaranG. SreekuttyA.R. SubramaniyanS. MadeshS. PriyaP.S. PachaiappanR. HatamlehA.A. Al-DosaryM.A. ArockiarajJ. Skeletal and neurological risks demonstrated in zebrafish due to second-hand cigarette smoke and the neutralization of luteolin.Tissue Cell20238510225910.1016/j.tice.2023.102259 37922675
    [Google Scholar]
  88. TalbottH.E. MascharakS. GriffinM. WanD.C. LongakerM.T. Wound healing, fibroblast heterogeneity, and fibrosis.Cell Stem Cell20222981161118010.1016/j.stem.2022.07.006 35931028
    [Google Scholar]
  89. GriffinM.F. desJardins-ParkH.E. MascharakS. BorrelliM.R. LongakerM.T. Understanding the impact of fibroblast heterogeneity on skin fibrosis.Dis. Model. Mech.2020136dmm04416410.1242/dmm.044164 32541065
    [Google Scholar]
  90. ZhangY. WangJ. ZhouS. XieZ. WangC. GaoY. ZhouJ. ZhangX. LiQ. Flavones hydroxylated at 5, 7, 3′ and 4′ ameliorate skin fibrosis via inhibiting activin receptor-like kinase 5 kinase activity.Cell Death Dis.201910212410.1038/s41419‑019‑1333‑7 30741930
    [Google Scholar]
  91. EksteinS.F. WylesS.P. MoranS.L. MevesA. Keloids: A review of therapeutic management.Int. J. Dermatol.202160666167110.1111/ijd.15159 32905614
    [Google Scholar]
  92. AndrewsJ.P. MarttalaJ. MacarakE. RosenbloomJ. UittoJ. Keloids: The paradigm of skin fibrosis — pathomechanisms and treatment.Matrix Biol.201651374610.1016/j.matbio.2016.01.013 26844756
    [Google Scholar]
  93. ZhangX. LiuW. WeiS. Luteolin affects keloid fibroblast proliferation and apoptosis by regulating FRAT1 gene expression.Cell. Mol. Biol.202066318519010.14715//cmb/2020.66.3.30 32538769
    [Google Scholar]
  94. LiuD. ZhangC. ZhangJ. XuG.T. ZhangJ. Molecular pathogenesis of subretinal fibrosis in neovascular AMD focusing on epithelial-mesenchymal transformation of retinal pigment epithelium.Neurobiol. Dis.202318510625010.1016/j.nbd.2023.106250 37536385
    [Google Scholar]
  95. ZhangC. ZhangY. HuX. ZhaoZ. ChenZ. WangX. ZhangZ. JinH. ZhangJ. Luteolin inhibits subretinal fibrosis and epithelial-mesenchymal transition in laser-induced mouse model via suppression of Smad2/3 and YAP signaling.Phytomedicine202311615486510.1016/j.phymed.2023.154865 37201365
    [Google Scholar]
  96. MurakamiY. ImaizumiT. HashizumeK. TezukaY. OkuY. NishiyaN. SanbeA. KurosakaD. Inhibition of connective tissue growth factor expression in adult retinal pigment epithelial-19 cells by blocking yes-associated protein/transcriptional coactivator with pdz-binding motif activity.J. Ocul. Pharmacol. Ther.202440424625210.1089/jop.2023.0141 38517736
    [Google Scholar]
  97. BeyerG. HabtezionA. WernerJ. LerchM.M. MayerleJ. Chronic pancreatitis.Lancet20203961024949951210.1016/S0140‑6736(20)31318‑0 32798493
    [Google Scholar]
  98. SinghV.K. YadavD. GargP.K. Diagnosis and management of chronic pancreatitis.JAMA2019322242422243410.1001/jama.2019.19411 31860051
    [Google Scholar]
  99. YuQ. ZhuJ. ShengX. XuL. HuK. ChenG. WuW. CaiW. ChenW. YinG. Luteolin ameliorates experimental chronic pancreatitis induced by trinitrobenzenesulfonic acid in rats.Pancreas201847556857610.1097/MPA.0000000000001035 29595544
    [Google Scholar]
  100. ShiM. ChenZ. GongH. PengZ. SunQ. LuoK. WuB. WenC. LinW. Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches.Phytother. Res.202438288091110.1002/ptr.8066 38088265
    [Google Scholar]
  101. YaoC. DaiS. WangC. FuK. WuR. ZhaoX. YaoY. LiY. Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies.Biomed. Pharmacother.202316711546410.1016/j.biopha.2023.115464 37713990
    [Google Scholar]
  102. ChenT. LiL.P. LuX.Y. JiangH.D. ZengS. Absorption and excretion of luteolin and apigenin in rats after oral administration of Chrysanthemum morifolium extract.J. Agric. Food Chem.200755227327710.1021/jf062088r 17227053
    [Google Scholar]
  103. MiyashitaA. ItoJ. ParidaI.S. SyojiN. FujiiT. TakahashiH. NakagawaK. Improving water dispersibility and bioavailability of luteolin using microemulsion system.Sci. Rep.20221211194910.1038/s41598‑022‑16220‑4 35831358
    [Google Scholar]
  104. DongX. LanW. YinX. YangC. WangW. NiJ. Simultaneous determination and pharmacokinetic study of quercetin, luteolin, and apigenin in rat plasma after oral administration of matricaria chamomilla l. extract by HPLC-UV.Evid. Based Complement. Alternat. Med.20172017837058410.1155/2017/8370584 28373891
    [Google Scholar]
  105. ShiF. PanH. LuY. DingL. An HPLC–MS/MS method for the simultaneous determination of luteolin and its major metabolites in rat plasma and its application to a pharmacokinetic study.J. Sep. Sci.201841203830383910.1002/jssc.201800585 30101558
    [Google Scholar]
  106. AliF. SiddiqueY.H. Bioavailability and pharmaco-therapeutic potential of luteolin in overcoming alzheimer’s disease.CNS Neurol. Disord. Drug Targets201918535236510.2174/1871527318666190319141835 30892166
    [Google Scholar]
  107. WittemerS.M. PlochM. WindeckT. MüllerS.C. DrewelowB. DerendorfH. VeitM. Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans.Phytomedicine2005121-2283810.1016/j.phymed.2003.11.002 15693705
    [Google Scholar]
  108. KureA. NakagawaK. KondoM. KatoS. KimuraF. WatanabeA. ShojiN. HatanakaS. TsushidaT. MiyazawaT. Metabolic fate of luteolin in rats: Its relationship to anti-inflammatory effect.J. Agric. Food Chem.201664214246425410.1021/acs.jafc.6b00964 27170112
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575408729250811073556
Loading
/content/journals/mrmc/10.2174/0113895575408729250811073556
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test