Skip to content
2000
image of An In-depth Analysis of Luteolin Regarding its Preclinical, Clinical and Nanoformulations Perspectives

Abstract

A natural product is a natural compound or substance produced by a living organism- that is, found in nature. The term natural product has also been prolonged for commercial purposes to refers to dietary supplements, cosmetics and food produced from natural sources without added artificial ingredients. Luteolin, a bioflavonoid found abundantly in various fruits, vegetables, and medicinal plants has gained significant attention in recent years due to its potential pharmacological properties. This comprehensive review explores the multifaceted aspects of luteolin, encompassing clinical studies, experimental research, kinetic analyses, nanotechnology-based formulations, and synergistic interactions with conventional drugs. The introduction section describes the various sources and biological functions of luteolin and emphasizes its importance in the realm of medicine. The clinical studies section provides insights into the therapeutic potential of luteolin in various human diseases, highlighting its efficacy, safety profile, and potential mechanisms of action. Experimental studies exploring luteolin's mechanisms of action, cellular interactions, and therapeutic effects in various disease models. It elucidates underlying the biological mechanism of luteolin, shedding light on its antioxidant, anti-inflammatory, anti-cancer, and neuroprotective effects. Furthermore, a detailed pharmacokinetic study examines the absorption, distribution, metabolism, and excretion (ADME) of luteolin, offering valuable information for optimizing its dosing regimens and enhancing therapeutic outcomes. The integration of nanotechnology in luteolin formulations is discussed, focusing on innovative nanoformulations that improve its solubility, stability, and targeted delivery, thus enhancing its bioavailability and efficacy. Additionally, this review delves into the synergistic interactions between luteolin and conventional drugs, emphasizing the potential for combination therapies to enhance treatment outcomes and reduce adverse effects. The synergistic mechanisms, preclinical and clinical evidence, and future prospects of these combinations are explored in detail. Future applications of luteolin appear to be very promising in a variety of fields, including personalized medicine, disease-specific medicines, and preventative healthcare.

Loading

Article metrics loading...

/content/journals/npj/10.2174/0122103155316738240901181513
2025-01-10
2025-04-06
Loading full text...

Full text loading...

References

  1. Harborne J.B. Williams C.A. Advances in flavonoid research since 1992. Phytochemistry 2000 55 6 481 504 10.1016/S0031‑9422(00)00235‑1 11130659
    [Google Scholar]
  2. Birt D.F. Hendrich S. Wang W. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol. Ther. 2001 90 2-3 157 177 10.1016/S0163‑7258(01)00137‑1 11578656
    [Google Scholar]
  3. Mencherini T. Picerno P. Scesa C. Aquino R. Triterpene, antioxidant, and antimicrobial compounds from Melissa officinalis. J. Nat. Prod. 2007 70 12 1889 1894 10.1021/np070351s 18004816
    [Google Scholar]
  4. Ross J.A. Kasum C.M. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu. Rev. Nutr. 2002 22 1 19 34 10.1146/annurev.nutr.22.111401.144957 12055336
    [Google Scholar]
  5. Chan T.S. Galati G. Pannala A.S. Rice-Evans C. O’Brien P.J. Simultaneous detection of the antioxidant and pro-oxidant activity of dietary polyphenolics in a peroxidase system. Free Radic. Res. 2003 37 7 787 794 10.1080/1071576031000094899 12911276
    [Google Scholar]
  6. Hempel J Pforte H Raab B Engst W Böhm H Jacobasch G Flavonols and flavones of parsley cell suspension culture change the antioxidative capacity of plasma in rats. Nahrung 1999 43 3 201 10.1002/(SICI)1521‑3803(19990601)43:3<201::AID‑FOOD201>3.0.CO;2‑1
    [Google Scholar]
  7. Le Marchand L. Cancer preventive effects of flavonoids—a review. Biomed. Pharmacother. 2002 56 6 296 301 10.1016/S0753‑3322(02)00186‑5 12224601
    [Google Scholar]
  8. Li Y.L. Li J. Wang N.L. Yao X.S. Flavonoids and a new polyacetylene from Bidens parviflora Willd. Molecules 2008 13 8 1931 1941 10.3390/molecules13081931 18794794
    [Google Scholar]
  9. Brody J.S. Spira A. State of the art. Chronic obstructive pulmonary disease, inflammation, and lung cancer. Proc. Am. Thorac. Soc. 2006 3 6 535 537 10.1513/pats.200603‑089MS 16921139
    [Google Scholar]
  10. Perwez Hussain S. Harris C.C. Inflammation and cancer: An ancient link with novel potentials. Int. J. Cancer 2007 121 11 2373 2380 10.1002/ijc.23173 17893866
    [Google Scholar]
  11. Karin M. Lawrence T. Nizet V. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell 2006 124 4 823 835 10.1016/j.cell.2006.02.016 16497591
    [Google Scholar]
  12. Xagorari A. Papapetropoulos A. Mauromatis A. Economou M. Fotsis T. Roussos C. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J. Pharmacol. Exp. Ther. 2001 296 1 181 187 11123379
    [Google Scholar]
  13. Qinwufeng G. Jiacheng L. Xiaoling L. Tingru C. Yunyang W. Yanlong Y. Formula suppresses JAK1/STAT3 and MAPK signaling alleviates atopic dermatitis-like skin lesions. J. Ethnopharmacol. 2022 295 115428 10.1016/j.jep.2022.115428 35659915
    [Google Scholar]
  14. Kumazawa Y. Kawaguchi K. Takimoto H. Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor α. Curr. Pharm. Des. 2006 12 32 4271 4279 10.2174/138161206778743565 17100629
    [Google Scholar]
  15. Lien E.J. Ren S. Bui H.H. Wang R. Quantitative structure-activity relationship analysis of phenolic antioxidants. Free Radic. Biol. Med. 1999 26 3-4 285 294 10.1016/S0891‑5849(98)00190‑7 9895218
    [Google Scholar]
  16. Sen N. Das B.B. Ganguly A. Banerjee B. Sen T. Majumder H.K. Leishmania donovani: Intracellular ATP level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells. Exp. Parasitol. 2006 114 3 204 214 10.1016/j.exppara.2006.03.013 16707127
    [Google Scholar]
  17. Wing-Cheung Leung H. Kuo C.L. Yang W.H. Lin C.H. Lee H.Z. Antioxidant enzymes activity involvement in luteolin-induced human lung squamous carcinoma CH27 cell apoptosis. Eur. J. Pharmacol. 2006 534 1-3 12 18 10.1016/j.ejphar.2006.01.021 16469309
    [Google Scholar]
  18. Manju V. Nalini N. Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine. Ital. J. Biochem. 2005 54 3-4 268 275 16688936
    [Google Scholar]
  19. Chung J.H. Photoaging in Asians. Photodermatol. Photoimmunol. Photomed. 2003 19 3 109 121 10.1034/j.1600‑0781.2003.00027.x 12914595
    [Google Scholar]
  20. Hausenloy D.J. Tsang A. Mocanu M.M. Yellon D.M. Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am. J. Physiol. Heart Circ. Physiol. 2005 288 2 H971 H976 10.1152/ajpheart.00374.2004 15358610
    [Google Scholar]
  21. Liao P.H. Hung L.M. Chen Y.H. Kuan Y.H. Zhang F.B.Y. Lin R.H. Shih H.C. Tsai S.K. Huang S.S. Cardioprotective effects of luteolin during ischemia-reperfusion injury in rats. Circ. J. 2011 75 2 443 450 10.1253/circj.CJ‑10‑0381 21178298
    [Google Scholar]
  22. Hanahan D Weinberg RA The hallmarks of cancer. cell 2000 100 1 57 70
    [Google Scholar]
  23. Galati G. Teng S. Moridani M.Y. Chan T.S. O’Brien P.J. Cancer chemoprevention and apoptosis mechanisms induced by dietary polyphenolics. Drug Metabol. Drug Interact. 2000 17 1-4 311 350 10.1515/DMDI.2000.17.1‑4.311 11201302
    [Google Scholar]
  24. Fang J. Zhou Q. Shi X. Jiang B. Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells. Carcinogenesis 2006 28 3 713 723 10.1093/carcin/bgl189 17065200
    [Google Scholar]
  25. Han D.H. Denison M.S. Tachibana H. Yamada K. Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids. Biosci. Biotechnol. Biochem. 2002 66 7 1479 1487 10.1271/bbb.66.1479 12224631
    [Google Scholar]
  26. Knowles L.M. Zigrossi D.A. Tauber R.A. Hightower C. Milner J.A. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr. Cancer 2000 38 1 116 122 10.1207/S15327914NC381_16 11341036
    [Google Scholar]
  27. Massagué J. G1 cell-cycle control and cancer. Nature 2004 432 7015 298 306 10.1038/nature03094 15549091
    [Google Scholar]
  28. Casagrande F. Darbon J.M. Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK111Abbreviations: CDK, cyclin-dependent kinase; CKI, CDK inhibitor; PI 3-kinase, phosphatidylinositol 3-kinase; PKC, protein kinase C; DTT, dithiothreitol; RIPA, radioimmunoprecipitation assay buffer. Biochem. Pharmacol. 2001 61 10 1205 1215 10.1016/S0006‑2952(01)00583‑4 11322924
    [Google Scholar]
  29. Li W.X. Cui C.B. Cai B. Wang H.Y. Yao X.S. Flavonoids from Vitex trifolia L. inhibit cell cycle progression at G 2 /M phase and induce apoptosis in mammalian cancer cells. J. Asian Nat. Prod. Res. 2005 7 4 615 626 10.1080/10286020310001625085 16087636
    [Google Scholar]
  30. Caino M.C. Oliva J.L. Jiang H. Penning T.M. Kazanietz M.G. Benzo[a]pyrene-7,8-dihydrodiol promotes checkpoint activation and G2/M arrest in human bronchoalveolar carcinoma H358 cells. Mol. Pharmacol. 2007 71 3 744 750 10.1124/mol.106.032078 17114299
    [Google Scholar]
  31. Zhang L. Lau Y.K. Xi L. Hong R.L. Kim D.S.H.L. Chen C.F. Hortobagyi G.N. Chang C. Hung M.C. Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties. Oncogene 1998 16 22 2855 2863 10.1038/sj.onc.1201813 9671406
    [Google Scholar]
  32. Lee L.T. Huang Y.T. Hwang J.J. Lee P.P. Ke F.C. Nair M.P. Kanadaswam C. Lee M.T. Blockade of the epidermal growth factor receptor tyrosine kinase activity by quercetin and luteolin leads to growth inhibition and apoptosis of pancreatic tumor cells. Anticancer Res. 2002 22 3 1615 1627 12168845
    [Google Scholar]
  33. Matei D. Emerson R.E. Lai Y-C. Baldridge L.A. Rao J. Yiannoutsos C. Donner D.D. Autocrine activation of PDGFRα promotes the progression of ovarian cancer. Oncogene 2006 25 14 2060 2069 10.1038/sj.onc.1209232 16331269
    [Google Scholar]
  34. Hanahan D Weinberg RA The Hallmark of Cancer. Cell 2000 100 1 57 70
    [Google Scholar]
  35. Wajant H. Pfizenmaier K. Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003 10 1 45 65 10.1038/sj.cdd.4401189 12655295
    [Google Scholar]
  36. Huang Y.T. Hwang J.J. Lee P.P. Ke F.C. Huang J.H. Huang C.J. Kandaswami C. Middleton E. Jr Lee M.T. Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis‐associated properties in A431 cells overexpressing epidermal growth factor receptor. Br. J. Pharmacol. 1999 128 5 999 1010 10.1038/sj.bjp.0702879 10556937
    [Google Scholar]
  37. Lee H.J. Wang C.J. Kuo H.C. Chou F.P. Jean L.F. Tseng T.H. Induction apoptosis of luteolin in human hepatoma HepG2 cells involving mitochondria translocation of Bax/Bak and activation of JNK. Toxicol. Appl. Pharmacol. 2005 203 2 124 131 10.1016/j.taap.2004.08.004 15710173
    [Google Scholar]
  38. Horinaka M. Yoshida T. Shiraishi T. Nakata S. Wakada M. Nakanishi R. Nishino H. Matsui H. Sakai T. Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells. Oncogene 2005 24 48 7180 7189 10.1038/sj.onc.1208874 16007131
    [Google Scholar]
  39. Shi R. Huang Q. Zhu X. Ong Y.B. Zhao B. Lu J. Ong C.N. Shen H.M. Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase–mediated p53 phosphorylation and stabilization. Mol. Cancer Ther. 2007 6 4 1338 1347 10.1158/1535‑7163.MCT‑06‑0638 17431112
    [Google Scholar]
  40. Shi R.X. Ong C.N. Shen H.M. Luteolin sensitizes tumor necrosis factor-α-induced apoptosis in human tumor cells. Oncogene 2004 23 46 7712 7721 10.1038/sj.onc.1208046 15334063
    [Google Scholar]
  41. Cheng A.C. Huang T.C. Lai C.S. Pan M.H. Induction of apoptosis by luteolin through cleavage of Bcl-2 family in human leukemia HL-60 cells. Eur. J. Pharmacol. 2005 509 1 1 10 10.1016/j.ejphar.2004.12.026 15713423
    [Google Scholar]
  42. Yadav H.P. Li Y. The development of treatment for Parkinson’s disease. Adv. Parkin. Diseas. 2015 4 3 59 78 10.4236/apd.2015.43008
    [Google Scholar]
  43. Naz F. Siddique Y.H. Role of genes and treatments for Parkinson’s disease. “Open Biol”. Open Biol J. 2020 8 1
    [Google Scholar]
  44. Zhang Z. Xu P. Yu H. Shi L. Luteolin protects PC-12 cells from H2O2-induced injury by up-regulation of microRNA-21. Biomed. Pharmacother. 2019 112 108698 10.1016/j.biopha.2019.108698 30802826
    [Google Scholar]
  45. Feany M.B. Bender W.W. A Drosophila model of Parkinson’s disease. Nature 2000 404 6776 394 398 10.1038/35006074 10746727
    [Google Scholar]
  46. Siddique Y.H. Jyoti S. Naz F. Protective effect of luteolin on the transgenic Drosophila model of Parkinson’s disease. Braz. J. Pharm. Sci. 2018 54 3 54 10.1590/s2175‑97902018000317760
    [Google Scholar]
  47. Kong X. Huo G. Liu S. Li F. Chen W. Jiang D. Luteolin suppresses inflammation through inhibiting cAMP-phosphodiesterases activity and expression of adhesion molecules in microvascular endothelial cells. Inflammopharmacology 2019 27 4 773 780 10.1007/s10787‑018‑0537‑2 30276558
    [Google Scholar]
  48. Aziz N. Kim M.Y. Cho J.Y. Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. J. Ethnopharmacol. 2018 225 342 358 10.1016/j.jep.2018.05.019 29801717
    [Google Scholar]
  49. Coleta M. Campos M.G. Cotrim M.D. Lima T.C.M. Cunha A.P. Assessment of luteolin (3′,4′,5,7-tetrahydroxyflavone) neuropharmacological activity. Behav. Brain Res. 2008 189 1 75 82 10.1016/j.bbr.2007.12.010 18249450
    [Google Scholar]
  50. Dirscherl K. Karlstetter M. Ebert S. Kraus D. Hlawatsch J. Walczak Y. Moehle C. Fuchshofer R. Langmann T. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype. J. Neuroinflammation 2010 7 1 3 10.1186/1742‑2094‑7‑3 20074346
    [Google Scholar]
  51. Yang J.J. Zhou Q. Yan H.H. Zhang X.C. Chen H.J. Tu H.Y. Wang Z. Xu C.R. Su J. Wang B.C. Jiang B.Y. Bai X.Y. Zhong W.Z. Yang X.N. Wu Y.L. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br. J. Cancer 2017 116 5 568 574 10.1038/bjc.2016.456 28103612
    [Google Scholar]
  52. Paredes-Gonzalez X. Fuentes F. Jeffery S. Saw C.L.L. Shu L. Su Z.Y. Kong A.N.T. Induction of NRF2‐mediated gene expression by dietary phytochemical flavones apigenin and luteolin. Biopharm. Drug Dispos. 2015 36 7 440 451 10.1002/bdd.1956 25904312
    [Google Scholar]
  53. Zhu Z. Yan J. Jiang W. Yao X. Chen J. Chen L. Li C. Hu L. Jiang H. Shen X. Arctigenin effectively ameliorates memory impairment in Alzheimer’s disease model mice targeting both β-amyloid production and clearance. J. Neurosci. 2013 33 32 13138 13149 10.1523/JNEUROSCI.4790‑12.2013 23926267
    [Google Scholar]
  54. Masliah E. Terry R.D. Alford M. DeTeresa R. Hansen L.A. Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer’s disease. Am. J. Pathol. 1991 138 1 235 246 1899001
    [Google Scholar]
  55. Choi S.M. Kim B.C. Cho Y.H. Choi K.H. Chang J. Park M.S. Kim M.K. Cho K.H. Kim J.K. Effects of flavonoid compounds on β-amyloid-peptide-induced neuronal death in cultured mouse cortical neurons. Chonnam Med. J. 2014 50 2 45 51 10.4068/cmj.2014.50.2.45 25229015
    [Google Scholar]
  56. Zheng L. Kågedal K. Dehvari N. Benedikz E. Cowburn R. Marcusson J. Terman A. Oxidative stress induces macroautophagy of amyloid β-protein and ensuing apoptosis. Free Radic. Biol. Med. 2009 46 3 422 429 10.1016/j.freeradbiomed.2008.10.043 19038331
    [Google Scholar]
  57. Butterfield D.A. Perluigi M. Sultana R. Oxidative stress in Alzheimer’s disease brain: New insights from redox proteomics. Eur. J. Pharmacol. 2006 545 1 39 50 10.1016/j.ejphar.2006.06.026 16860790
    [Google Scholar]
  58. Aliev G. Miller J.P. Leifer D.W. Obrenovich M.E. Shenk J.C. Smith M.A. Lamanna J.C. Perry G. Lust D.W. Cohen A.R. Ultrastructural analysis of a murine model of congenital hydrocephalus produced by overexpression of transforming growth factor-beta1 in the central nervous system. J. Submicrosc. Cytol. Pathol. 2006 38 2-3 85 91 17784635
    [Google Scholar]
  59. Jiang D. Rauda I. Han S. Chen S. Zhou F. Aggregation pathways of the amyloid β(1-42) peptide depend on its colloidal stability and ordered β-sheet stacking. Langmuir 2012 28 35 12711 12721 10.1021/la3021436 22870885
    [Google Scholar]
  60. Sawmiller D. Li S. Shahaduzzaman M. Smith A. Obregon D. Giunta B. Borlongan C. Sanberg P. Tan J. Luteolin reduces Alzheimer’s disease pathologies induced by traumatic brain injury. Int. J. Mol. Sci. 2014 15 1 895 904 10.3390/ijms15010895 24413756
    [Google Scholar]
  61. Gilgun-Sherki Y. Rosenbaum Z. Melamed E. Offen D. Antioxidant therapy in acute central nervous system injury: current state. Pharmacol. Rev. 2002 54 2 271 284 10.1124/pr.54.2.271 12037143
    [Google Scholar]
  62. Comino-Sanz I.M. López-Franco M.D. Castro B. Pancorbo-Hidalgo P.L. The role of antioxidants on wound healing: A review of the current evidence. J. Clin. Med. 2021 10 16 3558 10.3390/jcm10163558 34441854
    [Google Scholar]
  63. Chen L.Y. Cheng H.L. Kuan Y.H. Liang T.J. Chao Y.Y. Lin H.C. Therapeutic potential of luteolin on impaired wound healing in streptozotocin-induced rats. Biomedicines 2021 9 7 761 10.3390/biomedicines9070761 34209369
    [Google Scholar]
  64. Azevedo M.F. Camsari Ç. Sá C.M. Lima C.F. Fernandes-Ferreira M. Pereira-Wilson C. Ursolic acid and luteolin‐7‐glucoside improve lipid profiles and increase liver glycogen content through glycogen synthase kinase‐3. Phytother. Res. 2010 24 S2 S220 S224 10.1002/ptr.3118 20127879
    [Google Scholar]
  65. Di S Wang Y Han L Bao Q Gao Z Wang Q Yang Y Zhao L Tong X The intervention effect of traditional Chinese medicine on the intestinal flora and its metabolites in glycolipid metabolic disorders. J. Altern. Complement. Med. 2019 2958920 10.1155/2019/2958920
    [Google Scholar]
  66. Dudek M. Kołodziejski P.A. Pruszyńska-Oszmałek E. Sassek M. Ziarniak K. Nowak K.W. Sliwowska J.H. Effects of high-fat diet-induced obesity and diabetes on Kiss1 and GPR54 expression in the hypothalamic–pituitary–gonadal (HPG) axis and peripheral organs (fat, pancreas and liver) in male rats. Neuropeptides 2016 56 41 49 10.1016/j.npep.2016.01.005 26853724
    [Google Scholar]
  67. Ampofo A.G. Boateng E.B. Beyond 2020: Modelling obesity and diabetes prevalence. Diabetes Res. Clin. Pract. 2020 167 108362 10.1016/j.diabres.2020.108362 32758618
    [Google Scholar]
  68. Tomás-Barberán F.A. Andrés-Lacueva C. Polyphenols and health: current state and progress. J. Agric. Food Chem. 2012 60 36 8773 8775 10.1021/jf300671j 22578138
    [Google Scholar]
  69. Jucá M.M. Cysne Filho F.M.S. de Almeida J.C. Mesquita D.S. Barriga J.R.M. Dias K.C.F. Barbosa T.M. Vasconcelos L.C. Leal L.K.A.M. Ribeiro J.E. Vasconcelos S.M.M. Flavonoids: biological activities and therapeutic potential. Nat. Prod. Res. 2020 34 5 692 705 10.1080/14786419.2018.1493588 30445839
    [Google Scholar]
  70. Song D. Cheng L. Zhang X. Wu Z. Zheng X. The modulatory effect and the mechanism of flavonoids on obesity. J. Food Biochem. 2019 43 8 12954 10.1111/jfbc.12954 31368555
    [Google Scholar]
  71. Hayasaka N. Shimizu N. Komoda T. Mohri S. Tsushida T. Eitsuka T. Miyazawa T. Nakagawa K. Absorption and metabolism of luteolin in rats and humans in relation to in vitro anti-inflammatory effects. J. Agric. Food Chem. 2018 66 43 11320 11329 10.1021/acs.jafc.8b03273 30280574
    [Google Scholar]
  72. Sangeetha R. Luteolin in the management of type 2 diabetes mellitus. Curr. Res. Nutr. Food Sci. 2019 7 2 393 398 10.12944/CRNFSJ.7.2.09
    [Google Scholar]
  73. Yasuda M.T. Fujita K. Hosoya T. Imai S. Shimoi K. Absorption and metabolism of luteolin and its glycosides from the extract of Chrysanthemum morifolium flowers in rats and Caco-2 cells. J. Agric. Food Chem. 2015 63 35 7693 7699 10.1021/acs.jafc.5b00232 25843231
    [Google Scholar]
  74. Shimoi K. Okada H. Furugori M. Goda T. Takase S. Suzuki M. Hara Y. Yamamoto H. Kinae N. Intestinal absorption of luteolin and luteolin 7‐ O ‐β‐glucoside in rats and humans. FEBS Lett. 1998 438 3 220 224 10.1016/S0014‑5793(98)01304‑0 9827549
    [Google Scholar]
  75. Wittemer S.M. Ploch M. Windeck T. Müller S.C. Drewelow B. Derendorf H. Veit M. Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans. Phytomedicine 2005 12 1-2 28 38 10.1016/j.phymed.2003.11.002 15693705
    [Google Scholar]
  76. Lin L.C. Pai Y.F. Tsai T.H. Isolation of luteolin and luteolin-7-O-glucoside from Dendranthema morifolium Ramat Tzvel and their pharmacokinetics in rats. J. Agric. Food Chem. 2015 63 35 7700 7706 10.1021/jf505848z 25625345
    [Google Scholar]
  77. Bélanger M. Allaman I. Magistretti P.J. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 2011 14 6 724 738 10.1016/j.cmet.2011.08.016 22152301
    [Google Scholar]
  78. Samodien E. Johnson R. Pheiffer C. Mabasa L. Erasmus M. Louw J. Chellan N. Diet-induced hypothalamic dysfunction and metabolic disease, and the therapeutic potential of polyphenols. Mol. Metab. 2019 27 1 10 10.1016/j.molmet.2019.06.022 31300352
    [Google Scholar]
  79. Panickar K.S. Effects of dietary polyphenols on neuroregulatory factors and pathways that mediate food intake and energy regulation in obesity. Mol. Nutr. Food Res. 2013 57 1 34 47 10.1002/mnfr.201200431 23125162
    [Google Scholar]
  80. Liu Y. Fu X. Lan N. Li S. Zhang J. Wang S. Li C. Shang Y. Huang T. Zhang L. Luteolin protects against high fat diet-induced cognitive deficits in obesity mice. Behav. Brain Res. 2014 267 178 188 10.1016/j.bbr.2014.02.040 24667364
    [Google Scholar]
  81. Bumke-Vogt C. Osterhoff M.A. Borchert A. Guzman-Perez V. Sarem Z. Birkenfeld A.L. Bähr V. Pfeiffer A.F.H. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells. PLoS One 2014 9 8 104321 10.1371/journal.pone.0104321 25136826
    [Google Scholar]
  82. Huang Q. Chen L. Teng H. Song H. Wu X. Xu M. Phenolic compounds ameliorate the glucose uptake in HepG2 cells’ insulin resistance via activating AMPK. J. Funct. Foods 2015 19 487 494 10.1016/j.jff.2015.09.020
    [Google Scholar]
  83. Wong T.Y. Lin S. Leung L.K. The flavone luteolin suppresses SREBP-2 expression and post-translational activation in hepatic cells. PLoS One 2015 10 8 135637 10.1371/journal.pone.0135637 26302339
    [Google Scholar]
  84. Kwon E.Y. Kim S.Y. Choi M.S. Luteolin-enriched artichoke leaf extract alleviates the metabolic syndrome in mice with high-fat diet-induced obesity. Nutrients 2018 10 8 979 10.3390/nu10080979 30060507
    [Google Scholar]
  85. Shon J.C. Kim W.C. Ryu R. Wu Z. Seo J.S. Choi M.S. Liu K.H. Plasma lipidomics reveals insights into anti-obesity effect of Chrysanthemum morifolium Ramat leaves and its constituent luteolin in high-fat diet-induced dyslipidemic mice. Nutrients 2020 12 10 2973 10.3390/nu12102973 33003339
    [Google Scholar]
  86. Nicolai A. Li M. Kim D.H. Peterson S.J. Vanella L. Positano V. Gastaldelli A. Rezzani R. Rodella L.F. Drummond G. Kusmic C. L’Abbate A. Kappas A. Abraham N.G. Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats. Hypertension 2009 53 3 508 515 10.1161/HYPERTENSIONAHA.108.124701 19171794
    [Google Scholar]
  87. Blüher M. Adipose tissue dysfunction in obesity. Exp. Clin. Endocrinol. Diabetes 2009 117 6 241 250 10.1055/s‑0029‑1192044 19358089
    [Google Scholar]
  88. Ding L. Jin D. Chen X. Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes. J. Nutr. Biochem. 2010 21 10 941 947 10.1016/j.jnutbio.2009.07.009 19954946
    [Google Scholar]
  89. Ando C. Takahashi N. Hirai S. Nishimura K. Lin S. Uemura T. Goto T. Yu R. Nakagami J. Murakami S. Kawada T. Luteolin, a food‐derived flavonoid, suppresses adipocyte‐dependent activation of macrophages by inhibiting JNK activation. FEBS Lett. 2009 583 22 3649 3654 10.1016/j.febslet.2009.10.045 19854181
    [Google Scholar]
  90. Kim D-K. Nepali S. Son J-S. Poudel B. Lee J.H. Lee Y-M. Luteolin is a bioflavonoid that attenuates adipocyte-derived inflammatory responses via suppression of nuclear factor-κB/mitogen-activated protein kinases pathway. Pharmacogn. Mag. 2015 11 43 627 635 10.4103/0973‑1296.160470 26246742
    [Google Scholar]
  91. Kwon S.M. Kim S. Song N.J. Chang S.H. Hwang Y.J. Yang D.K. Hong J.W. Park W.J. Park K.W. Antiadipogenic and proosteogenic effects of luteolin, a major dietary flavone, are mediated by the induction of DnaJ (Hsp40) Homolog, Subfamily B, Member 1. J. Nutr. Biochem. 2016 30 24 32 10.1016/j.jnutbio.2015.11.013 27012618
    [Google Scholar]
  92. Zhang L. Han Y.J. Zhang X. Wang X. Bao B. Qu W. Liu J. Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages. Diabetologia 2016 59 10 2219 2228 10.1007/s00125‑016‑4039‑8 27377644
    [Google Scholar]
  93. Kwon E.Y. Choi M.S. Luteolin targets the toll-like receptor signaling pathway in prevention of hepatic and adipocyte fibrosis and insulin resistance in diet-induced obese mice. Nutrients 2018 10 10 1415 10.3390/nu10101415 30282902
    [Google Scholar]
  94. Yoon H.J. Bang M.H. Kim H. Imm J.Y. Improvement of palmitate-induced insulin resistance in C2C12 skeletal muscle cells using Platycodon grandiflorum seed extracts. Food Biosci. 2018 25 61 67 10.1016/j.fbio.2018.08.002
    [Google Scholar]
  95. Yoo A. Jang Y.J. Ahn J. Jung C.H. Seo H.D. Ha T.Y. Chrysanthemi Zawadskii var. Latilobum attenuates obesity-induced skeletal muscle atrophy via regulation of PRMTs in skeletal muscle of mice. Int. J. Mol. Sci. 2020 21 8 2811 10.3390/ijms21082811 32316567
    [Google Scholar]
  96. Alpert M.A. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am. J. Med. Sci. 2001 321 4 225 236 10.1097/00000441‑200104000‑00003 11307864
    [Google Scholar]
  97. Wang J. Gao T. Wang F. Xue J. Ye H. Xie M. Luteolin improves myocardial cell glucolipid metabolism by inhibiting hypoxia inducible factor-1α expression in angiotensin II/hypoxia-induced hypertrophic H9c2 cells. Nutr. Res. 2019 65 63 70 10.1016/j.nutres.2019.02.004 30954346
    [Google Scholar]
  98. Abu-Elsaad N. El-Karef A. The falconoid luteolin mitigates the myocardial inflammatory response induced by high-carbohydrate/high-fat diet in wistar rats. Inflammation 2018 41 1 221 231 10.1007/s10753‑017‑0680‑8 29047036
    [Google Scholar]
  99. Yang J.T. Wang J. Zhou X.R. Xiao C. Lou Y.Y. Tang L.H. Zhang F.J. Qian L.B. Luteolin alleviates cardiac ischemia/reperfusion injury in the hypercholesterolemic rat via activating Akt/Nrf2 signaling. Naunyn Schmiedebergs Arch. Pharmacol. 2018 391 7 719 728 10.1007/s00210‑018‑1496‑2 29671020
    [Google Scholar]
  100. Akinola O.S. Caxton-Martins E.A. Akinola O.B. Ethanolic leaf extract of Vernonia amygdalina improves islet morphology and upregulates pancreatic G6PDH activity in streptozotocin-induced diabetic Wistar rats. Pharmacologyonline 2010 2 932 942
    [Google Scholar]
  101. Nekohashi M. Ogawa M. Ogihara T. Nakazawa K. Kato H. Misaka T. Abe K. Kobayashi S. Luteolin and quercetin affect the cholesterol absorption mediated by epithelial cholesterol transporter niemann-pick c1-like 1 in caco-2 cells and rats. PLoS One 2014 9 5 97901 10.1371/journal.pone.0097901 24859282
    [Google Scholar]
  102. Davis H.R. Jr Altmann S.W. Niemann–Pick C1 Like 1 (NPC1L1) an intestinal sterol transporter. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2009 1791 7 679 683 10.1016/j.bbalip.2009.01.002
    [Google Scholar]
  103. Ogawa M. Yamanashi Y. Takada T. Abe K. Kobayashi S. Effect of luteolin on the expression of intestinal cholesterol transporters. J. Funct. Foods 2017 36 274 279 10.1016/j.jff.2017.07.008
    [Google Scholar]
  104. Galindo R.J. Beck R.W. Scioscia M.F. Umpierrez G.E. Tuttle K.R. Glycaemic monitoring and management in advanced chronic kidney disease. Endocr. Rev. 2020 41 5 756 774 10.1210/endrev/bnaa017 32455432
    [Google Scholar]
  105. Gerich J.E. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet. Med. 2010 27 2 136 142 10.1111/j.1464‑5491.2009.02894.x 20546255
    [Google Scholar]
  106. Wang GG Lu XH Li W Zhao X Zhang C Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. J. Altern. Complement. Med 2011 2011 323171
    [Google Scholar]
  107. Zhang M. He L. Liu J. Zhou L. Luteolin attenuates diabetic nephropathy through suppressing inflammatory response and oxidative stress by inhibiting STAT3 pathway. Exp. Clin. Endocrinol. Diabetes 2021 129 10 729 739 10.1055/a‑0998‑7985 31896157
    [Google Scholar]
  108. Rajamanickam S. Agarwal R. Natural products and colon cancer: current status and future prospects. Drug Dev. Res. 2008 69 7 460 471 10.1002/ddr.20276 19884979
    [Google Scholar]
  109. Ferlay J. Autier P. Boniol M. Heanue M. Colombet M. Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann. Oncol. 2007 18 3 581 592 10.1093/annonc/mdl498 17287242
    [Google Scholar]
  110. Tsuzuki T. Nakatsu Y. Nakabeppu Y. Significance of error‐avoiding mechanisms for oxidative DNA damage in carcinogenesis. Cancer Sci. 2007 98 4 465 470 10.1111/j.1349‑7006.2007.00409.x 17425590
    [Google Scholar]
  111. Powell C.L. Swenberg J.A. Rusyn I. Expression of base excision DNA repair genes as a biomarker of oxidative DNA damage. Cancer Lett. 2005 229 1 1 11 10.1016/j.canlet.2004.12.002 16157213
    [Google Scholar]
  112. Liu J. Pharmacology of oleanolic acid and ursolic acid. J. Ethnopharmacol. 1995 49 2 57 68 10.1016/0378‑8741(95)90032‑2 8847885
    [Google Scholar]
  113. Seelinger G. Merfort I. Wölfle U. Schempp C.M. Anti-carcinogenic effects of the flavonoid luteolin. Molecules 2008 13 10 2628 2651 10.3390/molecules13102628 18946424
    [Google Scholar]
  114. Ramos A.A. Lima C.F. Pereira M.L. Fernandes-Ferreira M. Pereira-Wilson C. Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells: Evaluation by the comet assay. Toxicol. Lett. 2008 177 1 66 73 10.1016/j.toxlet.2008.01.001 18276086
    [Google Scholar]
  115. Halliwell B. Dietary polyphenols: Good, bad, or indifferent for your health? Cardiovasc. Res. 2007 73 2 341 347 10.1016/j.cardiores.2006.10.004 17141749
    [Google Scholar]
  116. Kilani-Jaziri S. Neffati A. Limem I. Boubaker J. Skandrani I. Sghair M.B. Bouhlel I. Bhouri W. Mariotte A.M. Ghedira K. Dijoux Franca M.G. Chekir-Ghedira L. Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus products towards K562 erythroleukemia cells. Chem. Biol. Interact. 2009 181 1 85 94 10.1016/j.cbi.2009.04.014 19446539
    [Google Scholar]
  117. Tsai S.J. Yin M.C. Antioxidative and anti-inflammatory protection of oleanolic acid and ursolic acid in PC12 cells. J. Food Sci. 2008 73 7 174 178 10.1111/j.1750‑3841.2008.00864.x 18803714
    [Google Scholar]
  118. Chakrabarti M. Ray S.K. Synergistic anti-tumor actions of luteolin and silibinin prevented cell migration and invasion and induced apoptosis in glioblastoma SNB19 cells and glioblastoma stem cells. Brain Res. 2015 1629 85 93 10.1016/j.brainres.2015.10.010 26471408
    [Google Scholar]
  119. Nakai E. Park K. Yawata T. Chihara T. Kumazawa A. Nakabayashi H. Shimizu K. Enhanced MDR1 expression and chemoresistance of cancer stem cells derived from glioblastoma. Cancer Invest. 2009 27 9 901 908 10.3109/07357900801946679 19832037
    [Google Scholar]
  120. Söderberg-Nauclér C. Rahbar A. Stragliotto G. Survival in patients with glioblastoma receiving valganciclovir. N. Engl. J. Med. 2013 369 10 985 986 10.1056/NEJMc1302145 24004141
    [Google Scholar]
  121. Umesalma S. Sudhandiran G. Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-kappaB, iNOS, COX-2, TNF-α, and IL-6 in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Basic Clin. Pharmacol. Toxicol. 2010 107 2 650 655 10.1111/j.1742‑7843.2010.00565.x 20406206
    [Google Scholar]
  122. Chiang C.T. Way T.D. Lin J.K. Sensitizing HER2-overexpressing cancer cells to luteolin-induced apoptosis through suppressing p21WAF1/CIP1 expression with rapamycin. Mol. Cancer Ther. 2007 6 7 2127 2138 10.1158/1535‑7163.MCT‑07‑0107 17620442
    [Google Scholar]
  123. Segal R. Lubart E. Leibovitz A. Iaina A. Caspi D. Renal effects of low dose aspirin in elderly patients. Isr. Med. Assoc. J. 2006 8 10 679 682 17125112
    [Google Scholar]
  124. Robak J. Shridi F. Wolbís M. Królikowska M. Screening of the influence of flavonoids on lipoxygenase and cyclooxygenase activity, as well as on nonenzymic lipid oxidation. Pol. J. Pharmacol. Pharm. 1988 40 5 451 458 3151014
    [Google Scholar]
  125. Iwashita K. Kobori M. Yamaki K. Tsushida T. Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. Biosci. Biotechnol. Biochem. 2000 64 9 1813 1820 10.1271/bbb.64.1813 11055382
    [Google Scholar]
  126. Yoon J.H. Baek S.J. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med. J. 2005 46 5 585 596 10.3349/ymj.2005.46.5.585 16259055
    [Google Scholar]
  127. Davis AE Patterson F Aspirin reduces the incidence of colonic carcinoma in the dimethylhydrazine rat animal model. Aus. NZ. J. medi. 1994 24 3 301 3 10.1111/j.1445‑5994.1994.tb02176.x
    [Google Scholar]
  128. Bhatnagar J. Tewari H.B. Bhatnagar M. Austin G.E. Comparison of carcinoembryonic antigen in tissue and serum with grade and stage of colon cancer. Anticancer Res. 1999 19 3B 2181 2187 10472328
    [Google Scholar]
  129. Lv GY Zhang YP Gao JL Yu JJ Lei J Zhang ZR Li B Zhan RJ Chen SH Combined antihypertensive effect of luteolin and buddleoside enriched extracts in spontaneously hypertensive rats. J. of ethnoph 2013 150 2 507 13
    [Google Scholar]
  130. Fernández S. Wasowski C. Paladini A.C. Marder M. Sedative and sleep-enhancing properties of linarin, a flavonoid-isolated from Valeriana officinalis. Pharmacol. Biochem. Behav. 2004 77 2 399 404 10.1016/j.pbb.2003.12.003 14751470
    [Google Scholar]
  131. Han S. Sung K. Yim D. Lee S. Lee C. Ha N. Kim K. The effect of linarin on lps-lnduced cytokine production and nitric oxide inhibition in murine macrophages cell line RAW264.7. Arch. Pharm. Res. 2002 25 2 170 177 10.1007/BF02976559 12009031
    [Google Scholar]
  132. Verhaar M.C. Strachan F.E. Newby D.E. Cruden N.L. Koomans H.A. Rabelink T.J. Webb D.J. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 1998 97 8 752 756 10.1161/01.CIR.97.8.752 9498538
    [Google Scholar]
  133. Obineche E. Abdulle A. Pathan J. Nagelkerke N.D. Plasma endothelin-1, homocysteine, and nitric oxide levels in a multiethnic hypertensive cohort from the united arab emirates. Hamdan Medi. J. 2010 3 3 153 159 10.4103/2227‑2437.231264
    [Google Scholar]
  134. Singh R.P. Agrawal P. Yim D. Agarwal C. Agarwal R. Acacetin inhibits cell growth and cell cycle progression, and induces apoptosis in human prostate cancer cells: structure-activity relationship with linarin and linarin acetate. Carcinogenesis 2005 26 4 845 854 10.1093/carcin/bgi014 15637089
    [Google Scholar]
  135. Morell E.A. Balkin D.M. Methicillin-resistant Staphylococcus aureus: a pervasive pathogen highlights the need for new antimicrobial development. J. Biomed. (Syd.) 2010 83 4 223 233 21165342
    [Google Scholar]
  136. Taj Y. Abdullah F.E. Kazmi S.U. Current pattern of antibiotic resistance in Staphylococcus aureus clinical isolates and the emergence of vancomycin resistance. J. Coll. Physicians Surg. Pak. 2010 20 11 728 732 21078245
    [Google Scholar]
  137. Hafiz S. Hafiz A.N. Ali L. Chughtai A.S. Memon B. Ahmed A. Hussain S. Sarwar G. Mughal T. Siddiqui S.J. Awan A. Zaki K. Fareed A. Methicillin resistant Staphylococcus aureus: a multicentre study. J. Pak. Med. Assoc. 2002 52 7 312 315 12481663
    [Google Scholar]
  138. Lin R.D. Chin Y.P. Lee M.H. Antimicrobial activity of antibiotics in combination with natural flavonoids against clinical extended‐spectrum β ‐lactamase (ESBL)‐producing Klebsiella pneumoniae. Phytother. Res. 2005 19 7 612 617 10.1002/ptr.1695 16161024
    [Google Scholar]
  139. Darwish R.M. Ra’ed J. Zarga M.H. Nazer I.K. Antibacterial effect of Jordanian propolis and isolated flavonoids against human pathogenic bacteria. Afr. J. Biotechnol. 2010 9 36
    [Google Scholar]
  140. Su Y. Ma L. Wen Y. Wang H. Zhang S. Studies of the in vitro antibacterial activities of several polyphenols against clinical isolates of methicillin-resistant Staphylococcus aureus. Molecules 2014 19 8 12630 12639 10.3390/molecules190812630 25153875
    [Google Scholar]
  141. Idrees F. Jabeen K. Khan M.S. Zafar A. Antimicrobial resistance profile of methicillin resistant staphylococcal aureus from skin and soft tissue isolates. J. Pak. Med. Assoc. 2009 59 5 266 269 19438125
    [Google Scholar]
  142. Xu H.X. Lee S.F. Activity of plant flavonoids against antibiotic‐resistant bacteria. Phytotherapy Research. Int. J. Devo. Pharmacol. Toxicol. Eval. Nat. 2001 15 1 39 43
    [Google Scholar]
  143. Lin Y Shi R Wang X Shen HM Luteolin, a flavonoid with potential for cancer prevention and therapy. Cur cancer drg. targets 2008 8 7 634 46 10.2174/156800908786241050
    [Google Scholar]
  144. Lee H.Z. Yang W.H. Bao B.Y. Lo P.L. Proteomic analysis reveals ATP-dependent steps and chaperones involvement in luteolin-induced lung cancer CH27 cell apoptosis. Eur. J. Pharmacol. 2010 642 1-3 19 27 10.1016/j.ejphar.2010.05.053 20553912
    [Google Scholar]
  145. Cai X. Ye T. Liu C. Lu W. Lu M. Zhang J. Wang M. Cao P. Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells. Toxicol. In Vitro 2011 25 7 1385 1391 10.1016/j.tiv.2011.05.009 21601631
    [Google Scholar]
  146. Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2018. CA Cancer J. Clin. 2018 68 1 7 30 10.3322/caac.21442 29313949
    [Google Scholar]
  147. Khan M.A. Jain V.K. Rizwanullah M. Ahmad J. Jain K. PI3K/AKT/mTOR pathway inhibitors in triple-negative breast cancer: a review on drug discovery and future challenges. Drug Discov. Today 2019 24 11 2181 2191 10.1016/j.drudis.2019.09.001 31520748
    [Google Scholar]
  148. Kamaruzman N.I. Aziz N.A. Poh C.L. Chowdhury E.H. Oncogenic signaling in tumorigenesis and applications of siRNA nanotherapeutics in breast cancer. Cancers (Basel) 2019 11 5 632 10.3390/cancers11050632 31064156
    [Google Scholar]
  149. Sharma A Jain N Sareen R Nanocarriers for diagnosis and targeting of breast cancer. Biomed Res Int 2013 2013 23865076 10.1155/2013/960821
    [Google Scholar]
  150. Rizwanullah M. Alam M. Harshita Mir S.R. Rizvi M.M.A. Amin S. Polymer-lipid hybrid nanoparticles: A next-generation nanocarrier for targeted treatment of solid tumors. Curr. Pharm. Des. 2020 26 11 1206 1215 10.2174/1381612826666200116150426 31951163
    [Google Scholar]
  151. Du M. Ouyang Y. Meng F. Ma Q. Liu H. Zhuang Y. Pang M. Cai T. Cai Y. Nanotargeted agents: an emerging therapeutic strategy for breast cancer. Nanomedicine (Lond.) 2019 14 13 1771 1786 10.2217/nnm‑2018‑0481 31298065
    [Google Scholar]
  152. Haider N. Fatima S. Taha M. Rizwanullah M. Firdous J. Ahmad R. Mazhar F. Khan M.A. Nanomedicines in diagnosis and treatment of cancer: An update. Curr. Pharm. Des. 2020 26 11 1216 1231 10.2174/18734286MTA1wMzYbx 32188379
    [Google Scholar]
  153. Adamczak A. Ożarowski M. Karpiński T.M. Antibacterial activity of some flavonoids and organic acids widely distributed in plants. J. Clin. Med. 2019 9 1 109 10.3390/jcm9010109 31906141
    [Google Scholar]
  154. Manzoor M.F. Ahmad N. Ahmed Z. Siddique R. Zeng X.A. Rahaman A. Muhammad Aadil R. Wahab A. Novel extraction techniques and pharmaceutical activities of luteolin and its derivatives. J. Food Biochem. 2019 43 9 12974 10.1111/jfbc.12974 31489656
    [Google Scholar]
  155. Lv P.C. Li H.Q. Xue J.Y. Shi L. Zhu H.L. Synthesis and biological evaluation of novel luteolin derivatives as antibacterial agents. Eur. J. Med. Chem. 2009 44 2 908 914 10.1016/j.ejmech.2008.01.013 18313801
    [Google Scholar]
  156. Qian W. Liu M. Fu Y. Zhang J. Liu W. Li J. Li X. Li Y. Wang T. Antimicrobial mechanism of luteolin against Staphylococcus aureus and Listeria monocytogenes and its antibiofilm properties. Microb. Pathog. 2020 142 104056 10.1016/j.micpath.2020.104056 32058023
    [Google Scholar]
  157. Imran M. Rauf A. Abu-Izneid T. Nadeem M. Shariati M.A. Khan I.A. Imran A. Orhan I.E. Rizwan M. Atif M. Gondal T.A. Mubarak M.S. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed. Pharmacother. 2019 112 108612 10.1016/j.biopha.2019.108612 30798142
    [Google Scholar]
  158. Alshehri S. Imam S.S. Altamimi M.A. Hussain A. Shakeel F. Elzayat E. Mohsin K. Ibrahim M. Alanazi F. Enhanced dissolution of luteolin by solid dispersion prepared by different methods: physicochemical characterization and antioxidant activity. ACS Omega 2020 5 12 6461 6471 10.1021/acsomega.9b04075 32258881
    [Google Scholar]
  159. Han X. Lu Y. Xie J. Zhang E. Zhu H. Du H. Wang K. Song B. Yang C. Shi Y. Cao Z. Zwitterionic micelles efficiently deliver oral insulin without opening tight junctions. Nat. Nanotechnol. 2020 15 7 605 614 10.1038/s41565‑020‑0693‑6 32483319
    [Google Scholar]
  160. Rizwanullah M. Amin S. Ahmad J. Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers. J. Drug Target. 2017 25 1 58 74 10.1080/1061186X.2016.1191080 27186665
    [Google Scholar]
  161. Eid R.K. Ashour D.S. Essa E.A. El Maghraby G.M. Arafa M.F. Chitosan coated nanostructured lipid carriers for enhanced in vivo efficacy of albendazole against Trichinella spiralis. Carbohydr. Polym. 2020 232 115826 10.1016/j.carbpol.2019.115826 31952620
    [Google Scholar]
  162. Ling Tan J.S. Roberts C.J. Billa N. Mucoadhesive chitosan-coated nanostructured lipid carriers for oral delivery of amphotericin B. Pharm. Dev. Technol. 2019 24 4 504 512 10.1080/10837450.2018.1515225 30132723
    [Google Scholar]
  163. Ling J.T.S. Roberts C.J. Billa N. Antifungal and mucoadhesive properties of an orally administered chitosan-coated amphotericin B nanostructured lipid carrier (NLC). AAPS PharmSciTech 2019 20 3 136 10.1208/s12249‑019‑1346‑7 30838459
    [Google Scholar]
  164. Liu M. Zhong X. Yang Z. Chitosan functionalized nanocochleates for enhanced oral absorption of cyclosporine A. Sci. Rep. 2017 7 1 41322 10.1038/srep41322 28112262
    [Google Scholar]
  165. Gartziandia O. Herran E. Pedraz J.L. Carro E. Igartua M. Hernandez R.M. Chitosan coated nanostructured lipid carriers for brain delivery of proteins by intranasal administration. Colloids Surf. B Biointerfaces 2015 134 304 313 10.1016/j.colsurfb.2015.06.054 26209963
    [Google Scholar]
  166. Gilani S.J. Bin-Jumah M. Rizwanullah M. Imam S.S. Imtiyaz K. Alshehri S. Rizvi M.M.A. Chitosan coated luteolin nanostructured lipid carriers: Optimization, in vitro-ex vivo assessments and cytotoxicity study in breast cancer cells. Coatings 2021 11 2 158 10.3390/coatings11020158
    [Google Scholar]
  167. Govindaraju K, Prabhu D, Arulvasu C, Karthick V, Changmai N. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7). Appl. Surf. Sci. 2016 371 415 424 10.1016/j.apsusc.2016.03.004
    [Google Scholar]
  168. Yang C. Liu H.Z. Fu Z.X. Lu W.D. Oxaliplatin long-circulating liposomes improved therapeutic index of colorectal carcinoma. BMC Biotechnol. 2011 11 1 21 10.1186/1472‑6750‑11‑21 21401960
    [Google Scholar]
  169. Majumdar D. Jung K.H. Zhang H. Nannapaneni S. Wang X. Amin A.R.M.R. Chen Z. Chen Z.G. Shin D.M. Luteolin nanoparticle in chemoprevention: In vitro and in vivo anticancer activity. Cancer Prev. Res. (Phila.) 2014 7 1 65 73 10.1158/1940‑6207.CAPR‑13‑0230 24403290
    [Google Scholar]
  170. Sporn MB Dunlop NM Newton DL Smith JM Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 1976 35 6 1332 8
    [Google Scholar]
  171. Guo L. Fan L. Ren J. Pang Z. Ren Y. Li J. Wen Z. Qian Y. Zhang L. Ma H. Jiang X. Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer. Int. J. Nanomedicine 2012 7 1449 1460 22619505
    [Google Scholar]
  172. Koudelka S. Turanek Knotigova P. Masek J. Prochazka L. Lukac R. Miller A.D. Neuzil J. Turanek J. Liposomal delivery systems for anti-cancer analogues of vitamin E. J. Control. Release 2015 207 59 69 10.1016/j.jconrel.2015.04.003 25861728
    [Google Scholar]
  173. Barenholz Y.C. Doxil® — The first FDA-approved nano-drug: Lessons learned. J. Control. Release 2012 160 2 117 134 10.1016/j.jconrel.2012.03.020 22484195
    [Google Scholar]
  174. Hioki A. Wakasugi A. Kawano K. Hattori Y. Maitani Y. Development of an in vitro drug release assay of PEGylated liposome using bovine serum albumin and high temperature. Biol. Pharm. Bull. 2010 33 9 1466 1470 10.1248/bpb.33.1466 20823558
    [Google Scholar]
  175. Haley B Frenkel E Nanoparticles for drug delivery in cancer treatment. Urol Oncol 2008 26 1 57 64 10.1016/j.urolonc.2007.03.015
    [Google Scholar]
  176. Pandurangan A.K. Esa N.M. Luteolin, a bioflavonoid inhibits colorectal cancer through modulation of multiple signaling pathways: a review. J. Cancer Prev. 2014 15 14 5501 5508 25081655
    [Google Scholar]
  177. Pratheeshkumar P. Son Y.O. Budhraja A. Wang X. Ding S. Wang L. Hitron A. Lee J.C. Kim D. Divya S.P. Chen G. Zhang Z. Luo J. Shi X. Luteolin inhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. PLoS One 2012 7 12 52279 10.1371/journal.pone.0052279 23300633
    [Google Scholar]
  178. Cukierman E. Khan D.R. The benefits and challenges associated with the use of drug delivery systems in cancer therapy. Biochem. Pharmacol. 2010 80 5 762 770 10.1016/j.bcp.2010.04.020 20417189
    [Google Scholar]
  179. Hicks A. Jolkkonen J. Challenges and possibilities of intravascular cell therapy in stroke. Acta Neurobiol. Exp. (Warsz.) 2009 69 1 1 11 10.55782/ane‑2009‑1724 19325636
    [Google Scholar]
  180. Mehta S.L. Manhas N. Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res. Brain Res. Rev. 2007 54 1 34 66 10.1016/j.brainresrev.2006.11.003 17222914
    [Google Scholar]
  181. Collino M. Aragno M. Mastrocola R. Gallicchio M. Rosa A.C. Dianzani C. Danni O. Thiemermann C. Fantozzi R. Modulation of the oxidative stress and inflammatory response by PPAR-γ agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Eur. J. Pharmacol. 2006 530 1-2 70 80 10.1016/j.ejphar.2005.11.049 16386242
    [Google Scholar]
  182. Neumar R. Molecular mechanisms of ischemic neuronal injury. Ann. Emerg. Med. 2000 36 5 483 506 10.1016/S0196‑0644(00)82028‑4 11054204
    [Google Scholar]
  183. Kelly P.J. Morrow J.D. Ning M. Koroshetz W. Lo E.H. Terry E. Milne G.L. Hubbard J. Lee H. Stevenson E. Lederer M. Furie K.L. Oxidative stress and matrix metalloproteinase-9 in acute ischemic stroke: the Biomarker Evaluation for Antioxidant Therapies in Stroke (BEAT-Stroke) study. Stroke 2008 39 1 100 104 10.1161/STROKEAHA.107.488189 18063832
    [Google Scholar]
  184. Chu C. Xu B. Huang W. GnRH analogue attenuated apoptosis of rat hippocampal neuron after ischemia–reperfusion injury. J. Mol. Histol. 2010 41 6 387 393 10.1007/s10735‑010‑9300‑8 20953819
    [Google Scholar]
  185. Donnini S. Solito R. Monti M. Balduini W. Carloni S. Cimino M. Bampton E.T.W. Pinon L.G.P. Nicotera P. Thorpe P.E. Ziche M. Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4. Cell Cycle 2009 8 8 1271 1278 10.4161/cc.8.8.8301 19305142
    [Google Scholar]
  186. Zhang H.Y. Yang D.P. Tang G.Y. Multipotent antioxidants: from screening to design. Drug Discov. Today 2006 11 15-16 749 754 10.1016/j.drudis.2006.06.007 16846803
    [Google Scholar]
  187. Tsai F.S. Peng W.H. Wang W.H. Wu C.R. Hsieh C.C. Lin Y.T. Feng I.C. Hsieh M.T. Effects of luteolin on learning acquisition in rats: Involvement of the central cholinergic system. Life Sci. 2007 80 18 1692 1698 10.1016/j.lfs.2007.01.055 17337279
    [Google Scholar]
  188. van Meeteren M.E. Hendriks J.J.A. Dijkstra C.D. van Tol E.A.F. Dietary compounds prevent oxidative damage and nitric oxide production by cells involved in demyelinating disease. Biochem. Pharmacol. 2004 67 5 967 975 10.1016/j.bcp.2003.10.018 15104250
    [Google Scholar]
  189. Deguchi K. Hayashi T. Nagotani S. Sehara Y. Zhang H. Tsuchiya A. Ohta Y. Tomiyama K. Morimoto N. Miyazaki M. Huh N. Nakao A. Kamiya T. Abe K. Reduction of cerebral infarction in rats by biliverdin associated with amelioration of oxidative stress. Brain Res. 2008 1188 1 8 10.1016/j.brainres.2007.07.104 18035335
    [Google Scholar]
  190. Bi J. Jiang B. Liu J.H. Lei C. Zhang X.L. An L.J. Protective effects of catalpol against H2O2-induced oxidative stress in astrocytes primary cultures. Neurosci. Lett. 2008 442 3 224 227 10.1016/j.neulet.2008.07.029 18652878
    [Google Scholar]
  191. Hunter A.J. Hatcher J. Virley D. Nelson P. Irving E. Hadingham S.J. Parsons A.A. Functional assessments in mice and rats after focal stroke. Neuropharmacology 2000 39 5 806 816 10.1016/S0028‑3908(99)00262‑2 10699446
    [Google Scholar]
  192. Ralhan R. Kaur J. Alkylating agents and cancer therapy. Expert Opin. Ther. Pat. 2007 17 9 1061 1075 10.1517/13543776.17.9.1061
    [Google Scholar]
  193. Singh A. Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010 29 34 4741 4751 10.1038/onc.2010.215 20531305
    [Google Scholar]
  194. Maemondo M. Inoue A. Kobayashi K. Sugawara S. Oizumi S. Isobe H. Gemma A. Harada M. Yoshizawa H. Kinoshita I. Fujita Y. Okinaga S. Hirano H. Yoshimori K. Harada T. Ogura T. Ando M. Miyazawa H. Tanaka T. Saijo Y. Hagiwara K. Morita S. Nukiwa T. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med. 2010 362 25 2380 2388 10.1056/NEJMoa0909530 20573926
    [Google Scholar]
/content/journals/npj/10.2174/0122103155316738240901181513
Loading
/content/journals/npj/10.2174/0122103155316738240901181513
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