Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Insights into Pharmacological Potential of Apigenin through Various Pathways on a Nanoplatform in Multitude of Diseases

Author(s): Ayesha Waheed, Saima Zameer, Kudsiya Ashrafi, Asad Ali, Niha Sultana, Mohd Aqil*, Yasmin Sultana and Zeenat Iqbal

Volume 29, Issue 17, 2023

Published on: 09 June, 2023

Page: [1326 - 1340] Pages: 15

DOI: 10.2174/1381612829666230529164321

Price: $65

conference banner
Abstract

Apigenin is a natural polyphenolic compound widely distributed as a glycoside in fruits and vegetables. Apigenin belongs to BCS class II with low solubility, which leads to poor absorption and bioavailability. It is mostly absorbed from the small intestine and extensively metabolized through glucuronidation and sulfation processes. Apigenin is known for its antioxidant and anti-inflammatory properties. It is also used as a chemopreventive drug in the management of various cancers. Pharmacological effects of apigenin have a wide range, from neuroprotective to treating renal disorders. Apigenin is non-toxic in nature and acts through various pathways (JAK/STAT, Wnt/β-catenin, MAPK/ERK, PI3K/Akt, and NF-κB) to exert its therapeutic efficacy. Numerous formulations have been researched to enhance the bioavailability and pharmacological effects of apigenin. Combinatorial therapies are also researched to minimize the side-effects of chemotherapeutic drugs. The review presents pharmacokinetic and pharmacodynamic aspects of apigenin. Apigenin is safe for the treatment and management of numerous diseases. It can be easily incorporated into nanoformulation alone or in combination with other active ingredients to widen the therapeutic window. This review intends to help in drug optimization and therapeutic efficacy maximization for future studies.

Keywords: Flavonoid, ADME, mechanism of action, pharmacological activity, drug delivery, antioxidant.

[1]
Tang D, Chen K, Huang L, Li J. Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert Opin Drug Metab Toxicol 2017; 13(3): 323-30.
[http://dx.doi.org/10.1080/17425255.2017.1251903] [PMID: 27766890]
[2]
Patel D, Shukla S, Gupta S. Apigenin and cancer chemoprevention: Progress, potential and promise (Review). Int J Oncol 2007; 30(1): 233-45.
[PMID: 17143534]
[3]
Bravo L. Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998; 56(11): 317-33.
[http://dx.doi.org/10.1111/j.1753-4887.1998.tb01670.x] [PMID: 9838798]
[4]
Lefort ÉC, Blay J. Apigenin and its impact on gastrointestinal cancers. Mol Nutr Food Res 2013; 57(1): 126-44.
[http://dx.doi.org/10.1002/mnfr.201200424] [PMID: 23197449]
[5]
Simirgiotis M, Schmeda-Hirschmann G, Bórquez J, Kennelly E. The Passiflora tripartita (Banana Passion) fruit: A source of bioactive flavonoid C-glycosides isolated by HSCCC and characterized by HPLC–DAD–ESI/MS/MS. Molecules 2013; 18(2): 1672-92.
[http://dx.doi.org/10.3390/molecules18021672] [PMID: 23358325]
[6]
McKay DL, Blumberg JB. A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). 2006; 20(7): 519-30.
[http://dx.doi.org/10.1002/ptr.1900] [PMID: 16628544]
[7]
Hertog MGL, Hollman PCH, Venema DP. Optimization of a quantitative HPLC determination of potentially anticarcinogenic flavonoids in vegetables and fruits. J Agric Food Chem 1992; 40(9): 1591-8.
[http://dx.doi.org/10.1021/jf00021a023]
[8]
Yang RY, Lin S, Kuo G. Content and distribution of flavonoids among 91 edible plant species. Asia Pac J Clin Nutr 2008; 17(S1) (Suppl. 1): 275-9.
[PMID: 18296355]
[9]
Miean KH, Mohamed S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem 2001; 49(6): 3106-12.
[http://dx.doi.org/10.1021/jf000892m] [PMID: 11410016]
[10]
Proestos C, Chorianopoulos N, Nychas GJE, Komaitis M. RP-HPLC analysis of the phenolic compounds of plant extracts. Investigation of their antioxidant capacity and antimicrobial activity. J Agric Food Chem 2005; 53(4): 1190-5.
[http://dx.doi.org/10.1021/jf040083t] [PMID: 15713039]
[11]
Škerget M, Kotnik P, Hadolin M, Hraš AR, Simonič M, Knez Ž. Phenols, proanthocyanidins, flavones and flavonols in some plant materials and their antioxidant activities. Food Chem 2005; 89(2): 191-8.
[http://dx.doi.org/10.1016/j.foodchem.2004.02.025]
[12]
Wang M, Firrman J, Liu LS, Yam K. A review on flavonoid apigenin: Dietary intake, ADME, antimicrobial effects, and interactions with human gut microbiota. Biomed Res Int 2019; 2019: 7010467.
[http://dx.doi.org/10.1155/2019/7010467] [PMID: 31737673]
[13]
Probst Y, Guan V, Kent K. A systematic review of food composition tools used for determining dietary polyphenol intake in estimated intake studies. Food Chem 2018; 238: 146-52.
[http://dx.doi.org/10.1016/j.foodchem.2016.11.010] [PMID: 28867085]
[14]
Li B, Robinson DH, Birt DF. Evaluation of properties of apigenin and [G-3H]apigenin and analytic method development. J Pharm Sci 1997; 86(6): 721-5.
[http://dx.doi.org/10.1021/js960383s] [PMID: 9188055]
[15]
Shakeel F, Alshehri S, Ibrahim MA, et al. Solubility and thermodynamic parameters of apigenin in different neat solvents at different temperatures. J Mol Liq 2017; 234: 73-80.
[http://dx.doi.org/10.1016/j.molliq.2017.03.057]
[16]
Biesaga M. Influence of extraction methods on stability of flavonoids. J Chromatogr A 2011; 1218(18): 2505-12.
[http://dx.doi.org/10.1016/j.chroma.2011.02.059] [PMID: 21411105]
[17]
Crespy V, Morand C, Manach C, Besson C, Demigne C, Remesy C. Part of quercetin absorbed in the small intestine is conjugated and further secreted in the intestinal lumen. Am J Physiol 1999; 277(1): G120-6.
[http://dx.doi.org/10.1152/ajpgi.1999.277.1.G120] [PMID: 10409158]
[18]
Ding S, Zhang Z, Song J, Cheng X, Jiang J, Jia X. Enhanced bioavailability of apigenin via preparation of a carbon nanopowder solid dispersion. Int J Nanomedicine 2014; 9(1): 2327-33.
[http://dx.doi.org/10.2147/IJN.S60938] [PMID: 24872695]
[19]
Zhang J, Huang Y, Liu D, Gao Y, Qian S. Preparation of apigenin nanocrystals using supercritical antisolvent process for dissolution and bioavailability enhancement. Eur J Pharm Sci 2013; 48(4-5): 740-7.
[http://dx.doi.org/10.1016/j.ejps.2012.12.026] [PMID: 23305994]
[20]
Zhao L, Zhang L, Meng L, Wang J, Zhai G. Design and evaluation of a self-microemulsifying drug delivery system for apigenin. Drug Dev Ind Pharm 2013; 39(5): 662-9.
[http://dx.doi.org/10.3109/03639045.2012.687378] [PMID: 22607130]
[21]
Zhang J, Liu D, Huang Y, Gao Y, Qian S. Biopharmaceutics classification and intestinal absorption study of apigenin. Int J Pharm 2012; 436(1-2): 311-7.
[http://dx.doi.org/10.1016/j.ijpharm.2012.07.002] [PMID: 22796171]
[22]
Chen T, Li LP, Lu XY, Jiang HD, Zeng S. Absorption and excretion of luteolin and apigenin in rats after oral administration of Chrysanthemum morifolium extract. J Agric Food Chem 2007; 55(2): 273-7.
[http://dx.doi.org/10.1021/jf062088r] [PMID: 17227053]
[23]
Gradolatto A, Basly JP, Berges R, et al. Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metab Dispos 2005; 33(1): 49-54.
[http://dx.doi.org/10.1124/dmd.104.000893] [PMID: 15466493]
[24]
Tang L, Zhou J, Yang CH, Xia BJ, Hu M, Liu ZQ. Systematic studies of sulfation and glucuronidation of 12 flavonoids in the mouse liver S9 fraction reveal both unique and shared positional preferences. J Agric Food Chem 2012; 60(12): 3223-33.
[http://dx.doi.org/10.1021/jf201987k] [PMID: 22352802]
[25]
Gradolatto A, Canivenc-Lavier MC, Basly JP, Siess MH, Teyssier C. Metabolism of apigenin by rat liver phase I and phase II enzymes and by isolated perfused rat liver. Drug Metab Dispos 2004; 32(1): 58-65.
[http://dx.doi.org/10.1124/dmd.32.1.58] [PMID: 14709621]
[26]
Das S, Rosazza JPN. Microbial and enzymatic transformations of flavonoids. J Nat Prod 2006; 69(3): 499-508.
[http://dx.doi.org/10.1021/np0504659] [PMID: 16562863]
[27]
Wang SWJ, Kulkarni KH, Tang L, et al. Disposition of flavonoids via enteric recycling: UDP-glucuronosyltransferase (UGT) 1As deficiency in Gunn rats is compensated by increases in UGT2Bs activities. J Pharmacol Exp Ther 2009; 329(3): 1023-31.
[http://dx.doi.org/10.1124/jpet.108.147371] [PMID: 19264971]
[28]
Ali F, Rahul , Naz F, Jyoti S, Siddique YH. Health functionality of apigenin: A review. Int J Food Prop 2017; 20(6): 1197-238.
[http://dx.doi.org/10.1080/10942912.2016.1207188]
[29]
Ng SP, Wong KY, Zhang L, Zuo Z, Lin G. Evaluation of the first- pass glucuronidation of selected flavones in gut by Caco-2 monolayer model. J Pharm Pharm Sci 2004; 8(1): 1-9.
[PMID: 15946592]
[30]
Hu M, Chen J, Lin H. Metabolism of flavonoids via enteric recycling: mechanistic studies of disposition of apigenin in the Caco-2 cell culture model. J Pharmacol Exp Ther 2003; 307(1): 314-21.
[http://dx.doi.org/10.1124/jpet.103.053496] [PMID: 12893842]
[31]
Spencer JPE, Abd El Mohsen MM, Rice-Evans C. Cellular uptake and metabolism of flavonoids and their metabolites: implications for their bioactivity. Arch Biochem Biophys 2004; 423(1): 148-61.
[http://dx.doi.org/10.1016/j.abb.2003.11.010] [PMID: 14989269]
[32]
Day AJ, Dupont MS, Ridley S, et al. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity. FEBS Lett 1998; 346(1): 71-5.
[http://dx.doi.org/10.1016/s0014-5793(98)01101-6] [PMID: 9771896]
[33]
Nielsen SE, Breinholt V, Justesen U, Cornett C, Dragsted LO. In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotica 2008; 28(4): 389-401.
[http://dx.doi.org/10.1080/004982598239498] [PMID: 9604302]
[34]
Galati G, Moridani MY, Chan TS, O’Brien PJ. Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation. Free Radic Biol Med 2001; 30(4): 370-82.
[http://dx.doi.org/10.1016/S0891-5849(00)00481-0] [PMID: 11182292]
[35]
Galati G, Chan T, Wu B, O’Brien PJ. Glutathione-dependent generation of reactive oxygen species by the peroxidase-catalyzed redox cycling of flavonoids. Chem Res Toxicol 1999; 12(6): 521-5.
[http://dx.doi.org/10.1021/tx980271b] [PMID: 10368315]
[36]
Nielsen SE, Young JF, Daneshvar B, et al. Effect of parsley ( Petroselinum crispum ) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects. Br J Nutr 1999; 81(6): 447-55.
[http://dx.doi.org/10.1017/S000711459900080X] [PMID: 10615220]
[37]
Meyer H, Bolarinwa A, Wolfram G, Linseisen J. Bioavailability of apigenin from apiin-rich parsley in humans. Ann Nutr Metab 2006; 50(3): 167-72.
[http://dx.doi.org/10.1159/000090736] [PMID: 16407641]
[38]
Salehi B, Venditti A, Sharifi-Rad M, et al. The therapeutic potential of apigenin. Int J Mol Sci 2019; 20(6): 1305.
[http://dx.doi.org/10.3390/ijms20061305] [PMID: 30875872]
[39]
Nozhat Z, Heydarzadeh S, Memariani Z, Ahmadi A. Chemoprotective and chemosensitizing effects of apigenin on cancer therapy. Cancer Cell Int 2021; 21(1): 574.
[http://dx.doi.org/10.1186/s12935-021-02282-3] [PMID: 34715860]
[40]
Way TD, Kao MC, Lin JK. Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway. J Biol Chem 2004; 279(6): 4479-89.
[http://dx.doi.org/10.1074/jbc.M305529200] [PMID: 14602723]
[41]
Banerjee K, Banerjee S, Das S, Mandal M. Probing the potential of apigenin liposomes in enhancing bacterial membrane perturbation and integrity loss. J Colloid Interface Sci 2015; 453: 48-59.
[http://dx.doi.org/10.1016/j.jcis.2015.04.030] [PMID: 25965432]
[42]
Singh G, Kumar P, Joshi SC. Treatment of dermatophytosis by a new antifungal agent ‘apigenin’. Mycoses 2014; 57(8): 497-506.
[http://dx.doi.org/10.1111/myc.12188] [PMID: 24708558]
[43]
Maggioni D, Garavello W, Rigolio R, Pignataro L, Gaini R, Nicolini G. Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. Int J Oncol 2013; 43(5): 1675-82.
[http://dx.doi.org/10.3892/ijo.2013.2072] [PMID: 23969487]
[44]
Seo SH, Ku JM, Choi HS, et al. Induction of caspase-dependent apoptosis by apigenin by inhibiting STAT3 signaling in HER2-overexpressing MDA-MB-453 breast cancer cells. Anticancer Res 2014; 34(6): 2869-82.
[PMID: 24922650]
[45]
Lapchak PA, Boitano PD. Effect of the pleiotropic drug CNB-001 on tissue plasminogen activator (TPA) protease activity in vitro: Support for combination therapy to treat acute ischemic stroke. J Neurol Neurophysiol 2014; 5(4): 214.
[PMID: 25364620]
[46]
Huang CH, Kuo PL, Hsu YL, et al. The natural flavonoid apigenin suppresses Th1- and Th2-related chemokine production by human monocyte THP-1 cells through mitogen-activated protein kinase pathways. J Med Food 2010; 13(2): 391-8.
[http://dx.doi.org/10.1089/jmf.2009.1229] [PMID: 20170340]
[47]
Campbell EL, Chebib M, Johnston GAR. The dietary flavonoids apigenin and (−)-epigallocatechin gallate enhance the positive modulation by diazepam of the activation by GABA of recombinant GABAA receptors. Biochem Pharmacol 2004; 68(8): 1631-8.
[http://dx.doi.org/10.1016/j.bcp.2004.07.022] [PMID: 15451406]
[48]
Telange DR, Patil AT, Pethe AM, Fegade H, Anand S, Dave VS. Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. Eur J Pharm Sci 2017; 108: 36-49.
[http://dx.doi.org/10.1016/j.ejps.2016.12.009] [PMID: 27939619]
[49]
Pamunuwa G, Karunaratne DN, Waisundara VY. Antidiabetic properties, bioactive constituents, and other therapeutic effects of Scoparia dulcis. Evid Based Complement Altern Med 2016; 2016: 8243215.
[http://dx.doi.org/10.1155/2016/8243215] [PMID: 27594892]
[50]
Wang QQ, Cheng N, Yi WB, Peng SM, Zou XQ. Synthesis, nitric oxide release, and α-glucosidase inhibition of nitric oxide donating apigenin and chrysin derivatives. Bioorg Med Chem 2014; 22(5): 1515-21.
[http://dx.doi.org/10.1016/j.bmc.2014.01.038] [PMID: 24508143]
[51]
Panda S, Kar A. Apigenin (4‘,5,7-trihydroxyflavone) regulates hyperglycaemia, thyroid dysfunction and lipid peroxidation in alloxan-induced diabetic mice. J Pharm Pharmacol 2010; 59(11): 1543-8.
[http://dx.doi.org/10.1211/jpp.59.11.0012] [PMID: 17976266]
[52]
Ren B, Qin W, Wu F, et al. Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats. Eur J Pharmacol 2016; 773: 13-23.
[http://dx.doi.org/10.1016/j.ejphar.2016.01.002] [PMID: 26801071]
[53]
Liu HJ, Fan YL, Liao HH, et al. Apigenin alleviates STZ-induced diabetic cardiomyopathy. Mol Cell Biochem 2017; 428(1-2): 9-21.
[http://dx.doi.org/10.1007/s11010-016-2913-9] [PMID: 28176247]
[54]
Shakeri F, Boskabady MH. A review of the relaxant effect of various medicinal plants on tracheal smooth muscle, their possible mechanism(s) and potency. J Ethnopharmacol 2015; 175: 528-48.
[http://dx.doi.org/10.1016/j.jep.2015.10.017] [PMID: 26456328]
[55]
Münch G, Venigalla M, Sonego S, Gyengesi E. Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer′s disease. Neural Regen Res 2015; 10(8): 1181-5.
[http://dx.doi.org/10.4103/1673-5374.162686] [PMID: 26487830]
[56]
Zhao L, Wang JL, Liu R, Li XX, Li JF, Zhang L. Neuroprotective, anti-amyloidogenic and neurotrophic effects of apigenin in an Alzheimer’s disease mouse model. Molecules 2013; 18(8): 9949-65.
[http://dx.doi.org/10.3390/molecules18089949] [PMID: 23966081]
[57]
Balez R, Steiner N, Engel M, et al. Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Sci Rep 2016; 6(1): 31450.
[http://dx.doi.org/10.1038/srep31450] [PMID: 27514990]
[58]
Avallone R, Zanoli P, Puia G, Kleinschnitz M, Schreier P, Baraldi M. Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol 2000; 59(11): 1387-94.
[http://dx.doi.org/10.1016/S0006-2952(00)00264-1] [PMID: 10751547]
[59]
Weng L, Guo X, Li Y, Yang X, Han Y. Apigenin reverses depression-like behavior induced by chronic corticosterone treatment in mice. Eur J Pharmacol 2016; 774: 50-4.
[http://dx.doi.org/10.1016/j.ejphar.2016.01.015] [PMID: 26826594]
[60]
Nakazawa T, Yasuda T, Ueda J, Ohsawa K. Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test. Biol Pharm Bull 2003; 26(4): 474-80.
[http://dx.doi.org/10.1248/bpb.26.474] [PMID: 12673028]
[61]
Chaurasiya ND, Ibrahim MA, Muhammad I, Walker LA, Tekwani BL. Monoamine oxidase inhibitory constituents of propolis: kinetics and mechanism of inhibition of recombinant human MAO-A and MAO-B. Molecules 2014; 19(11): 18936-52.
[http://dx.doi.org/10.3390/molecules191118936] [PMID: 25412041]
[62]
Li R, Zhao D, Qu R, Fu Q, Ma S. The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice. Neurosci Lett 2015; 594: 17-22.
[http://dx.doi.org/10.1016/j.neulet.2015.03.040] [PMID: 25800110]
[63]
Shukla S, Fu P, Gupta S. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer. Apoptosis 2014; 19(5): 883-94.
[http://dx.doi.org/10.1007/s10495-014-0971-6] [PMID: 24563225]
[64]
Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell Biosci 2017; 7(1): 50.
[http://dx.doi.org/10.1186/s13578-017-0179-x] [PMID: 29034071]
[65]
Lee Y, Sung B, Kang YJ, et al. Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells. Int J Oncol 2014; 44(5): 1599-606.
[http://dx.doi.org/10.3892/ijo.2014.2339] [PMID: 24626522]
[66]
Tseng TH, Chien MH, Lin WL, et al. Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression. Environ Toxicol 2017; 32(2): 434-44.
[http://dx.doi.org/10.1002/tox.22247] [PMID: 26872304]
[67]
Meng S, Zhu Y, Li JF, et al. Apigenin inhibits renal cell carcinoma cell proliferation. Oncotarget 2017; 8(12): 19834-42.
[http://dx.doi.org/10.18632/oncotarget.15771] [PMID: 28423637]
[68]
Zhang L, Cheng X, Gao Y, et al. Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells. Food Funct 2015; 6(11): 3464-72.
[http://dx.doi.org/10.1039/C5FO00671F] [PMID: 26292725]
[69]
Salmani JMM, Zhang XP, Jacob JA, Chen BA. Apigenin’s anticancer properties and molecular mechanisms of action: Recent advances and future prospectives. Chin J Nat Med 2017; 15(5): 321-9.
[http://dx.doi.org/10.1016/S1875-5364(17)30052-3] [PMID: 28558867]
[70]
Wang Q, Zeng P, Liu Y, Wen G, Fu X, Sun X. Inhibition of autophagy ameliorates atherogenic inflammation by augmenting apigenin-induced macrophage apoptosis. Int Immunopharmacol 2015; 27(1): 24-31.
[http://dx.doi.org/10.1016/j.intimp.2015.04.018] [PMID: 25899084]
[71]
Zhou Z, Tang M, Liu Y, Zhang Z, Lu R, Lu J. Apigenin inhibits cell proliferation, migration, and invasion by targeting Akt in the A549 human lung cancer cell line. Anticancer Drugs 2017; 28(4): 446-56.
[http://dx.doi.org/10.1097/CAD.0000000000000479] [PMID: 28125432]
[72]
Coombs MRP, Harrison ME, Hoskin DW. Apigenin inhibits the inducible expression of programmed death ligand 1 by human and mouse mammary carcinoma cells. Cancer Lett 2016; 380(2): 424-33.
[http://dx.doi.org/10.1016/j.canlet.2016.06.023] [PMID: 27378243]
[73]
Arsić I, Tadić V, Vlaović D, et al. Preparation of novel apigenin-enriched, liposomal and non-liposomal, antiinflammatory topical formulations as substitutes for corticosteroid therapy. Phytother Res 2011; 25(2): 228-33.
[http://dx.doi.org/10.1002/ptr.3245] [PMID: 20641055]
[74]
Shen LN, Zhang YT, Wang Q, Xu L, Feng NP. Enhanced in vitro and in vivo skin deposition of apigenin delivered using ethosomes. Int J Pharm 2014; 460(1-2): 280-8.
[http://dx.doi.org/10.1016/j.ijpharm.2013.11.017] [PMID: 24269286]
[75]
Kim BK, Cho AR, Park DJ. Enhancing oral bioavailability using preparations of apigenin-loaded W/O/W emulsions: In vitro and in vivo evaluations. Food Chem 2016; 206: 85-91.
[http://dx.doi.org/10.1016/j.foodchem.2016.03.052] [PMID: 27041302]
[76]
Jangdey MS, Gupta A, Saraf S. Fabrication, in-vitro characterization, and enhanced in-vivo evaluation of carbopol-based nanoemulsion gel of apigenin for UV-induced skin carcinoma. Drug Deliv 2017; 24(1): 1026-36.
[http://dx.doi.org/10.1080/10717544.2017.1344333] [PMID: 28687053]
[77]
Zhao X, Wang Z, Li X. Preparation, in-vitro release and antioxidant potential of formulation of apigenin with hydroxypropyl-β-cyclodextrin modified microemulsion. J Incl Phenom Macrocycl Chem 2016; 86(1-2): 93-102.
[http://dx.doi.org/10.1007/s10847-016-0644-x]
[78]
Lee NH, Park SH, Park SN. Preparation and characterization of novel pseudo ceramide-based nanostructured lipid carriers for transdermal delivery of apigenin. J Drug Deliv Sci Technol 2018; 48: 245-52.
[http://dx.doi.org/10.1016/j.jddst.2018.09.019]
[79]
Al Shaal L, Shegokar R, Müller RH. Production and characterization of antioxidant apigenin nanocrystals as a novel UV skin protective formulation. Int J Pharm 2011; 420(1): 133-40.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.018] [PMID: 21871547]
[80]
Munyendo WLL, Zhang Z, Abbad S, et al. Micelles of TPGS modified apigenin phospholipid complex for oral administration: preparation, in vitro and in vivo evaluation. J Biomed Nanotechnol 2013; 9(12): 2034-47.
[http://dx.doi.org/10.1166/jbn.2013.1704] [PMID: 24266259]
[81]
Pápay ZE, Kósa A, Böddi B, et al. Study on the pulmonary delivery system of apigenin-loaded albumin nanocarriers with antioxidant activity. J Aerosol Med Pulm Drug Deliv 2017; 30(4): 274-88.
[http://dx.doi.org/10.1089/jamp.2016.1316] [PMID: 28282259]
[82]
Ding B, Chen H, Wang C, Zhai Y, Zhai G. Preparation and in vitro evaluation of apigenin loaded lipid nanocapsules. J Nanosci Nanotechnol 2013; 13(10): 6546-52.
[http://dx.doi.org/10.1166/jnn.2013.7763] [PMID: 24245113]
[83]
Jangdey MS, Gupta A, Saraf S, Saraf S. Development and optimization of apigenin-loaded transfersomal system for skin cancer delivery: In vitro evaluation. Artif Cells Nanomed Biotechnol 2017; 45(7): 1452-62.
[http://dx.doi.org/10.1080/21691401.2016.1247850] [PMID: 28050929]
[84]
Zhu B, Li X, Xu X, et al. One-step phosphorylated poly(amide-amine) dendrimer loaded with apigenin for simultaneous remineralization and antibacterial of dentine. Colloids Surf B Biointerfaces 2018; 172: 760-8.
[http://dx.doi.org/10.1016/j.colsurfb.2018.09.036] [PMID: 30261466]
[85]
Sen K, Banerjee S, Mandal M. Dual drug loaded liposome bearing apigenin and 5-Fluorouracil for synergistic therapeutic efficacy in colorectal cancer. Colloids Surf B Biointerfaces 2019; 180(April): 9-22.
[http://dx.doi.org/10.1016/j.colsurfb.2019.04.035] [PMID: 31015105]
[86]
Akilandeswari K, Ruckmani K. Synergistic antibacterial effect of apigenin with β-lactam antibiotics and modulation of bacterial resistance by a possible membrane effect against methicillin resistant Staphylococcus aureus. Cell Mol Biol 2016; 62(14): 74-82.
[http://dx.doi.org/10.14715/cmb/2016.62.14.13] [PMID: 28145860]
[87]
Eumkeb G, Chukrathok S. Synergistic activity and mechanism of action of ceftazidime and apigenin combination against ceftazidime-resistant Enterobacter cloacae. Phytomedicine 2013; 20(3-4): 262-9.
[http://dx.doi.org/10.1016/j.phymed.2012.10.008] [PMID: 23218402]
[88]
Hu WJ, Liu J, Zhong LK, Wang J. Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling. Biomed Pharmacother 2018; 102(16): 681-8.
[http://dx.doi.org/10.1016/j.biopha.2018.03.111] [PMID: 29604587]
[89]
Erdogan S, Turkekul K, Serttas R, Erdogan Z. The natural flavonoid apigenin sensitizes human CD44 + prostate cancer stem cells to cisplatin therapy. Biomed Pharmacother 2017; 88: 210-7.
[http://dx.doi.org/10.1016/j.biopha.2017.01.056] [PMID: 28107698]
[90]
Medhat AM, Azab KS, Said MM, El Fatih NM, El Bakary NM. Antitumor and radiosensitizing synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice. Tumour Biol 2017; 39(10): 1010428317728480.
[http://dx.doi.org/10.1177/1010428317728480] [PMID: 29022496]
[91]
Mahbub AA, Le Maitre CL, Haywood-Small SL, Cross NA, Jordan-Mahy N. Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines. Cell Death Discov 2015; 1(1): 15043.
[http://dx.doi.org/10.1038/cddiscovery.2015.43] [PMID: 27551472]
[92]
Chen Z, Tian D, Liao X, et al. Apigenin combined with gefitinib blocks autophagy flux and induces apoptotic cell death through inhibition of HIF-1α, c-Myc, p-EGFR, and glucose metabolism in EGFR L858R+T790M-Mutated H1975 cells. Front Pharmacol 2019; 10(MAR): 260.
[http://dx.doi.org/10.3389/fphar.2019.00260]
[93]
Lee SH, Ryu JK, Lee KY, et al. Enhanced anti-tumor effect of combination therapy with gemcitabine and apigenin in pancreatic cancer. Cancer Lett 2008; 259(1): 39-49.
[http://dx.doi.org/10.1016/j.canlet.2007.09.015] [PMID: 17967505]
[94]
Korga-Plewko A, Michalczyk M, Adamczuk G, et al. Apigenin and hesperidin downregulate DNA repair genes in MCF-7 breast cancer cells and augment doxorubicin toxicity. Molecules 2020; 25(19): 4421.
[http://dx.doi.org/10.3390/molecules25194421] [PMID: 32993087]
[95]
Xia F, Li X, Wang B, et al. Combination therapy of LysGH15 and apigenin as a new strategy for treating pneumonia caused by Staphylococcus aureus. Appl Environ Microbiol 2016; 82(1): 87-94.
[http://dx.doi.org/10.1128/AEM.02581-15] [PMID: 26475103]
[96]
Yang L, Allred KF, Dykes L, Allred CD, Awika JM. Enhanced action of apigenin and naringenin combination on estrogen receptor activation in non-malignant colonocytes: Implications on sorghum-derived phytoestrogens. Food Funct 2015; 6(3): 749-55.
[http://dx.doi.org/10.1039/C4FO00300D] [PMID: 25553799]
[97]
Xu Y, Xin Y, Diao Y, et al. Synergistic effects of apigenin and paclitaxel on apoptosis of cancer cells. PLoS One 2011; 6(12): e29169.
[http://dx.doi.org/10.1371/journal.pone.0029169] [PMID: 22216199]
[98]
Mohan N, Banik NL, Ray SK. Combination of N-(4-hydroxyphenyl) retinamide and apigenin suppressed starvation-induced autophagy and promoted apoptosis in malignant neuroblastoma cells. Neurosci Lett 2011; 502(1): 24-9.
[http://dx.doi.org/10.1016/j.neulet.2011.07.016] [PMID: 21801811]
[99]
Sang Z, Wang K, Shi J, et al. Apigenin-rivastigmine hybrids as multi-target-directed liagnds for the treatment of Alzheimer’s disease. Eur J Med Chem 2020; 187: 111958.
[http://dx.doi.org/10.1016/j.ejmech.2019.111958] [PMID: 31865014]
[100]
Jin X, Yang Q, Zhang Y. Synergistic apoptotic effects of apigenin TPGS liposomes and tyroservatide: implications for effective treatment of lung cancer. Int J Nanomedicine 2017; 12: 5109-18.
[http://dx.doi.org/10.2147/IJN.S140096] [PMID: 28761344]
[101]
Dourado NS, Souza CS, de Almeida MMA, et al. Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin inin vitro models of neuroinflammation associated with alzheimer’s disease. Front Aging Neurosci 2020; 12(May): 119.
[http://dx.doi.org/10.3389/fnagi.2020.00119] [PMID: 32499693]
[102]
Chen P, Huo X, Liu W, Li K, Sun Z, Tian J. Apigenin exhibits anti-inflammatory effects in LPS-stimulated BV2 microglia through activating GSK3β/Nrf2 signaling pathway. Immunopharmacol Immunotoxicol 2020; 42(1): 9-16.
[http://dx.doi.org/10.1080/08923973.2019.1688345] [PMID: 31760890]
[103]
Che DN, Cho BO, Kim J, Shin JY, Kang HJ, Jang SI. Il. Effect of luteolin and apigenin on the production of IL-31 and IL-33 in lipopolysaccharides-activated microglia cells and their mechanism of action. Nutrients 2020; 12(3): 811.
[http://dx.doi.org/10.3390/nu12030811] [PMID: 32204450]
[104]
Ling C, Lei C, Zou M, et al. Neuroprotective effect of apigenin against cerebral ischemia/reperfusion injury. J Int Med Res 2020; 48(9): 300060520945859.
[http://dx.doi.org/10.1177/0300060520945859] [PMID: 32993408]
[105]
Aseervatham GSB, Suryakala U, Doulethunisha , Sundaram S, Bose PC, Sivasudha T. Expression pattern of NMDA receptors reveals antiepileptic potential of apigenin 8-C-glucoside and chlorogenic acid in pilocarpine induced epileptic mice. Biomed Pharmacother 2016; 82: 54-64.
[http://dx.doi.org/10.1016/j.biopha.2016.04.066] [PMID: 27470339]
[106]
Hashemi P, Fahanik Babaei J, Vazifekhah S, Nikbakht F. Evaluation of the neuroprotective, anticonvulsant, and cognition-improvement effects of apigenin in temporal lobe epilepsy: Involvement of the mitochondrial apoptotic pathway. Iran J Basic Med Sci 2019; 22(7): 752-8.
[PMID: 32373296]
[107]
Shao C, Yuan J, Liu Y, et al. Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis. Proc Natl Acad Sci USA 2020; 117(19): 10155-64.
[http://dx.doi.org/10.1073/pnas.1917946117] [PMID: 32327603]
[108]
Rahmati M, Ghannadian SM, Kasiri N, et al. Modulation of Th17 proliferation and IL-17A gene expression by acetylated form of apigenin in patients with multiple sclerosis. Immunol Invest 2021; 50(2-3): 216-29.
[http://dx.doi.org/10.1080/08820139.2020.1726381] [PMID: 32100582]
[109]
Siddique YH, Jyoti S. Alteration in biochemical parameters in the brain of transgenic Drosophila melanogaster model of Parkinson’s disease exposed to apigenin. Integr Med Res 2017; 6(3): 245-53.
[http://dx.doi.org/10.1016/j.imr.2017.04.003] [PMID: 28951838]
[110]
Patil SP, Jain PD, Sancheti JS, Ghumatkar PJ, Tambe R, Sathaye S. RETRACTED: Neuroprotective and neurotrophic effects of Apigenin and Luteolin in MPTP induced parkinsonism in mice. Neuropharmacology 2014; 86: 192-202.
[http://dx.doi.org/10.1016/j.neuropharm.2014.07.012] [PMID: 25087727]
[111]
Anusha C, Sumathi T, Joseph LD. Protective role of apigenin on rotenone induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis. Chem Biol Interact 2017; 269(10): 67-79.
[http://dx.doi.org/10.1016/j.cbi.2017.03.016] [PMID: 28389404]
[112]
Yu W, Sun H, Zha W, Cui W, Xu L, Min Q, et al. Apigenin attenuates adriamycin-induced cardiomyocyte Apoptosis via the PI3K/AKT/mTOR pathway. Evid-based Complement Altern Med 2017; 2017: 2590676.
[http://dx.doi.org/10.1155/2017/2590676] [PMID: 28684964]
[113]
Jahedsani A, Khezri S, Ahangari M, Bakhshii S, Salimi A. Apigenin attenuates Aluminum phosphide-induced cytotoxicity via reducing mitochondrial/Lysosomal damages and oxidative stress in rat Cardiomyocytes. Pestic Biochem Physiol 2020; 167: 104585.
[http://dx.doi.org/10.1016/j.pestbp.2020.104585] [PMID: 32527440]
[114]
Thangaiyan R, Robert BM, Arjunan S, Govindasamy K, Nagarajan RP. Preventive effect of apigenin against isoproterenol-induced apoptosis in cardiomyoblasts. J Biochem Mol Toxicol 2018; 32(11): e22213.
[http://dx.doi.org/10.1002/jbt.22213] [PMID: 30152906]
[115]
Zare MFR, Rakhshan K, Aboutaleb N, et al. Apigenin attenuates doxorubicin induced cardiotoxicity via reducing oxidative stress and apoptosis in male rats. Life Sci 2019; 232(April): 116623.
[http://dx.doi.org/10.1016/j.lfs.2019.116623] [PMID: 31279781]
[116]
Zhang T, Yan T, Du J, Wang S, Yang H. Apigenin attenuates heart injury in lipopolysaccharide-induced endotoxemic model by suppressing sphingosine kinase 1/sphingosine 1-phosphate signaling pathway. Chem Biol Interact 2015; 233: 46-55.
[http://dx.doi.org/10.1016/j.cbi.2014.12.021] [PMID: 25557508]
[117]
Mahajan UB, Chandrayan G, Patil CR, et al. The protective effect of apigenin on myocardial injury in diabetic rats mediating activation of the PPAR-γ pathway. Int J Mol Sci 2017; 18(4): 756.
[http://dx.doi.org/10.3390/ijms18040756] [PMID: 28375162]
[118]
Li YW, Xu J, Zhu GY, et al. Apigenin suppresses the stem cell-like properties of triple-negative breast cancer cells by inhibiting YAP/TAZ activity. Cell Death Discov 2018; 4(1): 105.
[http://dx.doi.org/10.1038/s41420-018-0124-8] [PMID: 30479839]
[119]
Vrhovac Madunić I, Madunić J, Antunović M, et al. Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells. Naunyn Schmiedebergs Arch Pharmacol 2018; 391(5): 537-50.
[http://dx.doi.org/10.1007/s00210-018-1486-4] [PMID: 29541820]
[120]
Lee HH, Jung J, Moon A, Kang H, Cho H. Antitumor and anti-invasive effect of apigenin on human breast carcinoma through suppression of IL-6 expression. Int J Mol Sci 2019; 20(13): 3143.
[http://dx.doi.org/10.3390/ijms20133143] [PMID: 31252615]
[121]
Chen X, Xu H, Yu X, Wang X, Zhu X, Xu X. Apigenin inhibits in vitro and in vivo tumorigenesis in cisplatin-resistant colon cancer cells by inducing autophagy, programmed cell death and targeting m-TOR/PI3K/Akt signalling pathway. J BUON 2019; 24(2): 488-93.
[PMID: 31127995]
[122]
Cheng Y, Han X, Mo F, et al. Apigenin inhibits the growth of colorectal cancer through down-regulation of E2F1/3 by miRNA-215-5p. Phytomedicine 2021; 89: 153603.
[http://dx.doi.org/10.1016/j.phymed.2021.153603] [PMID: 34175590]
[123]
Chen M, Wang X, Zha D, et al. Apigenin potentiates TRAIL therapy of non-small cell lung cancer via upregulating DR4/DR5 expression in a p53-dependent manner. Sci Rep 2016; 6(1): 35468.
[http://dx.doi.org/10.1038/srep35468] [PMID: 27752089]
[124]
Chien MH, Lin YW, Wen YC, et al. Targeting the SPOCK1-snail/slug axis-mediated epithelial-to-mesenchymal transition by apigenin contributes to repression of prostate cancer metastasis. J Exp Clin Cancer Res 2019; 38(1): 246.
[http://dx.doi.org/10.1186/s13046-019-1247-3] [PMID: 30606223]
[125]
Erdogan S, Doganlar O, Doganlar ZB, et al. The flavonoid apigenin reduces prostate cancer CD44+ stem cell survival and migration through PI3K/Akt/NF-κB signaling. Life Sci 2016; 162: 77-86.
[http://dx.doi.org/10.1016/j.lfs.2016.08.019] [PMID: 27569589]
[126]
Imran M, Aslam Gondal T, Atif M, et al. Apigenin as an anticancer agent. Phytother Res 2020; 34(8): 1812-28.
[http://dx.doi.org/10.1002/ptr.6647] [PMID: 32059077]
[127]
Li J, Bai L, Li X, et al. Antidiabetic potential of flavonoids from traditional Chinese medicine: A review. Am J Chin Med 2019; 47(5): 933-57.
[http://dx.doi.org/10.1142/S0192415X19500496] [PMID: 31248265]
[128]
Hossain CM, Ghosh MK, Satapathy BS, Dey NS, Mukherjee B. Apigenin causes biochemical modulation, GLUT4 and CD38 alterations to improve diabetes and to protect damages of some vital organs in experimental diabetes. Am J Pharmacol Toxicol 2014; 9(1): 39-52.
[http://dx.doi.org/10.3844/ajptsp.2014.39.52]
[129]
Hajiaghaalipour F, Khalilpourfarshbafi M, Arya A, Arya A. Modulation of glucose transporter protein by dietary flavonoids in type 2 diabetes mellitus. Int J Biol Sci 2015; 11(5): 508-24.
[http://dx.doi.org/10.7150/ijbs.11241] [PMID: 25892959]
[130]
Wang N, Yi WJ, Tan L, et al. Apigenin attenuates streptozotocin-induced pancreatic β cell damage by its protective effects on cellular antioxidant defense. In Vitro Cell Dev Biol Anim 2017; 53(6): 554-63.
[http://dx.doi.org/10.1007/s11626-017-0135-4] [PMID: 28181104]
[131]
Chen H, Mrazek AA, Wang X, et al. Design, synthesis, and characterization of novel apigenin analogues that suppress pancreatic stellate cell proliferation in vitro and associated pancreatic fibrosis in vivo. Bioorg Med Chem 2014; 22(13): 3393-404.
[http://dx.doi.org/10.1016/j.bmc.2014.04.043] [PMID: 24837156]
[132]
Mrazek AA, Porro LJ, Bhatia V, et al. Apigenin inhibits pancreatic stellate cell activity in pancreatitis. J Surg Res 2015; 196(1): 8-16.
[http://dx.doi.org/10.1016/j.jss.2015.02.032] [PMID: 25799526]
[133]
Hicks DF, Goossens N, Blas-García A, et al. Transcriptome-based repurposing of apigenin as a potential anti-fibrotic agent targeting hepatic stellate cells. Sci Rep 2017; 7: 42563.
[http://dx.doi.org/10.1038/srep42563] [PMID: 28256512]
[134]
Malik S, Suchal K, Khan SI, et al. Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways. Am J Physiol Renal Physiol 2017; 13(2): F414-22.
[http://dx.doi.org/10.1152/ajprenal.00393.2016] [PMID: 28566504]
[135]
Li P, Bukhari SNA, Khan T, et al. Apigenin-loaded solid lipid nanoparticle attenuates diabetic nephropathy induced by streptozotocin nicotinamide through Nrf2/HO-1/NF-kB signalling pathway. Int J Nanomedicine 2020; 15: 9115-24.
[http://dx.doi.org/10.2147/IJN.S256494] [PMID: 33244230]
[136]
Luan RL, Meng XX, Jiang W. Protective effects of apigenin against paraquat-induced acute lung injury in mice. Inflammation 2016; 39(2): 752-8.
[http://dx.doi.org/10.1007/s10753-015-0302-2] [PMID: 26782361]
[137]
Chumsakul O, Wakayama K, Tsuhako A, et al. Apigenin regulates activation of microglia and counteracts retinal degeneration. J Ocul Pharmacol Ther 2020; 36(5): 311-9.
[http://dx.doi.org/10.1089/jop.2019.0163] [PMID: 32379991]
[138]
Morimoto Y, Baba T, Sasaki T, Hiramatsu K. Apigenin as an anti-quinolone-resistance antibiotic. Int J Antimicrob Agents 2015; 46(6): 666-73.
[http://dx.doi.org/10.1016/j.ijantimicag.2015.09.006] [PMID: 26526895]
[139]
Liu R, Zhang H, Yuan M, et al. Synthesis and biological evaluation of apigenin derivatives as antibacterial and antiproliferative agents. Molecules 2013; 18(9): 11496-511.
[http://dx.doi.org/10.3390/molecules180911496] [PMID: 24048283]
[140]
Wu Q, Yu C, Yan Y, Chen J, Zhang C, Wen X. Antiviral flavonoids from Mosla scabra. Fitoterapia 2010; 81(5): 429-33.
[http://dx.doi.org/10.1016/j.fitote.2009.12.005] [PMID: 20006976]
[141]
Shibata C, Ohno M, Otsuka M, et al. The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels. Virology 2014; 462-463(1): 42-8.
[http://dx.doi.org/10.1016/j.virol.2014.05.024] [PMID: 25092460]
[142]
Fonseca-Silva F, Canto-Cavalheiro MM, Menna-Barreto RFS, Almeida-Amaral EE. Effect of apigenin on Leishmania amazonensis is associated with reactive oxygen species production followed by mitochondrial dysfunction. J Nat Prod 2015; 78(4): 880-4.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00011] [PMID: 25768915]
[143]
Huh S, Lee J, Jung E, et al. A cell-based system for screening hair growth-promoting agents. Arch Dermatol Res 2009; 301(5): 381-5.
[http://dx.doi.org/10.1007/s00403-009-0931-0] [PMID: 19277688]
[144]
Park CH, Min SY, Yu HW, et al. Effects of apigenin on RBL-2H3, RAW264.7, and HaCaT cells: Anti-allergic, anti-inflammatory, and skin-protective activities. Int J Mol Sci 2020; 21(13): 4620.
[http://dx.doi.org/10.3390/ijms21134620] [PMID: 32610574]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy