Abstract
Chrysin (a flavonoid) has shown various promising pharmacological activities viz. anticancer, anti-diabetic, immune-modulation, antidepressant, and anti-asthmatic. Additionally, it exhibited potential protective effects against various toxins on different organs like the liver, brain, kidney, and heart. A multitude of studies have been conducted to explore the possible targets for its possible mechanism of action. However, its therapeutic applications have been limited due to its poor oral bioavailability. The major reason for its poor bioavailability is its extensive first-pass metabolism. A critical review of the pharmacological properties of chrysin and its associated molecular targets has not been discussed as yet comprehensively. Therefore, the emphasis of the present work is to provide an in-depth understanding of molecular targets accountable for the pharmacological actions of chrysin. Moreover, a schematic diagram was made for the first time to represent the comprehensive pharmacokinetic properties of chrysin, which helps to understand the biopharmaceutical aspect for its successful delivery. An in-depth understanding of the biopharmaceutical properties of chrysin will help in adopting a suitable formulation approach to overcome poor oral bioavailability. Additionally, it facilitates to study the possible pharmacokinetic interactions of chrysin with other drugs. Hence, we found that chrysin is a miraculous natural agent with myriad therapeutic properties, and its benefit can be exploited with an in-depth understanding of molecular targets, pharmacological actions, and biopharmaceutical attributes.
Keywords: Chrysin, chemopreventive, anticancer, protective effect, antidepressant, antidiabetic, antiviral, pharmacokinetic.
Graphical Abstract
[http://dx.doi.org/10.1111/bph.13779] [PMID: 28500635]
[http://dx.doi.org/10.1111/bph.14943] [PMID: 31799702]
[http://dx.doi.org/10.1016/j.phrs.2018.06.007] [PMID: 29890252]
[http://dx.doi.org/10.1016/j.arabjc.2010.09.016]
[http://dx.doi.org/10.1002/ptr.2072] [PMID: 17199238]
[http://dx.doi.org/10.1016/j.neuint.2015.09.006] [PMID: 26386393]
[http://dx.doi.org/10.1016/j.phytochem.2017.09.016] [PMID: 29161583]
[http://dx.doi.org/10.1007/s13105-012-0215-6] [PMID: 23104078]
[PMID: 20811719]
[http://dx.doi.org/10.1080/10942912.2019.1579835]
[http://dx.doi.org/10.1021/acs.jafc.1c01109] [PMID: 33979145]
[http://dx.doi.org/10.1016/j.toxlet.2015.01.008] [PMID: 25596314]
[http://dx.doi.org/10.1080/1028415X.2017.1418786] [PMID: 29284373]
[http://dx.doi.org/10.1016/0091-3057(94)90103-1] [PMID: 7906886]
[http://dx.doi.org/10.1016/j.biopha.2018.11.111] [PMID: 30551498]
[http://dx.doi.org/10.1016/j.ejphar.2016.09.005] [PMID: 27609609]
[http://dx.doi.org/10.1007/s43450-021-00164-3]
[http://dx.doi.org/10.1016/j.neuint.2019.104612] [PMID: 31785348]
[http://dx.doi.org/10.1007/978-981-15-7305-7_13]
[PMID: 30535473]
[http://dx.doi.org/10.3390/biom10101374] [PMID: 32992587]
[http://dx.doi.org/10.1016/j.jep.2013.09.047] [PMID: 24140586]
[http://dx.doi.org/10.1002/jbt.22313] [PMID: 30801880]
[http://dx.doi.org/10.1016/j.pharep.2015.08.014] [PMID: 26922533]
[http://dx.doi.org/10.1177/1534735416645184] [PMID: 27151585]
[http://dx.doi.org/10.1159/000444929] [PMID: 27058958]
[http://dx.doi.org/10.1016/j.pbb.2015.04.010] [PMID: 25931267]
[http://dx.doi.org/10.1016/j.neuroscience.2014.12.048] [PMID: 25592430]
[http://dx.doi.org/10.1007/s11064-020-02982-8] [PMID: 32040722]
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.030] [PMID: 25769424]
[http://dx.doi.org/10.1016/j.cbi.2015.03.003] [PMID: 25770930]
[http://dx.doi.org/10.1016/j.pharep.2014.06.004] [PMID: 25443734]
[PMID: 24518551]
[http://dx.doi.org/10.1016/j.toxrep.2014.02.003] [PMID: 28962239]
[http://dx.doi.org/10.1016/j.taap.2014.05.018] [PMID: 24932515]
[http://dx.doi.org/10.1016/j.neuroscience.2014.01.004] [PMID: 24412705]
[http://dx.doi.org/10.4103/2231-0738.106993]
[http://dx.doi.org/10.1074/jbc.M113.464669] [PMID: 23888052]
[http://dx.doi.org/10.3892/or.2013.2667] [PMID: 23969634]
[http://dx.doi.org/10.1002/jat.2941] [PMID: 24122885]
[http://dx.doi.org/10.1016/j.toxlet.2012.11.013] [PMID: 23194824]
[http://dx.doi.org/10.1016/j.bbrc.2012.05.123] [PMID: 22659738]
[http://dx.doi.org/10.2478/v10039-012-0042-6] [PMID: 23183767]
[http://dx.doi.org/10.1016/j.taap.2011.11.013] [PMID: 22155348]
[http://dx.doi.org/10.1111/j.2042-7158.2012.01470.x] [PMID: 22571266]
[http://dx.doi.org/10.3390/scipharm85010004] [PMID: 28134775]
[http://dx.doi.org/10.1002/cncr.27742] [PMID: 22991264]
[http://dx.doi.org/10.1016/j.taap.2011.08.004] [PMID: 21856323]
[http://dx.doi.org/10.3109/13880209.2010.521754] [PMID: 21501099]
[http://dx.doi.org/10.1016/j.taap.2010.12.004] [PMID: 21167192]
[http://dx.doi.org/10.1039/C4NJ02329C]
[http://dx.doi.org/10.1111/j.1440-1681.2004.04072.x]
[http://dx.doi.org/10.1111/j.1447-0594.2012.00843.x] [PMID: 22469068]
[http://dx.doi.org/10.1080/004982599237903] [PMID: 10647909]
[http://dx.doi.org/10.1155/2015/602360] [PMID: 25810809]
[http://dx.doi.org/10.1016/j.taap.2011.05.001] [PMID: 21601588]
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2014010291] [PMID: 24941299]
[http://dx.doi.org/10.1021/jf9504733]
[http://dx.doi.org/10.1177/1559325817711782] [PMID: 28694744]
[http://dx.doi.org/10.1517/17425255.4.10.1265] [PMID: 18798697]
[http://dx.doi.org/10.1007/s00429-012-0491-5] [PMID: 23262920]
[http://dx.doi.org/10.1248/bpb.33.1814] [PMID: 21048305]
[http://dx.doi.org/10.1016/S1043-6618(03)00248-2] [PMID: 14597150]
[http://dx.doi.org/10.1016/j.neulet.2010.08.064] [PMID: 20813161]
[http://dx.doi.org/10.1016/j.neulet.2019.05.036] [PMID: 31121284]
[http://dx.doi.org/10.1016/j.cbi.2017.10.019] [PMID: 29054324]
[http://dx.doi.org/10.1021/acs.jafc.6b01707] [PMID: 27245668]
[http://dx.doi.org/10.3390/ijms150712270] [PMID: 25014398]
[http://dx.doi.org/10.3748/wjg.v20.i25.8082] [PMID: 25009380]
[http://dx.doi.org/10.1371/journal.pone.0185685]
[http://dx.doi.org/10.1016/j.bjbas.2015.02.012]
[http://dx.doi.org/10.1007/s11010-013-1830-4] [PMID: 24154663]
[http://dx.doi.org/10.1007/s00210-019-01741-z] [PMID: 31620822]
[http://dx.doi.org/10.3109/15376516.2012.759306] [PMID: 23256457]
[http://dx.doi.org/10.3892/etm.2017.4181] [PMID: 28565752]
[http://dx.doi.org/10.1021/acs.chemrestox.9b00332] [PMID: 31625388]
[http://dx.doi.org/10.1016/j.lfs.2020.118965] [PMID: 33383050]
[http://dx.doi.org/10.1016/j.ejphar.2014.01.065] [PMID: 24509133]
[http://dx.doi.org/10.1007/s11010-013-1819-z] [PMID: 24065391]
[http://dx.doi.org/10.1007/s11010-021-04105-5] [PMID: 33677805]
[http://dx.doi.org/10.1177/1074248418810809] [PMID: 30497287]
[http://dx.doi.org/10.3109/13880209.2014.986688] [PMID: 25857322]
[http://dx.doi.org/10.1161/ATVBAHA.113.302781] [PMID: 24311381]
[http://dx.doi.org/10.1007/s10735-018-9793-0] [PMID: 30225683]
[http://dx.doi.org/10.1016/j.cbi.2016.03.015] [PMID: 26972669]
[http://dx.doi.org/10.1016/j.ejphar.2020.173389] [PMID: 32707190]
[http://dx.doi.org/10.2174/1871525717666190114145137] [PMID: 30648526]
[http://dx.doi.org/10.1038/s41598-017-05005-9] [PMID: 28684738]
[http://dx.doi.org/10.1159/000438626] [PMID: 26784294]
[http://dx.doi.org/10.1371/journal.pone.0125285]
[http://dx.doi.org/10.3109/08923973.2010.543686] [PMID: 21214421]
[http://dx.doi.org/10.1159/000491056] [PMID: 29969785]
[http://dx.doi.org/10.1111/nep.13180] [PMID: 29030945]
[http://dx.doi.org/10.1159/000495750] [PMID: 31259175]
[http://dx.doi.org/10.1024/0300-9831/a000653] [PMID: 32349632]
[http://dx.doi.org/10.1093/alcalc/agr038] [PMID: 21531755]
[PMID: 26112963]
[http://dx.doi.org/10.1016/j.fct.2014.01.026] [PMID: 24486618]
[http://dx.doi.org/10.1177/0748233711430978] [PMID: 22173955]
[http://dx.doi.org/10.1007/s12011-020-02268-8] [PMID: 32613487]
[http://dx.doi.org/10.1016/j.biopha.2017.06.003] [PMID: 28609844]
[http://dx.doi.org/10.1016/j.lfs.2019.116797] [PMID: 31472146]
[http://dx.doi.org/10.1016/j.ejphar.2017.07.017] [PMID: 28690190]
[PMID: 18478816]
[http://dx.doi.org/10.1016/j.procbio.2019.05.018]
[http://dx.doi.org/10.1016/j.jneuroim.2015.08.017] [PMID: 26531689]
[http://dx.doi.org/10.1016/j.bbi.2019.02.005] [PMID: 30738841]
[http://dx.doi.org/10.1146/annurev-pathol-011110-130327] [PMID: 20887193]
[http://dx.doi.org/10.1016/j.cppeds.2013.10.001] [PMID: 24295606]
[http://dx.doi.org/10.1128/IAI.01220-05] [PMID: 16926416]
[http://dx.doi.org/10.1017/S0265021507003389] [PMID: 18289433]
[http://dx.doi.org/10.1111/jfbc.13359] [PMID: 32614079]
[http://dx.doi.org/10.1097/FJC.0000000000000989] [PMID: 33818552]
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.04.034] [PMID: 15223063]
[http://dx.doi.org/10.1186/s40880-017-0217-4] [PMID: 28629389]
[http://dx.doi.org/10.3390/antiox8050137] [PMID: 31109072]
[http://dx.doi.org/10.1016/j.jnutbio.2016.11.007] [PMID: 27951449]
[http://dx.doi.org/10.1590/S1807-59322011000600026] [PMID: 21808878]
[http://dx.doi.org/10.1016/j.biopha.2019.109004] [PMID: 31128404]
[http://dx.doi.org/10.1080/01635581.2019.1637006] [PMID: 31287738]
[http://dx.doi.org/10.2147/DDDT.S160020] [PMID: 29662304]
[http://dx.doi.org/10.2147/DDDT.S189476] [PMID: 30774307]
[http://dx.doi.org/10.21873/anticanres.13165] [PMID: 30711947]
[http://dx.doi.org/10.1186/s12935-021-01906-y] [PMID: 33858433]
[http://dx.doi.org/10.1016/S2222-1808(14)60585-5]
[http://dx.doi.org/10.3390/molecules23010067] [PMID: 29283418]
[http://dx.doi.org/10.1016/j.ejmech.2010.02.049] [PMID: 20346546]
[http://dx.doi.org/10.1016/j.taap.2014.05.007] [PMID: 24848621]
[http://dx.doi.org/10.1016/B978-0-12-374001-4.00033-X]
[http://dx.doi.org/10.1186/s13223-018-0279-0] [PMID: 30275843]
[http://dx.doi.org/10.3390/nu5062128] [PMID: 23752494]
[http://dx.doi.org/10.1016/j.intimp.2016.01.005] [PMID: 26780233]
[PMID: 11269363]
[http://dx.doi.org/10.4062/biomolther.2015.095] [PMID: 26336587]
[http://dx.doi.org/10.3390/molecules25215017] [PMID: 33138197]
[http://dx.doi.org/10.1007/s00203-021-02351-1] [PMID: 33950349]
[http://dx.doi.org/10.1016/j.arcmed.2014.05.006] [PMID: 24880005]
[http://dx.doi.org/10.1016/j.antiviral.2006.04.014] [PMID: 16730806]
[http://dx.doi.org/10.1038/s41598-020-74715-4] [PMID: 33077836]
[http://dx.doi.org/10.1016/j.psc.2011.11.005] [PMID: 22370487]
[http://dx.doi.org/10.1370/afm.349] [PMID: 16189062]
[http://dx.doi.org/10.1016/S0161-813X(03)00097-4] [PMID: 14697896]
[http://dx.doi.org/10.1007/s00213-007-0903-z] [PMID: 17694388]
[http://dx.doi.org/10.1001/jamapsychiatry.2017.2432] [PMID: 28854296]
[http://dx.doi.org/10.1016/j.jad.2013.05.015] [PMID: 23721923]
[http://dx.doi.org/10.1055/s-2007-979551] [PMID: 8738312]
[http://dx.doi.org/10.1016/j.jep.2016.03.053] [PMID: 27021688]
[http://dx.doi.org/10.1155/2018/2963565]
[http://dx.doi.org/10.1016/j.neuint.2016.01.009] [PMID: 26845377]
[http://dx.doi.org/10.1016/j.fct.2018.04.052] [PMID: 29704578]
[http://dx.doi.org/10.1016/j.nbd.2016.07.010] [PMID: 27425886]
[http://dx.doi.org/10.1371/journal.pone.0172270]
[http://dx.doi.org/10.1016/j.bbr.2020.112590] [PMID: 32184157]
[http://dx.doi.org/10.1080/03639045.2019.1576726] [PMID: 30724621]
[PMID: 11259985]
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00851] [PMID: 27983856]
[http://dx.doi.org/10.1021/jf5056979] [PMID: 25715997]
[http://dx.doi.org/10.3390/ijms19124073] [PMID: 30562928]
[http://dx.doi.org/10.1124/dmd.120.000085] [PMID: 32661014]
[http://dx.doi.org/10.1016/j.jddst.2016.01.002]
[http://dx.doi.org/10.3109/21691401.2015.1029633] [PMID: 26148177]
[http://dx.doi.org/10.1016/j.jpba.2016.10.020] [PMID: 27894779]
[http://dx.doi.org/10.1016/j.npep.2016.03.002] [PMID: 27021394]
[http://dx.doi.org/10.1080/02652048.2018.1559369] [PMID: 30557060]
[http://dx.doi.org/10.2991/ic3me-15.2015.197]
[http://dx.doi.org/10.1016/j.colsurfb.2020.111429] [PMID: 33130524]