Abstract
Cardiometabolic diseases (CMD) have caused a great burden in terms of morbidity and mortality worldwide. The vicious cycle of CMD consists of type II diabetes, hypertension, dyslipidemia, obesity, and atherosclerosis. They have interlinked pathways, interacting and interconnecting with each other. The natural flavonoid chrysin has been shown to possess a broad spectrum of therapeutic activities for human health. Herein, we did an in-depth investigation of the novel mechanisms of chrysin’s cardioprotection against cardiometabolic disorders. Studies have shown that chrysin protects the cardiovascular system by enhancing the intrinsic antioxidative defense system. This antioxidant property enhanced by chrysin protects against several risk factors of cardiometabolic disorders, including atherosclerosis, vascular inflammation and dysfunction, platelet aggregation, hypertension, dyslipidemia, cardiotoxicity, myocardial infarction, injury, and remodeling, diabetes-induced injuries, and obesity. Chrysin also exhibited anti-inflammatory mechanisms through inhibiting pro-inflammatory pathways, including NF-κB, MAPK, and PI3k/Akt. Furthermore, chrysin modulated NO, RAS, AGE/RAGE, and PPARs pathways which contributed to the risk factors of cardiometabolic disorders. Taken together, the mechanisms in which chrysin protects against cardiometabolic disorder are more than merely antioxidation and anti-inflammation in the cardiovascular system.
Keywords: Chrysin, metabolic syndrome, diabetes mellitus, cardiovascular diseases, flavonoid, cardioprotective effects.
Graphical Abstract
[1]
de Zeeuw D, Bakker SJL. Does the metabolic syndrome add to the diagnosis and treatment of cardiovascular disease? Nat Clin Pract Cardiovasc Med 2008; 5(1)(Suppl. 1): S10-4.
[http://dx.doi.org/10.1038/ncpcardio1271] [PMID: 18580860]
[http://dx.doi.org/10.1038/ncpcardio1271] [PMID: 18580860]
[2]
Flordellis CS, Ilias I, Papavassiliou AG. New therapeutic options for the metabolic syndrome: What’s next? Trends Endocrinol Metab 2005; 16(6): 254-60.
[http://dx.doi.org/10.1016/j.tem.2005.06.001] [PMID: 16002303]
[http://dx.doi.org/10.1016/j.tem.2005.06.001] [PMID: 16002303]
[3]
Lind L, Sundström J, Ärnlöv J, Risérus U, Lampa E. A longitudinal study over 40-years to study the metabolic syndrome as a risk factor for cardiovascular diseases. Sci Rep 2021; 11(1): 2978.
[http://dx.doi.org/10.1038/s41598-021-82398-8] [PMID: 33536506]
[http://dx.doi.org/10.1038/s41598-021-82398-8] [PMID: 33536506]
[4]
Chatterjee A, Harris SB, Leiter LA, Fitchett DH, Teoh H, Bhattacharyya OK. Managing cardiometabolic risk in primary care: Summary of the 2011 consensus statement. Can Fam Physician 2012; 58(4): 389-393, e196-e201.
[PMID: 22611605]
[PMID: 22611605]
[5]
Kirk EP, Klein S. Pathogenesis and pathophysiology of the cardiometabolic syndrome. J Clin Hypertens (Greenwich) 2009; 11(12): 761-5.
[http://dx.doi.org/10.1111/j.1559-4572.2009.00054.x] [PMID: 20021538]
[http://dx.doi.org/10.1111/j.1559-4572.2009.00054.x] [PMID: 20021538]
[6]
Timpson NJ, Lawlor DA, Harbord RM, et al. C-reactive protein and its role in metabolic syndrome: Mendelian randomisation study. Lancet 2005; 366(9501): 1954-9.
[http://dx.doi.org/10.1016/S0140-6736(05)67786-0] [PMID: 16325697]
[http://dx.doi.org/10.1016/S0140-6736(05)67786-0] [PMID: 16325697]
[7]
Farkhondeh T, Llorens S, Pourbagher-Shahri AM, et al. An Overview of the role of adipokines in cardiometabolic diseases. Molecules 2020; 25(21): E5218.
[http://dx.doi.org/10.3390/molecules25215218] [PMID: 33182462]
[http://dx.doi.org/10.3390/molecules25215218] [PMID: 33182462]
[8]
Talebi M, Talebi M, Farkhondeh T, Samarghandian S. Biological and therapeutic activities of thymoquinone: Focus on the Nrf2 signaling pathway. Phytother Res 2020; 35(4): 1739-53.
[http://dx.doi.org/10.1002/ptr.6905] [PMID: 33051921]
[http://dx.doi.org/10.1002/ptr.6905] [PMID: 33051921]
[9]
Pourbagher-Shahri AM, Farkhondeh T, Ashrafizadeh M, Talebi M, Samargahndian S. Curcumin and cardiovascular diseases: Focus on cellular targets and cascades. Biomed Pharmacother 2021; 136: 111214.
[http://dx.doi.org/10.1016/j.biopha.2020.111214] [PMID: 33450488]
[http://dx.doi.org/10.1016/j.biopha.2020.111214] [PMID: 33450488]
[10]
Bt Hj Idrus R, Sainik NQAV, Nordin A, Saim AB, Sulaiman N. Cardioprotective effects of honey and its constituent: An evidence-based review of laboratory studies and clinical trials. Int J Environ Res Public Health 2020; 17(10): E3613.
[http://dx.doi.org/10.3390/ijerph17103613] [PMID: 32455701]
[http://dx.doi.org/10.3390/ijerph17103613] [PMID: 32455701]
[11]
Hjemdahl P. Can the metabolic syndrome be explained by a unifying concept? Lancet Diabetes Endocrinol 2015; 3(2): 96-8.
[http://dx.doi.org/10.1016/S2213-8587(14)70072-5] [PMID: 25618291]
[http://dx.doi.org/10.1016/S2213-8587(14)70072-5] [PMID: 25618291]
[12]
Huang PL. eNOS, metabolic syndrome and cardiovascular disease. Trends Endocrinol Metab 2009; 20(6): 295-302.
[http://dx.doi.org/10.1016/j.tem.2009.03.005] [PMID: 19647446]
[http://dx.doi.org/10.1016/j.tem.2009.03.005] [PMID: 19647446]
[13]
Siedler M, Murad MH, Falck-Ytter Y, et al. Guidelines about physical activity and exercise to reduce cardiometabolic risk factors: Protocol for a systematic review and critical appraisal. BMJ Open 2020; 10(1): e032656.
[http://dx.doi.org/10.1136/bmjopen-2019-032656] [PMID: 31980508]
[http://dx.doi.org/10.1136/bmjopen-2019-032656] [PMID: 31980508]
[14]
Roshanravan B, Yousefizadeh S, Apaydin Yildirim B, et al. The effects of Berberis vulgaris L. and Berberis aristata L. in metabolic syndrome patients: A systematic and meta-analysis study. Arch Physiol Biochem 2020; 1-12.
[http://dx.doi.org/10.1080/13813455.2020.1828482] [PMID: 33040642]
[http://dx.doi.org/10.1080/13813455.2020.1828482] [PMID: 33040642]
[15]
Goldstein MR, Mascitelli L, Pezzetta F. On treating metabolic syndrome: Emphasise lifestyle change. Lancet Oncol 2010; 11(5): 415.
[http://dx.doi.org/10.1016/S1470-2045(10)70055-3] [PMID: 20434715]
[http://dx.doi.org/10.1016/S1470-2045(10)70055-3] [PMID: 20434715]
[16]
Atanasov AG, Zotchev SB, Dirsch VM, et al. Natural products in drug discovery: Advances and opportunities. Nat Rev Drug Discov 2021; 20(3): 200-16.
[http://dx.doi.org/10.1038/s41573-020-00114-z] [PMID: 33510482]
[http://dx.doi.org/10.1038/s41573-020-00114-z] [PMID: 33510482]
[17]
Hashim K-N, Chin K-Y, Ahmad F. The mechanism of honey in reversing metabolic syndrome. Molecules 2021; 26(4): 808.
[http://dx.doi.org/10.3390/molecules26040808] [PMID: 33557218]
[http://dx.doi.org/10.3390/molecules26040808] [PMID: 33557218]
[18]
Farkhondeh T, Samarghandian S, Bafandeh F. The cardiovascular protective effects of chrysin: A narrative review on experimental researches. Cardiovasc Hematol Agents Med Chem 2019; 17(1): 17-27.
[http://dx.doi.org/10.2174/1871525717666190114145137] [PMID: 30648526]
[http://dx.doi.org/10.2174/1871525717666190114145137] [PMID: 30648526]
[19]
Atrahimovich D, Avni D, Khatib S. Flavonoids-macromolecules interactions in human diseases with focus on alzheimer, atherosclerosis and cancer. Antioxidants 2021; 10(3): 423.
[http://dx.doi.org/10.3390/antiox10030423] [PMID: 33802084]
[http://dx.doi.org/10.3390/antiox10030423] [PMID: 33802084]
[20]
Saponara S, Fusi F, Iovinelli D, et al. Flavonoids and hERG channels: Friends or foes? Eur J Pharmacol 2021; 899: 174030.
[http://dx.doi.org/10.1016/j.ejphar.2021.174030] [PMID: 33727059]
[http://dx.doi.org/10.1016/j.ejphar.2021.174030] [PMID: 33727059]
[21]
Rana AC, Gulliya B. Chemistry and pharmacology of flavonoids-a review. Indian J Pharm Edu Res 2019; 53(1): 8-20.
[http://dx.doi.org/10.5530/ijper.53.1.3]
[http://dx.doi.org/10.5530/ijper.53.1.3]
[22]
Talebi M, Zarshenas MM, Yazdani E, Moein M. Preparation and evaluation of possible antioxidant activities of Rose traditional tablet”[Qurs-e-Vard]” a selected Traditional Persian Medicine [TPM] formulation via various procedures. Curr Drug Discov Technol 2021; 18(5): e2809202018631.
[http://dx.doi.org/10.2174/1570163817666200929114517] [PMID: 32990537]
[http://dx.doi.org/10.2174/1570163817666200929114517] [PMID: 32990537]
[23]
Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients 2020; 12(2): E457.
[http://dx.doi.org/10.3390/nu12020457] [PMID: 32059369]
[http://dx.doi.org/10.3390/nu12020457] [PMID: 32059369]
[24]
Talebi M, Kakouri E, Talebi M, et al. Nutraceuticals-based therapeutic approach: Recent advances to combat pathogenesis of Alzheimer’s disease. Expert Rev Neurother 2021; 21(6): 625-42.
[http://dx.doi.org/10.1080/14737175.2021.1923479] [PMID: 33910446]
[http://dx.doi.org/10.1080/14737175.2021.1923479] [PMID: 33910446]
[25]
Ullah A, Munir S, Badshah SL, et al. Important flavonoids and their role as a therapeutic agent. Molecules 2020; 25(22): E5243.
[http://dx.doi.org/10.3390/molecules25225243] [PMID: 33187049]
[http://dx.doi.org/10.3390/molecules25225243] [PMID: 33187049]
[26]
Mani R, Natesan V. Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochemistry 2018; 145: 187-96.
[http://dx.doi.org/10.1016/j.phytochem.2017.09.016] [PMID: 29161583]
[http://dx.doi.org/10.1016/j.phytochem.2017.09.016] [PMID: 29161583]
[27]
Samarghandian S, Farkhondeh T, Azimi-Nezhad M. Protective effects of chrysin against drugs and toxic agents. Dose Response 2017; 15(2): 1559325817711782.
[http://dx.doi.org/10.1177/1559325817711782] [PMID: 28694744]
[http://dx.doi.org/10.1177/1559325817711782] [PMID: 28694744]
[28]
Talebi M, Talebi M, Farkhondeh T, Samarghandian S. Molecular mechanism-based therapeutic properties of honey. Biomed Pharmacother 2020; 130: 110590.
[http://dx.doi.org/10.1016/j.biopha.2020.110590] [PMID: 32768885]
[http://dx.doi.org/10.1016/j.biopha.2020.110590] [PMID: 32768885]
[29]
Sharma P, Kumari A, Gulati A, Krishnamurthy S, Hemalatha S. Chrysin isolated from Pyrus pashia fruit ameliorates convulsions in experimental animals. Nutr Neurosci 2019; 22(8): 569-77.
[http://dx.doi.org/10.1080/1028415X.2017.1418786] [PMID: 29284373]
[http://dx.doi.org/10.1080/1028415X.2017.1418786] [PMID: 29284373]
[30]
Sun A, Sun Q, Liu R. Isolation and purification of baicalein and chrysin from the extracts of Oroxylum indicum by high speed counter-current chromatography. Fenxi Huaxue. Chin J Anal Chem 2006; 34(Suppl.): S243-6.
[31]
Williams CA, Harborne JB, Newman M, Greenham J, Eagles J. Chrysin and other leaf exudate flavonoids in the genus Pelargonium. Phytochemistry 1997; 46(8): 1349-53.
[http://dx.doi.org/10.1016/S0031-9422(97)00514-1] [PMID: 9419900]
[http://dx.doi.org/10.1016/S0031-9422(97)00514-1] [PMID: 9419900]
[32]
Meckes M, Paz D, Acosta J, Mata R. The effects of chrysin and pinostrobin, two flavonoids isolated from Teloxys graveolens leaves, on isolated guinea-pig ileum. Phytomedicine 1998; 5(6): 459-63.
[http://dx.doi.org/10.1016/S0944-7113(98)80042-1] [PMID: 23196029]
[http://dx.doi.org/10.1016/S0944-7113(98)80042-1] [PMID: 23196029]
[33]
Nagasaka M, Hashimoto R, Inoue Y, et al. Anti-tumorigenic activity of chrysin from oroxylum indicum via non-genotoxic p53 activation through the ATM-Chk2 pathway. Molecules 2018; 23(6): E1394.
[http://dx.doi.org/10.3390/molecules23061394] [PMID: 29890668]
[http://dx.doi.org/10.3390/molecules23061394] [PMID: 29890668]
[34]
Rauf A, Khan R, Raza M, et al. Suppression of inflammatory response by chrysin, a flavone isolated from Potentilla evestita Th. Wolf. In silico predictive study on its mechanistic effect. Fitoterapia 2015; 103: 129-35.
[http://dx.doi.org/10.1016/j.fitote.2015.03.019] [PMID: 25819005]
[http://dx.doi.org/10.1016/j.fitote.2015.03.019] [PMID: 25819005]
[35]
Saadawi S, Jalil J, Jasamai M, Jantan I. Inhibitory effects of acetylmelodorinol, chrysin and polycarpol from Mitrella kentii on prostaglandin E2 and Thromboxane B2 production and platelet activating factor receptor binding. Molecules 2012; 17(5): 4824-35.
[http://dx.doi.org/10.3390/molecules17054824] [PMID: 22538486]
[http://dx.doi.org/10.3390/molecules17054824] [PMID: 22538486]
[36]
Seetharaman P, Gnanasekar S, Chandrasekaran R, Chandrakasan G, Kadarkarai M, Sivaperumal S. Isolation and characterization of anticancer flavone chrysin (5,7-dihydroxy flavone)-producing endophytic fungi from Passiflora incarnata L. leaves. Ann Microbiol 2017; 67(4): 321-31.
[http://dx.doi.org/10.1007/s13213-017-1263-5]
[http://dx.doi.org/10.1007/s13213-017-1263-5]
[37]
Dinda B, SilSarma I, Dinda M, Rudrapaul P. Oroxylum indicum (L.) Kurz, an important Asian traditional medicine: From traditional uses to scientific data for its commercial exploitation. J Ethnopharmacol 2015; 161: 255-78.
[http://dx.doi.org/10.1016/j.jep.2014.12.027] [PMID: 25543018]
[http://dx.doi.org/10.1016/j.jep.2014.12.027] [PMID: 25543018]
[38]
Li J, Du Q, Li N, Du S, Sun Z. Alpiniae oxyphyllae Fructus and Alzheimer’s disease: An update and current perspective on this traditional Chinese medicine. Biomed Pharmacother 2021; 135: 111167.
[http://dx.doi.org/10.1016/j.biopha.2020.111167] [PMID: 33383373]
[http://dx.doi.org/10.1016/j.biopha.2020.111167] [PMID: 33383373]
[39]
Zhang MR, Jiang K, Yang JL, Shi YP. Flavonoids as key bioactive components of Oxytropis falcata bunge, a traditional anti-inflammatory and analgesic Tibetan medicine. Nat Prod Res 2020; 34(23): 3335-52.
[http://dx.doi.org/10.1080/14786419.2019.1574786] [PMID: 30821521]
[http://dx.doi.org/10.1080/14786419.2019.1574786] [PMID: 30821521]
[40]
Viswanatha GL, Shylaja H, Kumar HY, Venkataranganna MV, Prasad NBL. Traditional uses, phytochemistry, and ethnopharmacology of Colebrookea oppositifolia Smith: A mini-review 2021; 21: 209-9.
[http://dx.doi.org/10.1007/s13596-020-00513-y]
[http://dx.doi.org/10.1007/s13596-020-00513-y]
[41]
Meng L, Chen S, Zhou L, Liu Z, Li S, Kang W. Chemical constituents and pharmacological effects of genus patrinia: A review. Curr Pharmacol Rep 2020; 6(6): 380-414.
[http://dx.doi.org/10.1007/s40495-020-00240-7]
[http://dx.doi.org/10.1007/s40495-020-00240-7]
[42]
Farkhondeh T, Folgado SL, Pourbagher-Shahri AM, Ashrafizadeh M, Samarghandian S. The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway. Biomed Pharmacother 2020; 127: 110234.
[http://dx.doi.org/10.1016/j.biopha.2020.110234] [PMID: 32559855]
[http://dx.doi.org/10.1016/j.biopha.2020.110234] [PMID: 32559855]
[43]
Chen Q, Rahman K, Wang SJ, Zhou S, Zhang H. Scutellaria barbata: A review on chemical constituents, pharmacological activities and clinical applications. Curr Pharm Des 2020; 26(1): 160-75.
[http://dx.doi.org/10.2174/1381612825666191216124310] [PMID: 31840605]
[http://dx.doi.org/10.2174/1381612825666191216124310] [PMID: 31840605]
[44]
Zhao T, Tang H, Xie L, et al. Scutellaria baicalensis Georgi. (Lamiaceae): A review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. J Pharm Pharmacol 2019; 71(9): 1353-69.
[http://dx.doi.org/10.1111/jphp.13129] [PMID: 31236960]
[http://dx.doi.org/10.1111/jphp.13129] [PMID: 31236960]
[45]
Larit F, Nael MA, Benyahia S, et al. Secondary metabolites from the aerial parts of Cytisus villosus Pourr. Phytochem Lett 2018; 24: 1-5.
[http://dx.doi.org/10.1016/j.phytol.2017.12.012] [PMID: 30374367]
[http://dx.doi.org/10.1016/j.phytol.2017.12.012] [PMID: 30374367]
[46]
Kamat S, Kumari M, Sajna KV, Jayabaskaran C. Endophytic fungus, Chaetomium globosum, associated with marine green alga, a new source of Chrysin. Sci Rep 2020; 10(1): 18726.
[http://dx.doi.org/10.1038/s41598-020-72497-3] [PMID: 33127928]
[http://dx.doi.org/10.1038/s41598-020-72497-3] [PMID: 33127928]
[47]
Liu Y, Song X, He J, Zheng X, Wu H. Synthetic derivatives of chrysin and their biological activities. Med Chem Res 2014; 23(2): 555-63.
[http://dx.doi.org/10.1007/s00044-013-0711-4]
[http://dx.doi.org/10.1007/s00044-013-0711-4]
[48]
Villas-Boas GR, Lavorato SN, Paes MM, et al. Modulation of the serotonergic receptosome in the treatment of anxiety and depression: A narrative review of the experimental evidence. Pharmaceuticals (Basel) 2021; 14(2): 1-46.
[http://dx.doi.org/10.3390/ph14020148] [PMID: 33673205]
[http://dx.doi.org/10.3390/ph14020148] [PMID: 33673205]
[49]
Sawant O, Khan T. Management of periorbital hyperpigmentation: An overview of nature-based agents and alternative approaches. Dermatol Ther 2020; 33(4): e13717.
[http://dx.doi.org/10.1111/dth.13717] [PMID: 32472659]
[http://dx.doi.org/10.1111/dth.13717] [PMID: 32472659]
[50]
Kurek-Górecka A, Górecki M, Rzepecka-Stojko A, Balwierz R, Stojko J. Bee products in dermatology and skin care. Molecules 2020; 25(3): E556.
[http://dx.doi.org/10.3390/molecules25030556] [PMID: 32012913]
[http://dx.doi.org/10.3390/molecules25030556] [PMID: 32012913]
[51]
Angelopoulou E, Pyrgelis ES, Piperi C. Neuroprotective potential of chrysin in Parkinson’s disease: Molecular mechanisms and clinical implications. Neurochem Int 2020; 132: 104612.
[http://dx.doi.org/10.1016/j.neuint.2019.104612] [PMID: 31785348]
[http://dx.doi.org/10.1016/j.neuint.2019.104612] [PMID: 31785348]
[52]
Ye Q, Liu K, Shen Q, et al. Reversal of multidrug resistance in cancer by multi-functional flavonoids. Front Oncol 2019; 9: 487.
[http://dx.doi.org/10.3389/fonc.2019.00487] [PMID: 31245292]
[http://dx.doi.org/10.3389/fonc.2019.00487] [PMID: 31245292]
[53]
Pingili RB, Pawar AK, Challa SR, Kodali T, Koppula S, Toleti V. A comprehensive review on hepatoprotective and nephroprotective activities of chrysin against various drugs and toxic agents. Chem Biol Interact 2019; 308: 51-60.
[http://dx.doi.org/10.1016/j.cbi.2019.05.010] [PMID: 31085170]
[http://dx.doi.org/10.1016/j.cbi.2019.05.010] [PMID: 31085170]
[54]
Zeinali M, Rezaee SA, Hosseinzadeh H. An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances. Biomed Pharmacother 2017; 92: 998-1009.
[http://dx.doi.org/10.1016/j.biopha.2017.06.003] [PMID: 28609844]
[http://dx.doi.org/10.1016/j.biopha.2017.06.003] [PMID: 28609844]
[55]
Talebi M, Talebi M, Farkhondeh T, et al. Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin. Cancer Cell Int 2021; 21(1): 214.
[http://dx.doi.org/10.1186/s12935-021-01906-y] [PMID: 33858433]
[http://dx.doi.org/10.1186/s12935-021-01906-y] [PMID: 33858433]
[56]
Pang X, Zhang X, Jiang Y, Su Q, Li Q, Li Z. Autophagy: Mechanisms and therapeutic potential of flavonoids in cancer. Biomolecules 2021; 11(2): 1-35.
[http://dx.doi.org/10.3390/biom11020135] [PMID: 33494431]
[http://dx.doi.org/10.3390/biom11020135] [PMID: 33494431]
[57]
L Suraweera T, Rupasinghe HPV, Dellaire G, Xu Z. Regulation of Nrf2/ARE pathway by dietary flavonoids: A friend or foe for cancer management? Antioxidants 2020; 9(10): 1-44.
[http://dx.doi.org/10.3390/antiox9100973] [PMID: 33050575]
[http://dx.doi.org/10.3390/antiox9100973] [PMID: 33050575]
[58]
Afrin S, Haneefa SM, Fernandez-Cabezudo MJ, Giampieri F, Al-Ramadi BK, Battino M. Therapeutic and preventive properties of honey and its bioactive compounds in cancer: An evidence-based review. Nutr Res Rev 2020; 33(1): 50-76.
[http://dx.doi.org/10.1017/S0954422419000192] [PMID: 31791437]
[http://dx.doi.org/10.1017/S0954422419000192] [PMID: 31791437]
[59]
Ganai SA, Sheikh FA, Baba ZA. Plant flavone Chrysin as an emerging histone deacetylase inhibitor for prosperous epigenetic-based anticancer therapy. Phytother Res 2020.
[http://dx.doi.org/10.1002/ptr.6869] [PMID: 32930436]
[http://dx.doi.org/10.1002/ptr.6869] [PMID: 32930436]
[60]
Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells. J Cell Physiol 2019; 234(7): 10421-31.
[http://dx.doi.org/10.1002/jcp.27710] [PMID: 30387147]
[http://dx.doi.org/10.1002/jcp.27710] [PMID: 30387147]
[61]
Khater M, Ravishankar D, Greco F, Osborn HMI. Metal complexes of flavonoids: Their synthesis, characterization and enhanced antioxidant and anticancer activities. Future Med Chem 2019; 11(21): 2845-67.
[http://dx.doi.org/10.4155/fmc-2019-0237] [PMID: 31722558]
[http://dx.doi.org/10.4155/fmc-2019-0237] [PMID: 31722558]
[62]
Ancuceanu R, Dinu M, Dinu-Pirvu C, Anuţa V, Negulescu V. Pharmacokinetics of B-ring unsubstituted flavones. Pharmaceutics 2019; 11(8): E370.
[http://dx.doi.org/10.3390/pharmaceutics11080370] [PMID: 31374885]
[http://dx.doi.org/10.3390/pharmaceutics11080370] [PMID: 31374885]
[63]
Begum S, Rashida Anjum MS, Poojitha Harisree G, Sivalakshmi N, Priyanka P, Bharathi K. Antioxidant activity of piperazine compounds: A brief review. Asian J Chem 2020; 32(9): 2105-18.
[http://dx.doi.org/10.14233/ajchem.2020.22832]
[http://dx.doi.org/10.14233/ajchem.2020.22832]
[64]
Zhu Y, Yao X, Long J, Li R, Liu Y, Yang Z, et al. Fluorine-containing chrysin derivatives: synthesis and biological activity. Nat Prod Commun 2019; 14(9): 1934578X1987892.
[http://dx.doi.org/10.1177/1934578X19878921]
[http://dx.doi.org/10.1177/1934578X19878921]
[65]
Anandhi R, Annadurai T, Anitha TS, et al. Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in Triton WR-1339-induced hypercholesterolemic rats. J Physiol Biochem 2013; 69(2): 313-23.
[http://dx.doi.org/10.1007/s13105-012-0215-6] [PMID: 23104078]
[http://dx.doi.org/10.1007/s13105-012-0215-6] [PMID: 23104078]
[66]
Veerappan R, Malarvili T. Chrysin pretreatment improves angiotensin system, cGMP concentration in L-NAME induced hypertensive rats. Indian J Clin Biochem 2019; 34(3): 288-95.
[http://dx.doi.org/10.1007/s12291-018-0761-y] [PMID: 31391718]
[http://dx.doi.org/10.1007/s12291-018-0761-y] [PMID: 31391718]
[67]
Yamamoto Y. Effects of dietary chrysin supplementation on blood pressure and oxidative status of rats fed a high-fat high-sucrose diet. Food Sci Technol Res 2014; 20(2): 295-300.
[http://dx.doi.org/10.3136/fstr.20.295]
[http://dx.doi.org/10.3136/fstr.20.295]
[68]
Wang D, Hiebl V, Xu T, et al. Impact of natural products on the cholesterol transporter ABCA1. J Ethnopharmacol 2020; 249: 112444.
[http://dx.doi.org/10.1016/j.jep.2019.112444] [PMID: 31805338]
[http://dx.doi.org/10.1016/j.jep.2019.112444] [PMID: 31805338]
[69]
Wang S, Zhang X, Liu M, et al. Chrysin inhibits foam cell formation through promoting cholesterol efflux from RAW264.7 macrophages. Pharm Biol 2015; 53(10): 1481-7.
[http://dx.doi.org/10.3109/13880209.2014.986688] [PMID: 25857322]
[http://dx.doi.org/10.3109/13880209.2014.986688] [PMID: 25857322]
[70]
Zarzecki MS, Araujo SM, Bortolotto VC, de Paula MT, Jesse CR, Prigol M. Hypolipidemic action of chrysin on Triton WR-1339-induced hyperlipidemia in female C57BL/6 mice. Toxicol Rep 2014; 1: 200-8.
[http://dx.doi.org/10.1016/j.toxrep.2014.02.003] [PMID: 28962239]
[http://dx.doi.org/10.1016/j.toxrep.2014.02.003] [PMID: 28962239]
[71]
Khezri S, Sabzalipour T, Jahedsani A, Azizian S, Atashbar S, Salimi A. Chrysin ameliorates aluminum phosphide-induced oxidative stress and mitochondrial damages in rat cardiomyocytes and isolated mitochondria. Environ Toxicol 2020; 35(10): 1114-24.
[http://dx.doi.org/10.1002/tox.22947] [PMID: 32432806]
[http://dx.doi.org/10.1002/tox.22947] [PMID: 32432806]
[72]
Mantawy EM, El-Bakly WM, Esmat A, Badr AM, El-Demerdash E. Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Eur J Pharmacol 2014; 728(1): 107-18.
[http://dx.doi.org/10.1016/j.ejphar.2014.01.065] [PMID: 24509133]
[http://dx.doi.org/10.1016/j.ejphar.2014.01.065] [PMID: 24509133]
[73]
Mantawy EM, Esmat A, El-Bakly WM, Salah ElDin RA, El-Demerdash E. Mechanistic clues to the protective effect of chrysin against doxorubicin-induced cardiomyopathy: Plausible roles of p53, MAPK and AKT pathways. Sci Rep 2017; 7(1): 4795.
[http://dx.doi.org/10.1038/s41598-017-05005-9] [PMID: 28684738]
[http://dx.doi.org/10.1038/s41598-017-05005-9] [PMID: 28684738]
[74]
Anghel N, Cotoraci C, Ivan A, et al. Chrysin attenuates cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity. Histol Histopathol 2015; 30(12): 1465-75.
[http://dx.doi.org/10.14670/HH-11-641] [PMID: 26112963]
[http://dx.doi.org/10.14670/HH-11-641] [PMID: 26112963]
[75]
Yang M, Xiong J, Zou Q, Wang DD, Huang CX. Chrysin attenuates interstitial fibrosis and improves cardiac function in a rat model of acute myocardial infarction. J Mol Histol 2018; 49(6): 555-65.
[http://dx.doi.org/10.1007/s10735-018-9793-0] [PMID: 30225683]
[http://dx.doi.org/10.1007/s10735-018-9793-0] [PMID: 30225683]
[76]
Rani N, Bharti S, Bhatia J, Nag TC, Ray R, Arya DS. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation. Chem Biol Interact 2016; 250: 59-67.
[http://dx.doi.org/10.1016/j.cbi.2016.03.015] [PMID: 26972669]
[http://dx.doi.org/10.1016/j.cbi.2016.03.015] [PMID: 26972669]
[77]
Rani N, Bharti S, Bhatia J, et al. Inhibition of TGF-β by a novel PPAR-γ agonist, chrysin, salvages β-receptor stimulated myocardial injury in rats through MAPKs-dependent mechanism. Nutr Metab (Lond) 2015; 12(1): 11.
[http://dx.doi.org/10.1186/s12986-015-0004-7] [PMID: 25774203]
[http://dx.doi.org/10.1186/s12986-015-0004-7] [PMID: 25774203]
[78]
Zhao S, Liang M, Wang Y, et al. Chrysin suppresses vascular endothelial inflammation via inhibiting the NF-κB signaling pathway. J Cardiovasc Pharmacol Ther 2019; 24(3): 278-87.
[http://dx.doi.org/10.1177/1074248418810809] [PMID: 30497287]
[http://dx.doi.org/10.1177/1074248418810809] [PMID: 30497287]
[79]
Villar IC, Vera R, Galisteo M, et al. Endothelial nitric oxide production stimulated by the bioflavonoid chrysin in rat isolated aorta. Planta Med 2005; 71(9): 829-34.
[http://dx.doi.org/10.1055/s-2005-871296] [PMID: 16206037]
[http://dx.doi.org/10.1055/s-2005-871296] [PMID: 16206037]
[80]
El-Bassossy HM, Abo-Warda SM, Fahmy A. Chrysin and luteolin attenuate diabetes-induced impairment in endothelial-dependent relaxation: Effect on lipid profile, AGEs and NO generation. Phytother Res 2013; 27(11): 1678-84.
[http://dx.doi.org/10.1002/ptr.4917] [PMID: 23296950]
[http://dx.doi.org/10.1002/ptr.4917] [PMID: 23296950]
[81]
Lo HM, Wu MW, Pan SL, Peng CY, Wu PH, Wu WB. Chrysin restores PDGF-induced inhibition on protein tyrosine phosphatase and reduces PDGF signaling in cultured VSMCs. J Nutr Biochem 2012; 23(6): 667-78.
[http://dx.doi.org/10.1016/j.jnutbio.2011.03.011] [PMID: 21803557]
[http://dx.doi.org/10.1016/j.jnutbio.2011.03.011] [PMID: 21803557]
[82]
Liu G, Xie W, He AD, et al. Antiplatelet activity of chrysin via inhibiting platelet αIIbβ3-mediated signaling pathway. Mol Nutr Food Res 2016; 60(9): 1984-93.
[http://dx.doi.org/10.1002/mnfr.201500801] [PMID: 27006308]
[http://dx.doi.org/10.1002/mnfr.201500801] [PMID: 27006308]
[83]
Olas B. Honey and its phenolic compounds as an effective natural medicine for cardiovascular diseases in humans? Nutrients 2020; 12(2): E283.
[http://dx.doi.org/10.3390/nu12020283] [PMID: 31973186]
[http://dx.doi.org/10.3390/nu12020283] [PMID: 31973186]
[84]
Farkhondeh T, Abedi F, Samarghandian S. Chrysin attenuates inflammatory and metabolic disorder indices in aged male rat. Biomed Pharmacother 2019; 109: 1120-5.
[http://dx.doi.org/10.1016/j.biopha.2018.10.059] [PMID: 30551362]
[http://dx.doi.org/10.1016/j.biopha.2018.10.059] [PMID: 30551362]
[85]
Andrade N, Marques C, Andrade S, et al. Effect of chrysin on changes in intestinal environment and microbiome induced by fructose-feeding in rats. Food Funct 2019; 10(8): 4566-76.
[http://dx.doi.org/10.1039/C9FO01142K] [PMID: 31314039]
[http://dx.doi.org/10.1039/C9FO01142K] [PMID: 31314039]
[86]
Ahmed OAA, Azhar AS, Tarkhan MM, Balamash KS, El-Bassossy HM. Antiglycation activities and common mechanisms mediating vasculoprotective effect of quercetin and chrysin in metabolic syndrome. Evid Based Complement Alternat Med 2020; 2020: 3439624.
[http://dx.doi.org/10.1155/2020/3439624] [PMID: 32802123]
[http://dx.doi.org/10.1155/2020/3439624] [PMID: 32802123]
[87]
Andrade N, Andrade S, Silva C, et al. Chronic consumption of the dietary polyphenol chrysin attenuates metabolic disease in fructose-fed rats. Eur J Nutr 2020; 59(1): 151-65.
[http://dx.doi.org/10.1007/s00394-019-01895-9] [PMID: 30631887]
[http://dx.doi.org/10.1007/s00394-019-01895-9] [PMID: 30631887]
[88]
Eckel RH, Alberti KG, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2010; 375(9710): 181-3.
[http://dx.doi.org/10.1016/S0140-6736(09)61794-3] [PMID: 20109902]
[http://dx.doi.org/10.1016/S0140-6736(09)61794-3] [PMID: 20109902]
[89]
Furlow B. Gut microbe composition and metabolic syndrome. Lancet Diabetes Endocrinol 2013; 1(1): s4-5.
[http://dx.doi.org/10.1016/S2213-8587(13)70128-1] [PMID: 24622597]
[http://dx.doi.org/10.1016/S2213-8587(13)70128-1] [PMID: 24622597]
[90]
Greenhill C. Gut microbiota, host genetics and diet interact to affect the risk of developing obesity and the metabolic syndrome. Nat Rev Endocrinol 2015; 11(11): 630.
[http://dx.doi.org/10.1038/nrendo.2015.152]
[http://dx.doi.org/10.1038/nrendo.2015.152]
[91]
Cercato C, Fonseca FA. Cardiovascular risk and obesity. Diabetol Metab Syndr 2019; 11(1): 74.
[http://dx.doi.org/10.1186/s13098-019-0468-0] [PMID: 31467596]
[http://dx.doi.org/10.1186/s13098-019-0468-0] [PMID: 31467596]
[92]
Salazar J, Cano C, Pérez JL, et al. Role of dietary polyphenols in adipose tissue browning: A narrative review. Curr Pharm Des 2020; 26(35): 4444-60.
[http://dx.doi.org/10.2174/1381612826666200701211422] [PMID: 32611294]
[http://dx.doi.org/10.2174/1381612826666200701211422] [PMID: 32611294]
[93]
Zhang X, Li X, Fang H, et al. Flavonoids as inducers of white adipose tissue browning and thermogenesis: Signalling pathways and molecular triggers. Nutr Metab (Lond) 2019; 16(1): 47.
[http://dx.doi.org/10.1186/s12986-019-0370-7] [PMID: 31346342]
[http://dx.doi.org/10.1186/s12986-019-0370-7] [PMID: 31346342]
[94]
Li H, Qi J, Li L. Phytochemicals as potential candidates to combat obesity via adipose non-shivering thermogenesis. Pharmacol Res 2019; 147: 104393.
[http://dx.doi.org/10.1016/j.phrs.2019.104393] [PMID: 31401211]
[http://dx.doi.org/10.1016/j.phrs.2019.104393] [PMID: 31401211]
[95]
Talebi M, Talebi M, Farkhondeh T, Mishra G, İlgün S, Samarghandian S. New insights into the role of the Nrf2 signaling pathway in green tea catechin applications. Phytother Res 2021; 35(6): 3078-112.
[http://dx.doi.org/10.1002/ptr.7033] [PMID: 33569875]
[http://dx.doi.org/10.1002/ptr.7033] [PMID: 33569875]
[96]
Choi JH, Yun JW. Chrysin induces brown fat-like phenotype and enhances lipid metabolism in 3T3-L1 adipocytes. Nutrition 2016; 32(9): 1002-10.
[http://dx.doi.org/10.1016/j.nut.2016.02.007] [PMID: 27133810]
[http://dx.doi.org/10.1016/j.nut.2016.02.007] [PMID: 27133810]
[97]
Kong M, Xie K, Lv M, et al. Anti-inflammatory phytochemicals for the treatment of diabetes and its complications: Lessons learned and future promise. Biomed Pharmacother 2021; 133: 110975.
[http://dx.doi.org/10.1016/j.biopha.2020.110975] [PMID: 33212375]
[http://dx.doi.org/10.1016/j.biopha.2020.110975] [PMID: 33212375]
[98]
Ramírez-Espinosa JJ, Saldaña-Ríos J, García-Jiménez S, et al. Chrysin induces antidiabetic, antidyslipidemic and anti-inflammatory effects in athymic nude diabetic mice. Molecules 2017; 23(1): E67.
[http://dx.doi.org/10.3390/molecules23010067] [PMID: 29283418]
[http://dx.doi.org/10.3390/molecules23010067] [PMID: 29283418]
[99]
Samarghandian S, Azimi-Nezhad M, Samini F, Farkhondeh T. Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol 2016; 94(4): 388-93.
[http://dx.doi.org/10.1139/cjpp-2014-0412] [PMID: 26863330]
[http://dx.doi.org/10.1139/cjpp-2014-0412] [PMID: 26863330]
[100]
Farkhondeh T, Samarghandian S, Pourbagher-Shahri AM, Sedaghat M. The impact of curcumin and its modified formulations on Alzheimer’s disease. J Cell Physiol 2019; 234(10): 16953-65.
[http://dx.doi.org/10.1002/jcp.28411] [PMID: 30847942]
[http://dx.doi.org/10.1002/jcp.28411] [PMID: 30847942]
[101]
Anitha TA, Rajadurai M. Antioxidative potential of chrysin, a flavone in streptozotocin-nicotinamide-induced diabetic rats. Biomed Preven Nutr 2014; 4(4): 511-7.
[http://dx.doi.org/10.1016/j.bionut.2014.08.008]
[http://dx.doi.org/10.1016/j.bionut.2014.08.008]
Article Metrics
28
1