The Functionality of Apigenin as a Novel Cardioprotective Nutraceutical with Emphasize on Regulating Cardiac Micro RNAs

  • Venus Shahabi Raberi Department of Cardiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Mahboubeh Esmati School of medicine, North Khorasan University of Medical science, Bojnourd, Iran
  • Haleh Bodagh Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Reza Ghasemi Department of Cardiology, Torbat Heydarieh University of Medical Sciences, Torbat Heydarieh, Iran
  • Mehrdad Ghazal Department of Psychiatric Nursing, Islamic Azad University of Medical Sciences, Tehran, Iran
  • Azita Matinpour School of Nursing and Midwifery, Iran University of Medical Sciences, Tehran, Iran
  • Mohsen Abbasnezhad Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Keywords: Cardiovascular Diseases, MicroRNAs, Antioxidants, Reactive Oxygen Species, Apigenin

Abstract

Cardiovascular diseases (CVDs) are considered the most common disorder and the leading cause of mortality globally. The etiology of CVDs depends on a variety of genetic and acquired parameters. Nowadays, a dramatic surge appeared in published reports to find the association between microRNAs (miRNAs) and CVDs in order to understand the cause of the disease, rapid diagnosis with the introduction of valid biomarkers, and target as a therapeutic approach. Apigenin is a novel nutraceutical flavonoid that cardioprotective properties are suggested. The current review aimed to evaluate the beneficial features of this phytochemical against CVDs with an emphasis on its ability to regulate the miRNAs. The findings demonstrated that Apigenin could regulate cardiac miRNAs, including miR-103, miR-122-5p, miR-15b, miR-155, and miR-33. Consequently, preventing CVDs is possible through different effects such as the promotion of cholesterol efflux, prevention of hyperlipidemia, alteration in ATP Binding Cassette Subfamily A Member 1 (ABCA1) levels, reducing of cardiocytes apoptosis, and retarding myocytes fibrosis. Also, it can regulate signaling pathways, protect against endothelial dysfunction, maintain oxidative balance, and decrease inflammatory factors and reactive oxygen species. Hence, apigenin regulatory characteristics affecting miRNAs expression could introduce this flavonoid as a novel cardioprotective phytochemical against different CVDs.

References

Afzal M. Recent updates on novel therapeutic targets of cardiovascular diseases. Mol Cell Biochem. 2021;476(1):145-55.

https://doi.org/10.1007/s11010-020-03891-8

PMid:32845435

Şahin B, İlgün G. Risk factors of deaths related to cardiovascular diseases in World Health Organization (WHO) member countries. Health Soc Care Community. 2022;30(1):73-80.

https://doi.org/10.1111/hsc.13156

PMid:32909378

Rottapel RE, Hudson LB, Folta SC. Cardiovascular health and African-American women: A qualitative analysis. Am J Health Behav. 2021;45(4):735-45.

https://doi.org/10.5993/AJHB.45.4.12

PMid:34340740

Bassey IE, Akpan UO, Nehemiah ED, Arekong R, Okonkwo OL, Udoh AE. Cardiovascular Disease Risk Factors and Cardiac Markers among Male Cement Workers in Calabar, Nigeria. Journal of Chemical Health Risks. 2017;7(2):85-94.

Kazibwe J, Tran PB, Annerstedt KS. The household financial burden of non-communicable diseases in low-and middle-income countries: a systematic review. Health Res Policy Syst. 2021;19(1):1-15.

https://doi.org/10.1186/s12961-021-00732-y

PMid:34154609 PMCid:PMC8215836

Timmis A, Vardas P, Townsend N, Torbica A, Katus H, De Smedt D, et al. European Society of Cardiology: cardiovascular disease statistics 2021. Eur Heart J. 2022;43(8):716-99.

https://doi.org/10.1093/eurheartj/ehab892

PMid:35016208

Efremova O, Kamyshnikova L, Veysalov S, Sviridova M, Obolonkova N, Gayvoronskaya M, et al. Investigation on the Association of Cardiovascular Markers with Severity of Chronic Pyelonephritis. Arch Razi Inst. 2022;77(1):315-21.

Rezaei M, Sanagoo A, Jouybari L, Behnampoo N, Kavosi A. The effect of probiotic yogurt on blood glucose and cardiovascular biomarkers in patients with type II diabetes: a randomized controlled trial. Evid Based Care J. 2017;6(4):26-35.

Blaum C, Brunner FJ, Kröger F, Braetz J, Lorenz T, Goßling A, et al. Modifiable lifestyle risk factors and C-reactive protein in patients with coronary artery disease: Implications for an anti-inflammatory treatment target population. Eur J Prev Cardiol. 2021;28(2):152-8.

https://doi.org/10.1177/2047487319885458

PMid:33838040

Mannoh I, Hussien M, Commodore-Mensah Y, Michos ED. Impact of social determinants of health on cardiovascular disease prevention. Curr Opin Cardiol. 2021;36(5):572-9.

https://doi.org/10.1097/HCO.0000000000000893

PMid:34397464

Ndejjo R, Musinguzi G, Nuwaha F, Bastiaens H, Wanyenze RK. Understanding factors influencing uptake of healthy lifestyle practices among adults following a community cardiovascular disease prevention programme in Mukono and Buikwe districts in Uganda: A qualitative study. PLoS One. 2022;17(2):e0263867.

https://doi.org/10.1371/journal.pone.0263867

PMid:35176069 PMCid:PMC8853581

Elkoustaf RA, Nwaokoro M, Lahti DA, Yao JF, Gin N, Cotter TM, et al. Bridging the Gender Divide in Cardiovascular Rehabilitation: a Work in Progress. J Am Coll Cardiol. 2022;79(9_Supplement):1596.

https://doi.org/10.1016/S0735-1097(22)02587-6

Joseph P, Kutty VR, Mohan V, Kumar R, Mony P, Vijayakumar K, et al. Cardiovascular disease, mortality, and their associations with modifiable risk factors in a multi-national South Asia cohort: a PURE substudy. Eur Heart J. 2022;43(30):2831-40.

https://doi.org/10.1093/eurheartj/ehac249

PMid:35731159

Pederiva C, Capra ME, Biasucci G, Banderali G, Fabrizi E, Gazzotti M, et al. Lipoprotein (a) and family history for cardiovascular disease in paediatric patients: A new frontier in cardiovascular risk stratification. Data from the LIPIGEN paediatric group. Atherosclerosis. 2022;349:233-9.

https://doi.org/10.1016/j.atherosclerosis.2022.04.021

PMid:35562202

Andergassen D, Rinn JL. From genotype to phenotype: genetics of mammalian long non-coding RNAs in vivo. Nat Rev Genet. 2022;23(4):229-43.

https://doi.org/10.1038/s41576-021-00427-8

PMid:34837040

Fang Y, Dai X. Emerging roles of extracellular non-coding RNAs in vascular diseases. J Cardiovasc Transl Res. 2022:1-8.

https://doi.org/10.1007/s12265-022-10237-w

PMid:35460016

Tanase DM, Gosav EM, Petrov D, Teodorescu D-S, Buliga-Finis ON, Ouatu A, et al. MicroRNAs (miRNAs) in Cardiovascular Complications of Rheumatoid Arthritis (RA): What Is New? Int J Mol Sci. 2022;23(9):5254.

https://doi.org/10.3390/ijms23095254

PMid:35563643 PMCid:PMC9101033

Wronska A. The role of microRNA in the Development, Diagnosis, and Treatment of Cardiovascular Disease-Recent Developments. Journal of Pharmacology and Experimental Therapeutics. 2022.

https://doi.org/10.1124/jpet.121.001152

PMid:35779862

Altintaş N, Onur T, Yilmaz ÖS. Effects of microRNAs in hypertension disease. The Euro Res J. 2022;8(1):131-8.

https://doi.org/10.18621/eurj.855796

Improta-Caria AC. Physical Exercise and MicroRNAs: Molecular Mechanisms in Hypertension and Myocardial Infarction. Arq Bras Cardiol. 2022;118:1147-9.

https://doi.org/10.36660/abc.20210538

PMid:35703656 PMCid:PMC9345150

Li H, Chen M, Feng Q, Zhu L, Bai Z, Wang B, et al. MicroRNA‐34a in coronary heart disease: Correlation with disease risk, blood lipid, stenosis degree, inflammatory cytokines, and cell adhesion molecules. J Clin Lab Anal. 2022;36(1):e24138.

https://doi.org/10.1002/jcla.24138

Li H, Zhan J, Chen C, Wang D. MicroRNAs in cardiovascular diseases. Med Review. 2022;2(9):140-68.

https://doi.org/10.1515/mr-2021-0001

Santovito D, Weber C. Non-canonical features of microRNAs: Paradigms emerging from cardiovascular disease. Nat Rev Cardiol. 2022:1-19.

https://doi.org/10.1038/s41569-022-00680-2

PMid:35304600

Jenča D, Melenovský V, Stehlik J, Staněk V, Kettner J, Kautzner J, et al. Heart failure after myocardial infarction: incidence and predictors. ESC Heart Failure. 2021;8(1):222-37.

https://doi.org/10.1002/ehf2.13144

PMid:33319509 PMCid:PMC7835562

Abbasi A, Movahedpour A, Amiri A, Najaf MS, Mostafavi-Pour Z. Darolutamide as a second-generation androgen receptor inhibitor in the treatment of prostate cancer. Curr Mol Med. 2021;21(4):332-46.

https://doi.org/10.2174/18755666MTA5dNjU2w

https://doi.org/10.2174/1566524020666200903120344

PMid:32881669

Samare-Najaf M, Samareh A, Jamali N, Abbasi A, Clark CC, Khorchani MJ, et al. Adverse Effects and Safety of Etirinotecan Pegol, a Novel Topoisomerase Inhibitor, in Cancer Treatment: A Systematic Review. Curr Cancer Ther Rev. 2021;17(3):234-43.

https://doi.org/10.2174/1573394717666210202103502

Jafari Khorchani M, Samare-Najaf M, Abbasi A, Vakili S, Zal F. Effects of quercetin, vitamin E, and estrogen on Metabolic-Related factors in uterus and serum of ovariectomized rat models. Gynecol Endocrinol. 2021;37(8):764-8.

https://doi.org/10.1080/09513590.2021.1879784

PMid:33525940

Samare-Najaf M, Zal F, Safari S. Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol. 2020;96:316-26.

https://doi.org/10.1016/j.reprotox.2020.07.015

PMid:32810592

Samare-Najaf M, Zal F, Safari S, Koohpeyma F, Jamali N. Stereological and histopathological evaluation of doxorubicin-induced toxicity in female rats' ovary and uterus and palliative effects of quercetin and vitamin E. Hum Exp Toxicol. 2020;39(12):1710-24.

https://doi.org/10.1177/0960327120937329

PMid:32666839

Jamali N, Kazemi A, Saffari-Chaleshtori J, Samare-Najaf M, Mohammadi V, Clark CC. The effect of cinnamon supplementation on lipid profiles in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials. Complement Ther Med. 2020;55:102571.

https://doi.org/10.1016/j.ctim.2020.102571

PMid:33220625

Jamali N, Zal F, Mostafavi-Pour Z, Samare-Najaf M, Poordast T, Dehghanian A. Ameliorative effects of quercetin and metformin and their combination against experimental endometriosis in rats. Reprod Sci. 2021;28(3):683-92.

https://doi.org/10.1007/s43032-020-00377-2

PMid:33141412

Jamali N, Soureshjani EH, Mobini G-R, Samare-Najaf M, Clark CC, Saffari-Chaleshtori J. Medicinal plant compounds as promising inhibitors of coronavirus (COVID-19) main protease: an in silico study. J Biomol Struct Dyn. 2021:1-12.

https://doi.org/10.1080/07391102.2021.1906749

PMid:33970805

Da Purificação NRC, Garcia VB, Frez FCV, Sehaber CC, Lima KRDA, De Oliveira Lima MF, et al. Combined use of systemic quercetin, glutamine and alpha-tocopherol attenuates myocardial fibrosis in diabetic rats. Biomed Pharmacother. 2022;151:113131.

https://doi.org/10.1016/j.biopha.2022.113131

PMid:35643067

Jamali N, Jalali M, Saffari-Chaleshtori J, Samare-Najaf M, Samareh A. Effect of cinnamon supplementation on blood pressure and anthropometric parameters in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials. Diabetes Metab Syndr. 2020;14(2):119-25.

https://doi.org/10.1016/j.dsx.2020.01.009

PMid:32032898

Fan Z-k, Wang C, Yang T, Li X, Guo X, Li D. Flavonoid subclasses and CHD risk: a meta-analysis of prospective cohort studies. Br J Nutr. 2021:1-11.

https://doi.org/10.1017/S0007114521003391

PMid:34470681

Li Xq, Wang C, Yang T, Fan Zk, Guo Xf. A meta‐analysis of prospective cohort studies of flavonoid subclasses and stroke risk. Phytother Res. 2022;36(3):1103-14.

https://doi.org/10.1002/ptr.7376

PMid:35023220

Lee Y, Im E. Regulation of miRNAs by natural antioxidants in cardiovascular diseases: Focus on SIRT1 and eNOS. Antioxidants. 2021;10(3):377.

https://doi.org/10.3390/antiox10030377

PMid:33802566 PMCid:PMC8000568

Shao D, Lian Z, Di Y, Zhang L, Zhang Y, Kong J, et al. Dietary compounds have potential in controlling atherosclerosis by modulating macrophage cholesterol metabolism and inflammation via miRNA. npj Sci of Food. 2018;2(1):1-9.

https://doi.org/10.1038/s41538-018-0022-8

PMid:31304263 PMCid:PMC6550192

Cannataro R, Fazio A, La Torre C, Caroleo MC, Cione E. Polyphenols in the Mediterranean diet: From dietary sources to microRNA modulation. Antioxidants. 2021;10(2):328.

https://doi.org/10.3390/antiox10020328

PMid:33672251 PMCid:PMC7926722

Alrekabi DG, Hamad MN. Phytochemical investigation of Sonchus oleraceus (Family: Asteraceae) cultivated in Iraq, isolation and identification of quercetin and Apigenin. J Pharm Sci. 2018;10(9):2242-8.

Gao R, Lou Q, Hao L, Qi G, Tian Y, Pu X, et al. Comparative genomics reveal the convergent evolution of CYP82D and CYP706X members related to flavone biosynthesis in Lamiaceae and Asteraceae. PlJ. 2022;109(5):1305-18.

https://doi.org/10.1111/tpj.15634

PMid:34907610

Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, et al. The therapeutic potential of Apigenin. Int J Mol Sci. 2019;20(6):1305.

https://doi.org/10.3390/ijms20061305

PMid:30875872 PMCid:PMC6472148

Grumezescu AM, Holban AM. Therapeutic, probiotic, and unconventional foods. Elsevier; 2018.

Hostetler GL, Ralston RA, Schwartz SJ. Flavones: food sources, bioavailability, metabolism, and bioactivity. Adv Nutr. 2017;8(3):423-35.

https://doi.org/10.3945/an.116.012948

PMid:28507008 PMCid:PMC5421117

Mahajan UB, Chandrayan G, Patil CR, Arya DS, Suchal K, Agrawal YO, 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.

https://doi.org/10.3390/ijms18040756

PMid:28375162 PMCid:PMC5412341

Liu H-J, Fan Y-L, Liao H-H, Liu Y, Chen S, Ma Z-G, et al. Apigenin alleviates STZ-induced diabetic cardiomyopathy. Mol Cell Biochem. 2017;428(1):9-21.

https://doi.org/10.1007/s11010-016-2913-9

PMid:28176247

Cardenas H, Arango D, Nicholas C, Duarte S, Nuovo GJ, He W, et al. Dietary apigenin exerts immune-regulatory activity in vivo by reducing NF-κB activity, halting leukocyte infiltration and restoring normal metabolic function. Int J Mol Sci. 2016;17(3):323.

https://doi.org/10.3390/ijms17030323

PMid:26938530 PMCid:PMC4813185

Li D, Ma J, Wang L, Xin S. Apigenin prevent abdominal aortic aneurysms formation by inhibiting the NF-κB signaling pathway. J Cardiovasc Pharmacol. 2020;75(3):229-39.

https://doi.org/10.1097/FJC.0000000000000785

PMid:31821190

Ihm S-H, Park S-H, Lee J-O, Kim O-R, Park E-H, Kim K-R, et al. A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice. Plants. 2021;10(11):2493.

https://doi.org/10.3390/plants10112493

PMid:34834858 PMCid:PMC8618780

Samsonov MV, Podkuychenko NV, Khapchaev AY, Efremov EE, Yanushevskaya EV, Vlasik TN, et al. AICAR Protects Vascular Endothelial Cells from Oxidative Injury Induced by the Long-Term Palmitate Excess. Int J Mol Sci. 2021;23(1):211.

https://doi.org/10.3390/ijms23010211

PMid:35008640 PMCid:PMC8745318

Little PJ, Askew CD, Xu S, Kamato D. Endothelial dysfunction and cardiovascular disease: history and analysis of the clinical utility of the relationship. Biomedicines. 2021;9(6):699.

https://doi.org/10.3390/biomedicines9060699

PMid:34203043 PMCid:PMC8234001

Miao X, Jin C, Zhong Y, Feng J, Yan C, Xia X, et al. Data-independent acquisition-based quantitative proteomic analysis reveals the protective effect of Apigenin on palmitate-induced lipotoxicity in human aortic endothelial cells. J. Agric. Food Chem. J Agr Food Chem. 2020;68(33):8836-46.

https://doi.org/10.1021/acs.jafc.0c03260

PMid:32687348

Yamagata K, Hashiguchi K, Yamamoto H, Tagami M. Dietary apigenin reduces induction of LOX-1 and NLRP3 expression, leukocyte adhesion, and acetylated low-density lipoprotein uptake in human endothelial cells exposed to trimethylamine-N-oxide. J Cardiovasc Pharmacol. 2019;74(6):558-65.

https://doi.org/10.1097/FJC.0000000000000747

PMid:31815868

Jiang L, Qiao Y, Wang Z, Ma X, Wang H, Li J. Inhibition of microRNA‐103 attenuates inflammation and endoplasmic reticulum stress in atherosclerosis through disrupting the PTEN‐mediated MAPK signaling. J Cell Physiol. 2020;235(1):380-93.

https://doi.org/10.1002/jcp.28979

PMid:31232476

Wang J-X, Zhang X-J, Li Q, Wang K, Wang Y, Jiao J-Q, et al. MicroRNA-103/107 regulate programmed necrosis and myocardial ischemia/reperfusion injury through targeting FADD. Circ Res. 2015;117(4):352-63.

https://doi.org/10.1161/CIRCRESAHA.117.305781

PMid:26038570

Zaafan MA, Abdelhamid AM. The cardioprotective effect of microRNA-103 inhibitor against isoprenaline-induced myocardial infarction in mice through targeting FADD/RIPK pathway. Eur Rev Med Pharmacol Sci. 2021;25(2):837-44

Qi H, Ren J, E M, Zhang Q, Cao Y, Ba L, et al. MiR‐103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV 3 channel in rat hearts. J Cell Mol Med. 2019;23(3):1926-39.

https://doi.org/10.1111/jcmm.14095

PMid:30604587 PMCid:PMC6378213

Wang Z, Zhang H, Liu Z, Ma Z, An D, Xu D. Apigenin attenuates myocardial infarction-induced cardiomyocyte injury by modulating Parkin-mediated mitochondrial autophagy. J Biosci. 2020;45(1):1-9.

https://doi.org/10.1007/s12038-020-00047-0

Badacz R, Kleczyński P, Legutko J, Żmudka K, Gacoń J, Przewłocki T, et al. Expression of miR-1-3p, miR-16-5p and miR-122-5p as possible risk factors of secondary cardiovascular events. Biomedicines. 2021;9(8):1055.

https://doi.org/10.3390/biomedicines9081055

PMid:34440258 PMCid:PMC8391895

Šatrauskienė A, Navickas R, Laucevičius A, Krilavičius T, Užupytė R, Zdanytė M, et al. Mir-1, miR-122, miR-132, and miR-133 are related to subclinical aortic atherosclerosis associated with metabolic syndrome. Int J Environ Res. 2021;18(4):1483.

https://doi.org/10.3390/ijerph18041483

PMid:33557426 PMCid:PMC7915826

Shi Y, Zhang Z, Yin Q, Fu C, Barszczyk A, Zhang X, et al. Cardiac‐specific overexpression of miR‐122 induces mitochondria‐dependent cardiomyocyte apoptosis and promotes heart failure by inhibiting Hand2. J Cell Mol Med. 2021;25(11):5326-34.

https://doi.org/10.1111/jcmm.16544

PMid:33942477 PMCid:PMC8178264

Liu Y, Song J-W, Lin J-Y, Miao R, Zhong J-C. Roles of microRNA-122 in cardiovascular fibrosis and related diseases. Cardiovasc Toxicol. 2020;20(5):463-73.

https://doi.org/10.1007/s12012-020-09603-4

PMid:32856216 PMCid:PMC7451782

Feng W, Ying Z, Ke F, Mei-Lin X. Apigenin suppresses TGF-β1-induced cardiac fibroblast differentiation and collagen synthesis through the downregulation of HIF-1α expression by miR-122-5p. Phytomedicine. 2021;83:153481.

https://doi.org/10.1016/j.phymed.2021.153481

PMid:33607460

Wang F, Zhang J, Niu G, Weng J, Zhang Q, Xie M, Li C, Sun K. Apigenin inhibits isoproterenol-induced myocardial fibrosis and Smad pathway in mice by regulating oxidative stress and miR-122-5p/155-5p expressions. Drug Dev Res. 2022;83(4):1003-15.

https://doi.org/10.1002/ddr.21928

PMid:35277868

Zhu Y, Yang T, Duan J, Mu N, Zhang T. MALAT1/miR-15b-5p/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway. Aging (Albany N Y). 2019;11(4):1089-109.

https://doi.org/10.18632/aging.101766

PMid:30787203 PMCid:PMC6402525

Niu S, Xu L, Yuan Y, Yang S, Ning H, Qin X, et al. Effect of down-regulated miR-15b-5p expression on arrhythmia and myocardial apoptosis after myocardial ischemia reperfusion injury in mice. Biochem Biophys Res Commun. 2020;530(1):54-9.

https://doi.org/10.1016/j.bbrc.2020.06.111

PMid:32828315

Wang P, Sun J, Lv S, Xie T, Wang X. Apigenin alleviates myocardial reperfusion injury in rats by downregulating miR-15b. Med Sci Monit. 2019;25:2764.

https://doi.org/10.12659/MSM.912014

PMid:30983593 PMCid:PMC6481235

Faccini J, Ruidavets J-B, Cordelier P, Martins F, Maoret J-J, Bongard V, et al. Circulating miR-155, miR-145 and let-7c as diagnostic biomarkers of the coronary artery disease. Sci Rep. 2017;7(1):1-10.

https://doi.org/10.1038/srep42916

PMid:28205634 PMCid:PMC5311865

Qiu X-K, Ma J. Alteration in microRNA-155 level correspond to severity of coronary heart disease. Scand J Clin Lab Invest. 2018;78(3):219-23.

https://doi.org/10.1080/00365513.2018.1435904

PMid:29411649

Ding H, Wang Y, Hu L, Xue S, Wang Y, Zhang L, et al. Combined detection of miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 for screening of early heart failure diseases. Biosci Rep. 2020;40(3):BSR20191653.

https://doi.org/10.1042/BSR20191653

PMid:32124924 PMCid:PMC7080642

Wang F, Fan K, Zhao Y, Xie M-L. Apigenin attenuates TGF-β1-stimulated cardiac fibroblast differentiation and extracellular matrix production by targeting miR-155-5p/c-Ski/Smad pathway. J Ethnopharmacol. 2021;265:113195.

https://doi.org/10.1016/j.jep.2020.113195

PMid:32800930

Wang H, Bei Y, Huang P, Zhou Q, Shi J, Sun Q, et al. Inhibition of miR-155 protects against LPS-induced cardiac dysfunction and apoptosis in mice. Mol Ther Nucleic Acids. 2016;5:e374.

https://doi.org/10.1038/mtna.2016.80

PMid:27727247 PMCid:PMC5095684

Arango D, Diosa‐Toro M, Rojas‐Hernandez LS, Cooperstone JL, Schwartz SJ, Mo X, et al. Dietary Apigenin reduces LPS‐induced expression of miR‐155 restoring immune balance during inflammation. Mol Nutr Food Res. 2015;59(4):763-72.

https://doi.org/10.1002/mnfr.201400705

PMid:25641956 PMCid:PMC7955240

Reddy LL, Shah SA, Ponde CK, Rajani RM, Ashavaid TF. Circulating miRNA-33: a potential biomarker in patients with coronary artery disease. Biomarkers. 2019;24(1):36-42.

https://doi.org/10.1080/1354750X.2018.1501760

PMid:30022694

Xie Z, Ma P. MiR-33 may be a Biological Marker for Coronary Heart Disease. J Clin Lab. 2018;64(10):1755-60.

https://doi.org/10.7754/Clin.Lab.2018.180538

PMid:30336533

Chen Z, Ding H-S, Guo X, Shen J-J, Fan D, Huang Y, et al. MiR-33 promotes myocardial fibrosis by inhibiting MMP16 and stimulating p38 MAPK signaling. Oncotarget. 2018;9(31):22047.

https://doi.org/10.18632/oncotarget.25173

PMid:29774121 PMCid:PMC5955156

Price NL, Singh AK, Rotllan N, Goedeke L, Wing A, Canfrán-Duque A, et al. Genetic ablation of miR-33 increases food intake, enhances adipose tissue expansion, and promotes obesity and insulin resistance. Cell Rep. 2018;22(8):2133-45.

https://doi.org/10.1016/j.celrep.2018.01.074

PMid:29466739 PMCid:PMC5860817

Afonso MS, Sharma M, Schlegel M, Van Solingen C, Koelwyn GJ, Shanley LC, et al. miR-33 silencing reprograms the immune cell landscape in atherosclerotic plaques. Circ Res. 2021;128(8):1122-38.

https://doi.org/10.1161/CIRCRESAHA.120.317914

PMid:33593073 PMCid:PMC8049965

Ren K, Jiang T, Zhou H-F, Liang Y, Zhao G-J. Apigenin retards atherogenesis by promoting ABCA1-mediated cholesterol efflux and suppressing inflammation. Cell Physiol Biochem. 2018;47(5):2170-84.

https://doi.org/10.1159/000491528

PMid:29975943

Published
2022-12-17
How to Cite
Shahabi Raberi , V., Esmati , M., Bodagh, H., Ghasemi , R., Ghazal , M., Matinpour , A., & Abbasnezhad, M. (2022). The Functionality of Apigenin as a Novel Cardioprotective Nutraceutical with Emphasize on Regulating Cardiac Micro RNAs. Galen Medical Journal, 11, e2535. https://doi.org/10.31661/gmj.v11i.2535
Section
Review Article