Abstract
Quercetin (QCT) is a natural polyphenolic compound enriched in human food, mainly in vegetables, fruits and berries. QCT and its main derivatives, such as rhamnetin, rutin, hyperoside, etc., have been documented to possess many beneficial effects in the human body including their positive effects in the cardiovascular system. However, clinical implications of QCT and its derivatives are still rare. In the current paper we provide a complex picture of the most recent knowledge on the effects of QCT and its derivatives in different types of cardiac injury, mainly in ischemia-reperfusion (I/R) injury of the heart, but also in other pathologies such as anthracycline-induced cardiotoxicity or oxidative stress-induced cardiac injury, documented in in vitro and ex vivo, as well as in in vivo experimental models of cardiac injury. Moreover, we focus on cardiac effects of QCT in presence of metabolic comorbidities in addition to cardiovascular disease (CVD). Finally, we provide a short summary of clinical studies focused on cardiac effects of QCT. In general, it seems that QCT and its metabolites exert strong cardioprotective effects in a wide range of experimental models of cardiac injury, likely via their antioxidant, anti-inflammatory and molecular pathways-modulating properties; however, ageing and presence of lifestyle-related comorbidities may confound their beneficial effects in heart disease. On the other hand, due to very limited number of clinical trials focused on cardiac effects of QCT and its derivatives, clinical data are inconclusive. Thus, additional well-designed human studies including a high enough number of patients testing different concentrations of QCT are needed to reveal real therapeutic potential of QCT in CVD. Finally, several negative or controversial effects of QCT in the heart have been reported, and this should be also taken into consideration in QCT-based approaches aimed to treat CVD in humans.
Highlights
During the last decades, constantly growing interest of the effects of flavonoids and other polyphenols on human health has been noticed
Extensive research is focused on exploring the beneficial effects of QCT for human health at all body systems including cardiovascular, nervous, gastrointestinal and others, as well as on uncovering molecular mechanisms involved in QCT action in the body
Another group of QCT derivatives are C-glycosides, which are very rare in nature
Summary
Constantly growing interest of the effects of flavonoids and other polyphenols on human health has been noticed. Flavonoids are a group of polyphenolic compounds present in the diet representing a promising therapeutic and/or preventive agents for a variety of diseases including cardiovascular disease, diabetes mellitus, hypertension and cancer [1,2,3,4]. Extensive research is focused on exploring the beneficial effects of QCT for human health at all body systems including cardiovascular, nervous, gastrointestinal and others, as well as on uncovering molecular mechanisms involved in QCT action in the body. Increasing evidence of beneficial effects of QCT in different types of heart disease, the aIimn loinfethweipthreisnecnretarseivnigeweviisdteonscuemofmbaerniezfiecciuarlreeffnetcktsnoowf QleCdTgeinondipffoetreennttiatylpcaersdoifohperaorttecdtiisveeaeseff,etchtes aoifmQoCfTthaendprietssednetrirveavtiievwesiisntodisfufemremntatryizpeescuorfrceanrtdkiancowinljeudryg.eTohne ppoatpeenrtifaolccuasrdmiaoipnrloyteocntitvheeerffeceecntst oexf pQeCriTmaenndtailtsstduedriievsaetxivpelsoriinndgiefffeferectnstotyf tpheiss oflfacvaorndoiaidc iinnjiunrvy.itTroheaspwapeellrafsoicnuvs imvoaimnloydoenlstohfecraercdeinact einxjpuerryi,maenndtapl rsotuvdidieesdeextpailloerdinignfeoffremctastioofnthaibsofluatvpornoopidosiendinmveicthroanaissmweslilnavsoilnvevdivionmcaorddeilascoeffcfeacrtdsiaocf iQnCjuTrya,nadnditspdroerviivdaetidveetsa. QCT affects oafnmuumltbiperleoafctpivhiytsieiosliongfliucaelnpcirnogcemssaensy, adniffderisenbtesliigevneadlintgo pbaethbwenaeyfsi.ciTahl uins, vQaCriTouasffehcutsmaannudmisbeearsoesf pinhcylusidoilnoggiccaanl cperro,coebsesesist,yaannddisdbiaeblieetvees,dgtaostbreoibnetneestfiinciaallainndvarerinoaulsdhisuemasaens [d6i–s8e]a.ses including cancer, obesiItny acnardddioiavbaestceusl,agrassytrsoteinmte,sQtinCaTl aannddrecenratladiniseQaCseTs-c[6o–n8t]a.ining food have been shown to exert stronIgn caanrtdi-ihovyapsecrutelanrsisvyesteemffe, cQtsCTinanbdotcherteaxinpeQriCmTe-cnotanltaainniinmgaflosoadnhdavheubmeeannsshtohwronutgohexneurtmsetrroonugs amnetic-hhaynpiesmrtesnssuivche aeffs eactttesninuabtoiothn eoxf poexridimateinvteasltarnesims, aalfsfeacntidnghuinmtraancseltlhurloarugphronteuimn kerinouassemcaescchaadneiss,mass swueclhl aass vaitaterneumaotidoenlionfgooxfidexattrivaceesltlurelassr,maffaetrcitxining tihnetrvacaeslcluullaatruprero[t9e–i1n2k].inase cascades, as well as via remoIdnealidndgiotifoenxttoraictselvluaslacrumlaraterfifxecints,thQeCvTashcauslabteuerne s[h9–o1w2n]. to exert robust heart-protective effects in differInenatdkdiintdiosnotfociatsrdviaascciunljaurryeff, eincctslu, dQiCngT ihsacshebmeeina-rsehpoewrfnustoioenxe(Ir/tRr)oibnujustryh,edaortx-oprruobteicctiniv-einedffueccetds icnarddiiffoetroexnictiktyin, ddsiaobfectaicrdciaacrdiniojumryy,oipnactlhuydianngdiscohtheemrsia-[r1e3p–e1r7f]u. sCioanrd(Ii/oRp)riontjeucrtyiv, edoexfofercutbsicoifn-QinCdTucaerde caasrsdoicoiatotexdiciwtyi,thdiaafbfeecttiicncgamrdaionmy ydoifpfeartehnyt asnigdnaoltihnegrspa[1th3–w1a7y].s aCnadrdpirooptreointesc,tiinvceluedffiencgtsinohf iQbiCtiTonaroef aaspsoopctioatseisdanwditdhecarffeeacstiinnggomxiadnaytivdeiffsterreesns,tassigwneallliansgafpfeacthtiwngayinsflaanmdmpartootreyinpsr,otienicnlsuidninthgeihnehairbtit[i1o4n– o1f6,1a8p]o. ptosis and decreasing oxidative stress, as well as affecting inflammatory proteins in the heartI[n14li–n1e6w,18it]h. increasing evidence of beneficial effects of QCT in different types of heart disease, the aIimn loinfethweipthreisnecnretarseivnigeweviisdteonscuemofmbaerniezfiecciuarlreeffnetcktsnoowf QleCdTgeinondipffoetreennttiatylpcaersdoifohperaorttecdtiisveeaeseff,etchtes aoifmQoCfTthaendprietssednetrirveavtiievwesiisntodisfufemremntatryizpeescuorfrceanrtdkiancowinljeudryg.eTohne ppoatpeenrtifaolccuasrdmiaoipnrloyteocntitvheeerffeceecntst oexf pQeCriTmaenndtailtsstduedriievsaetxivpelsoriinndgiefffeferectnstotyf tpheiss oflfacvaorndoiaidc iinnjiunrvy.itTroheaspwapeellrafsoicnuvs imvoaimnloydoenlstohfecraercdeinact einxjpuerryi,maenndtapl rsotuvdidieesdeextpailloerdinignfeoffremctastioofnthaibsofluatvpornoopidosiendinmveicthroanaissmweslilnavsoilnvevdivionmcaorddeilascoeffcfeacrtdsiaocf iQnCjuTrya,nadnditspdroerviivdaetidveetsa. iFleindailnlyf,oprmotaetnitoinaladbioffuictupltrioepsoosfeQdCmTeucsheainnishmums iannvsoalvreedouintlicnaerddiianctheffe epcatpseorf, QinCclTudanindgitpsodteenritviaalticvoensf.oFuinnadlilny,gpfoatcetnortisatlhdaitffimcuayltiaefsfeocftQQCCTTuesfefiicniehnucymiannps raerveeonuttinlignecdaridnitahceinpjaupreyr., including potential confounding factors that may affect QCT efficiency in preventing cardiac injury
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