Ntu 2: Cov txiaj ntsig muaj peev xwm ntawm Flavonoids Rau Kev Loj Hlob Ntawm Atherosclerosis Los Ntawm Lawv Cov nyhuv ntawm Vascular Smooth Muscle Excitability

Yog xav paub ntxiv, hu rautina.xiang@wecistanche.com

Nyem qhov txuas mus kawm ntu 1:https://www.xjcistanche.com/news/part1-potential-benefits-of-flavonoids-on-the-55147149.html

3. Flavonoids hauv Atherosclerosis

3.1. Cov Ntsiab Lus

3.1.1. Classification thiab Structure

Flavonoidsmuaj cov qauv yooj yim uas muaj ob lub nplhaib los yog phenyl, A thiab B, thiab ib lub nplhaib heterocyclic C; lub nplhaib kawg yog tsim nrog cov pa atom (Daim duab 2). Lawv cov qauv yooj yim muaj 15 carbons uas tuaj yeem sau luv ua C6-C3-C6 [12,102], thiab lawv yuav muaj ntau tshaj li ib qho kev hloov pauv sib txawv vim cov flavonoid cov qauv hauv paus yuav raug kev hloov kho. Cov kev hloov kho no suav nrog kev nce lossis txo qis hauv cov pawg hydroxyl, flavonoid core, lossis hydroxyl pawg methylation, ortho hydroxyl pawg methylation, dimerization, tsim ntawm bisulfates, thiab hydroxyl pawg glycosylation los tsim flavonoids O-glycosides lossis glycosylation ntawm flavonoid's core. los tsim cov flavonoids C-glycosides. Feem ntau ntawm lawv yog cov hauv qab no: chalcones, aurones, flavanols, catechins, flavones, flavonols, flavanones, isoflavones, thiab anthocyanidins. Qee tus cwj pwm kom paub qhov txawv raws li lawv cov qauv, piv txwv li, isoflavones, muaj lub nplhaib B nyob rau hauv txoj hauj lwm 3 ntawm Cring [103](Table 3).

3.1.2.Flavonoids Khoom noj khoom haus thiab nqus

Anthocyanidins feem ntau pom muaj nyob rau hauv cov nroj tsuag pigments, thaum flavanols nyob rau hauv txiv hmab txiv ntoo thiab tshuaj yej, flavonols nyob rau hauv zaub thiab txiv hmab txiv ntoo, flavanones nyob rau hauv citrus, flavones nyob rau hauv zaub, isoflavones nyob rau hauv legumes, chalcones nyob rau hauv zaub thiab txiv hmab txiv ntoo, thiab aurones nyob rau hauv flowering nroj tsuag. Txawm li cas los xij, lawv cov teebmeem physiological nyob ntawm lawv cov bioavailability, pib nrog cov txheej txheem nqus. Feem ntau, peb noj ntau dua ntawm anthocyanins, flavonols, flavan-3-ols, thiab flavanones. Lub ntuj daim ntawv ntawmflavonoidsHauv cov nroj tsuag yog glycosides. Peb haus lawv li -glycosides, tshwj tsis yog rau catechins. EnzVmes hydrolyze cov tebchaw nyob rau hauv txhuam ciam teb ntawm cov hnyuv me epithelial hlwb. Cov aglycones tso tawm yog lipophilic, thiab lawv tuaj yeem hla daim nyias nyias los ntawm kev sib kis mus rau hauv cov hlwb yam tsis muaj kev pabcuam thauj khoom; Txawm li cas los xij, qib permeability nyob ntawm qhov loj thiab hydrophobicity. Ua ntej lawv nkag mus rau hauv cov hlab ntsha, lawv tau metabolized los ntawm enzymes thiab hloov mus rau sulfate, glucuronide, thiab / lossis methylated metabolites. Kev nqus rau feem ntau ntawm lawv tshwm sim hauv cov hnyuv me (Table 3). Yog tias tsis nqus, lawv txav mus rau hauv qhov chaw plab hnyuv uas cuam tshuam nrog microbiota thiab tsim tawm ntawm lwm cov metabolites [104,105]. Aurones tau siv rau cov tshuaj zas xim thiab kev tsim tshuaj; Lawv qhov kev nqus tau kwv yees yog nyob rau hauv txoj hnyuv uas pom los ntawm silico pharmacokinetic ADMET tsis muaj [106].

Nyem qhov no kom paub ntau yam khoom

3.1.3. Antioxidant Mechanisms ntawm Flavonoids

Cov yam ntxwv flavonoid qauv muab lawv cov khoom tiv thaiv oxidative. Qee zaum, lawv tawm tsam ob lub hom phiaj ib txhij; Piv txwv li, nws tau pom tias inhibition ntawm cholesterol-LDL oxidation [110,111] thiab platelet aggregation tuaj yeem tshwm sim nrog tsuas yog ib qho sib xyaw [112]. Hauv lwm qhov xwm txheej, lawv inhibit oxidases, piv txwv li, lipoxygenase thiab cyclooxygenase [113,114], lossis ua rau kev hloov pauv hlau chelation ntawm hlau lossis tooj liab [115], tswj cov ntshav ntshav [116].

Kev noj cov flavonoids hauv cov zaub mov noj qab haus huv yog siab dua lwm cov tshuaj antioxidants xws li cov vitamins C lossis E thiab carotene [117]. Qee cov flavonoids muaj peev xwm ua tau zoo ntawm cov dawb radicals neutralizing lawv los ntawm kev pub dawb electron thiab hloov hydrogen; Qhov no yog cov ntaub ntawv ntawm quercetin thiab myricetin vim hais tias lawv muaj ortho hydroxyl pawg nyob rau hauv lub nplhaib B ntawm txoj hauj lwm C3' thiab C4', los yog C4' thiab C5' (Daim duab 3). Cov yam ntxwv no, ua ke nrog cov qauv flavonol, muab lawv lub peev xwm antioxidant zoo dua [118].

Lwm cov tshuaj tiv thaiv kab mob antioxidant yog ua tau rau ib qho C3-OH lossis C5-OH flavone los ntawm electron pub dawb qhov twg daim ntawv tautomeric tuaj yeem coj tus cwj pwm ua antioxidant hauv vivo los ntawm inhibiting pro-oxidant enzymes (Daim duab 4) [119] .

Ferric ion chelators tiv thaiv kev khi ntawm cov hlau rau cov khoom ntawm daim nyias nyias thiab tiv thaiv cov nag lossis daus ntawm Fe (OH) 3; Cov txheej txheem no zam cov hydroxyl radicals lossis peroxides tsim (Daim duab 5) [120].

Qee qhov kev xav tau tau piav qhia rau flavonoids kom muaj peev xwm tiv thaiv qee qhov oxidases, xws li OH pawg tsawg kawg ntawm C7 lossis ib qho ntxiv OH ntawm C5, suav nrog ob daim ntawv cog lus ntawm C2 thiab C3 hauv lub nplhaib benzopyrone. Cov pab pawg catechol nyob rau hauv lub nplhaib B tuaj yeem tshwm sim kom muaj kev cuam tshuam ntawm xanthine oxidase (Daim duab 6). Qhov no enzyme catalyzes oxidation ntawm xanthine thiab hypoxanthine rau uric acid [121-123]; Qhov no tuaj yeem siv los ua lub hauv paus los tsim cov inhibitors rau cov enzyme no.

Flavonoids tuaj yeem cuam tshuam lipoxygenases yog tias lawv ua tiav cov qauv kev qhia tshwj xeeb xws li ob daim ntawv cog lus ntawm C2 thiab C3, pawg carbonyl hauv C4, thiab pawg catecholgroup hauv B nplhaib (OH hauv C4' yog qhov tseem ceeb, ua ke nrog OH hauv C3' lossis C5) .Ib qho dhau ntawm OH pawg txo qis lipophilic affinity ntawm flavonoids (Daim duab 7)[124].

Nws paub tias aglycones tuaj yeem tiv thaiv lipids, txij li cov flavonoids tsis muaj glycosides pawg tsis muaj dej-soluble, ntau reactive, thiab lawv tuaj yeem nyob ze rau lipids dua li glycosyl-flavonoids. Lawv tuaj yeem koom nrog lipoxygenase cov tshuaj tiv thaiv pub hydrogen nrog ib lub tshuab hluav taws xob hauv cov kauj ruam kawg ntawm cov tshuaj tiv thaiv kom tau txais cov lipid ruaj khov uas yav tas los oxidized (Daim duab 8) [125,126].

3.2.Qhov cuam tshuam ntawm Flavonoids hauv Atherosclerosis

Kev noj cov flavonoids hauv kev noj zaub mov tsis tu ncua tau cuam tshuam nrog txo cov kev pheej hmoo ntawm atherosclerosis, uas yog tej zaum vim lawv cov antioxidant thiab vasoactive zog [127]. Cov txiaj ntsig zoo muaj feem xyuam rau kev noj qab haus huv ntawm cov hlab ntsha, suav nrog inhibition ntawm LDL oxidation [128], kev ua haujlwm tiv thaiv platelet [129], txo cov kab mob atherosclerotic [130], txo cov ntshav siab [131], kev ua haujlwm endothelial zoo [132], thiab Txhim kho vascular du leeg ua haujlwm [133] Cov teebmeem ntawm VSMC tuaj yeem cuam tshuam nrog ion channel kev ua haujlwm hloov kho vim tias cov nyhuv ua rau vasodilation feem ntau. Cov nyhuv ntawm apigenin los yog Diocletian ntawm cov poov tshuaj raws txo lawv cov haujlwm thiab ua rau vasorelaxation. Lwm cov flavonoids tsim cov vasorelaxation tag nrho, piv txwv li, flavones thiab flavanones xws li acacetin, chrysin, apigenin, hesperetin, pinocembrin, luteolin, 4'-hydroxyflavanone, 5-hydroxy flavone, 5-methoxyflavone, {{12} }hydroxyflavanone, thiab 7-hydroxy flavone; Kev so ib nrab yog pom nrog quercetin, quercitrin, hesperidin, thiab rhoifolin; thiab qee qhov ntawm lawv tsis tsim kev so xws li quercetagetin thiab baicalein [134].

Cov tshuaj tiv thaiv atherosclerosis tau kawm feem ntau hauv ob pawg loj ntawm flavonoids: flavonols thiab flavan-3-ols vim tias lawv yog cov khoom sib xyaw ntau tshaj plaws hauv tib neeg cov zaub mov. Lawv kuj yog cov qauv zoo sib xws; ob leeg muaj ib pawg hydroxyl ntawm C3; Txawm li cas los xij, flavonols muaj ib pawg carbonyl ntawm C4 thiab ob daim ntawv cog lus ntawm C2 thiab C3 los ntawm lub nplhaib heterocyclic, thaum flavan-3-ols tsis. Lawv cov txiaj ntsig tau raug kawm hauv ntau cov haujlwm lom neeg nrog cov kev tshawb pom hauv qab no: LDL oxidation raug txo qis ex vivo, siv quercetin thiab glabridin [93,94], ntshav LDL-oxidation hauv apoE-/- nas raug txo nrog kev kho myricitrin [91], aortic ROS raug txo nrog kaempferol [92], thiab plasma rog concentration raug txo nrog quercetin [135].

Flavonoids txo qisoxidative kev nyuaj siablos ntawm kev tshem tawm cov dawb radicals thiab reactive oxygen hom [136], downregulating cyclooxygenases thiab lipoxygenases [137-139], upregulating cellular antioxidants [140], thiab txhim khoanti-inflammatorykev ua haujlwm [141].Nyob rau hauv kev nce qib ntawm atherosclerosis, flavonoids tuaj yeem zam kev tsim cov thrombus thiab txhim kho lipid thiab qabzib metabolism [142-144].

Thaum peb haus cov flavonoids, peb metabolize lawv mus rau hauv glycosides lossis aglycones. Agly-cones muaj liposoluble ntau dua thiab muaj peev xwm cuam tshuam nrog cell membranes dua li glycoside flavonoids [145,146]. Cov yam ntxwv no pab kom lawv nyob rau hauv kev sib cuag nrog ion raws.

3.3. Cov nyhuv ntawm Flavonoids hauv VSMC's Ion Channels

Ion channels ntawm plasma membrane ntawm VSMC cuam tshuam los ntawm flavonoids. Cov kev hloov kho nyob ntawm seb qhov twg flavonoid ua haujlwm rau lawv. Cov nqaij mos ntawm lub cell membrane muaj peev xwm hloov kho ncaj qha los ntawm kev txav ntawm calcium ions los ntawm cov cellular compartment mus rau hauv cytoplasmic qhov chaw thiab indirectly los ntawm calcium tso tawm los ntawm sarcoplasmic reticulum thiab mitochondria, raws li peb tau hais ua ntej [86].

Kev noj zaub mov kom zoo ntawm flavonoids cuam tshuam rau txoj kev loj hlob ntawmkab mob plawvlos ntawm kev tiv thaiv bioactivity ntawm endothelial nitric oxide. Flavonoids kuj cuam tshuam nrog cov teeb liab cascades ntawm o. Lawv tuaj yeem tiv thaiv kev tsim tawm ntau dhau ntawm NO thiab nws cov txiaj ntsig tsis zoo. Hauv cov ntaub so ntswg noj qab haus huv, flavonoids tuaj yeem ua rau endothelial nitric oxide synthase (Enos) kev ua, uas yog tsim nyog los tsim vasodilation. Hauv oxidative kev nyuaj siab thiab inflammatory mob, flavonoids inhibit NFkB txoj kev los tiv thaivmob. Flavonoids txo cov qib peroxynitrite thiab superoxide thiab tiv thaiv cov overexpression ntawm ROS-generating enzymes [147].

Fusi et al. (2017) kawm los ntawm docking tsom xam kev cuam tshuam ntawm flavonoids thiab Cav1.2 channel lc subunit. Lawv txheeb xyuas ob pawg ntawm flavonoids; thawj pab inhibited calcium tam sim no: scutellarein, morin, 5-hydroxy flavone, trihydroxyflavone, (±)-naringenin, daidzein, genistein, chrysin, resokaempferol, galangin, thiab baicalein, thiab pawg thib ob txhawb cov calcium tam sim no: myricetin, quercetin, isorhamnetin, luteolin, apigenin, kaempferol, thiab tamarixetin. Txoj kev tshawb no pom qhov sib txawv ntawm kev sib cuam tshuam ntawm flavonoid; epigallocatechin gallate cuam tshuam rau Cav1.2 tam sim no nyob rau hauv ib qho kev ywj pheej ntawm endothelium, thaum epicatechin gallate tsis cuam tshuam rau lawv. Hesperetin thiab cardamon nyob rau hauv block Cav1.2 raws thiab nce Kv tam sim no, ua rau vasorelaxation. Tib lub sijhawm, kaempferol 3-O-(6'-trans-p-coumaroyl)- -D-glucopyranoside(salidroside) ua rau ib feem inhibition ntawm Cav1.2 raws hauv vascular du nqaij [148].

Lwm cov txheej txheem uas cuam tshuam rau atherosclerosis suav nrog cov nyhuv ntawm flavonoids ntawm ion channel rau kev tswj ntshav siab. Marunaka (2017) qhia txog kev ua quercetin sab nraum cov hlab ntsha uas txhawb nqa Na plus -K ntxiv rau -2Cl- cotransporter 1 (NKCC1), tswj cov cytosolic Cl-concentration hauv lub ntsws endothelial hlwb. Qhov siab chloride concentration downregulates cov lus qhia ntawm epithelial Na * raws, tswj cov ntshav ntim los ntawm Nat reabsorption nrog rau qhov txo qis hauv ntshav siab [149].

Tsis ntev los no, Fusi et al. (2020) tau kawm txog cov txiaj ntsig zoo ntawm flavonoids ntawm cov hlab plawv, hais txog kev kawm txog cov poov tshuaj raws los ntawm kev txheeb xyuas docking. Lawv piav qhia txog kev sib cuam tshuam ntawm flavonoid-channel ntawm qib molecular thiab cuam tshuam nrog cov pov thawj kev sim. Lawv tau pom tias cov teebmeem vasodilator tseem ceeb cuam tshuam nrog kev qhib K raws. Hauv qee qhov kev sim, cov nyhuv yog nyob ntawm koob tshuaj; Piv txwv li, baicalin ntawm txhua hnub koob tshuaj ntawm 50 mus rau 200 mg / kg lub cev qhov hnyav txo qis ntshav siab hauv kev sim nrog cov nas hypertensive vim ATP-dependent K ntxiv (KATp) ua kom [150].

4. Cov teebmeem ntawm Flavonoids ntawm Atherosclerosis los ntawm Kev Hloov Kho ntawm Ion Channel hauv VSMC Kev Ua Haujlwm

Flavonoids tuaj yeem ua rau muaj kev cuam tshuam ntawm cov ion sib txawv hauv VSMC thiab tsim cov kev hloov pauv hauv kev loj hlob ntawm atherosclerosis. Cov teebmeem tuaj yeem hloov kho ion channel kev ua haujlwm thiab hloov pauv ion tam sim no thiab vascular tone. Ob peb flavonoids inhibit calcium tam sim no, ua rau vasorelaxation; qhov no yog cov ntaub ntawv ntawm genistein, phloretin, thiab biochanin-A, uas ua los ntawm cov txheej txheem endothelium-tsis ywj pheej; Cov txheej txheem no tsis koom nrog ATP-sensitive potassium raws tab sis yuav koom nrog lwm cov channel [151]. Scutellarin relaxes nas aortic rings nyob rau hauv daim ntawv ntawm koob tshuaj los ntawm inhibiting calcium tam sim no; Cov txheej txheem no yog ywj siab ntawm qhov voltage-dependent calcium channels, qhia txog kev koom tes ntawm lwm cov calcium channel rau calcium influx mediation thaum lub sij hawm contraction. Cov neeg sib tw rau qhov kev nqis tes no suav nrog cov channel tsis xaiv cation, receptor-operated calcium channels (ROCCs), thiab khw muag khoom calcium channels (SOCCs), thiab lwm yam. Raws li cov txiaj ntsig no, scutellarin yog siv los kho cov kab mob ischemic lossis kub siab ntsig txog atherosclerosis [152]. Lwm yam kev ua ub no muaj feem xyuam nrog kev ua kom muaj zog flavonoid yog los tiv thaiv platelet aggregation thiab inhibition ntawm cov leeg nqaij leeg proliferation [153]. Daidzein, genistein, apigenin, thiab trans-resveratrol inhibit SOCCs thiab impede platelet aggregation thiab thrombus tsim, nrog rau cov nyhuv uas cuam tshuam rau cov tub txib thib ob [154].

Epigallocatechin los ntawm cov tshuaj yej ntsuab tuaj yeem ua tau ntawm ob theem: thawj, nce calcium influx los tsim endothelium-ywj siab vasoconstriction, thiab thib ob, los ntawm inhibiting voltage-gated calcium channel induce vasodilation. Kev kho mob ntev ntawm 200 mg / kg / hnub ntawm epigallocatechin txo qis systolic ntshav siab nyob rau hauv cov nas hypertensive; Hauv cov nas tsis muaj zog, cov teebmeem tau tshwm sim ntawm ib koob ntawm 25-100 mg / kg / hnub[155,156]. （一）-Epigallocatechin-3-gallate thiab (-)-epicatechin-3-gallate txo cov kev ua ntawm Karp channels ntawm tsawg concentrations, tab sis ntau dua concentrations kiag li inhibit lub channel [157]. Quercetin yog flavonoid uas ua rau L-hom Ca2 ntxiv rau hauv VSMCs; Txawm li cas los xij, quercetin-induced vasorelaxant mechanisms muaj feem cuam tshuam ntau dua li qhov nce hauv Ca2 influx. Ntawm qhov tod tes, rutin, glycoside daim ntawv ntawm quercetin, ua tsuas yog thaum lub sij hawm endothelium-dependent so vim nws qis liposolubility [158]. Quercetin txo qis cell nto qhia ntawmhlab ntshacell adhesion molecules thiab txo lipid peroxidation [109]. Cov teebmeem quercetin tseem ceeb tau pom nyob rau hauv cov hlab ntsha tsis kam piv rau cov hlab ntsha conductive [107].

Ua kom cov calcium-activated potassium channels yog ib txoj hauv kev tseem ceeb hauv flavonoid-induced vasorelaxation. Kaempferol activates BKCa channels ntawm endothelial hlwb, ua rau daim nyias nyias hyperpolarization, thiab cov txheej txheem no txhawb rau vasodilation [159], thaum puerarin activates BKCa raws ntawm cov leeg nqaij, ua rau vasodilation [160]. Diocletian generates hypotension hauv cov nas ib txwm, uas yog tshwm sim los ntawm kev qhib KCa channels [161. Saponara et al. (2006) pom tau hais tias naringenin activates BKCa channels thiab dilates aortic rings [162]. Cov txiaj ntsig tib yam tau txais nrog quercetin, puerarin, epigallocatechin, thiab proanthocyanidins los ntawm ion channel activation, hyperpolarization, thiab vasorelaxation [162-164]. Kev koom tes ntawm BKCa agonists hauv atherosclerosis yog txo cov ntshav siab thiab txhim kho lwm cov tsos mob plawv [160].

Genistein inhibits Kv tam sim no nrog kev rov qab qeeb ntawm qhov hluav taws xob-gated potassium channels [165]. Kev ua kom cov poov tshuaj channel qhia pom cov teebmeem vasodilatory. Tilianin tsim cov vasorelaxation uas tej zaum yuav raug tsim vim yog qhib ntawm cov poov tshuaj raws [166]. Kolaviron, amentoflavone, pinocembrin, luteolin, thiab cardamon hauv kev ua ntawm ob qhov teebmeem: ua ntej, los ntawm kev txo cov calcium tam sim no thiab, thib ob, los ntawm kev nce cov poov tshuaj tam sim no, ob qho tib si nce vasodilation [167-171].

Calderone thiab al. (2004) tshawb xyuas endothelium-ywj siab vasorelaxant nyhuv ntawm flavonoids mediated los ntawm cov poov tshuaj raws. Lawv cov txiaj ntsig tau pom tias ob lub flavonoids yuav luag tsis muaj txiaj ntsig: baicalein thiab quercetagetin. Quercetin, quercitrin, rhoifolin, thiab hesperidin muaj ib feem ntawm vasorelaxant teebmeem, thaum tus so pom tag nrho cov vasorelaxant cuam tshuam, xws li acacetin, apigenin, chrysin, hesperetin, luteolin, pinocembrin, 4'-hydroxyflavanone, 5-, hydroxy{v. 5}}methoxyflavone, 6-hydroxyflavanone, thiab 7-hydroxy flavone, tag nrho cov ntawm lawv yog cov flavanones thiab flavones pawg. Txoj kev tshawb no xaus kev sib raug zoo ntawm cov qauv flavonoid thiab kev coj ua loj, calcium-activated potassium channels. Nws zoo nkaus li tias muaj C5-OH pab pawg yog qhov tsim nyog rau kev sib cuam tshuam thiab kev koom tes ntawm ATP-sensitive potassium channels [134].

Ntawm qhov tod tes, acacetin tiv thaiv atrial fibrillation, inhibits ultrarapid ncua sij hawm rectifier potassium tam sim no, thiab thaiv cov acetylcholine-activated potassium tam sim no, ua tiav lub sijhawm ntev ntawm qhov kev ua tau zoo thiab lub sijhawm zoo refractory, tiv thaiv atrial fibrillation [172]. Cov kev tshawb fawb tau pom tias isoliquiritigenin inhibits atherosclerosis los ntawm thaiv TRPC5 channel qhia hauv VSMCs. Qhov chaw ua haujlwm hauv khw no qhib qhov kev hloov pauv ntawm cov noob teb thaum ntxov kom loj hlob thiab tsiv teb tsaws [108].

Table 4 piav qhia txog cov teebmeem ntawm flavonoids ntawm ion channels thiab lawv cov kev cuam tshuam rau kev loj hlob ntawm atherosclerosis; Daim duab 9 piav qhia txog qhov chaw ntawm cov ion channel uas qhia txog cov teebmeem ntawm flavonoids.

Endothelial, atrium du nqaij thiab vascular du leeg hlwb raug nthuav tawm. Cov kab yog inhibited (kab liab) lossis txhawb nqa (ntsuab xub xub) los ntawm flavonoids, ua rau muaj kev cuam tshuam sib txawv thaum lub sij hawm atherosclerosis. IKur: ultrarapid ncua sijhawm rectifier K ntxiv rau tam sim no; IK: potassium tam sim no; ICA: calcium tam sim no; Kv1.5: voltage-dependent poov tshuaj channel; BKCa: loj-conductance calcium-activated potassium channel; Karp: ATP activated potassium channel; Cav1.2: voltage-dependent calcium-channel; SKCa: me me conductance potassium channel; KCa: calcium-activated potassium channel; TRPC5: hloov pauv receptor muaj peev xwm canonical 5 channel.

5. Cov kev xav yav tom ntej hauv kev kho mob

Cov teebmeem ntawm oxidants tau lees paub rau ntau xyoo lawm, thiab ntau cov txheej txheem pathogenic tau raug txheeb xyuas hauv ntau yam kab mob. Cov ntaub ntawv ntawm atheroscle-rosis yog ib qho piv txwv zoo vim tias kev kis kab mob yuav tsis tshwm sim yam tsis muaj oxidation ntawm lipids, raws li tau txheeb xyuas ntau ntawm no. Txawm li cas los xij, nyob rau hauv oxidative kev nyuaj siab, lipids tsis yog tib qho cuam tshuam rau cov molecules. Lub luag haujlwm ntawm lwm cov kev hloov pauv ntawm cov qauv molecular yuav tsum tau txiav txim siab rau kev nkag siab zoo ntawm lub cev thiab kev tsim tshuaj yav tom ntej. Nrog rau qhov kev tshuaj xyuas no, peb tau sim hais txog lub luag haujlwm ntawm voltage-gated ion channels hauv VSMCs. Membrane muaj peev xwm tswj tau yog transcendental rau cov leeg ua haujlwm thiab nyob ntawm kev ua haujlwm zoo ntawm txhua qhov kev coj ua ionic. Tseem muaj ntau cov lus nug tsis teb txog lub luag haujlwm tshwj xeeb ntawm oxidized channel thaum pib thiab kev loj hlob ntawm atherosclerosis. Unraveling cov kab mob tshwj xeeb ntawm txhua hom channel yuav qhib cov hom phiaj kho mob tshiab uas tuaj yeem tiv thaiv kab mob plawv. Ntawm no, peb tau qhia qhov loj ion channel cuam tshuam los ntawm oxidation; kev siv zog ntxiv los piav qhia txog yuav ua li cas thiab thaum twg lawv ua haujlwm tsis raug cuam tshuam rau kev txhim kho kab mob.

Ntawm qhov tod tes, cov txiaj ntsig zoo ntawm cov khoom noj nthuav dav peb cov kev xaiv rau kev nrhiav cov khoom ntuj tshiab uas tuaj yeem siv rau ntau theem ntawm atherosclerosis. Txawm hais tias cov tshuaj tiv thaiv oxidative, antithrombotic, anti-inflammatory, thiab vasorelaxant mechanisms ntawm flavonoids paub, lub peev xwm ntawm lawv cov txiaj ntsig yuav tsum tau nthuav dav rau cov hom phiaj tshiab molecular uas tsis feem ntau xav txog. Raws li qhia hauv Table 4, cov teebmeem ntawm flavonoids ntawm ion channel tau piav qhia ntau yam; Txawm li cas los xij, kev sib txuas ntawm lawv cov kev ua haujlwm kho kom zoo thiab txhim kho kab mob yuav tsum tau ua kom ntxaws.

Cov txheej txheem antioxidant ntawm flavonoids yog suav tias yog ib feem ntawm cov tshuaj chemistry; Nws yog ib qho tsim nyog yuav tsum ua kom tob rau lawv cov qauv thiab kev sib raug zoo thiab lub luag haujlwm ntawm pharmacokinetics thiab pharmacodynamics rau lawv cov txiaj ntsig [173]. Nanotechnology tuaj yeem ua lub luag haujlwm tseem ceeb sai sai los txhim kho bioavailability ntawm cov tebchaw. Kev ua haujlwm yav tom ntej nrog kev pab ntawm network pharmacology txoj hauv kev yuav xav tau los nrhiav cov hom phiaj tseem ceeb hauv kev kho mob atherosclerosis. Nyob rau hauv cov ntaub ntawv ntawm quercetin, ib qho ntawm feem ntau kawm flavonoids, kev tshawb fawb network tsis ntev los no tau txheeb xyuas 47 lub hom phiaj ntawm cov kab mob plawv thiab 12 txoj hauv kev ntawm Kyoto Encyclopedia of Genes thiab Genomes, uas tej zaum yuav muaj kev sib koom ua ke kho cov teebmeem. Cov kev tshawb fawb xws li docking tsom xam yuav tshem tawm cov txheej txheem meej uas cov flavonoids cuam tshuam nrog cov lipids tshwj xeeb thiab cov hom phiaj protein [174]. Peb txoj hauj lwm qhia tau hais tias yuav ua li cas noj zaub mov zoo thiab cov tshuaj ib txwm siv ua ke nrog cov txheej txheem bioinformatical zoo los qhia txog cov hom phiaj molecular ntawm natural compounds nrog siab precision los txhawb kev tsim tshuaj.

6. Cov lus xaus

Hauv kev xaus, flavonoids muaj kev cuam tshuam ncaj qha lossis tsis ncaj rau cov ion raws thiab vascular du leeg ua haujlwm; Lawv yog cov tshuaj vasodilator,antioxidants, txo cov tshuaj tiv thaiv peroxidative, inhibit platelet aggregation, thiab txo thrombotic nyiam.

Ntawm cov kev ua ub no, lawv muaj peev xwm antioxidant los tiv thaiv LDL, txo qis cov pa oxygen reactive thiab oxidizing enzymes, lawv cov kev ua ntawm cov hlau ions, txhawb cov endogenous antioxidant muaj peev xwm. Kev sib xyaw ua ke, ua haujlwm ntawm cov hom phiaj sib txawv, suav nrog ion channel, cuam tshuam rau kev txhim kho atherosclerosis hauv txoj hauv kev tseem ceeb, txhim kho vascular du leeg ua haujlwm.

Cov ntaub ntawv

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