Cov teebmeem ntawm Suav Herbal Tshuaj Rau Zog Metabolism hauv Ischemic Heart Diseases-Ⅰ

Taw qhia

Ischemic heart disease (IHD) yog qhov ua rau tuag ntau tshaj plaws ntawm cov kab mob plawv, uas ua rau muaj kev cuam tshuam loj heev rau kev sib raug zoo thiab kev lag luam. Lub Ntiaj Teb Burden of Disease Study of 2017 (GBD 2017) tau tshaj tawm tias tag nrho cov neeg tuag los ntawm IHD tau nce los ntawm 7.30 txog 8.93 lab ntawm 2007 thiab 2017 nyob rau theem thoob ntiaj teb (GBD 2017 Ua rau Kev Tuag Sib Koom Tes, 2018). IHD muaj feem ntau ntawm cov kab mob plawv (xws li angina, nonfatal myocardial infarction, thiab coronary death), asymptomatic myocardial ischemia, mob plawv nres, thiab ischemic plawv tsis ua hauj lwm (Wong, 2014; Guo et al., 2018). Cov kev kho tam sim no feem ntau yog nyob ntawm kev kho mob xws li statins, tshuaj antiplatelet, beta-receptor blockers (b-blockers), thiab angiotensin-hloov-enzyme inhibitors (ACEIs), ntxiv rau cov txheej txheem phais xws li percutaneous coronary intervention (PCI) thiab coronary artery bypass graft (CABG) phais. Txawm hais tias cov kev kho mob thiab kev phais mob no tau ua pov thawj tias muaj txiaj ntsig zoo hauv kev txo cov neeg mob thiab kev tuag tom qab IHD, ntau lab tus neeg mob tseem muaj cov tsos mob ntawm kev kho mob, suav nrog mob hauv siab, mob plawv, ua tsis taus pa, thiab qaug zog. Yog li ntawd, tsim cov tswv yim kho tshiab uas muaj cov txheej txheem sib txawv hauv myocardial ischemia thiab txawm tias rov ua dua yog qhov tseem ceeb.

NATURAL CISTANCHE TUBULOSA rau kev kho mobISCHEMIC HEART DISEASEPHGS75% ECH 30% ACT 12%

Lub plawv lub zog metabolism plays lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm cov kab mob plawv. Van Bilsen et al. (2004) tau npaj lub tswv yim ntawm myocardial metabolic remodeling. Nrog rau txoj kev loj hlob ntawm kev tshawb fawb niaj hnub thiab cov thev naus laus zis siab, kev hloov pauv hauv myocardial energetics xws li hloov pauv hauv kev siv hluav taws xob substrate, cuam tshuam mitochondrial oxidative phosphorylation, thiab txo qis hauv adenosine triphosphate (ATP) hloov pauv thiab kev siv lub peev xwm tau txais kev lees paub tias ua lub luag haujlwm tseem ceeb hauv kev ua haujlwm. mechanisms ntawm IHD (Fukushima li al., 2015; Tuomainen thiab Tavi, 2017). Kev tsis txaus ntawm lub zog ntawm lub plawv ua rau lub plawv tsis ua haujlwm, sab laug ventricular remodeling, thiab txawm tias lub plawv tsis ua haujlwm (HF). Yog li ntawd, cov pov thawj loj hlob tuaj txhawb tias kev hloov pauv ntawm lub plawv lub zog metabolism tuaj yeem yog ib qho txiaj ntsig zoo ntawm kev txhim kho plawv thiab ua kom qeeb ntawm HF (Neubauer, 2007; Lang et al., 2015; Qi and Young, 2015; Yang et al., 2016. ; Tuomainen and Tavi, 2017). Cov tshuaj suav tshuaj ntsuab (CHMs) tau nyiam ntau yam tsis ntev los no raws li qhov muaj peev xwm kho tau zoo rau kev tiv thaiv thiab kho myocardial ischemia los ntawm kev hloov pauv lub zog metabolism. Nws yog lub tswv yim tshiab rautiv thaiv lub ischemic myocardium tiv thaiv IHD. Qhov kev tshuaj xyuas no tsom mus rau qhov muaj peev xwm ua tau zoo ntawm cov tshuaj ntsuab, cov khoom siv bioactive tseem ceeb (MBC), thiab Suav tshuaj ntsuab cov qauv (CHF) hauv kev hloov kho plawv lub zog metabolism hauv IHD thiab cov txheej txheem cuam tshuam.

LUB TSEV KAWM NTAWV THIAB SIGNALING CARDIAC ENERGY METABOLISM FOR CHINESE HERBAL MEDICIINES

"Qi-blood" Txoj kev xav ntawm TCM yog txuas nrog Cardiac Energy Metabolism

Cov neeg laus lub siab noj qab nyob zoo muaj kev xav tau lub zog tas mus li thiab xav tau kev cog lus kom muab lub cev nrog cov ntshav thiab oxygen tsis tu ncua. Raws li lub zog ntawm cardiomyocytes, mitochondria tau txuas ntxiv muab lub zog xav tau rau cov leeg mob plawv. Raws li ib txwm muaj, yuav luag ntawm ATP tiam hauv cov neeg laus lub siab noj qab haus huv los ntawm mitochondrial oxidative phosphorylation, nrog rau qhov seem feem ntau yog los ntawm glycolysis. Hauv plawv ischemic, impaired mitochondrial oxidative phosphorylation muab cov khoom tsis txaus ntawm ATP rau cardiomyocytes. Cov pov thawj muaj qhia tias lub plawv lub zog metabolism hauv kev sib raug zoo nrog lub plawv ua haujlwm. Txo lub peev xwm rau lub plawv lub zog hloov ua rau lub plawv twj tso kua mis tsis ua haujlwm, cov ntshav khiav tsis zoo, lub plawv contractile tsis ua haujlwm, thiab txawm tias lub plawv tsis ua haujlwm (Huss and Kelly, 2005). Kev tshawb nrhiav cov tswv yim kho mob rau kev hloov kho plawv lub zog metabolism yog ib qho teeb meem loj hauv cov kab mob plawv.

Cov tshuaj suav tshuaj (TCM)yog tus cwj pwm los ntawm "Holistic tswvyim" uas lub cev yog suav tias yog tag nrho. Hauv TCM, Qi thiab ntshav yog cov khoom tseem ceeb ntawm cov kab mob, uas tswj lub neej ua haujlwm ntawm tib neeg. Qi muaj kev txhawb nqa, ua kom sov, sib sau ua ke, thiab tuav haujlwm, uas muab lub zog rau kev txhawb nqa cov ntshav thiab ua kom cov ntshav ntws hauv cov hlab ntsha. Raws li thawj Suav kev kho mob classic thiab keeb kwm ntawm TCM txoj kev xav, Suwen ntawm Yellow Emperor's Internal Classic piav qhia txog lub plawv tswj cov ntshav thiab cov hlab ntsha. Nws txhais tau hais tias Lub Plawv Qi txhawb nqa thiab ua kom tsim thiab kev ua haujlwm ntawm cov ntshav hauv cov hlab ntsha rau kev txhawb nqa lub cev thiab cov ntaub so ntswg, khaws cov kua dej hauv lub cev, thiab tswj kev ua haujlwm ntawm lub cev. Kev nplua nuj ntawm lub plawv-qui, txaus ntshav txaus, thiab vascular patency yog peb lub ntsiab lus tseem ceeb uas tswj cov ntshav ncig. Hauv plawv, Lub plawv-Qi tsav ATP synthesis ntawm ATP synthase hauv plawv mitochondria los muab lub zog tseem ceeb uas tsim nyog rau cov leeg mob plawv thiab so. Cov tsos mob ntawm myocardial ischemia hauv cov neeg mob kho mob feem ntau suav nrog hauv siab nruj, plawv dhia, ua tsis taus pa, thiab tsis muaj zog. Cov tsos mob ntawm myocardial ischemia sib raug rau cov tsos mob ntawm Heart Qi deficiency syndrome, uas ua rau cov ntshav ncig tsis zoo thiab mob plawv microcirculatory cuam tshuam ua rau cov ntshav stasis syndrome. Lub plawv Qi tsis txaus kuj tuaj yeem ua rau tsis txaus ntawm HeartYang, uas yog nrog los ntawm cov tsos mob xws li hws txias, thiab ua rau mob khaub thuas thiab mob khaub thuas. Tsis tas li ntawd, Lub Plawv Qi tsis muaj peev xwm tuaj yeem ua rau microvascular hyperpermeability, ua rau cov kua dej ntau dhau, phlegm, edema, thiab hemorrhage. Raws li "Qi-blood" txoj kev xav ntawm TCM, Suav tshuaj ntsuab tshuaj ntsuab uas tuaj yeem tonify lossis tswj Qi thiab qhib cov ntshav tau cog lus tias yog ib qho tseem ceeb ntawm kev kho mob rau kev hloov kho ntawm lub plawv lub zog metabolism hauv cardiology.

Lub Hom Phiaj Ua Tau Ntawm Lub Zog Lub Zog Metabolism rau Suav Tshuaj Ntsuab

Cov tshuaj suav tshuaj ntsuab, xws li tshuaj ntsuab botanical, muaj keeb kwm ntev ntawm kev siv tshuaj kho mob hauv kev kho mob plawv thiab muaj cov khoom ntawm ntau lub hom phiaj pharmacological. Lawv tuav lub peev xwm zoo thiab tshwj xeeb hauv kev tswj hwm lub plawv lub zog metabolism, tshwj xeeb tshaj yog nyob rau hauv kev ua haujlwm ntawm mitochondrial, lipid metabolism, thiab qabzib metabolism. Qee lub hom phiaj tau piav qhia hauv qab no, categorized los ntawm cov txheej txheem ntawm lub plawv lub zog metabolism. Cov txheej txheem metabolic koom nrog hauv plawv lub zog metabolism muaj peb lub ntsiab lus (Daim duab 1), uas yog, lub zog substrate nyiam, mitochondrial oxidative phosphorylation, thiab ATP hloov thiab siv (Neubauer, 2007).

Kev siv hluav taws xob substrate sawv cev rau thawj feem. Cardiomyocytes tuaj yeem metabolize tag nrho cov chav kawm ntawm lub zog substrates, suav nrog fatty acids, qabzib, glycogen, lactate, ketone lub cev, thiab qee cov amino acids (Heggermont li al., 2016). Dawb fatty acids (FFA) thiab qabzib ua ntej nkag mus rau myocardium los ntawm cov ntshav thiab tom qab ntawd hloov mus rau fatty acyl-coenzyme A (acyl-CoA) thiab glycolytic kawg cov khoom pyruvate hauv cytoplasm ntawm cardiomyocytes. Long-chain fatty acyl-CoA raug thauj mus rau hauv mitochondria ntawm carnitine palmitoyl transferase 1 thiab 2 (CPT1 thiab CPT2), hos pyruvate raug coj mus rau hauv mitochondria los ntawm mitochondrial pyruvate carrier (MPC) (Arumugam et al., 2016; ., 2018).

Qhov thib ob tivthaiv yog mitochondrial oxidative phosphorylation, uas muab ntau tshaj 95% ntawm ATP xav tau los ntawm lub siab paub tab. Feem ntau, fatty acid beta-oxidation (FAO), lub hauv paus loj ntawm mitochondrial oxidative phosphorylation, muab ntau tshaj li ob feem peb ntawm lub zog xav tau nyob rau hauv cov neeg laus myocardium, nrog rau qhov seem yog muab los ntawm oxidation ntawm substrates xws li carbohydrates, lactate, ketone. lub cev, thiab ntau cov amino acids (Heggermont li al., 2016). Cov mitochondrial substrate fluxes ntawm cov txheej txheem metabolic (tshwj xeeb tshaj yog fatty acid beta-oxidation thiab pyruvate oxidation) yield acetyl coenzyme A (acetyl-CoA), uas tom qab nkag mus rau tricarboxylic acid (TCA) voj voog (Kolwicz li al., 2013). Nicotinamide adenine dinucleotide (NADH) thiab flavin adenine dinucleotide (FADH2) yog tsim los ntawm TCA voj voog thiab beta-oxidation, raws li (Schwarz li al., 2014). NADH thiab FADH2 pub cov hluav taws xob hluav taws xob siab rau hauv mitochondrial electron thauj saw (ETC), tsim cov electrochemical gradient los ntawm ETC complexes ( complex IV) hla lub puab mitochondrial membrane (IMM) uas tom qab tsav ATP synthesis (Huss thiab Kelly, 2005). Ntawm lawv, ATP synthase (complex V), raws li cov kauj ruam kawg ntawm mitochondrial oxidative phosphorylation, generates ATP los ntawm phosphorylating adenosine diphosphate (ADP). Kev hloov ntawm electrons ntawm complexes yog kho los ntawm ubiquinone (CoQ) thiab cytochrome c (cyt c). Raws li kev tsim NADH thiab FADH2, TCA lub voj voog tseem tsim cov citrate ntau dhau hauv cytosol, qhov uas nws hloov mus rau hauv acetyl CoA (Murphy li al., 2016; Noordali li al., 2018). Cytosolic acetyl CoA tau hloov dua siab tshiab rau hauv malonyl CoA ntawm acetyl CoA carboxylase (ACC), thaum malonyl CoA, lub zog inhibitor CPT-1, tuaj yeem hloov rov qab rau hauv acetyl CoA ntawm malonyl CoA decarboxylase (MCD), yog li tswj kev nkag. ntawm FFA mus rau hauv mitochondria ib zaug ntxiv (Fukushima li al., 2015; Noordali li al., 2018). Cov khoom thib peb suav nrog kev hloov pauv plawv ATP thiab siv los ntawm creatine kinase (CK) system (Neubauer, 2007; Fukushima li al., 2015). High-zog phosphates yog pauv los ntawm ATP tsim los ntawm oxidative phosphorylation hauv mitochondria rau creatine (Cr), yog li tsim phosphocreatine (PCr) thiab ADP los ntawm kev ua ntawm mitochondrial creatine kinase. Phosphocreatine tau nrawm nrawm los ntawm mitochondria mus rau hauv myofibrils thiab tom qab ntawd hloov kho ATP thiab Cr los ntawm kev ua ntawm myofibrillar creatine kinase (Neubauer, 2007). Tom qab ntawd, ATP yog siv los ntawm myosin ATPase los tsim lub zog ntawm lub plawv contraction, thaum cov dawb Cr diffuses rov qab mus rau mitochondria.

NATURAL CISTANCHE TUBULOSA FOR REGULATING CARDIOMETABOLISM PHGS75% ECH 30% ACT 12%

Qhov Ua Tau Transcriptional Signaling of Cardiac Energy Metabolism for Chinese Herbal Medicines

Cov txheej txheem ntawm lub plawv lub zog metabolism yog complex thiab feem ntau tswj los ntawm metabolic proteins (enzymes thiab transcriptional Cheebtsam) uas tswj cov kev qhia ntawm ib tug loj tus naj npawb ntawm cov noob koom nyob rau hauv myocardial zog metabolism los ntawm ntau yam metabolic txoj kev (Stanley li al., 2005). Hauv particular, mitochondrial qauv thiab kev ua haujlwm yog tswj hwm los ntawm ntau cov noob, suav nrog 37 encoded hauv mitochondrial DNA thiab ntau tus lej encoded hauv nuclear DNA (Ham thiab Raju, 2016). Nws tau dhau los ua kom pom tseeb tias ntau qhov kev sib tham ntawm nuclear-mitochondrial crosstalk thiab kev taw qhia txoj hauv kev ua lub luag haujlwm tseem ceeb hauv kev tswj lub plawv lub zog metabolism hauv cov mob ischemic (Qi thiab Young, 2015; Murphy li al., 2016).

Cov Tshuaj Suav Herbal kuj tseem tuaj yeem hloov kho ntau txoj hauv kev uas muaj peev xwm vim tias lawv cov khoom ntawm multicomponent. Qee txoj hauv kev tau piav qhia hauv qab no (Daim duab 2). Adenosine monophosphate-activated protein kinase (AMPK) yog ib qho tseem ceeb intracellular zog sensor, thiab nws ua kom muaj kev koom tes nyob rau hauv ntau txoj kev qhia, xws li modulating qabzib thiab fatty acid metabolism, mitochondrial muaj nuj nqi, thiab autophagy (Murphy li al., 2016; Nishida thiab Otsu , 2016). AMPK muaj peb lub subunits protein: ib lub catalytic subunit, muaj Thr172 qhov chaw uas yuav tsum tau phosphorylated rau AMPK ua kom, thiab ob txoj cai subunits (g thiab b) (Zaha and Young, 2012). AMPK kev ua haujlwm yog ib feem ua haujlwm los ntawm kev nce hauv AMP / ATP piv rau hauv cov xeev qis zog. Thaum lub sij hawm myocardial ischemia, qhov kev ua ntawm AMPK hauv myocardium yog qhib kom ua raws li cov lus teb hloov mus rau cardiomyocyte kev ntxhov siab, ua rau muaj kev hloov pauv hauv cov txheej txheem metabolic. Kev ua kom AMPK nce cellular qabzib los ntawm kev sib kho ntawm kev thauj mus los ntawm glucose transporter 4 (GLUT4) los ntawm cytosol mus rau sarcolemma membrane nyob rau hauv ischemia thaum ntxov adaptive theem (Russell li al., 2004; Qi thiab Young, 2015), thiab txhawb nqa. glycolysis los ntawm phosphofructokinase 2 (PFK2) phosphorylation (Marsin li al., 2000). AMPK tuaj yeem cuam tshuam kev ua haujlwm ntawm glycogen synthase (GS), uas tsis ncaj qha txhawb kev siv glycogen (Qi thiab Young, 2015). Tsis tas li ntawd, AMPK kuj tseem ua lub luag haujlwm tseem ceeb hauv kev hloov kho lipid metabolism. Activated AMPK pab txhawb lub myocardial uptake ntawm fatty acids los ntawm kev txhawb txoj kev hloov ntawm fatty acid transporter CD36 (Luiken li al., 2003). Lub caij no, Kev Ua Haujlwm ntawm AMPK txuas ntxiv ua rau txo qis ntawm malonyl-CoA qib los ntawm kev tsis ua haujlwm ntawm ACC, uas txhawb nqa cov roj acid oxidation zoo los ntawm kev txo qis CPT-1 kev tawm tsam (Dyck thiab Lopaschuk, 2006) (Daim duab 1). Meanwhile, cov txheej txheem ntawm mitochondrial biogenesis khaws cia nyob rau hauv ib tug dynamic tshuav nyiaj li cas, uas undergoes tas li fusion thiab fission. Dynamin-related protein 1 (Drp1) thiab Fission 1 (Fis1) yog paub los txhawb mitochondrial fission. Mitofusin 1 thiab 2 (MFN1 thiab MFN2) feem ntau yog nruab nrab sab nraud

membrane fusion, whereas Opa1 feem ntau yog lub luag hauj lwm rau puab membrane fusion. Mitochondrial dynamics imbalance ua rau muaj qhov tsis xws luag hauv mitochondrial morphology thiab mitochondrial dysfunction thaum lub sij hawm ischemic contexts. Hypoxia-induced AMPK activation tuaj yeem txhawb nqa mitochondrial fission los ntawm phosphorylation ntawm mitochondrial fission factor (MFF), uas yog suav tias yog mitochondrial txheej membrane receptor rau Drp1, ib qho tseem ceeb enzyme rau muab lub zog tsav tsheb hauv mitochondrial fission (Garcia thiab Shaw, 2. ). Tsis tas li ntawd, autophagy yog tswj hwm los ntawm AMPK ua kom, uas rov ua haujlwm tsis zoo ntawm myocardial los ntawm kev siv lub hom phiaj ntawm rapamycin (mTOR) (Wu li al., 2020a).

Peroxisome proliferator-activated receptor gamma (PPARg) coactivator (PGC-1a) yog tus cwj pwm zoo ntawm tus neeg nruab nrab ntawm mitochondrial biogenesis thiab ua pa, thiab nws cov haujlwm tseem tuaj yeem hloov kho los ntawm AMPK phosphorylation (Gundewar li al., 2009) ( Daim duab 2). Ntxiv rau AMPK phosphorylation, PGC- 1aactivity yog nruj tswj hwm los ntawm NAD+ -dependent deacetylase sirtuin-1 (SIRT1) deacetylation, uas txhawb nqa mitochondrial biogenesis (Fernandez-Marcos thiab Auwerx, 2011; Zaha thiab Young, 2012; Ham thiab Raju, 2016). Raws li ib tug cofactor, PGC-1a paub los tswj cov kev qhia ntawm ntau yam nuclear receptors thiab transcription yam, yog li tswj tag nrho cov metabolic phenotype ntawm cardiomyocytes. PGC-1ib qho kev hloov pauv mitochondrial biogenesis thiab oxidative phosphorylation los ntawm kev ua haujlwm ncaj qha rau kev ua pa nuclear (NRF1 thiab NRF2) thiab cov tshuaj estrogen-related receptor alpha (ERRa) transcription factor. NRF1 activates downstream synthesis of mitochondrial transcription factor A (mtTFA), uas tswj mtDNA replication, transcription, thiab txij nkawm (Kang and Hamasaki, 2005; Rowe et al., 2010). Raws li tus khub sib txuas lus tseem ceeb ntawm PGC-1a, ERRa tuaj yeem ua rau muaj kev nce ntxiv hauv kev qhia ntawm NRF2, modulating cardiomyocyte cycle thiab sib txawv, thiab mitochondrial biogenesis (Ham thiab Raju, 2016). PGC-1ib kuj co-activates PPARa, uas koom nrog hauv fatty acid metabolism hauv cardiomyocytes (Finck, 2007; Lehman et al., 2000). Tsis tas li ntawd, PGC-1ib qho kev ua kom muaj zog ua kom mitochondrial ua pa los ntawm kev nthuav tawm ntawm cytochrome c, cytochrome c oxidase subunits II thiab IV (COX II thiab IV), thiab ATP synthase (Choi et al., 2008; Espinoza et al. , 2010).

MODULATORY EFFECTS ntawm Suav tshuaj ntsuab tshuaj ntsuab ENERGY METABOLISM IN IHD

Lub plawv lub zog metabolism yog hloov tau yooj yim txog lub zog substrates, nrog lub zog sib npaug uas hloov kho los ntawm kev laus, nrog rau cov ntsiab lus ntawm lub cev thiab cov kab mob (Huss and Kelly, 2005; Arumugam li al., 2016). Ntxiv fatty acid beta-oxidation nrog kev laus yog nrog los ntawm kev nce qib ntawm glycolytic metabolism. Lub plawv fetal siv cov piam thaj oxidation los ua lub zog loj, thaum cov neeg laus myocardium muaj txiaj ntsig ntau nyob ntawm cov roj metabolism hauv fatty acid. Interestingly, thaum lub sij hawm ischemic mob, lub plawv metabolic profile qhia zoo sib xws nrog tus me nyuam hauv plab. Qhov tshwm sim no tau txiav txim siab rov qab mus rau "fetal theem" ​​(Tuomainen thiab Tavi, 2017). Ntxiv rau kev hloov pauv hauv kev siv lub plawv substrate, kev hloov pauv hauv mitochondrial ultrastructural thiab kev ua haujlwm ua lub luag haujlwm tseem ceeb hauv cov txheej txheem ntawm IHD. Cardiac mitochondria, raws li lub zog ntawm cardiomyocytes, koom nrog cov txheej txheem ntawm oxidative phosphorylation. Lawv tsis tsuas yog lub hauv paus ntawm ATP synthesis thiab reactive oxygen hom (ROS) ntau lawm hauv plawv myocytes tab sis kuj ua lub luag haujlwm tseem ceeb hauv cov txheej txheem ntawm apoptosis. Myocardial hypoxia / ischemia inhibits cov txheej txheem ntawm mitochondrial oxidative phosphorylation thiab hloov cov pyruvate rau lactate ua rau cellular acidification. Lub ischemic cardiomyocyte qhia tau hais tias muaj peev xwm txo qis rau kev sib txuas ntawm ATP, nce mitochondrial ROS ntau lawm, calcium influx, thiab txawm tias Ca2+ overload ua rau mitochondrial membrane permeability hloov, poob ntawm mitochondrial membrane peev (MMP), thiab mitochondrial. o nrog kev tso tawm ntawm cytochrome c. Cov xwm txheej no ua rau muaj kev ua kom apoptosome thiab caspase-mediated apoptosis (Ham thiab Raju, 2016). Nyob rau hauv reperfusion, muaj tshwm sim ib tug series ntawm mitochondrial derangements, nrog rau ceev ceev reestablishment ntawm oxidative phosphorylation, inhibition ntawm ua pa saw, mitochondrial ROS tsub zuj zuj, Ca2+ overload, mitochondrial membrane permeability hloov pore (mPTP) qhib, mitochondrial pendent. apoptosis, thiab txawm tias cell tuag (Ham thiab Raju, 2016; Wu li al., 2020a).

NATURAL CISTANCHE TUBULOSA rau kev txhim kho kev tiv thaiv kab mob PHGS75% ECH 30% ACT 12%

Cov kev kho niaj hnub no, xws li ACEIs thiab beta-blockers, muaj kev cuam tshuam ncaj qha rau ntawm lub plawv metabolism ntxiv rau lawv cov kev cuam tshuam classic, tab sis lawv tsis ncaj qha cuam tshuam rau lub plawv lub zog metabolism (Neubauer, 2007). Cov pov thawj loj hlob qhia tau hais tias kev hloov pauv ntawm cov metabolism hauv plawv tuaj yeem yog txoj hauv kev zoo rau cov neeg mob IHD (Noordali li al., 2018; Doehner li al., 2014; Heggermont et al., 2016). Paub cov kev hloov pauv metabolic xws li Trimetazidine, L-carnitine, thiab Coenzyme Q10 yog tam sim no siv hauv kev sim tshuaj. Cov txheej txheem metabolic ntawm cov modulators no feem ntau koom nrog inhibition ntawm fatty acid oxidation, stimulation ntawm qabzib oxidation, thiab kev tiv thaiv ntawm mitochondrial muaj nuj nqi (Suner thiab Cetin, 2016; Di Napoli li al., 2007; Xue et al., 2007; Fotino etal. ., 2013). Hauv TCM, Suav tshuaj ntsuab tau siv dav hauv kev kho mob plawv hauv cov chaw kho mob. CHMs muaj lawv qhov zoo uas yog vim muaj cov khoom siv tshuaj ntawm cov khoom siv sib xyaw, ntau lub hom phiaj, thiab ntau txoj hauv kev. Ntau cov kev tshawb fawb tau pom tias CHMs nrog ntxiv Qi lossis Yang thiab ua kom cov ntshav los yog daws cov ntshav stasis tuaj yeem tswj hwm lub zog metabolism hauv IHD (Wong and Ko, 2013; Chen et al., 2015; Zhang et al., 2013; Li. et al., 2018a).

Hauv tsab xov xwm no, peb tsuas yog sau cov txiaj ntsig metabolic thiab cov txheej txheem hauv qab ntawm cov tshuaj suav tshuaj ntsuab, cov tshuaj bioactive tseem ceeb ntawm CHMs, thiab Suav tshuaj ntsuab cov qauv hauv IHD, raws li (Table 1 thiab 2). Tshwj xeeb, tus qauv ntawm tus mob myocardial infarction feem ntau yog tshwm sim los ntawm sab laug anterior descending (LAD) coronary artery ligation, uas yog cov qauv siv phais tsiaj feem ntau. Tus qauv isoproterenol (Iso)-induced myocardial infarction model yog ib qho qauv zoo uas tsis yog phais MI (Kumar li al., 2016). Yog li, cov txheej txheem tseem ceeb suav nrog Iso-nrog rau MI qauv, LAD coronary artery ligation-induced MI qauv, thiab myocardial ischemia thiab reperfusion (I / R) tus qauv raug mob. Cov txheej txheem tseem ceeb suav nrog kev cob qhia kev tawm dag zog, kev tshuaj xyuas metabolomics, angiotensin II-induced HF qauv, plab aorta ligation-induced HF qauv, cobalt chloride-induced myocardial ischemia, thiab doxorubicin-induced myocardial raug mob.

Metabolic Effects thiab Mechanisms ntawm Tshuaj ntsuab thiab loj Bioactive Cheebtsam

Invigorating thiab Replenishing Qi

Astragalus mongholicus Bunge (Astragali Radix)

Astragalus mongholicus Bunge (Astragalus membranaceus, AM), tseem hu ua Huang-qi hauv Suav teb, suav hais tias yog ib qho ntawm cov tshuaj tseem ceeb ntxiv Qi. Classified as a top-grade herb in "Shen Nong Ben Cao Jing", Astragalus mongholicus Bunge yog dav siv los kho cov kab mob plawv (Ma et al., 2013). Cov kev tshawb fawb tsis ntev los no tau tsom mus rau nws cov teebmeem cardioprotective, tshwj xeeb tshaj yog cov uas cuam tshuam txog kev txhim kho lub zog metabolism. Astragali Radix extract (ARE) exerts a cardioprotective effect tiv thaiv LAD ligation-induced myocardial infarction los ntawm rectifying qib FFA, pyruvic acid (PA), thiab lactic acid (LA) nyob rau hauv cov ntshav thiab myocardial cov ntaub so ntswg, yog li ua tau ntau zog (Jin et al. ., 2014). Astragalosides yog roughly rho tawm los ntawm Astragali Radix. Astragalosides (5 mg / kg / hnub, ip) tau qhia txog kev tiv thaiv los ntawm rebalancing intracellular Ca2+ homeostasis thiab tswj lub zog metabolism hauv Iso-induced myocardial ischemic raug mob. Txawm li cas los xij, cov txheej txheem ntawm Astragalosides tseem tsis tau tshaj tawm (Chen li al., 2006). Astragaloside IV (AS-IV), ib qho tseem ceeb bioactive tivthaiv ntawm astragalosides, tau raug tshaj tawm los txhim kho lub plawv tsis ua haujlwm thiab hloov kho lub zog metabolism hauv MI nas qauv. Cov txheej txheem metabolic tuaj yeem kho tau los ntawm kev txhawb nqa ntawm Complex V thiab ATP synthase delta-subunit (ATP5D) qhia (Cui li al., 2018). Lwm qhov kev sim tau txheeb xyuas lub luag haujlwm metabolic ntawm ASIV hauv myocardial ischemia thiab ischemia / reperfusion raug mob. AS-IV kuj tau txhim kho qhov kev qhia ntawm ATP5D thiab Complex V (Tu li al., 2013). Cov txiaj ntsig no qhia tau tias AS-IV tuaj yeem tswj hwm lub zog metabolism los ntawm kev ua pa ntawm mitochondrial. Tsis tas li ntawd, AS-IV tuaj yeem hloov kho lub zog biosynthesis. Zhang et al. (2015) pom tias AS-IV txhim kho plawv hemodynamics, kho lub zog

biosynthesis, thiab upregulated ATP5D thiab PGC-1ib qho kev qhia hauv Iso-induced cardiac raug mob. Nyob rau hauv neonatal nas ventricular myocytes (NRVMs), cardioprotective mechanism ntawm AS-IV tej zaum yuav kho kom haum xeeb los ntawm regulating nuclear factor NF-kB/PGC-1a signaling (Zhang et al., 2015). Glycogen synthase kinase-3b (GSK-3b), ib qho serine/threonine protein kinase, cuam tshuam nrog mitochondrial proteins xws li PI3K-Akt, PGC-1a, thiab subunits ntawm mPTP, uas plays lub luag haujlwm tseem ceeb hauv kev hais txog mitochondrial biogenesis, mitochondrial permeability, thiab glycogen metabolism (Yang li al., 2017a). Formononetin yog lub ntsiab isoflavonoid compound ntawm Radix Astragali. Formononetin txhim kho GSK-3b thiab Akt phosphorylation hauv H9c2 hlwb thaum lub sij hawm oxygen-glucose deprivation (OGD) thiab reoxygenation, yog li txo GSK-3b kev ua si ntawm mPTP qhib (Cheng li al., 2016). Kaempferol, lub ntuj flavonoid, muaj nyob rau hauv Astragalus mongholicus Bunge thiab Panax ginseng CAMey. Kaempferol pom cov teebmeem cardioprotective los ntawm txoj kev mitochondrial tiv thaiv ischemia / reperfusion raug mob hauv NRVMs. Cov txheej txheem cardioprotective tuaj yeem kho los ntawm SIRT1 (Guo li al., 2015). Astragalus polysaccharides (AP) tuaj yeem ua tautxhim kho plawv zog biosynthesis thiab tiv thaiv Iso-induced cardiac ischemic raug moblos ntawm kev tswj cov qog nqaij hlav necrosis TNF-a/PGC-1ib qho kev taw qhia-mediated zog biosynthesis, ob qho tib si hauv vivo thiab hauv vitro. Ntawm lawv, ATP5D, PGC-1a, thiab pyruvate dehydrogenase kinase isoform 4 (PDK4) tag nrho nce, uas txhais tau hais tias AP tej zaum yuav cuam tshuam nrog lub zog metabolism (Luan li al., 2015).

Panax Ginseng CAMey. (RG)

Panax ginseng CAMey.(Radix ginseng), tseem hu ua Ren Shen, paub zoo txog nws cov "Qi-Replenishing" nyhuv hauv TCM thiab tau teev npe raws li cov tshuaj ntsuab zoo tshaj hauv "Shen Nong Ben Cao Jing". Hauv kaum xyoo dhau los, tus neeg sawv cev cov khoom xyaw nquag ntawm Radix ginseng (xws li Ginsenoside Rb1, Ginsenoside Rd, Ginsenoside Rg1, Ginsenoside Rg5, Panax ginsengPolysaccharide, thiab tag nrho cov ginsenosides) tau pom tias muaj kev cuam tshuam tseem ceeb ntawm lub zog metabolism. Ginsenoside Rb1 (Rb1), ib qho tseem ceeb muaj txiaj ntsig zoo ntawm Panax ginseng, tau pom tias yuav hloov kho lub zog metabolism hauv myocardial ischemia thiab reperfusion raug mob, hypertrophy, thiab txawm tias HF (Zheng li al., 2017). Hauv cov qauv nas ntawm myocardial infarction, Rb1 tuaj yeem nce qhov kev qhia ntawm mitochondrial ATP5D thiab complex V (Cui li al., 2018). Hauv ischemia/reperfusion raug mob, Rb1 txo qhov ntau thiab tsawg infarction, inhibited mPTP qhib, rov qab MMP, thiab upregulated p-AKT thiab p-GSK-3b qhia. Cov txiaj ntsig no qhia tau hais tias kev tiv thaiv kev tiv thaiv ntawm Rb1 tiv thaiv I / R-induced myocardial raug mob tuaj yeem cuam tshuam nrog kev tiv thaiv kev ua haujlwm mitochondrial (Li et al., 2016b). Ib yam li ntawd, Rb1 tuaj yeem tiv thaiv cov hlab plawv myocytes thiab hloov kho lub zog metabolism tiv thaiv I / R-induced myocardial raug mob los ntawm RhoA signaling pathway (Cui li al., 2017). Ginsenoside Rd (Rd) yog lwm cov tshuaj lom neeg muaj txiaj ntsig los ntawm Panax ginseng CAMey. Wang et al. (2013) pom tias Rd ua rau cov teebmeem cardioprotective los ntawm stabilizing MMP thiab attenuating tso tawm ntawm mitochondrial cytochrome c hauv myocardial ischemia / reperfusion raug mob. Raws li lub ntsiab lus tseem ceeb ntawm Radix ginseng, Ginsenoside Rg1 (Rg1) modulated zog metabolism hauv ischemia / reperfusion raug mob los ntawm kev txhim kho ATP cov ntsiab lus thiab kev ua ntawm mitochondria respiratory chain complexes, uas tej zaum yuav muaj feem cuam tshuam rau nws txoj kev khi rau RhoA thiab ua rau inhibition ntawm RhoA. /ROCK txoj kev (Li et al., 2018b). Hauv vitro, Rg1 kev kho mob (12.5 mM) tau ua kom muaj kev tiv thaiv cardioprotective los ntawm kev tswj cov mitochondrial dynamics thiab tau ua tiav los ntawm kev ua kom qis glutamate dehydrogenase (GDH) thiab MFN2 dysregulation. Txawm li cas los xij, Rg1 tsis muaj qhov cuam tshuam loj rau MFN1, OPA1, thiab Drp1 (Dong et al., 2016). Mitochondrial hexokinase-II (HK-II), uas yog ib qho tseem ceeb molecule hauv glycolysis, tuaj yeem khaws mitochondrial kev ncaj ncees thiab tiv thaiv mitochondrial tuag (Roberts thiab Miyamoto, 2015). Ginsenoside Rg5 (Rg5) ameliorated iso-induced ischemic myocardium raug mob los ntawm inhibiting fatty acid oxidation thiab tswj mitochondrial dynamics tsis txaus. Rg5 tuaj yeem txhim kho mitochondrial dysfunction los ntawm kev tswj hwm mitochondrial HKII khi thiab txo Drp1 recruitment rau mitochondria ntawm Akt activation (Yang li al., 2017c). Panax ginseng Polysaccharide (PGP) muaj cov teebmeem cardioprotective thiab tiv thaiv mitochondrial muaj nuj nqi hauv myocardial I / R raug mob. Hauv vitro, PGP txo qhov tso tawm ntawm mitochondrial cytochrome c, tswj MMP, thiab rov ua pa mitochondrial (Zuo li al., 2018). Tag nrho cov ginsenosides (TGS) ntawm RG tau tshaj tawm los txhim kho lub zog metabolism los ntawm kev ua kom cov piam thaj metabolism thiab ua kom TCA lub voj voog ntsig txog cov protein qhia hauv ischemic nas myocardium (Wang li al., 2012).

Rhodiola rosea L. (RR) Rhodiola rosea L., ib tsob nroj paub zoo nyob rau hauv Tibet, tau raug pom los kho ntau hom kab mob plawv, suav nrog IHD, arrhythmia, thiab angina pectoris (Yu et al., 2014; Liu et al. ib., 2016). Salidroside (SAL) yog lub ntsiab tivthaiv muab rho tawm thiab purified los ntawm Rhodiola. Chang et al. (2016) tau tshaj tawm tias SAL muaj cov teebmeem cardioprotective los ntawm kev tswj lub zog metabolism hauv cov hlab ntsha ntawm cov hlab ntsha occlusion-induced myocardial raug mob. SAL tau txhim kho ATP thiab glycogen cov ntsiab lus los ntawm AMPK/PGC-1aaxis thiab AMPK/NFkB cov kev taw qhia (Chang XY li al., 2016).

Ganoderma Lucidum (GL)

Ganoderma lucidum (Reishi Mushroom), nrov npe hu ua Lingzhi nyob rau hauv cov teb chaws Es Xias, muaj antioxidative thiab cardioprotective teebmeem. Ganoderma lucidum extract ameliorated myocardial ischemic raug mob los ntawm kev txhim kho mitochondrial dysfunction nyob rau hauv induced myocardial infarction nas. Cov txheej txheem yuav muaj feem xyuam rau cov dej num ntawm cov enzymes ntawm TCA lub voj voog thiab mitochondrial respiratory chain complexes xws li complexes I, II, III, thiab IV (Sudheesh li al., 2013). Ganoderma atrium polysaccharide (PSG-1) yog suav tias yog ib qho tseem ceeb ntawm bioactive ingredient hauv Ganoderma Lucidum. Li et al. (2010) tau tshaj tawm tias PSG-1 tiv thaiv cardiomyocytes los ntawm mitochondrial txoj hauv kev hauv hypoxia/reoxygenation-induced NRVM raug mob. PSG-1 txo qhov tso tawm ntawm cytochrome c los ntawm mitochondria mus rau hauv cytosol thiab txhim kho MMP qib (Li li al., 2010).

Gynostemma pentaphyllum (Thunb.) Makino (GPM)

Raws li ib qho ntawm cov tshuaj Qi ntxiv, Gynostemma pentaphyllum (Thunb.) Makino tawm dag zog los tiv thaiv hypertensive, tiv thaiv hyperlipidemia, tiv thaiv kab mob, thiab tiv thaiv kev laus (Zhang li al., 2018a). Gypenosides (GP) yog cov saponins loj ntawm Gynostemma pentaphyllum, uas muaj cov teebmeem cardioprotective hauv myocardial infarction nas. Yus et al. (2016) pom tias GP txo qis myocardial infarct loj thiab tiv thaiv mitochondrial muaj nuj nqi hauv myocardial ischemia-reperfusion raug mob. GP txhim kho qib ATP, tswj cov kev ua haujlwm enzymatic ntawm mitochondrial respiration saw, thiab tswj cov mitochondrial membrane kev ncaj ncees (Yu li al., 2016).

NATURAL CISTANCHE TUBULOSA rau kev kho mob CARDIOVASCULAR DISEASES PHGS75% ECH 30% ACT 12%