Modulatory Effects Of Chinese Herbal Medicines On Energy Metabolism in Ischemic Heart Diseases Part Ⅱ
Mar 04, 2022
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Replenishing thiab Activating Ntshav
Panax notoginseng (Burkill) FHChen (PNG)
Panax notoginseng (Burkill) FHChen, lub npe hu ua San qi, San chi, thiab / los yog Tian qi hauv Suav teb, yog cov ntshav-replenishing thiab stasis- daws TCM tshuaj ntsuab dav siv los kho cov kab mob plawv. Panax Notoginseng tuaj yeem txo qis MI loj thiab CK qib hauv cov qauv nas ntawm myocardial ischemia (Han li al., 2013). Muaj peb lub ntsiab saponins ntawm Panax Notoginseng, suav nrog Rg1, Rb1, thiab Notoginsenoside R1 (R1). R1 yog qhov tseem ceeb ntawm Panax notoginseng thiab ua haujlwm tseem ceeb hauv kev tiv thaiv kab mob los ntawm kev tiv thaiv kev tsis zoo ntawm lub zog metabolism. Lub zog metabolism-txuas nrog kev hloov pauv ntawm R1 tuaj yeem kho los ntawm kev cuam tshuam cov haujlwm ntawm ROCK, thiab txhawb nqa ATP5D qhia thiab ATP cov ntsiab lus hauv ischemia / reperfusion-induced myocardial raug mob (Nws li al., 2014).
Salvia miltiorrhiza Bunge (SM)
Salvia miltiorrhiza Bunge (tseem hu ua Danshen), lwm cov ntshav ntxiv thiab stasis daws TCM tshuaj ntsuab, tau qhia cov lus cog tseg rau ntau yam kab mob plawv. Salvianolic acid A (Danshensu) yog ib qho ntawm cov dej-soluble compounds uas tau muab los ntawm Salvia miltiorrhiza thiab tau tshaj tawm los txo cov mob plawv I/R los ntawm inhibiting MPTP qhib thiab qhia txog ATP synthase c-subunit (Gao li al., 2017. ). 3, 4-Dihydroxylphenyl lactic acid (DLA) yog lwm lub npe rau Salvianic acid A, uas tau pom tias txo qis infarction loj thiab txhim kho mitochondrial aerobic ua pa hauv myocardial I/R raug mob. NADH dehydrogenase 1 alpha subcomplex 10 (NDUFA10) belongs rau ib qho ntawm cov subunits ntawm mitochondrial Complex I. DLA tuaj yeem tswj cov kev ua pa ntawm mitochondrial los ntawm kev txhim kho NDUFA10 thiab SIRT1 qhia (Yang li al., 2015). Sirtuin3 (SIRT3), lwm NAD ntxiv rau -dependent deacetylase ntxiv rau SIRT1, modulates succinate dehydrogenase complex, subunit A, flavoprotein variant (SDHA). Total Salvianolic Acid Injection (TSI) yog ib qho kev npaj ntawm cov tshuaj nquag muab rho tawm los ntawm Salvia miltiorrhiza Bunge. TSI muaj cov teebmeem tseem ceeb cardioprotective los ntawm regulating mitochondrial respiratory chain in ischemia / reperfusion-induced myocardial raug mob. TSI txo infarction size and enhanced NDUFA10 and SDHA protein expression via the activation of SIRT1 and SIRT3 (Huang et al., 2019). Tanshinone IIA (TIIA), lwm lub monomer cais tawm ntawm Salvia miltiorrhiza, tau tshaj tawm los tiv thaiv lub plawv ua haujlwm tiv thaiv MI thiab I / R raug mob. Jin thiab Li (2013) pom tias TIIA tiv thaiv mitochondrial muaj nuj nqi hauv hypoxia-induced H9c2 hlwb raug mob, uas tej zaum yuav koom nrog cov kev cai ntawm mitochondrial ROS tiam, ATP cov ntsiab lus, thiab intracellular nitric oxide (NO) theem (Jin thiab Li, 2013). Txawm li cas los xij, cov txheej txheem ntawm TIIA tseem tsis tau tshwm sim.
Carthamus tinctorius L
Carthamus tinctorius L (CTL) yog dav siv nyob rau hauv cov teb chaws Esxias, uas exerts lub peev xwm tseem ceeb ntawm anticoagulation, ua rau cov ntshav coronary txaus, thiab kho cov kab mob ischemic cardiovascular (Zhou li al., 2014). Hydroxysafflflor Yellow A (HSYA) yog ib tug neeg sawv cev tseem ceeb ntawm Carthamus tinctorius L. HSYA txo cov ntshav CK-MB thiab LDH qib, mitochondrial ROS tsub zuj zuj, thiab poob ntawm MMP hauv iso induced myocardial ischemic raug mob. Hauv vitro, HSYA tau nce PGC-1a thiab Nrf2 protein qhia hauv H9c2 hlwb raug OGD raug mob (Chen li al., 2016). HKII, nyob rau sab nraud mitochondrial membrane, tswj lub plawv mitochondrial muaj nuj nqi thiab cellular qabzib metabolism (Roberts thiab Miyamoto, 2015). Min thiab Wei (2017) tau nkag mus tob rau hauv cov txheej txheem cardioprotective ntawm HSYA hauv ischemia-reperfusion myocardial raug mob. Lawv pom tias HSYA tau siv cov teebmeem cardioprotective los ntawm kev kho cov mitochondrial zog metabolism. Cov txheej txheem ntawm HSYA no tuaj yeem kho los ntawm Akt / HKII ywj siab ntawm ERK / GSK-b teeb liab txoj hauv kev. Ua ke, cov txiaj ntsig no qhia tias HSYA txhim kho kev raug mob myocardial hauv kev kho mob ua ntej ntawm myocardial ischemia.
Boswellia serrata Roxb.
Boswellia serrata Roxb. (BSR) raug suav hais tias yog ib qho ntawm kev txhawb nqa ntshav ncig rau kev kho mob TCM tshuaj ntsuab. Kev sib xyaw ntawm Carthamus tinctorius L thiab Boswellia serrata Roxb. yog dav siv rau kev kho mob plawv ischemic (Chen li al., 2016). Acetyl-11-keto-b-boswellic acid (AKBA) tau lees paub tias yog lub ntsiab lus tseem ceeb ntawm Boswellia serrata Roxb., uas muaj cov txiaj ntsig zoo ib yam li Hydroxysafflflor Yellow A hauv H9c2 hlwb raug OGD raug mob. AKBA tau txhim kho mitochondrial membrane muaj peev xwm thiab nce PGC-1a thiab Nrf2 protein qhia, qhia tias lub luag haujlwm muaj txiaj ntsig ntawm AKBA hauv OGD-induced myocardial ischemic raug mob tuaj yeem raug ntaus nqi los ntawm kev txhim kho mitochondrial biogenesis (Chen li al. , 2016).
Ntxoov Yias thiab Ntxawm Yang
Cistanche deserticola Ma
Cistanche deserticola Ma, kuj hu uaHerba Cistanche(HC), yog "Yang-invigorating" Suav tshuaj ntsuab.Herba Cistanche Extracttiv thaiv myocardial ischemia / reperfusion raug mob los ntawm kev txhim kho mitochondrial ATP tiam. Glutathione (GSH) yog thawj kab tiv thaiv kev puas tsuaj oxidative.Herba Cistanche Extractmuajtxhim kho mitochondrial ua palos ntawm kev nce qib mitochondrial GSH, txo qis mitochondrial oxidized glutathione (GSSG), txhim kho MMP, thiab txo cov qib mitochondrial Ca2 ntxiv (Siu thiab Ko, 2010). Lwm txoj kev tshawb fawb qhia txog cov nyhuv cardioprotective ntawmHerba Cistanchesfeem (HCF1) hauv vitro thiab hauv vivo. Hauv vitro, HCF1 ntawm 30 ng / mL tseem ceeb txhim kho mitochondrial ATP tiam muaj peev xwm (ATP-GC), mitochondrial ROS ntau lawm, thiab mitochondrial ua pa. Hauv vivo, HCF1 tseem ceeb txhim kho mitochondrial GSH raws li txoj cai thiab txhim kho ATP-GC cov ntsiab lus hauv I / R cov poj niam laus nas. Kuj ceeb tias, lawv pom tias cov tshuaj HCF1 tsawg tsawg tau txo qis cov ntaub so ntswg ATP hauv cov nas uas tsis yog-I/R, thaum cov ntaub so ntswg ATP los ntawm HCF-1 tau txo qis hauv I/R nas. Qhov tshwm sim no hauv cov nas uas tsis yog-I/R tuaj yeem cuam tshuam nrog HCF-induced sustained mitochondrial uncoupling, thaum nyob rau hauv I/R nas nws yuav cuam tshuam rau qhov nce hauv ATP-GC los ntawm HCF-1 (Wong and Ko, 2013 ). b-sitosterol (BS), raws li hydrophobic compound ntawm HCF1, txo LDH qib thiab nce cellular glutathione redox cycling hauv myocardial I / R poj niam nas. Tab sis BS tsis muaj qhov cuam tshuam loj rau mitochondrial ATP-GC hauv txiv neej lossis poj niam nas myocardium (Wong et al., 2014). Yog li ntawd, cov teebmeem ntawm mitochondrial ATP-GC nyob rau hauvCistanche deserticola Ma extracttej zaum yuav nyob ntawm lwm cov tebchaw, uas yuav tsum tau kawm ntxiv.
Cynomorium coccineum subsp. songaricum (Rupr.) J.Léonard
Cynomorium coccineum subsp. songaricum (Rupr.) J. Léonard (tseem hu ua Cynomorii herba) (CCS), lwm "Yang-invigorating" Suav tonic tshuaj ntsuab, tau pom los txhim kho mitochondrial ATP-GC hauv H9c2 hlwb. Chen and Ko (2013) cais bioactivate feem (HCY2) thiab ursolic acid (UA) los ntawm cynomorii herba. Lawv tau pom tias HCY2 thiab UA tuaj yeem tiv thaiv myocardial ischemia / reoxygenation hauv cov txiv neej thiab poj niam nas. HCY2 thiab UA tuaj yeem tiv thaiv kev ua haujlwm mitochondrial los ntawm kev txo qis LDH qib, txhim kho cov ntaub so ntswg plawv ATP thiab mitochondrial ATP-GC qib, thiab txhim kho mitochondrial GSH / GSSG piv thiab glutathione reductase (GR) kev ua.
Lwm yam Extractive Compounds ntawm Suav Herba
Berberine
Berberine, ib qho isoquinoline alkaloid cais los ntawm Coptis Chinensis Franch., yog siv dav hauv kev kho mob raws plab hauv cov tebchaws Esxias. Wang et al. (2015b) tau tshaj tawm tias berberine (200 mg / kg / hnub) tau siv cov teebmeem cardioprotective los ntawm kev txo qis myocardial apoptosis thiab txhim kho mitochondrial dysfunction hauv myocardial ischemia / reperfusion. Txawm li cas los xij, cov txheej txheem metabolic ntawm berberine tseem tsis meej. Berberine kev kho mob (100 mg / kg / hnub, ig) txhim kho kev ua haujlwm ntawm lub plawv thiab txo qhov loj ntawm infarction. Berberine tuaj yeem muaj cov teebmeem cardioprotective los ntawm kev tswj hwm AMPK phosphorylation hauv ischemia-reperfusion myocardial raug mob. Interestingly, lawv pom tias berberine downregulated p-AMPK qhia, thiab txo cov ADP/ATP thiab AMP/ATP piv rau peri-infarct. Hauv qhov sib piv, berberine upregulated p-AMPK qhia thiab nce ADP / ATP thiab AMP / ATP piv rau hauv cov cheeb tsam uas tsis yog ischemia. Txawm li cas los xij, qhov tshwm sim no tseem tsis tau tshwm sim (Chang li al., 2012).
Crude Terpene Glycosides
Crude terpene glycosides (CS-TG), raws li cov khoom tseem ceeb hauv Paeonia lactic flora Pall., suav nrog paeoniflorin, albiflorin, thiab enzoylpaeoniflorin. Crude terpene glycosides tau pom tias txo qis plawv hypertrophy, inhibit cardiomyocyte apoptosis thiab txhawb cov ntshav khiav (Ke li al., 2017). Ke et al. (2017) tau ua tus qauv myocardial ischemia hauv cov nas noj nrog 300 mg / kg / hnub CS-TG. CS-TG txo qis CK thiab LDH qib hauv cov ntshav thiab txhim kho cov metabolism hauv lub zog. Cov nas kho nrog CS-TG txhim kho lub zog metabolism hauv ISO-induced myocardial ischemic raug mob, uas tej zaum yuav muaj feem xyuam rau nce cov ntsiab lus ATP thiab glycogen, tiv thaiv mitochondrial ultrastructure, thiab txo qis p-AMPK qhia (Ke li al., 2017). Hauv qhov sib piv, ntau cov kev tshawb fawb qhia tias kev ua kom AMPK phosphorylation txhawb zog metabolism los ntawm kev tswj cov piam thaj thiab lipid metabolism (Luiken li al., 2003; Russell li al., 2004; Qi and Young, 2015). AMPK ua kom tseem txhawb nqa mitochondrial fission ntawm MFF phosphorylation (Garcia thiab Shaw, 2017). Qhov tsis sib haum xeeb ntawm kev tswj hwm thiab kev txo qis ntawm AMPK phosphorylation thaum lub sij hawm ischemia tuaj yeem nyob ntawm hom cell, myocardial ischemic qauv, pathophysiological teeb tsa, thiab lub sijhawm ischemic. Tsis tas li ntawd, inhibition ntawm AMPK yuav muaj feem cuam tshuam nrog lwm cov txheej txheem xws li myocardial acidosis thiab apoptosis.
Ginkgo biloba L. Extract
Ginkgo biloba L. (GBE) extract yog ib qho ntawm feem ntau siv tshuaj ntsuab thiab nthuav tawm ntau yam tshuaj ua haujlwm. GBE tau dav siv los kho cov kab mob plawv.
Kev tshawb fawb los ntawm Wang et al. (2016b) tau tshaj tawm tias GBE (200 mg / kg / hnub) kev kho ua ntej tuaj yeem ua kom muaj txiaj ntsig zoo ntawm fatty acid, glyceride, thiab amino acid qib, yog li ua rau cov teebmeem cardioprotective hauv ISO-induced myocardial ischemia hauv nas. Lwm txoj kev tshawb nrhiav pom tias kev kho GBE uncoupled mitochondrial oxidative phosphorylation thiab txo cov mitochondrial dawb radicals hauv ischemic nas plawv rau 10 thiab 18 hnub (Bernatoniene li al., 2011).
Luteolin
Luteolin yog polyphenolic compound tau los ntawm zaub, txiv hmab txiv ntoo, thiab tshuaj ntsuab. Hauv vivo, Hu et al. (2016) tau tshaj tawm tias Luteolin tuaj yeem txhim kho kev mob plawv hauv cov nas qus tom qab myocardial infarction. Lub caij no, kev kho luteolin tau pom los txhim kho MMP qib, ATP cov ntsiab lus, citrate synthase (CS) kev ua, thiab cov dej num ntawm complexes IV induced los ntawm hypoxia nyob rau hauv neonatal nas ventricular cardiomyocytes. Cov teebmeem cardioprotective ntawm luteolin cuam tshuam nrog kev txhim kho hauv mitochondrial biogenesis tuaj yeem raug siv los ntawm inhibition ntawm mammalian sterile 20-zoo li kinase 1 (Mst1) qhia.
Quercetin
Quercetin, flavone siv los ua cov khoom noj ntxiv, ua kom muaj zog antioxidant. Punithavathi thiab Prince (2010) tau qhia tias quercetin txo qis myocardial infarct loj thiab tiv thaiv mitochondrial dysfunction hauv isoproterenol-kho myocardial infarcted nas. Lwm txoj kev tshawb fawb kuj pom quercetin (10 mg / kg) kev kho mob ua ntej elicited cardioprotective teebmeem, suav nrog ameliorating lipids tsub zuj zuj thiab hloov cov qib lipoproteins thiab enzymes koom nrog hauv lipid metabolism hauv isoproterenol-kho myocardial infarcted nas (Prince, 2010). Txawm li cas los xij, kev tiv thaiv mechanism tseem tsis meej.
Resveratrol
Resveratrol yog lub ntuj polyphenol los ntawm ntau cov khoom noj uas cog, suav nrog blueberries, txiv hmab txiv ntoo, thiab cranberries. Ntau qhov kev tshawb fawb tau tshaj tawm tias resveratrol siv cov teebmeem cardioprotective (Kanamori li al., 2013; Sung et al., 2015; Fourny et al., 2019). Kanamori et al. (2013) tau tshawb xyuas qhov cuam tshuam ntawm resveratrol hauv cov nas myocardial infarction thiab pom tias resveratrol tuaj yeem txhim kho myocardial zog los ntawm kev txhim kho cov ntsiab lus ATP thiab nce p-AMPK ua kom muaj zog. Tsis tas li ntawd, Fourny et al. (2019) kuj tau tsom mus rau cov teebmeem cardioprotective ntawm resveratrol tiv thaiv I / R raug mob, uas cuam tshuam rau kev txhim kho mitochondrial dysfunction. Lawv pom tias cov txheej txheem hauv qab no tuaj yeem cuam tshuam nrog kev nthuav qhia ntau ntxiv ntawm p-AKT, eNOS, thiab SIRT1, uas ua rau muaj zog metabolism.
Tetrandrine
Tetrandrine (TTD), ib qho bisbenzylisoquinoline alkaloid cais los ntawm Stephania tetrandra S. Moore, tau pom tias muaj kev tiv thaiv kab mob plawv ntawm myocardial fibrosis thiab myocardial infarction (Teng li al., 2015). Hauv vivo, tetrandrine (50 mg / kg) pretreatment tseem ceeb txhim kho lub plawv ua haujlwm, txo qhov loj me me, thiab txo cov ntshav LDH hauv myocardial ischemia thiab kev raug mob rov qab. Hauv neonatal nas cardiomyocytes, kev kho tetrandrine (10 mM) txo qis mitochondrial ROS tsub zuj zuj, txhim kho MMP, attenuated mitochondrial cytochrome c tso, thiab txhim kho p-AKT thiab p-GSK-3b protein qhia. Qhov tshwm sim no tuaj yeem cuam tshuam txog kev ua haujlwm mitochondrial (Yang li al., 2017b).
Metabolic Effects ntawm Suav Herbal Formula thiab Associated Mechanisms
Ntxiv rau cov tshuaj ntsuab thiab cov khoom siv bioactive tseem ceeb tau piav qhia saum toj no, peb kuj tseem sau cov txiaj ntsig metabolic thiab cov txheej txheem cuam tshuam ntawm Suav tshuaj ntsuab cov qauv hauv IHD. Suav tshuaj ntsuab cov qauv (xws li decoctions, Suav patent tshuaj, thiab txhaj tshuaj), uas yog hais txog kev sib xyaw ntawm cov tshuaj ntsuab raws li TCM txoj kev xav, tau siv dav hauv Suav kev kho mob. Txawm li cas los xij, kev tshawb fawb ntawm cov qauv tau ntsib ntau yam teeb meem thiab cov teeb meem vim qhov nyuaj cuam tshuam nrog cov tshuaj pharmacological ntawm ntau hom tshuaj ntsuab, ntau yam, thiab ntau lub hom phiaj. Nyob rau hauv xyoo tas los no, cov kws tshawb fawb pib hais txog qhov nyuaj ntawm biology hauv cov qauv los ntawm cov qauv kev xav uas siv cov kev tshawb fawb niaj hnub thiab cov thev naus laus zis xws li kev tswj kom zoo, metabonomics, thiab molecular biology. Cov thev naus laus zis tshiab yog qhov tseem ceeb rau kev ua kom tus qauv tsim thiab kev lag luam ntawm CHMs thiab txheeb xyuas qhov kev kho kom zoo rau cov kab mob plawv.
Decoctions
Buyang Huanwu Decoction
Buyang Huanwu Decoction (BYHWD), ib tug classic TCM mis ntawm qi-replenishing thiab stasis-tawm txoj kev, yog muaj Astragalus mongholicus Bunge, Angelica Sinensis (Oliv.) Diels, Radix Paeoniae Rubra, Ligusticum striatum DC, Sementhasica, thiab tinctorius L. BYHWD yuav txo tau MI raug mob los ntawm kev tswj lub zog metabolism hauv cov nas uas muaj kab mob plawv (Wang et al., 2011). Txawm li cas los xij, cov txheej txheem metabolic ntawm BYHWD tseem tsis tau tshwm sim.
Shengmai San
Shengmai San (SMS), ib tug paub zoo TCM tshuaj muaj xws li Panax ginsengC.A.Mey, Ophiopogon japonicas (Thunb.) Ker Gawl, thiab Schisandra chinensis (Turcz.) Baill yog dav siv los kho cov kab mob plawv, angina pectoris, thiab HF hauv kev kho mob. SMS dej extract tseem ceeb txhim kho lub plawv muaj nuj nqi, nce ATPase kev ua si thaum lub sij hawm 3 lub lis piam nyob rau hauv lub MI-induced plawv tsis ua hauj lwm nas qauv. Hauv vitro, SMS (400 µg / mL) tuaj yeem txhim kho mitochondrial muaj nuj nqi los ntawm kev txhim kho MMP thiab ATP qib. Tsis tas li ntawd, SMS inhibited phosphorylation ntawm Drp1 ntawm Ser 616 thiab nce phosphorylation ntawm Drp1 ntawm Ser 637 hauv OGD-induced cardiomyocytes raug mob (Yang li al., 2017d). Drp1 muaj ob qhov chaw phosphorylation loj. Phosphorylation ntawm Drp1 ntawm Ser616 ua rau mitochondrial fission, thaum Drp1 phosphorylation ntawm Ser637 inhibits mitochondrial fission thiab induces mitochondrial fusion thiab elongation (Willems li al., 2015). Cov txiaj ntsig no qhia tau hais tias cov txheej txheem ntawm SMS tuaj yeem cuam tshuam nrog inhibiting mitochondrial fission los ntawm Drp1 txoj kev taw qhia.
Yiqihuoxue Decoction
Yiqihuoxue Decoction (YQHX) yog tsim los ntawm Danggui Buxue decoction (DBD) TCM mis, uas yog kev lees paub kev kho mob rau IHD nrog Qi deficiency thiab ntshav stasis syndrome. Li et al. (2018a) tau tshaj tawm tias 28-hnub kev tswj hwm ntawm YQHX, ib qho qauv uas muaj Astragalus membranaceus, Angelica Sinensis (Oliv.) Diels, Panax ginseng, Ligusticum striatum DC., thiab Panax notoginseng, tuaj yeem txhim kho lub plawv thiab kev ua haujlwm ntawm mitochondr. hauv myocardial ischemic nas nrog LAD phais. YQHX kev kho mob tseem ceeb nce PGC-1 ib qho kev qhia, txhim kho mitochondrial ultrastructure, thiab nce mitochondrial ATP cov ntsiab lus. Hauv vitro, YQHX feem ntau txo qis LDH thiab ROS qib, rov qab los ntawm mitochondrial morphology, thiab nce MMP. Lub caij no, YQHX upregulated PGC-1a thiab NRF-1 protein qhia los ntawm kev ua kom p-AMPK phosphorylation tshwm sim los ntawm ischemia / hypoxia-induced H9c2 hlwb raug mob. Ntawm lawv, AMPK, PGC- 1a, NRF-1, thiab Tfam tag nrho yog nce ntxiv uas txhais tau hais tias cov teebmeem cardioprotective ntawm YQHX tuaj yeem cuam tshuam txog kev txhim kho mitochondrial dysfunction.
Gualou Xiebai Decoction
Gualou Xiebai Decoction (GLXB), daim ntawv tshuaj TCM classic, yog siv dav rau kev kho mob plawv. GLXB yog tsim los ntawm Trichosanthis Pericarpium, Allium macrostemon Bunge, thiab cawv tau raug npaj hauv AD 200-205 los ntawm tus kws kho mob nto moo Zhang Zhong-Jing. Cov nas kho nrog GLXB nthuav tawm qhov txo qis hauv myocardial infarct loj, nrog rau kev txhim kho plawv thiab cov qauv myocardial tom qab myocardial I / R raug mob, uas zoo li yuav ua tiav los ntawm kev hloov pauv ntawm lub zog metabolism los ntawm inhibition ntawm RhoA / ROCK signaling pathway ( Yan et al., 2018).
Suav Patent Tshuaj
QishenYiqi Capsule
Qishen Yiqi capsule (QSYQ), cov tshuaj siv tshuaj kho mob muaj xws li rho tawm los ntawm Astragalus membranaceus, Salvia miltiorrhiza Bunge, Panax notoginseng, thiab Dalbergia odorifera, tau txais kev pom zoo rau kev kho mob hauv Suav teb thiab tau siv dav los kho cov kab mob plawv xws li IHD, angina. pectoris, thiab ischemic HF (Jianxin li al., 2016; Zhang li al., 2018b). Cov kev tshawb fawb tshuaj tsis ntev los no tau pom tias QSYQ tuaj yeem hloov kho lub zog metabolism thiab txhim kho lub plawv ua haujlwm hauv cov nas ischemic nrog LAD coronary artery ligation (Cui li al., 2018; Zhang et al., 2018d). Zhang et al. (2018d) tau txheeb xyuas 24 cov khoom xyaw tshuaj hauv QSYQ ntawm UPLC-Q-TOP/MS hauv cov qauv tsis zoo thiab zoo. QSYQ kev kho mob tuaj yeem txo qis mitochondrial tsis ua haujlwm thiab tiv thaiv tus lej nuclei thiab mitochondrial loj tiv thaiv kev raug mob hypoxia / ischemia, txawm li cas los xij, cov txheej txheem metabolic tseem tsis tau tshwm sim. Ib yam li ntawd, QSYQ tau pom tias tswj cov metabolism hauv lub zog hauv cov qauv nas ntawm lub plawv I / R raug mob (Lin li al., 2013; Chen et al., 2015).
Qiliqiangxin Capsule
Qiliqiangxin capsule (QLQX) yog ib qho tshuaj {{0}} tshuaj ntsuab suav tshuaj siv dav siv los kho myocardial infarction thiab txawm tias lub plawv tsis ua haujlwm hauv kev kho mob. Hauv cov nas ovariectomized, QLQX ({12}}.5 g / kg) kev kho mob tseem ceeb txo qis kev kho plawv thiab ua kom lub zog metabolism tom qab myocardial infarction los ntawm kev txhawb nqa kev qhia ntawm lipid metabolism ntsig txog noob thiab ua kom PPARg (Shen li al., 2) 017). Hauv cov nas thawj lub plawv microvascular endothelial hlwb (CMECs) raug hypoxia, QLQX tau pom los txhim kho kev siv cov piam thaj thiab tiv thaiv CMECs tiv thaiv kev raug mob hypoxia los ntawm kev txhawb nqa hypoxia-inducible factor 1-alpha (HIF-1a) -dependent glycolysis (Wang et al., 2018a). Zhao et al. (2019) tau ua kev phais mob myocardial infarction hauv txiv neej SD nas noj nrog (0.25, 0.5, thiab 1.0 g / kg / hnub) QLQX. 4 lub lis piam tom qab myocardial infarction, QLQX kev kho mob tiv thaiv lub plawv ua haujlwm, ameliorated mitochondria-dependent apoptosis, thiab txhim kho p-AKT thiab p GSK3b qhia. Tsis tas li ntawd, QLQX kuj tswj hwm mitochondrial fission, txo mPTP qhib, thiab txhim kho MMP qib hauv oxidative stress-induced cardiomyocytes raug mob. Ua ke, cov kev tshawb pom no qhia tias QLQX tuaj yeem tswj hwm lub zog metabolism los ntawm kev ua kom cov lipid metabolism, txhim kho kev siv cov piam thaj, thiab tswj cov mitochondrial fission.
Compound Danshen Dripping Pill
Compound Danshen dripping pill (CDDP) muaj Radix Salvia miltiorrhiza, Radix Notoginseng, thiab Borneolum, uas yog dav siv los kho cov kab mob plawv ischemic. Guo et al. (2016) tsim cov qauv nas ntawm tus mob myocardial ischemia tshwm sim los ntawm isoproterenol thiab pom tias CDDP pretreatment tuaj yeem ua rau ATP ntau lawm thiab hloov cov qauv metabolomic hauv ischemic nas myocardium los ntawm kev txhawb kev hloov pauv mus rau cov roj ntsha metabolism.
DanQi ntsiav tshuaj
DanQi ntsiav tshuaj (DQP) yog tsim los ntawm ob hom tshuaj ntsuab, uas yog, Salvia Miltiorrhiza thiab Panax Notoginseng. Cov txheej txheem tau teev tseg hauv Suav Pharmacopoeia xyoo 2010 thiab tau dav siv rau kev kho mob ntawm IHD. Cov kev tshawb fawb pharmacological tsis ntev los no tau pom tias kev kho DQP tuaj yeem txhim kho lub plawv muaj nuj nqi thiab hloov cov lipid metabolism hauv cov qauv nas ntawm MI (Wang et al., 2015a; Chang H. et al., 2016; Wang et al., 2016a; Jiao et al., 2018), nrog rau txhawb nqa qhov kev nthuav qhia tseem ceeb ntawm CPT-1A, CD36, thiab PPAra. Ntawm lawv, CPT-1A, CD36, thiab PPAra kab lus tau nce ntxiv uas txhais tau hais tias cov txheej txheem metabolic ntawm DQP tuaj yeem cuam tshuam nrog lipid metabolism. Zhang et al. (2018c) ua HF tom qab MI nas qauv thiab oxygen-glucose deprivation-reperfusion (OGD/R)-induced H9c2 cell, raug mob qauv. Lawv pom tias DQP muaj cov kev ua zoo sib xws raws li kev xaiv PPARg activator (Rosiglitazone), uas tau cawm lub plawv ua haujlwm, thiab tswj cov ntsiab lus tseem ceeb hauv lipid thiab qabzib metabolism hauv MI-induced HF nas qauv los ntawm txoj kev PPARg. Txhawm rau txuas ntxiv qee yam ntawm cov txheej txheem metabolic ntawm DQP ntawm PPARg, H9c2 hlwb tau kho nrog / tsis muaj PPARg inhibitor (T0070907) thiab DQP. Lawv pom tias qhov nce ntawm ATP cov ntsiab lus thiab PPARg qhia ntawm DQP tuaj yeem cuam tshuam los ntawm T0070907 hauv OGD / R induced H9c2 cell raug mob. Tsis tas li ntawd, DQP kuj tau hais kom tswj hwm lub zog metabolism hauv nas ischemic myocardium los ntawm AMPK/SIRT1-PGC-1 txoj kev taw qhia (Meng li al., 2019).
Yangxinshi ntsiav tshuaj
Yangxinshi ntsiav tshuaj (YXS) yog tsim los ntawm 13 tshuaj ntsuab, uas tau siv dav los tiv thaiv thiab kho lub hauv siab nruj, angina pectoris, thiab kab mob plawv. Nws yog dav siv nyob rau hauv replenishing Qi, activating ntshav ncig, thiab daws cov ntshav stasis nyob rau hauv cov chaw kho mob. Zhang et al. (2018b) pom 25 metabolites los ntawm metabolic profiles hauv ischemia-reperfusion raug mob. Cov metabolites feem ntau koom nrog hauv lub zog metabolism, fatty acid metabolism, thiab amino acid metabolism. Txawm li cas los xij, cov txheej txheem ntawm YXS yuav tsum tau tshawb nrhiav ntxiv. Lwm txoj kev tshawb fawb tau nkag mus tob rau hauv cov txheej txheem cardioprotective ntawm YXS. YXS kev kho mob tseem ceeb txo qis infarct loj, tiv thaiv lub plawv ua haujlwm, thiab txhim kho lub zog metabolism hauv cov nas uas muaj lub plawv tsis ua haujlwm ntev. YXS txhim kho lub zog metabolism los ntawm kev nce p-AMPK, PGC-1a, GLUT4, thiab HIF-1 ib qho kev qhia (Wu et al., 2020b).
Txhaj tshuaj
Shengmai Txhaj
Shengmai txhaj tshuaj (SMI) tau pom zoo los ntawm Tuam Tshoj Food and Drug Administration (CFDA) hauv 1995, uas tau siv dav los tiv thaiv thiab kho mob plawv thiab mob HF. SMI yog tsim los ntawm ob hom tshuaj ntsuab, suav nrog Panax ginseng CAMey. thiab Ophiopogon japonicus (Thunb.) Ker Gawl. Wang et al. (2018b) siv iTRAQ-raws li proteomic mus kom ze los txheeb xyuas qhov sib txawv ntawm cov proteins ntawm SMI, thiab pom tias lawv txoj haujlwm tau cuam tshuam nrog mitochondrial oxidative phosphorylation. SMI tseem ceeb nce ATP5D, NDUFB10, thiab TNNC1 protein qhia hauv cov nas nrog myocardial ischemic raug mob. Hauv vitro, SMI nce ATP thiab MMP cov ntsiab lus thiab muaj txiaj ntsig zoo ntawm kev ua pa ntawm mitochondrial vim yog hypoxia. Lwm qhov kev sim tau txheeb xyuas cov teebmeem metabolic ntawm SMI tiv thaiv ischemia-reperfusion raug mob. SMI txo cov mitochondrial loj, txhim kho MMP, thiab inhibited mPTP qhib. Kev kho SMI tau nce MFN1, MFN2, thiab OPA mRNA qhia, thiab txo qis thiab Fis mRNA qhia. Cov txiaj ntsig no txhais tau tias cov txiaj ntsig cardioprotective ntawm SMI tuaj yeem cuam tshuam nrog mitochondrial dynamics (Yu li al., 2019).
Xuesaitong Txhaj
Kev txhaj tshuaj Xuesaitong (XST) feem ntau yog tsim los ntawm Panax Notoginseng saponins, uas tau siv dav los tiv thaiv thiab kho cov kab mob plawv-cerebral vascular. Kev kho XST txhim kho PDH kev ua haujlwm, ib qho tseem ceeb enzyme hloov pauv pyruvate rau acetyl CoA hauv mitochondria thiab cuam tshuam rau TCA lub voj voog, nrog rau nce Na plus -K plus -ATPase thiab Ca2 plus -Mg2 ntxiv -ATPase, thiab nce intracellular ATP thiab acetyl- CoA qib hauv hypoxia / reoxygenation mob. XST tseem ceeb txhim kho pyruvate dehydrogenase E1 alpha (PDHA1) thiab ATP synthase 5A (ATP5A) protein qhia hauv H9c2 hlwb nrog hypoxia / reoxygenation raug mob. Cov proteins no feem ntau cuam tshuam nrog lub plawv lub zog metabolism (Zhao li al., 2017).
YiQiFuMai Hmoov Txhaj
YiQiFuMai hmoov txhaj tshuaj (YQFM) yog tsim los ntawm TCMs paub zoo tshuaj Shengmaisan, uas yog dav siv rau kev kho mob ntawm angina pectoris, kab mob plawv, thiab mob plawv tsis ua hauj lwm. YQFM yog tsim los ntawm peb hom tshuaj ntsuab, suav nrog Panax ginseng CAMey., Ophiopogon japonicas (Thunb.) Ker Gawl, thiab Schisandra chinensis (Turcz.) Baill. YQFM tseem ceeb txo qis kev cuam tshuam cov hlab ntsha hauv lub plawv ua rau lub plawv tsis ua haujlwm los ntawm kev txhim kho plawv thiab txo qis kev ua haujlwm mitochondrial hauv cov nas. Tsis tas li ntawd, YQFM tseem ceeb inhibited Drp1 phosphorylation ntawm Ser616 thiab nce Mfn2 qhia hauv HF nas thiab OGD induced NRVMs raug mob (Zhang li al., 2019). Nws qhia tias YQFM tuaj yeem txhim kho lub zog metabolism los ntawm kev tswj cov mitochondrial dynamics. Hauv kev tshawb fawb sib txawv tau piav qhia hauv ischemia / reperfusion-Induced myocardial raug mob, YQFM tuaj yeem tswj hwm lub zog metabolism los ntawm kev ua kom AMPK phosphorylation (Li li al., 2016a).
Cov ntsiab lus thiab cov kev xav
Nyob rau xyoo kaum xyoo dhau los, kev mob siab ntxiv tau tsom mus rau kev hloov kho ntawm lub plawv lub zog metabolism hauv kev kho mob rau cov kab mob plawv (Neubauer, 2007). Kev hloov pauv ntawm lub plawv lub zog metabolism, cov txheej txheem nyuaj nrog kev siv substrate, mitochondrial oxidative phosphorylation, thiab ATP hloov pauv thiab siv, ua lub luag haujlwm tseem ceeb hauv kev mob plawv thiab kev kho mob (Daim duab 1). Lub plawv metabolic network muaj qhov nyuaj thiab hloov tau yooj yim hauv kev siv lub zog substrate thaum lub sijhawm hypoxic / ischemic mob. Nyob rau theem pib ntawm kev kho plawv, kev hloov pauv hauv kev xaiv myocardial substrate yog ib feem suav tias yog ib qho kev them nyiaj thiab kev tiv thaiv uas tuaj yeem cuam tshuam lub plawv tsis zoo. Nyob rau hauv sib piv, nyob rau hauv cov theem siab, tsis tu ncua ischemia / hypoxia thiab tom qab reperfusion tuaj yeem ua rau txo qis hauv fatty acid oxidation thiab nce hauv qabzib oxidation, uas ntxiv rau lipotoxicity, lactic acidosis, tsawg ATP ntau lawm, contractile tsis ua hauj lwm, thiab nce mus rau HF. . Cov txheej txheem no qhia tau hais tias kev sib raug zoo ntawm lub plawv lub zog metabolism thiab IHD yog ob sab. Kev ntsuas qhov tsis sib xws ntawm cov metabolism hauv lub zog ntawm lub sijhawm sib txawv tuaj yeem txhim kho kev siv tshuaj hauv kev kho IHD.
Cov tshuaj suav tshuaj ntsuab muaj peev xwm kho tau zoo rau kev kho mob ntawm IHD los ntawm kev hloov kho ntawm lub plawv metabolism. Hauv qhov kev tshuaj xyuas no, peb tsuas yog sau cov txiaj ntsig metabolic thiab cov txheej txheem hauv qab ntawm cov tshuaj ntsuab, cov khoom siv bioactive loj, thiab suav tshuaj ntsuab cov qauv hauv IHD. Ntau lub teeb liab txoj hauv kev thiab ntau lub hom phiaj yog txuam nrog CHMs-kho cov teebmeem ntawm lub zog metabolism hauv IHD (Daim duab 3). Cov ntsiab lus muaj raws li hauv qab no: (1) Cov txheej txheem ntawm tshuaj ntsuab, MBC, thiab CHF hauv kev txo qis MI-vim lub zog metabolism tsis zoo tuaj yeem koom nrog kev txhawb nqa mitochondrial biogenesis, tswj fatty acid thiab qabzib metabolism, modulating mitochondrial ua pa, thiab tswj qhov sib npaug ntawm mitochondrial. dynamics. (2) Suav tshuaj ntsuab cov qauv uas tuaj yeem hloov kho lub zog metabolism hauv IHD feem ntau muaj Qi-replenishing thiab/los yog Ntshav-cov tshuaj ntsuab. Tsis tas li ntawd, Qi-replenishing thiab/lossis Ntshav-activate CHMs, tshwj xeeb tshaj yog Qi-replenishing tshuaj ntsuab thiab lawv cov khoom tseem ceeb, feem ntau ua lub luag haujlwm tseem ceeb hauv kev tswj hwm lub zog metabolism hauv IHD. Nws qhia tias Qi-replenishing teebmeem ntawm CHMs yuav muaj feem xyuam rau kev tswj lub zog metabolism, tshwj xeeb tshaj yog muaj nuj nqi mitochondrial. (3) Tsis tas li ntawd, Qi-replenishing tshuaj ntsuab los yog kev sib xyaw ntawm Qi replenishing thiab ntshav-activates tshuaj ntsuab yuav ua kom muaj txiaj ntsig zoo ntawm cov hlab plawv lub zog metabolism dua li kev kho mob monotherapy nrog ntshav-tiv thaiv tshuaj ntsuab. Noj QSYQ ua piv txwv, Cui et al. (2018) piv rau kev koom tes ntawm tsib yam tseem ceeb (AS IV, Rb1, Rg1, R1, thiab DLA) hauv QSYQ thiab QSYQ rau lawv lub peev xwm los tswj lub zog metabolism hauv ischemia-induced nas myocardial raug mob. Lawv pom tias QSYQ thiab nws tsib yam tuaj yeem txhim kho cov qauv plawv. Tshwj xeeb, QSYQ tseem ceeb txhim kho lub plawv muaj nuj nqi thiab hloov kho lub zog metabolism. Lub tshuab ntawm QSYQ tuaj yeem tiv thaiv ischemia-induced nas myocardial raug mob los ntawm kev nce cov ntsiab lus ATP, txhim kho cTnI thiab ATP5D qhia, thiab txhim kho ATP synthase kev ua. Txawm li cas los xij, tsib yam ntawm QSYQ muaj qhov sib txawv ntawm kev tswj hwm lub zog metabolism. AS-IV thiab Rb1 kev kho mob tuaj yeem nce qib ATP, ATP5D protein qhia, thiab ATP synthase kev ua haujlwm, feem. Hauv daim ntawv cog lus, R1 tsuas yog ua kom muaj txiaj ntsig zoo ntawm cTnI protein qhia. Rg1, R1, thiab DLA ntawm QSYQ tsis muaj kev cuam tshuam ntawm ATP ntau lawm, ATP5D qhia txog ATP synthase kev ua. Cov ntaub ntawv no qhia tias tsib yam hauv QSYQ tawm dag zog ua haujlwm, txhawb ATP ntau lawm, cTnI thiab ATP5D qhia, thiab ATP synthase kev ua. Ntawm lawv, AS-IV thiab Rb1 muaj nyob rau hauv cov tebchaw ntawm Qi-replenishing tshuaj ntsuab, whereas R1 thiab DLA belongs rau cov tebchaw ntawm cov ntshav-activating tshuaj ntsuab. Yog li ntawd, cov nyhuv cardioprotective ntawm CHMs ntawm lub zog metabolism hauv myocardial ischemia feem ntau yog nyob ntawm kev sib koom ua ke ntawm kev sib txuas ntawm Qi-replenishing thiab Ntshav activating CHMs. Tsis tas li ntawd, cov kev tshawb fawb yuav muab cov qauv hauv paus rau cov txiaj ntsig ntawm cov tshuaj bioactive loj los ntawm CHMs. Cov ntsiab lus tseem ceeb bioactive nrog lub zog metabolism hauv kev tswj hwm kev ua haujlwm tau txheeb xyuas hauv CHMs, xws li AS-IV, Rb1, Rg1, Rd, thiab R1, feem ntau yog cov pab pawg ntawm saponin compounds uas feem ntau muab rho tawm los ntawm Astragalus membranaceus, Panax ginseng, thiab Panax notoginseng, raws. Cov no muaj peev xwm tswj hwm mitochondrial biogenesis thiab mitochondrial ua pa los ntawm ntau lub hom phiaj thiab txoj hauv kev.
Tam sim no, cov teebmeem thiab cov txheej txheem ntawm CHMs ntawm lub plawv lub zog metabolism tseem tsis tau paub meej thiab qee qhov tsis sib haum xeeb hauv cov kev tshawb fawb sim, uas tuaj yeem raug ntaus nqi rau cov tshuaj complex thiab pharmacological ntawm Suav tshuaj ntsuab. Kev tsim kho ntxiv ntawm lub platform ntawm cov kev tshawb fawb ntawm TCM complex cov tshuaj thiab lawv cov zaub mov txawv yog qhov tseem ceeb los qhia meej txog kev sib raug zoo ntawm cov tshuaj suav tshuaj sib txawv. Lub caij no, peb yuav tsum tau them sai sai rau txoj kev tshawb fawb txog tshuaj toxicology preclinical los xyuas kom meej cov tshuaj ntsuab muaj kev nyab xeeb thiab kev ua tau zoo ntawm kev txhim kho lub zog metabolism hauv IHD. Lub plawv lub zog metabolism tom qab myocardial ischemia yog cov txheej txheem dynamic thiab hloov tau yooj yim. Kev tshawb fawb ntxiv yuav tsum sib piv cov kev hloov pauv ntawm lub zog metabolism hauv lub sijhawm sib txawv tom qab myocardial ischemia. Tsis tas li ntawd, muaj cov txheej txheem nyuaj pathological tshwm sim los ntawm ntau yam kab mob hauv IHD, uas yog nrog rau lwm cov tsos mob thiab ua ke nrog lwm cov kab mob plawv. Txawm li cas los xij, cov qauv tsiaj feem ntau yog tsim los rau kev cuam tshuam ib leeg xwb. Yog li, peb yuav tsum tsim cov qauv sib xyaw ua ke ntau dua li cov qauv nas ntawm MI ua ke nrog ntshav qab zib, uas yog ze dua rau kev kho mob. Hauv kev sim tshuaj, txawm hais tias TCMs muaj keeb kwm ntev ntawm kev siv tshuaj kho mob hauv kev kho mob ntawm IHD, cov ntaub ntawv pov thawj zoo rau lawv cov txiaj ntsig feem ntau tseem tsis muaj. Cov kev tshawb fawb soj ntsuam ntawm niaj hnub tshuaj suav tshuaj niaj hnub tseem muaj ntau yam teeb meem, suav nrog kev nkag siab tsis txaus ntawm kev sau npe tshuaj ntsuam xyuas, kev txhim kho ntawm cov txheej txheem kho mob, kev tswj tsis zoo, thiab cov ntaub ntawv tshawb fawb tsis zoo (Zhang li al., 2013). Yog li ntawd, kev tshawb fawb soj ntsuam ntxiv, suav nrog kev tsim qauv nruj dua, ob qhov muag tsis pom kev, thiab cov kev sim loj loj yuav tsum tau ua thiab yuav tsum koom nrog kev tshawb xyuas ntau npaum li cas, sijhawm tswj hwm, kev siv tshuaj noj, thiab kev xa khoom. Lub caij no, yuav tsum tau yaum cov kws tshawb fawb los ua qhov kev sau npe thoob ntiaj teb ntawm kev sim tshuaj, uas ntxiv txhim kho qhov kev sim tsim thiab zam kev xaiv thiab tshaj tawm kev tsis ncaj ncees. Kev ntsuam xyuas ntxiv ntxiv ntawm qhov tsis zoo ntawm TCMs yog qhov tseem ceeb los txhim kho qhov tseeb ntawm kev soj ntsuam kev soj ntsuam thiab txo qhov tshwm sim ntawm cov tshuaj tsis zoo. Tsis tas li ntawd, peb yuav tsum tau saib xyuas ntau ntxiv rau qhov tshwm sim tsis zoo cuam tshuam nrog kev siv tshuaj kom ntseeg tau tias kev ncaj ncees thiab qhov tseeb ntawm TCMs tau tshwm sim hauv kev tshawb fawb soj ntsuam. Tam sim no, feem ntau cov kev tshawb fawb soj ntsuam ntawm TCM cov tshuaj hauv IHD feem ntau siv cov placebo ua pawg tswj hwm thiab tsis muaj kev sib piv rau cov tshuaj kho mob. Yog li, kev tsim cov kev tshawb fawb soj ntsuam xav tau los sib piv cov pab pawg tswj hwm sab hnub poob los ntsuas qhov ua tau zoo ntawm TCM. Cov yam ntxwv ntawm TCM xws li kev tshawb xav ntawm kev kho mob raws li kev sib txawv ntawm cov tsos mob kuj ua rau muaj kev nyuaj thiab nyuaj ntawm kev tshawb fawb soj ntsuam. Nws yog ib qho tsim nyog los tsim kom muaj kev tshawb fawb tshiab thiab ntau yam ntawm cov txheej txheem sib xyaw kom haum rau cov yam ntxwv ntawm cov tshuaj suav tshuaj.
AUTHOR CONTRIBUTIONS
FL tau tsim lub ntsiab lus thiab sau cov ntawv sau. JL thiab SL tau pab kho cov ntawv sau thiab kos daim duab thiab sab laj cov ntaub ntawv. SG thiab PL tau kho thiab hloov cov ntawv sau.
NYIAJ
Txoj haujlwm no tau txais kev txhawb nqa los ntawm National Natural Science Foundation ntawm Tuam Tshoj (No. 81473552), thiab Postdoctoral Science Foundation ntawm Tuam Tshoj (No. 2019TQ0043).
