PART 2 Phenylethanol Glycosides Tiv Thaiv Myocardial Hypertrophy Induced Los ntawm Abdominal Aortic Constriction Ntawm ECE 1 Demethylation Inhibition Thiab PI3K PKB ENOS Pathway Enhancement

Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com

Thov nyem qhov no mus rau Part 1

Hauv kev tshawb fawb yav dhau los, peb pom tias ECE-1 demethylation ua haujlwm ntawm kev kub siab thiab tej zaum yuav muaj kev cuam tshuam rau kev tsim cov ET-1 [13]. Raws li, peb xav paub seb CPhGs(PHENYLETHANOLD Glycoside los ntawm CISTANCHE)yuav cuam tshuam rau qib demethylation ntawm ECE-1. Raws li pom nyob rau hauv daim duab 7, piv nrog cov sham pab pawg neeg, qib methylation ntawm ECE-1 nyob rau hauv cov ntaub so ntswg myocardial tau nce ntau heev hauv AAC pawg. Nyob rau tib lub sijhawm, nws tau txo qis hauv AC 125, 250, thiab 500 mg / kg pawg piv nrog AAC pawg. -e theem ntawm ECE-1 gene demethylation hauv AC 125 mg / kg pawg tau ntau dua li hauv pawg AV; tsis muaj qhov sib txawv tseem ceeb hauv AC 125 mg / kg pawg, tab sis qhov poob tseem ceeb tau pom hauv AC 500 mg / kg pawg thaum piv rau AV pawg.

3.7. CPhGs(Phenylethanoild Glycoside los ntawm CISTANCHE)Txo qhov nthuav tawm ntawm ECE-1 hauv Myocardial Ntsws ntawm nas tom qab AAC.

Txhawm rau nkag siab ntxiv txog cov txiaj ntsig ntawm ECE-1 methylation, peb tau kuaj pom qhov qhia ntawm mRNA, protein, thiab immunohistochemistry ntawm ECE-1 hauv cov ntaub so ntswg myocardial. Raws li pom nyob rau hauv daim duab 8, piv nrog cov sham pawg, cov txheeb ze qhia theem ntawm ECE-1 mRNA, txheeb ze qhia cov qib protein, thiab qhov nruab nrab thaj tsam ntawm myocardial immunohistochemistry tau txo qis heev hauv pawg AAC. Daim duab 8(c) qhia tias piv nrog AAC pab pawg, qhov txheeb ze qhia theem ntawm ECE-1 mRNA raug txo qis hauv AC 250 thiab 500 mg / kg pawg; thaum piv rau AV pab pawg, lawv tau muaj txiaj ntsig ntau dua hauv AC 125 thiab 250 mg / kg pawg tab sis tsis txawv qhov txawv hauv AC 500 mg / kg pawg. Lub caij no, raws li tau pom hauv daim duab 8(a) thiab 8(b), piv nrog AAC pawg, cov txheeb ze qhia qib ntawm ECE{13}} cov protein tau txo qis hauv AC 250 thiab 500 mg / kg pawg; Txawm li cas los xij, lawv tsis txawv qhov txawv ntawm AC 250 thiab 500 mg / kg pawg piv rau cov hauv AV pawg. Cov duab 8(d) thiab 8(e) qhia tias, piv nrog AAC pawg, thaj chaw qhia ntawm ECE-1 hauv cov ntaub so ntswg myocardial ntawm nas tau txo qis hauv AC 125, 250, thiab 500 mg / kg pawg. ; Txawm li cas los xij, piv nrog AV pawg, nws yog qhov tseem ceeb dua hauv AC 125 thiab 250 mg / kg pawg thiab tsis pom qhov txawv ntawm AC500 mg / kg pawg.

3.8. CPhGs(Phenylethanoild Glycoside los ntawm CISTANCHE)Txo cov Plasma ET-1 Qib hauv nas tom qab AAC.

Peb kuj tau ntsuas plasma ET-1 qib hauv cov nas los ntawm ELISA, raws li pom hauv daim duab 9, piv nrog rau pawg sham, cov ntshav plasma ntawm ET-1 hauv pawg AAC tau nce ntau heev. Lub caij no, cov qib ntshav plasma ntawm ET-1 tau pom qhov nce nce hauv AC 125 mg / kg pawg tab sis qhia tias tsis muaj qhov sib txawv tseem ceeb hauv AC 250 thiab 500 mg / kg pawg thaum piv rau cov hauv pawg AV. 3.9. CPhGs(Phenylethanoild Glycoside los ntawm CISTANCHE)Nce kev nthuav qhia ntawm PI3K / PKB / eNOS Txoj Kev hauv nas tom qab AAC. PI3K/PKB/eNOS yog txoj hauv kev tseem ceeb hauv cov txheej txheem ntawm myocardial hypertrophy thiab muaj kev sib txuas tseem ceeb nrog ET-1 [14–16]. -eeffore, peb ntxiv kuaj cov proteins qhia theem ntawm PI3K / PKB / eNOS txoj hauv kev nas myocardial. Raws li pom nyob rau hauv daim duab 10, piv nrog sham pawg, cov txheeb zeqhia theem ntawm p-PI3K, p-PKB, thiab p-eNOS cov proteins hauv AAC pawg tau txo qis; Txawm li cas los xij piv nrog cov pab pawg AAC, qhov txheeb ze qhia theem ntawm p-PI3K tau nce ntau hauv AC 250 thiab 500 mg / kg pawg. Nyob rau tib lub sijhawm, cov txheeb ze qhia theem tau pom qhov qis qis hauv AC 125 mg / kg pawg thiab tsis pom qhov txawv ntawm AC 250 thiab 500 mg / kg pawg piv rau cov pawg AV. Raws li pom hauv daim duab 10(b), piv nrog AAC pab pawg, cov txheeb ze qhia theem ntawm p-PKB tau nce ntau hauv AC 250 thiab 500 mg / kg pawg. Lub caij no, lawv tau qis dua hauv AC 125 mg / kg pawg thiab tsis txawv ntau hauv AC 250 thiab 500 mg / kg pawg piv rau cov pab pawg AV. Raws li pom nyob rau hauv daim duab 10(c), piv nrog AAC pawg, cov txheeb ze qhia theem ntawm p-eNOS tau nce ntau hauv AC 125, 250, thiab 500 mg / kg pawg; Txawm li cas los xij, piv nrog cov pab pawg AV, cov qib kev txheeb ze tau nthuav tawm qhov kev poob qis hauv AC 125 thiab 250 mg / kg pawg tab sis tsis pom qhov txawv ntawm AC 500 mg / kg pawg.

CISTANCHE BENEFIT

4. Kev sib tham

Piv nrog rau cov neeg mob ntshav siab, cov neeg mob ntshav siab thiab mob plawv hypertrophy muaj 6-8 lub sij hawm nce qhov tshwm sim ntawm myocardial infarction, mob plawv tsis ua hauj lwm, thiab txawm tias lub plawv tuag tam sim ntawd, uas cuam tshuam rau kev kho mob thiab kev mob ntshav siab [23, 24] . Nyob rau hauv cov xwm txheej zoo li no, kev kho mob ntshav siab yuav tsum tsis txhob txwv rau kev tswj ntshav siab. Yog li, qhov thim rov qab ntawm lub plawv hypertrophy, uas yog qhov tseem ceeb, kuj tsim nyog muaj kev txhawj xeeb loj. Hauv cov neeg mob uas mob plawv hypertrophy, cardiomyocyte protein synthesis yog nce nyob rau hauv tus lej, loj loj, thickened nyob rau hauv cell phab ntsa, nrog rau qhov tshwm sim ntawm ntau sarcomere, interstitial fifibroblast proliferation, thiab cardiac collagen proliferation. Nyob rau tib lub sijhawm, kev qhia ntawm cov cim cardiac hypertrophy, xws li ANP, BNP, thiab -MHC mRNA, kuj nce ntxiv [25–27]. Raws li ib txwm suav tshuaj rau kev kho mob ntawm poj niam infertility thiab txiv neej impotence, lub qia ntawmCistanche tubulosayog thawj zaug sau tseg hauv Shen Nong's Materia Medica hauv ca. 100 BC thiab tam sim no tau dav siv los ua ib hom zaub mov noj qab haus huv hauv cheeb tsam Southeast Asia [28]. Nyob rau xyoo tas los no,Cistanche tubulosatau txais kev saib xyuas ntawm cov zej zog kho mob vim tias nws cov haujlwm tseem ceeb hauv kev lom neeg. Raws li ib txwm tshuaj antifatigue, tsis tsuas yogCistanche tubulosamuaj cov haujlwm ntawm kev tiv thaiv cov leeg, tab sis kuj nws cov extract tuaj yeem txhim kho ATP cia thiab txo cov leeg nqaij tom qab qoj ib ce hauv nas [29]. Raws li cov txiaj ntsig ntawm ex vivo thwmsim, Cistanche tubulosa kuj muaj kev tiv thaiv tiv thaiv statin-induced leeg nqaij toxicity nrog kev pab los ntawm txoj kev caspase [30]. Tsis tas li ntawd, cov kws tshawb fawb tau kawm txog cov tshuaj pharmacological ntawm Cistanche tubulosa hauv kev tiv thaiv kab mob plawv thiab lwm yam thiab pom tiasCistanche tubulosatuaj yeem cuam tshuam qhov nce ntawm cov ntshav qabzib yoo mov thiab cov ntshav qabzib tom qab, txhim kho insulin tsis kam, thiab ameliorate dyslipidemia, nrog rau inhibit qhov hnyav hauv db / db nas [31].

Cistanche tubulosa extract

Cov kev tshawb fawb yav dhau los tau pom tias CPhGs(PHENYLETHANOLD Glycoside los ntawm CISTANCHE)tuaj yeem txo qhov kev puas tsuaj ntawm cov dawb radicals rau myocardial mitochondrial membrane thiab plasma omentum, txo cov ntsiab lus malondialdehyde, txo myocardial ultrastructural kev puas tsuaj, nce myocardial mitochondrial antioxidant enzyme kev ua, txo myocardial infarct loj, txhim kho cov haujlwm ntawm phosphocreatine hauv myocardial tiv thaiv cov ntaub so ntswg, cuam ​​tshuam rau ischemic myocardium [9, 10, 32]. Peb tsom los tshawb txog cov txiaj ntsig ntawm CPhGs ntawm kev kub siab tshaj qhov ua rau mob plawv hypertrophy. Hauv txoj kev tshawb no, nws tau pom tias CPhGs txo qis LVPWT, LVED, HWI, AMC, thiab plawv hypertrophy gene theem (ie, ANP, BNP, thiab -MHC), nce EF thiab FS, inhibited cardiac hypertrophy, thiab txhim kho lub plawv dhia hauv nas. . Tsis tas li ntawd, kev mob plab yog ib qho ntawm cov phenotypes tseem ceeb hauv pathogenesis ntawm plawv hypertrophy [33]. Qee cov kws tshawb fawb tau pom tias kev tshem tawm ntawm IL-6 tuaj yeem ua rau lub siab ntau dhau-vim sab laug ventricular hypertrophy thiab tsis ua haujlwm [34]. Thiab peb pom tias CPhGs tsis tuaj yeem txo qis cov ntshav IL-6 qib ntawm nas tom qab AAC tab sis kuj txo qis lwm yam proinflammatory, xws li COX-1, IL-1 , thiab TNF- . Tsis tas li ntawd, CPhGs tseem tuaj yeem txo COX-2 thiab HMGB-1 protein cuam tshuam rau qhov mob. -e cov teebmeem ntawm CPhGs tau koob tshuaj raws li kev siv tshuaj ntau ntxiv. Tsis tas li ntawd, nws tsim nyog hais tias qhov koob tshuaj ntau ntawm CPhGs pab pawg muaj kev tiv thaiv tseem ceeb ntawm cov nas hypertrophic, zoo ib yam li cov txiaj ntsig ntawm pawg valsartan zoo. -yog li ntawd, CPhGs tuaj yeem yog tus neeg sawv cev tshuaj muaj peev xwm los tiv thaiv kev kub ntxhov ntau dhau ntawm lub plawv hypertrophy. DNA methylation yog hais txog cov txheej txheem hloov pauv DNA molecular DNA methylation uas S-adenosyl-L-methionine ua tus methyl pub dawb kom tau txais ib pawg methyl los ntawm covalent bonding nyob rau hauv catalysis ntawm DNA methyltransferases [35]. Nws paub zoo tias ET-1 yog cov vasoconstrictor muaj zog tshaj plaws thiab tuaj yeem ua rau cov hlab ntsha thiab cov hlab ntsha medullary, uas ua rau txo qis natriuresis thiab nce ntshav siab [36–38]. Ua tus enzyme tseem ceeb hauv cov kauj ruam kawg ntawm kev tsim cov endothelin, ECE- 1 tsis yog tsuas yog koom nrog ET-1 hauv cov kab mob plawv, tab sis kuj tuaj yeem tswj hwm ET-1 ntau lawm. -us, ECE-1 tuaj yeem yog qhov tseem ceeb rau kev txhim kho thiab kev loj hlob ntawm tus kab mob [39]. Hauv kev sim hauv vitro ntawm vascular endothelial hlwb, methylation ntawm CpG kob hauv ECE-1c txhawb nqa cheeb tsam txo nws cov kev ua haujlwm transcriptional, ua rau txo qis kev qhia ntawm ECE-1c, ntxiv rau txo qis ntawm ET. -1 thiab txo cov ntshav siab hauv vivo, thiab kab ntawm kev hloov pauv no qhia tias ECE-1 methylation tuaj yeem koom nrog hauv pathology ntawm ntshav siab [40, 41]. Hauv peb txoj kev tshawb fawb yav dhau los, peb kuj tau pom muaj kev nce ntxiv demethylation ntawm ECE-1 hauv cov neeg mob ntshav siab [35]. -e cov txiaj ntsig ntawm txoj kev tshawb fawb tam sim no tau pom tias CPhGs txo qis ECE-1 demethylation, txo ECE-1 mRNA thiab protein qhia, thiab txo cov ntshav ET-1 qib hauv myocardium ntawm nas nrog lub siab dhau. -induced cardiac hypertrophy tom qab AAC. Txawm hais tias CPhGs cuam tshuam rau ECE-1 qib demethylation thiab seb lawv puas tiv thaiv lub plawv hypertrophy hauv nas tsis tau qhia meej. PI3K yog txoj hauv kev kawg rau cardiomyocyte hypertrophy los ntawm contractile mus rau hom hypertrophic [42]. Ob qho isoforms ntawm PI3K tuaj yeem koom nrog hauv cardiomyocyte hypertrophy, uas Pll0 koom nrog hauv lub cev hypertrophy, thaum p110c koom nrog hauv pathological hypertrophy. P110, thaum nplawm tawm hauv nas, tuaj yeem tiv thaiv kab mob plawv thiab ua lub luag haujlwm tseem ceeb hauv kev loj hlob thiab kev loj hlob ntawm cardiomyocyte hypertrophy [43]. PKB yog lub hauv paus rau txoj kev taw qhia no. Nws qhov kev ua kom muaj peev xwm hloov kho molecular muaj nuj nqi los ntawm kev ua kom los yog inhibiting downstream los yog molecules los ntawm phosphorylation [44]. PI3K/PKB tseem yog ib txoj hauv kev tseem ceeb ntawm kev taw qhia tom qab ET-1, thiab cov kev tshawb fawb tau pom tias ET-1 tuaj yeem ua rau nws tus kheej induce fifibroblast tsis kam mus rau apoptosis los ntawm PI3K / PKB signaling activation [45].

Cistanche tubulosa ntxiv

Lwm cov kev tshawb fawb tau pom tias ET-1 tuaj yeem tswj hwm cov haujlwm ntawm eNOS thiab tso tawm NO los ntawm endothelin receptor B1 [46]. Raws li ib qho tseem ceeb vasodilator, TSIS muaj peev xwm tiv thaiv cov vasoconstrictive los ntawm ET-1 los ntawm ntau theem thiab tswj cov hlab plawv zoo [47]. Hauv txoj kev tshawb no, qhov nruab nrab thiab siab koob tshuaj CPhGs(PHENYLETHANOLD Glycoside los ntawm CISTANCHE)cov pab pawg tau pom qhov nce ntxiv hauv p-PI3K, p-PKB, thiab p-ENOS. Txawm li cas los xij, pawg CPhGs siab tau muaj txiaj ntsig zoo ib yam li AV pawg, uas tau qhia ntxiv tias CPhGs tuaj yeem cuam tshuam lub plawv hypertrophy hauv cov nas tom qab AAC los ntawm kev ua kom PI3K / PKB / eNOS teeb liab txoj hauv kev. Lwm cov kev tshawb fawb kuj tau pom qhov sib txuas ntawm PI3K / PKB txoj hauv kev thiab cov lus teb inflammatory [48, 49]. Zou thiab lwm tus kws tshawb fawb tau tshaj tawm tias hauv kev mob ntsws asthma, Brahman-hais txog cov noob caj noob ces ua lub luag haujlwm tseem ceeb hauv kev tswj cov hlab ntsws o thiab cuam tshuam rau PI3K / Akt / mTOR txoj hauv kev [50]. Tsis tas li ntawd, CPhGs kuj txo qis qhov qhia txog kev mob ntsig txog cov noob hauv cov ntaub so ntswg myocardial. -erefore, peb kwv yees tias CPhGs tuaj yeem txo qhov kev mob tshwm sim hauv cov nas muaj kev ntxhov siab ntau dhau los ntawm kev nce PI3K / PKB / eNOS txoj kev taw qhia. Zuag qhia tag nrho, peb txoj kev tshawb fawb yog thawj zaug los qhia txog kev tiv thaiv kev tiv thaiv ntawm CPhGs ntawm kev kub siab tshaj qhov ua rau mob plawv hypertrophy hauv cov nas tom qab AAC, uas tej zaum yuav cuam tshuam rau lub luag haujlwm CPhGs ua si hauv kev txo qis demethylation ntawm ECE-1 thiab txhim kho PI3K/PKB txoj kev. -is nrhiav muab lub tswv yim tshiab rau kev tshawb fawb soj ntsuam ntawm kev kub siab hypertrophy thiab kev txhim kho cov tshuaj kho tshiab los tiv thaiv, tswj, thiab thim rov qab kub siab hypertrophy. Txawm hais tias tseem muaj ntau cov lus nug tseem ceeb tos kom daws tau, kev nkag siab ntxiv ntawm cov txheej txheem uas CPhGs thiab PI3K / PKB kho cov lus teb ua rau mob tuaj yeem ua rau lub teeb tshiab ntawm kev tshawb nrhiav kev kho mob plawv yav tom ntej.

5. Cov lus xaus

Peb cov txiaj ntsig tau pom tias CPhGs(PHENYLETHANOLD Glycoside los ntawm CISTANCHE)ameliorated myocardial hypertrophy nas los ntawm AAC, uas tej zaum yuav cuam tshuam nrog ECE-1 demethylation inhibition thiab PI3K/PKB/eNOS enhancemen

Cistanche tubulosa ntxiv

Cov ntaub ntawv muaj

Tag nrho cov ntaub ntawv muaj nyob rau hauv txoj kev tshawb no muaj nyob rau ntawm kev thov los ntawm kev tiv tauj nrog tus neeg sau ntawv. Kev tsis sib haum xeeb ntawm kev txaus siab -e cov kws sau ntawv tshaj tawm tsis muaj kev tsis sib haum xeeb ntawm kev txaus siab.

Cov neeg sau ntawv koom tes

Shu-Ping You, Tao Liu, Jun Zhao, thiab Qiong-Ling Fan tau xeeb thiab tsim qhov kev sim. Qiong-Ling Fan, Jia-Wei Wang, thiab Shi-Lei Zhang tau ua haujlwm rau cov txheej txheem. Qiong-Ling Fan, Jia-Wei Wang, Shi-Lei Zhang, thiab Shu Ping Koj tau tshuaj xyuas cov ntaub ntawv. Qiong-Ling Fan, Jia-Wei Wang, thiab Shi-Lei Zhang sau cov ntawv sau. Shu-Ping You, Tao Liu, thiab Jun Zhao tau tshuaj xyuas cov ntawv sau. Txhua tus kws sau ntawv tau nyeem thiab pom zoo cov ntawv sau kawg.

Kev lees paub

-yog kev ua haujlwm tau txais nyiaj los ntawm ib txoj haujlwm tseem ceeb ntawm National Key Laboratory Jointly Founded by the Provincial and Ministry in Xinjiang Uyghur Autonomous Region (SKLHIDCA-2018-3), National Natural Science Foundation of China (no. 8156140127), thiab ib txoj haujlwm hluas Ntawm Kev Tshawb Fawb Txog Kev Tshawb Fawb Hauv Xinjiang Uyghur Autonomous Region Higher Education Institution (XJEDU2019Y027).

Cov ntaub ntawv

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