Neuroprotective Effects Of Cistanches Herba Therapy Rau Cov Neeg Mob Mob Alzheimer's Disease
Mar 02, 2022
Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com
Nan Li, Jianping Wang, Jun Ma, Zhiqiang Gu, Chao Jiang, Lie Yu, thiab Xiaojie Fu
Abstract
Cistanches Herba(CH) xav tias yog "Yang-invigorating" cov ntaub ntawv hauv cov tshuaj suav tshuaj. Peb soj ntsuam cov teebmeem neuroprotective ntawmCistanches HerbantawmAlzheimer tus kab mob(AD) cov neeg mob. Nruab nrab AD(Alzheimer tus kab mob)cov neeg koom tau muab faib ua 3 pawg:Cistanche Herbacapsule (CH, 𝑛=10), Donepezil ntsiav tshuaj (DON, 𝑛=8), thiab pab pawg tswj tsis tau kho (𝑛=6). Peb tau soj ntsuam kev ua tau zoo los ntawm MMSE thiab ADAS-cog thiab tshawb xyuas qhov hloov pauv ntawm hippocampus los ntawm 1.5 T MRI scans. Protein, mRNA levels, and secretions of total-tau (T-tau), tumor necrosis factor-𝛼 (TNF-𝛼), and interleukin- (IL) 1𝛽 (IL{12}}𝛽) in cerebrospinal fluid (CSF) tau kuaj pom los ntawm Western blot, RT-PCR, thiab ELISA. Cov qhab nias tau pom qhov sib txawv ntawm qhov sib txawv tom qab 48 lub lis piam ntawm kev kho mob piv rau pawg tswj hwm. Lub caij no, kev hloov pauv ntawm cov hippocampus me ntsis hauv cov pab pawg kho mob tab sis txawv hauv pawg tswj hwm; theem ntawm T-tau, TNF-𝛼, thiab IL-1𝛽 tau txo qis piv rau cov hauv pawg tswj hwm.Cistanches Herbatuaj yeem txhim kho kev txawj ntse thiab kev muaj peev xwm ua neej nyob nruab nrab ntawm AD(Alzheimer tus kab mob)Cov neeg mob, txo qis qhov hloov pauv ntawm hippocampus, thiab txo qis T-tau, TNF-𝛼, thiab IL-1𝛽. Nws qhia tiasCistanches Herbamuaj peev xwm neuroprotective cuam tshuam rau nruab nrab AD (Alzheimer tus kab mob).
1. Taw qhia
Alzheimer tus kab mob(AD) yog ib qho ntawm cov tsos mob tshwm sim los ntawm neurodegeneration uas yog tus cwj pwm los ntawm kev puas tsuaj loj hauv kev txawj ntse thiab muaj peev xwm rau kev nyob ywj pheej. Nws kwv yees tias muaj txog 28.4 lab tus tib neeg ntawm AD(Alzheimer tus kab mob)thoob ntiaj teb xyoo 2010 [1]. Tam sim no tsis muaj kab mob hloov kho los tiv thaiv lossis kho AD(Alzheimer tus kab mob)muaj. Hyperphosphorylated tau protein uas yog aggregating intracellularly hauv AD(Alzheimer tus kab mob)lub hlwb thiab tsim cov neurofibrillary tangles thiab amyloid-beta (A𝛽) protein uas yog accumulating extracellular nyob rau hauv AD(Alzheimer tus kab mob)lub hlwb thiab lub tsev cortical senile plaques yog lub ntsiab neuropathological cim ntawm AD. Nce cov ntsiab lus ntawm tag nrho-tau (T-tau) hauv cov kua cerebrospinal (CSF) tau pom muaj nyob hauv AD(Alzheimer tus kab mob)[2]. Qhov kev loj hlob ntawm atrophy ntawm ntau lub hlwb hauv cheeb tsam hauv AD kuj tau pom dav dav, tshwj xeeb tshaj yog nyob rau hauv hippocampus uas yog ib cheeb tsam koom nrog hauv kev paub, nco, thiab kev kawm. Postmortem cov ntaub ntawv qhia pom thaum ntxov neuropathological lesions thiab neuronal poob hauv hippocampus [3]. Raws li magnetic resonance imaging (MRI) tuaj yeem taug qab hippocampus atrophy hauv nruab nrab thiab lig xeev ntawm AD.(Alzheimer tus kab mob), nws tuaj yeem yog lwm tus cim ntawm AD(Alzheimer tus kab mob)[4]. Tsis ntev los no neuroinflammation los ntawm qhov txawv txav tshwm sim neuroglia tau tshwm sim los ua ib qho tseem ceeb ntawm cov txheej txheem AD [5]. Kev nce qib ntawm A𝛽 thiab qhov tso tawm ua rau muaj kev ua haujlwm ntev ntawm lub cev tiv thaiv kab mob thiab kev cuam tshuam ntawm microglial clearance functions. Cov ntaub ntawv kab mob kis tau qhia txog lub luag haujlwm tseem ceeb hauv kev ua kom lub cev tiv thaiv kab mob hauv ib txwm muaj raws li kev txhawb nqa kab mob [6]. Cov cytokines ntseeg tau koom nrog hauv kev sib sau ntawm amyloid plaques thiab ua kom muaj kev phom sij ntawm A𝛽 los ntawm kev koom tes hauv cov txheej txheem inflammatory [7]. Cov pov thawj ntxiv qhia tau hais tias lub hlwb tuaj yeem pib lub cev tiv thaiv kab mob zoo rau kev raug mob [8, 9] thiab txhawb nqa lub cev tiv thaiv kab mob peripheral [10, 11]. Circulating cytokines tuaj yeem hla cov ntshav-hlwb barrier (BBB) los ntawm kev thauj mus los yooj yim [12, 13]. TNF-𝛼, IL-1𝛽, thiab proinflammatory cytokines twb tau raug pov thawj los ntawm cov nas hlwb los ntawm ionizing hluav taws xob [14, 15]. Tsis tas li ntawd, IL-1𝛽 tej zaum yuav muaj kev cuam tshuam sib txawv ntawm CNS hlwb: tsawg concentration ntawm IL-1𝛽 muaj kev tiv thaiv los ntawm kab lis kev cai cortical neurons tiv thaiv excitotoxicity, tab sis siab concentration ntawm IL- 1𝛽 muaj cov teebmeem neurotoxic [16] Ntau qhov kev tshawb fawb qhia txog lub luag haujlwm tseem ceeb ntawm cov cytokines hauv CNS o [17–21], thiab cov qib siab ntawm cov cytokines tuaj yeem ua rau muaj kev puas tsuaj rau neuronal hauv AD.(Alzheimer tus kab mob)lub cev [22]. Tam sim no, qee cov tswv yim kho mob los tiv thaiv kev kho mob hauv AD(Alzheimer tus kab mob)tau thov.
Cistanches Herba(CH), cov nroj tsuag holoparasitic ntawm Cistanche deserticola YC Ma uas yog cov khoom tseem ceeb rau tonify lub raum thiab ib tug "Yang-invigorating" cov ntaub ntawv nyob rau hauv tsoos suav tshuaj txoj kev xav [23]. Nws yog dav siv los kho qhov tsis nco qab thiab tsis hnov lus, ua kom muaj zog ntawm kev yug me nyuam, thiab txhim kho fertility muaj nuj nqi. Cov kev tshawb fawb yav dhau los tau pom tias CH muaj cov haujlwm tshuaj sib txawv: cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob [24–26]. Lub hauv paus tseem ceeb hauv CH yog phenylethanoid glycosides: xws li verbascoside thiab Echinacoside [27], uas xav tias muaj qee yam cuam tshuam rau hauv nruab nrab paj hlwb (CNS). Cov kev tshawb fawb tau tshaj tawm tias verbascoside qhia pom cov teebmeem neuroprotective tiv thaiv 1-methyl-4- phenyl Pyridium (MPP ntxiv) 5 uas tau raug pov thawj los ua rau muaj kev nco tsis txaus hauv vivo [28]. Echinacoside tuaj yeem cawm SH-SY5Y cov hlwb neuronal tom qab TNF-𝛼 ntxias apoptosis thiab txhim kho kev coj tus cwj pwm tsis zoo hauv tus qauv nas ntawm tus kab mob Parkinson [29, 30].
Txij li CH(Cistanches Herba)tau siv los kho qhov tsis nco qab tau ntau xyoo thiab nws cov ntsiab lus muaj qee qhov cuam tshuam rau CNS, nws kuj tseem muaj cov teebmeem neuroprotective ntawm AD.(Alzheimer tus kab mob). Hauv peb txoj kev tshawb fawb, peb tau txheeb xyuas cov neeg mob qhov kev paub thiab kev coj tus cwj pwm thiab ntsuas qhov cuam tshuam ntawm T-tau, TNF-𝛼, thiab IL-1𝛽. Tej yam tshwm sim ntawm CH (Cistanches Herba) tiv thaiv neurodegeneration tau pom.
Cistanches Herba
2. Cov ntaub ntawv thiab cov txheej txheem
2.1. Cov neeg mob
Txhua tus neeg mob tau sau ntawv tso cai. Txoj kev tshawb no tau ua raws li Txoj Cai ntawm Kev Ncaj Ncees ntawm Lub Koom Haum Kho Mob Ntiaj Teb (Kev Tshaj Tawm ntawm Helsinki) thiab tau pom zoo los ntawm Pawg Saib Xyuas Kev Ncaj Ncees ntawm Zhengzhou University (hnub tim: Kaum Ib Hlis 10, 2012).
26 tus neeg koom tau raug xaiv los ntawm lub tsev kho mob thib ob ntawm Zhengzhou University thiab lub tsev kho mob thib tsib ntawm Zhengzhou University los ntawm 2013 txog 2014. Lawv muaj keeb kwm kev kawm zoo sib xws thiab qhov nruab nrab tus nqi ntev ntawm cov tsos mob ua ntej kuaj mob yog 1.5 xyoo. Txhua tus neeg koom nrog hauv peb txoj kev tshawb fawb tau dhau los ntawm kev sib tham hauv chaw kho mob thiab kuaj los ntawm tus kws kho mob hlwb. Cov txheej txheem suav nrog yog MMSE thiab ADAS-cog, txij li 10 txog 20 thiab 29 txog 40. Cov txheej txheem cais tawm yog mob hnyav lossis mob ntev, tus kab mob qub, oncogenesis, kev kho ntawm Donepezil, memantine hydrochloride lossis Ginkgo biloba nplooj, kho cov tshuaj tiv thaiv kab mob lossis corticosteroids, thiab C-reactive protein (CRP) qib ⩾ 10 mg / L.
Tag nrho ntawm 20 AD(Alzheimer tus kab mob)Cov neeg mob tau tsim nyob rau hauv kev kho tshuaj: CH kho pab pawg: kev tswj qhov ncauj ntawmCistanches Herbacapsule 48 lub lis piam (0.9 g/hnub, txhua tus neeg, N=11) thiab pab pawg kho mob DON: kev tswj qhov ncauj ntawm Donepezil ntsiav tshuaj 48 lub lis piam (5 mg / hnub, txhua tus neeg, N{{6 }}). Rau tus neeg mob tau tso npe ua pawg tswj hwm (tsis muaj kev kho mob, 𝑛=6). Txhua tus neeg koom tau pom zoo thiab raug ceeb toom kom cojCistanches Herba(CH) capsule (0.3 g/capsule, 3 tsiav tshuaj ib hnub twg, LYYLYD pharmaceuticals Company, Changchun, Suav teb), Donepezil ntsiav tshuaj (5 mg/tablet, 1 ntsiav tshuaj ib hnub twg, Eisai China Inc., Suzhou, Tuam Tshoj), los yog tsis muaj dab tsi, ntsig txog. Txhua tus neeg mob tsis muaj tshuaj kho ua ntej qhov kev tshawb fawb no.
2.2. Cognitive Abilities Tests
Tag nrho cov kev ntsuam xyuas tau muab ua ntej thiab tom qab kev kho mob los ntawm cov kws ntsuas qhov muag tsis pom kev.
2.3. MRI
Rau txhua tus neeg koom, MRI scans tau ua ntawm GE 1.5 T Signa HDxt MRI scanner (General Electric Company, Fairfield, CT, USA). MRI ib ntus nyob rau hauv cov xwm txheej: TR=11.6 ms, TE=5 ms, spatial daws teeb meem=0.94 hli, thiab hlais thickness=1.2 hli. Tag nrho cov duab tau txheeb xyuas los ntawm kev siv cov software pob Analyze (Mayo Foundation, 1999) thiab Statistical Parametric Mapping (SPM99, Lub Tsev Kawm Ntawv ntawm Neurology, London, UK, tshwj xeeb yog siv los ntsuas qhov ntim ntawm tag nrho cov teeb meem grey) [33]. Hippocampal morphometry yog tswj los ntawm neuroradiologists (tes tracing) uas yog dig muag rau kev kuaj mob. Hippocampal cov txheej txheem tau kos rau hauv qhov xub xub pom uas siv "chaw txaus siab" cov cuab yeej siv hauv software Analyze. Tom qab ua tiav daim duab rau tag nrho cov xub-headed slices qhov twg hippocampus tau pom, qhov tseeb ntawm kab rov tav tau tswj hwm hauv coronal thiab sagittal views. Tom qab ntawd, ob sab hippocampal ntim thiab tag nrho lub hlwb ntim tau txiav txim siab siv cov txheej txheem tsis siv neeg ua haujlwm hauv MATLAB thiab SPM99.
2.4. Lumbar Puncture
Peb tau sau cov kua cerebrospinal ntawm cov neeg mob ntawm peb lub sijhawm: ua ntej kev kho tshuaj, 24 lub lis piam tom qab kev kho mob, thiab 48 lub lis piam tom qab kho. Tsis muaj leej twg ntawm cov neeg koom nrog lumbar puncture contraindications. Ua ntej ua qhov puncture, txhua tus yuav tsum tau qhia txog cov txheej txheem nrog rau cov kev pheej hmoo thiab cov txiaj ntsig thiab pom kev pom zoo los ntawm nws tus neeg saib xyuas. Tus neeg mob tau pw tsaug zog nrog lub nraub qaum flexed. Tom ntej no, qhov puncture point uas nyob rau hauv qhov kev sib tshuam ntawm qhov zoo tshaj plaws ntawm lub iliac crest thiab tus txha nraub qaum (L4 spinous theem) tau pom. Qhov chaw ntawm qhov chaw nruab nrab ntawm qhov chaw L3 thiab L4 tau sau npe. Qhov chaw no tau qis dua qhov kev txiav tawm ntawm tus txha caj qaum thiab muaj kev nyab xeeb dua rau kev ua haujlwm no. Cov tshuaj loog hauv zos tau infiltrated subcutaneously thiab ib rab koob ntawm tus txha caj qaum ntawm lub anatomical landmark tau txhaj raws txoj kev npaj. Yim milliliters ntawm cov kua tau sau thiab khaws cia ntawm −80∘ C rau kev sim ntxiv. Thaum tau txais cov qauv tsim nyog, rab koob raug muab tshem tawm thiab tus neeg mob pw ncaj nraim rau lwm 6 teev.
2.5 Rov qab transcription-polymerase Chain Reaction (RT-PCR)
Peb siv Trizol reagent (CWBIO, Beijing, Tuam Tshoj) kom rho tawm tag nrho RNA los ntawm CSF ntawm cov neeg koom nrog raws li cov chaw tsim khoom qhia thiab tsim thawj-strand cDNA los ntawm ThermoScript RT-PCR System (Invitrogen, Grand Island, New York, USA) nrog 1 μL random hexamer primer, 2 𝜇L 10 mM dNTP-Mix, 0.1 M DTT, thiab 1 𝜇L ThermoScript RT hauv DEPC-kho dej rau 20 𝜇L cov tshuaj tiv thaiv zaum kawg. Tom qab ntawd cov tshuaj tiv thaiv sib xyaw denatured ntawm 63∘C rau 5 feeb, ua raws li ntawm 45∘C ntawm 50 feeb thiab khaws cia ntawm -20∘ C.
Raws li cov ntaub ntawv ntawm gene bank, peb tsim cov primers thiab synthesized lawv los ntawm Sangon Biotech (Shanghai, Suav teb): T-tau, forward: 5 -CAAAAGCTCGCATGGTCAGT A-3 thiab thim rov qab: 5 -AGGGTTGGATCAGGGTCT{{ 6}} ; TNF-𝛼, pem hauv ntej: 5 -AGGC ATAGGGTTTTTTGAGGGCCAT{{10}} thiab thim rov qab: 5 -GGGACACAAGCAAGGAATCAAGGA TAC- 3 ; IL-1𝛽, pem hauv ntej: 5 -TGGCAGGTTCCTGATTT-3 thiab thim rov qab: 5 -AACTTGTT CGACAA CCCTC-3 ; tswj GADPH, pem hauv ntej: 5 -GGUCAUCCAUGACAAC UUUTT- 3 thiab thim rov qab: 5 -AAAGUUGUCAUGGAUGACCTT-3. Cov kev qhia theem ntawm mRNA tau ntsuas nrog RT PCR. Cov tshuaj tiv thaiv sib xyaw muaj 1 ug ntawm cov qauv cDNA, 1 μL primer, 2 𝜇L ntawm 10 mM dNTPs, 25 𝜇L Taq DNA polymerase (Sangon Biotech), thiab DEPC-kho dej rau qhov kawg ntim ntawm 50 𝜇L. PCR cov xwm txheej yog 98∘ C rau 30 vib nas this (denaturation), 55–58∘ C rau 30 vib nas this (annealing), thiab 72∘ C rau 60 vib nas this (extension) rau 30 cycles thiab tom qab ntawd ntawm 72∘ C rau 10 feeb, khaws cia ntawm 4∘ C. Cov khoom tawg tau raug lees paub los ntawm 1.0 feem pua agarose gel electrophoresis. PCR cov khoom loj ntawm T-tau, TNF-𝛼, thiab IL-1𝛽 yog 188 bp, 560 bp, thiab 298 bp.
Cistanches Herba thiab cistanche extract
3. Cov txiaj ntsig
3.1. Cistanches Herba tuaj yeem txhim kho kev txawj ntse
10 ntawm 11 tus neeg koom hauv CH(Cistanches Herba)pab pawg (tus nqi khaws cia yog 90.1 feem pua thiab tus nqi attrition yog 9.9 feem pua thiab ib tus neeg mob txiav tawm qhov kev kawm no vim ntuav hnyav), 8 ntawm 9 tus neeg koom hauv pawg Don (tus nqi tuav yog 88.9 feem pua thiab tus nqi attrition yog 11.1 feem pua. thiab ib tus neeg mob tau txiav tawm vim muaj kab mob peptic), thiab 6 ntawm 6 tus neeg koom nrog hauv pawg tswj hwm (tus nqi khaws cia yog 100 feem pua) ua tiav 48 lub lis piam qhib-label pilot kawm. Cov yam ntxwv kho mob ntawm AD(Alzheimer tus kab mob)Cov neeg mob tau nthuav tawm hauv Table 1. AD(Alzheimer tus kab mob)Cov neeg koom nrog kev kho mob lossis tsis muaj kev kho mob muaj lawv lub peev xwm kev txawj ntse tau soj ntsuam los ntawm MMSE thiab ADAS-cog, ntawm lub sijhawm ua raws (Daim duab 1(a) thiab 1(b)). Kev ntsuas hauv pab pawg kho mob tau pom cov qhab nia siab dua siv MMSE thiab cov qhab nia qis dua siv ADAS-cog ntawm 48 lub lis piam (𝑃 < 0.05),="" piv="" nrog="" pawg="" tswj="" hwm.="" txawm="" li="" cas="" los="" xij,="" tsis="" muaj="" qhov="" sib="" txawv="" ntawm="" cov="" pab="" pawg="" ntawm="" 24="" lub="" lis="" piam,="" thiab="" cov="" ntaub="" ntawv="" qhia="" me="" ntsis="" txawv="" ntawm="">(Cistanches Herba)thiab DON pawg (𝑃 > 0.05).
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3.2. Cistanches Herba tuaj yeem qeeb Hippocampus Atrophy
Qhov ntim ntawm ob sab hippocampus (HIP) hauv pawg tswj hwm ntsuas ntawm 48 lub lis piam yog 4.2 feem pua hauv qab qhov ntsuas ntawm cov ntaub ntawv ntsuas ntawm 0 lub lis piam. Thiab tsis muaj qhov pom kev hloov pauv ntawm hippocampus hauv pawg kho tshuaj (Daim duab 2(a)–2(f)).
3.3. Cistanches Herba tuaj yeem txo qhov kev qhia ntawm T-tau, TNF-𝛼, thiab IL-1𝛽 mRNAs thiab Proteins Levels of T-tau, TNF-𝛼, and IL-1𝛽.
T-tau, TNF-𝛼, and IL-1𝛽 mRNAs are downregulated significantly in the CH(Cistanches Herba)pab pawg kho mob thiab pab pawg kho mob DON, raws li (Daim duab 3(a)–3(c)) hauv 48 lub lis piam. Cov theem ntawm T-tau, TNF-𝛼, thiab IL-1𝛽 mRNAs pom muaj qhov tsis zoo (Figures 3(d)–3(f)). T-tau, TNF-𝛼, and IL-1𝛽 proteins also declined in the CH(Cistanches Herba)pab pawg kho mob thiab pab pawg kho mob DON piv rau kev tswj hwm (Daim duab 4(a)–4(g)). Tsis muaj qhov sib txawv ntawm qhov kev qhia ntawm mRNAs lossis qib protein ntawm CH(Cistanches Herba)pab pawg kho mob thiab DON pab pawg kho mob, qhiaCistanches Herbatuaj yeem txo T-tau, TNF-𝛼, thiab IL-1𝛽 mRNAs thiab qib protein raws li cov teebmeem tib yam li Donepezil tau ua.
3.4. Cistanches Herba tuaj yeem txwv tsis pub muaj T-tau, TNF-𝛼, thiab IL-1𝛽.
Cistanches Herbatau tshaj tawm tias koom nrog ntau hom kab mob inflammatory [35]. Peb ntsuas cov ntsiab lus ntawm TNF-𝛼 thiab IL-1𝛽 hauv CSF los ntawm ELISA. Lub caij no, peb tau soj ntsuam qhov concentrations ntawm T-tau hauv CSF los ntawm ELISA. Piv nrog rau pawg tswj hwm, T-tau, TNF-𝛼, thiab IL-1𝛽 theem hauv CSF tau qis dua (𝑃 < 0.01)="" hauv="" pab="" pawg="" kho="" mob,="" raws="" li="" pom="" hauv="" daim="" duab="" 5(a)="" -5(c),="" qhia="">Cistanches Herbatuaj yeem txo T-tau qib thiab inhibit inflammatory yam xws li TNF-𝛼 thiab IL-1𝛽 secretions hauv AD(Alzheimer tus kab mob)txheej txheem pathological. Nyob nruab nrab ntawm ob pawg kev kho mob, T-tau, TNF-𝛼, lossis IL-1𝛽 cov ntsiab lus tsis muaj qhov sib txawv (𝑃 > 0.05), qhia tias ob qho tshuaj tuaj yeem txo T-tau, TNF- 𝛼, thiab IL-1𝛽 theem thiab cov nyhuv ntawmCistanches Herbayog tib yam li Donepezil. Piv nrog rau pawg tswj hwm, T-tau, TNF-𝛼, thiab IL-1𝛽 cov ntsiab lus hauv pab pawg kho mob tau txo qis.
4. Kev sib tham
Peb cov kev tshawb fawb pom tau tiasCistanches Herbatuaj yeem txhim kho kev txawj ntse, qeeb hippocampus atrophy, thiab txo cov ntsiab lus ntawm T-tau, TNF-𝛼, thiab IL-1𝛽 hauv CSF ntawm nruab nrab AD(Alzheimer tus kab mob)cov neeg mob. Peb soj ntsuam cov txheeb ze hippocampal ntim tau ua los ntawm quotient ntawm hippocampal thiab tag nrho lub hlwb ntim thiab ua qhov tseeb ntawm kab rov tav los ntawm kev tswj hwm hauv coronal thiab sagittal views. Nws muaj peev xwm txo tau qhov yuam kev. Tsis muaj cov kws tshawb fawb yav dhau los tau tshaj tawm cov teebmeem neuroprotective ntawmCistanches Herbantawm AD(Alzheimer tus kab mob)cov neeg mob. Rau qhov zoo tshaj plaws ntawm peb txoj kev paub, qhov kev tshawb fawb no yog thawj zaug tshawb nrhiav cov txiaj ntsig kho mob ntawmCistanches Herbahauv AD(Alzheimer tus kab mob)cov neeg mob.
"Yin/Yang Theory" yog ib qho qauv ntawm cov tshuaj suav tshuaj (TCM), uas ntseeg tias tib neeg lub cev qauv yog ib qho chaw organic thiab lub ntiaj teb yog kev sib koom ua ke ntawm kev tawm tsam lub zog, uas yog, Yin thiab Yang. Raws li Yin / Yang Txoj Kev Xav, Qi yog cais raws li Yang, thaum lub ntsiab lus, cov ntshav, thiab cov kua hauv lub cev yog Yin. Tag nrho lawv tsim lub hauv paus ntawm tib neeg lub cev. Nrog rau lub tswv yim Yin/Yang, TCM piav qhia cov tsos mob thiab qhia txog kev kho mob. Yang / Qi tsav cov kev ua ub no hauv tib neeg lub cev thiab txhim kho lub zog hauv tib neeg lub cev. Kev tsis txaus hauv Yang/Qi qhia lub luag haujlwm tseem ceeb hauv Alzheimer's disease [36].Cistanches Herbayog xav tias yog ib yam khoom ntawm Yang-invigoration nyob rau hauv tib neeg lub cev. Tej zaum nws yuav yog kev xaiv kho mob rau AD(Alzheimer tus kab mob). Hauv peb txoj kev tshawb fawb, peb sim soj ntsuam qhov cuam tshuam ntawmCistanches Herbantawm AD(Alzheimer tus kab mob)los ntawm txoj kev xav ntawm Western tshuaj. Lub caij no, peb xaiv Donepezil los piv nrogCistanches Herbalos soj ntsuam nws cov teebmeem kev kho mob. Donepezil, tus paub zoo acetylcholinesterase inhibitor (AChE) pom zoo los ntawm FDA, tau ua pov thawj los tiv thaiv los ntawm A𝛽 thiab tau toxicity hauv cov qauv tsiaj thiab hlwb [37]. Lub xyoo 1- xyoo, kev sim tshuaj placebo tau tshaj tawm tias cov neeg mob kho mob ua tiav tau txo qis los ntawm kwv yees li ib nrab ntawm ntau npaum li cov placebo-kho cov neeg mob ntawm qhov ntsuas thoob ntiaj teb ntawm cov tsos mob dementia [38]. Thiab qhov kev tshawb fawb ua ntej tau pom tias kev tswj hwm ntawm donepezil rau AD(Alzheimer tus kab mob)Cov neeg mob rau 1 lub hlis ua rau txo qis ntawm IL-6 thiab IL-1 hauv cov hlwb mononuclear ntawm cov ntshav peripheral, qhia txog cov tshuaj tiv thaiv kab mob ntawm tus neeg sawv cev no. Donepezil kuj tau ua pov thawj cov tshuaj tiv thaiv kab mob hauv apolipoprotein E-knockout nas uas tau qhia txog kev txwv ntawm TNF- 𝛼 hauv aorta [39].
Peb kawm txog kev cuam tshuam ntawmCistanches Herbalos tshawb xyuas seb nws puas tuaj yeem ua lub luag haujlwm tseem ceeb hauv pathophysiology ntawm AD(Alzheimer tus kab mob)hauv CSF. Ib qho kev sib txawv tseem ceeb hauv kev txawj ntse ntawm cov pab pawg kho tshuaj thiab cov pab pawg tswj tau pom. Mohs et al. [40] kuj tau tshaj tawm tias Donepezil tau txais txiaj ntsig los txhim kho kev txawj ntse ntawm AD(Alzheimer tus kab mob). Kev tsom xam ntawm T-tau, TNF-𝛼, thiab IL-1𝛽 cov lus qhia hauv CSF peb tau ua tau pom tias txhua tus tau hloov pauv loj heev hauv 48 lub lis piam los ntawm kev kho mob. Peb qhov kev tshawb pom tau pom cov mRNA kab lus ntawm T-tau, TNF-𝛼, thiab IL-1𝛽, thiab qib ntawm cov proteins no txo qis tom qab kev kho mob los ntawmCistanches Herba, thiab muaj qhov txo qis nrog kev ncua sij hawm kho mob. Nws qhiaCistanches Herbatuaj yeem hla cov hlab ntsha hlwb (BBB) thiab koom nrog cov txheej txheem pathological ntawm AD(Alzheimer tus kab mob). Cistanches Herbatej zaum yuav muaj peev xwm rov qab tau lub hlwb kev tswj hwm lub cev.
Cov kev tshawb fawb tsis ntev los no tau qhia tias carbohydrates hauvCistanches Herbamuaj qhov cuam tshuam hauv nruab nrab paj hlwb (CNS) thiab nws tuaj yeem cuam tshuam kev ua haujlwm ntawm cytokines [24, 41]. Tej zaum nws yuav yog vim qee yam ntawm cov khoom xyaw nquag. Phenylethanoid glycosides (PhGs), sib cais thiab purified los ntawmCistanches Herba, raug suav hais tias yog cov ntsiab lus bioactive, uas ntau cov kev tshawb fawb tau pom tias muaj cov kab mob lom neeg muaj feem cuam tshuam nrog cov kab mob tua kab mob, cytotoxic, anti-inflammatory, thiab neuroprotective kev ua ub no. Hauv Mannami txoj kev tshawb fawb, PhGs tuaj yeem tiv thaiv kev sib sau ntawm A𝛽42 thiab txwv tsis pub A𝛽42-induced cytotoxic teebmeem ntawm tib neeg neuroblastoma SH-SY5Y hlwb los ntawm kev txhawb nqa kev qhia ntawm mRNA ntawm glycolytic enzymes thiab intracellular ATP [42]. PhGs tuaj yeem ua rau kom muaj kev nco txog kev kawm ntawm apolexis nrawm nrawm los ntawm kev txhim kho mRNA qhia ntawm phosphoglycerate kinase [43]. Park qhov kev sim tau pom ib qho 17 kD N-terminal tau tawg tawg tsim los ntawm calpain cleavage, muaj cov residues amino acid 45-230, uas tau npaj los kho A𝛽-induced toxicity [44]. Cov kev tshawb fawb ntawm tau immunotherapy qhia tias tau txhaj tshuaj tiv thaiv kab mob ua rau kev ua kom muaj zog ntxiv uas ua rau muaj kev cuam tshuam los ntawm tus neeg sawv cev uas ua rau proteolysis ntawm A𝛽 [45]. Cov no txhais tau tias qee qhov kev sib raug zoo ntawm A𝛽 thiab tau. Txawm li cas los xij, kev tshawb fawb me me tau dag hauv kev sib tham txog kev cuam tshuam ntawm A𝛽 thiab tau lossis PhGs thiab tau protein. Hauv peb cov kev tshawb fawb, peb kwv yees PhGs tuaj yeem cuam tshuam rau tau pathology hauv AD(Alzheimer tus kab mob)los ntawm kev cuam tshuam kev sib sau ntawm A𝛽, tab sis qhov tseeb mechanism tsis paub. Cov kev tshawb fawb txog kev muaj peev xwm tiv thaiv kab mob hauv vitro tau tshaj tawm tias PhGs tuaj yeem cuam tshuam IL-10 thiab TNF- 𝛼 ntau lawm hauv peritoneal macrophages. Lawv kuj tau raug pov thawj tias muaj kev cuam tshuam los ntawm koob tshuaj ntawm inhibitions ntawm cov noob thiab cov protein qhia ntawm chemokines qhib los ntawm interferon- (IFN-) g thiab TNF-𝛼 [46]. Txawm li cas los xij, hauv peb txoj kev tshawb fawb, peb tsis tau cais PhGs los ntawmCistanches Herbathiab tsom ntsoov rau lawv. Kev tshawb fawb ntxiv nrog ntau txoj hauv kev xws li cell biology, molecular biology, thiab cog chemistry yuav tsum tau ua kom pom cov kev ua ntawmCistanches Herbathiab nws cov khoom.
Inflamation yog ib qho kev paub zoo hauv etiopathogenesis ntawm cov kab mob neurodegenerative, xws liAlzheimer tus kab mob(AD) [47]. Cov kev tshawb fawb thaum ntxov tau ua pov thawj tias lub cev tiv thaiv kab mob hauv lub cev thiab cov kab ke ntxiv hauv lub hlwb ntawm cov neeg mob AD tau qhib. Thiab cov amyloid plaques yeej ib txwm nyob ib puag ncig los ntawm activated microglia, uas tuaj yeem ua rau nod-zoo li receptors (NLRs) hauv cytoplasm. Cov NLRs no ua rau kev ua kom muaj zog thiab muaj zog ntawm cytosolic protein complexes li inflammasomes. Cov complexes tuaj yeem ua rau cov kab mob pro-inflammatory caspases, tshwj xeeb yog caspase-1, uas tom qab ntawd ua rau cov proinflammatory cytokines xws li TNF-𝛼 thiab IL-1𝛽 qhib [48]. Cov kev tshawb fawb yav dhau los tau tshaj tawm tiasCistanches Herbatxhim kho lub cev tiv thaiv kab mob [49, 50]. Peb cov kev tshawb fawb tau pom tias cov theem ntawm TNF-𝛼 thiab IL-1𝛽 hauv CFS ntawm pab pawg kho tshuaj tau qis dua li hauv pawg tswj hwm ntawm 24 lub lis piam thiab 48 lub lis piam. Peb hypothesized tiasCistanches Herbatej zaum yuav txuas nrog txoj kev neuroinflamation hauv AD(Alzheimer tus kab mob)hlwb.
5. Cov lus xaus
Peb txoj kev tshawb fawb tau pomCistanches Herbatuaj yeem txhim kho kev txawj ntse hauv AD(Alzheimer tus kab mob)thiab qeeb tus neeg mob lub hippocampus atrophy, suppress cov kab lus ntawm T-tau, TNF-𝛼, thiab IL-1𝛽 hauv CSF ntawm AD(Alzheimer tus kab mob)Cov neeg mob zoo ib yam li Donepezil, tab sisCistanches Herbayog pheej yig dua thiab yooj yim dua kom tau, yog li nws yuav yog ib hom kev siv tau los hloov tau rau Donepezil, tshwj xeeb tshaj yog nyob rau hauv Suav teb lossis lwm lub tebchaws tsim.
Cov teebmeem ntawm Cistanches Herba: ANTI-Mob Alzheimer
Cov ntawv luv
CH: Cistanches Herba
DON: Donepezil
PhGs: Phenylethanoid glycosides
TCM: Tshuaj suav tshuaj
Cov ntaub ntawv
[1] M. Tub Vaj Ntxwv, R. Bryce, E. Albanese, A. Wimo, W. Ribeiro, thiab CP Ferri, "Lub ntiaj teb nthuav dav ntawm dementia: kev tshuaj xyuas thiab metaanalysis," Alzheimer's & Dementia, vol. 9, nre. 1, nr 63–75, 2013.
[2] N. Mattsson, H. Zetterberg, O. Hansson, et al., "CSF biomarkers thiab incipient Alzheimer kab mob hauv cov neeg mob uas muaj kev paub tsis meej," Phau ntawv Journal of the American Medical Association, vol. 302, Nr. 4, pp. 385–393, 2009.
[3] G. Bartzokis, JL Cummings, D. Sultzer, VW Henderson, KH Nuechterlein, thiab J. Mintz, "White matter structural integrity in healthy aging laus and patient with Alzheimer disease: a magnetic resonance imaging study," Archives of Neurology , vol. 60, nr. 3, pp. 393–398, 2003.
[4] CR Jack Jr., M. Slomkowski, S. Gracon, et al., "MRI raws li ib tug biomarker ntawm kab mob kev loj hlob nyob rau hauv ib tug kho mob sim ntawm milameline rau AD(Alzheimer tus kab mob)", Neurology, vol. 60, no. 2, pp. 253–260, 2003.
[5] F. Sardi, L. Fassina, L. Venturini, et al., "Alzheimer's disease, autoimmunity, thiab o. Qhov zoo, qhov phem thiab qhov phem," Autoimmunity Reviews, vol. 11, nr. 2, pp. 149–153, 2011.
[6] A. Aguzzi, BA Barres, thiab ML Bennett, "Microglia: scapegoat, saboteur, los yog lwm yam?" Science, vol. 339, Nr. 6116, pp. 156–161, 2013.
[7] MR Emmerling, MD Watson, CA Raby, thiab K. Spiegel, "Lub luag haujlwm ntawm kev ntxiv hauv Alzheimer's kab mob pathology," Biochimica thiab Biophysica Acta—Molecular Basis of Disease, vol. 1502, Nr. 1, pp. 158–171, 2000.
[8] A. Trivedi, AD Olivas, thiab LJ Noble-Haeusslein, "Inflammation and spinal cord raug mob: infiltrating leukocytes as determinants of raug mob thiab kho cov txheej txheem," Clinical Neuroscience Research, vol. 6, nre. 5, pp. 283–292, 2006.
[9] GM Lewitus, H. Cohen, thiab M. Schwartz, "Kev txo qis kev ntxhov siab tom qab los ntawm kev txhaj tshuaj tiv thaiv kab mob," Brain, Behavior, and Immunity, vol. 22, nr. 7, pp. 1108–1114, 2008.
[10] R. Shechter, A. London, C. Varol, et al., "Infiltrating blood-derived macrophages yog cov hlwb tseem ceeb ua lub luag haujlwm tiv thaiv kev mob rov qab los ntawm kev raug mob txha caj qaum hauv nas," PLoS Tshuaj, vol. 6, nre. 7, Tshooj ID e1000113, 2009.
[11] K. Baruch thiab M. Schwartz, "CNS-specific T hlwb zoo li lub hlwb ua haujlwm ntawm choroid plexus," Lub hlwb, tus cwj pwm, thiab kev tiv thaiv, vol. 34, p.m. 11–16, 2013.
[12] W. Pan, C. Yu, H. H. 294, Nr. 6, p. C1436–C1442, 2008.
