Kev Kho Mob Tshiab Rau Alzheimer's Disease: fluoxetine Thiab Wheatgrass
Mar 24, 2022
Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com
Ntu Ⅰ: Cov teebmeem tshwm sim ntawm Fluoxetine thiab Triticum aestivum tawm tsam Aluminium-Induced Alzheimer's Disease hauv nas: Qhov Ua Tau Rau Hepatotoxicity thiab Nephrotoxicity
Karema Abu-Elfotuh, Ghada M.Ragab, Ahmad Salahuddin, Lubna Jamil thiab Ekram Nemr Abd Al Haleem
Abstract:Keeb kwm:Alzheimer tus kab mob(AD) yog ib hom mob neurological uas ua rau muaj kev puas hlwb loj heev. Hepatic thiab lub raum tsis ua haujlwm yuav ua rau AD (Alzheimer tus kab mob) los ntawm kev cuam tshuam -amyloid homeostasis ntawm lub periphery thiab ua rau metabolic tsis ua hauj lwm.WheatgrassTriticum aestivum (Triticum aestivum) tau pom tias muaj cov tshuaj tua kab mob antioxidant thiab tiv thaiv kab mob. Qhov kev ua haujlwm no tsom mus kawm txog cov txiaj ntsig ntawm txhuas ntawm cov hlwb neuronal, nws qhov tshwm sim ntawm daim siab thiab ob lub raum, thiab lub luag haujlwm ua tau ntawmfluoxetinethiabhom qoob mogkua txiv nyob rau hauv attenuating no pathological mob. Txoj Kev: Cov nas tau muab faib ua tsib pawg. Control, AD(Alzheimer tus kab mob)(AlCl3), Fluoxetine (Fluoxetine thiab AlCl3),Wheatgrass(Wheatgrass thiab AlCl3), thiab pawg ua ke (fluoxetine, hom qoob mog, thiab AlCl3). Txhua pab pawg tau muab kev kho mob sib txawv txhua hnub rau tsib lub lis piam. Cov ntsiab lus: AlCl nce siab rau lub siab thiab lub raum enzymes, tshaj tawm ntawm oxidative kev nyuaj siab, thiab cov cim inflammatory. Tsis tas li ntawd, tsub zuj zuj ntawm tau protein thiab A , qhov siab ntawm ACHE thiab GSK -3, down-regulation ntawm BDNF thiab -catenin qhia hauv lub hlwb. Kev tshuaj xyuas histopathological ntawm daim siab, lub raum, thiab lub hlwb tau lees paub qhov tshuaj lom no thaum kho AD(Alzheimer tus kab mob)pab pawg nrogfluoxetine, hom qoob mog, los yog ua ke uas alleviates toxic insults. Cov ntsiab lus: Fluoxetine thiabhom qoob mogKev sib xyaw ua ke tau pom tias muaj txiaj ntsig zoo rau kev tiv thaiv kab mob hauv kev kho AD(Alzheimer tus kab mob)dua li fluoxetine ib leeg thiab muaj kev tiv thaiv ntawm daim siab thiab raum cov ntaub so ntswg.
Ntsiab lus:Alzheimer tus kab mob; Triticum; - catenin; GSK-3 ; - amyloid; tau protein; BDNF; hepatotoxicity; nephrotoxicity
Anti-Alzheimer tus kab mob: cistanche tubulosa extract
NYEM QHOV NO RAU PART Ⅰ
3. Kev sib tham
Vim nws tus nqi qis, aluminium cookware tseem siv nyob rau hauv ntau lub chav ua noj Egyptian, tshwj xeeb tshaj yog nyob rau hauv cov cheeb tsam nyob deb nroog, nrog rau ntau lub teb chaws tsim. Peb txoj kev tshawb fawb tau tsom mus rau qhov cuam tshuam ntawm txhuas ntawm kev puas siab puas ntsws thiab nws qhov tshwm sim ntawm daim siab thiab lub raum thiab lub luag haujlwm ntawmhom qoob mogkua txiv ib leeg los yog ua ke nrogfluoxetinehauv attenuating cov teebmeem no.
Hauv peb qhov kev sim, AlCl3 pawg tau txhaj tshuaj txhua hnub nrog AlCl3 (70 mg / kg ip) rau tsib lub lis piam ua tiav; cov txiaj ntsig ntawm cov pab pawg no tau nthuav tawm qhov kev cuam tshuam ntawm AD (Alzheimer tus kab mob), which was proved by behavioral testing (MWT).
Hais txog kev soj ntsuam histological, raug AlCl3 ua rau muaj kev hloov pauv ntawm histopathological loj heev thiab pom nyob rau hauv hippocampus, nrog rau cov neuronal degeneration nyob rau ntau thaj tsam ntawm hippocampus thiab cytoplasmic vacuolization, hemorrhage, thiab gliosis yog zoo tib yam rau kev kawm yav dhau los 30. Raws li nws muaj monogic, glutramine thiab glutoma. cholinergic axon terminals, lub hippocampus yog qhov ntxov tshaj plaws thiab feem ntau cuam tshuam cheeb tsam hauv lub hlwb hauv AD (Alzheimer tus kab mob) [31].
AlCl3 cuam tshuam rau hauv cov txheej txheem metabolic thiab redox nyob rau hauv lub hauv nruab nrab paj hlwb, thiab nws muaj nyob rau hauv cov ntshav yog txuas mus rau ib qho kev pheej hmoo ntawm AD (Alzheimer tus kab mobib.) [32]. Cov txiaj ntsig ntawm txoj haujlwm no tau pom qhov hloov pauv tseem ceeb hauv ntau lub hlwb biochemical tsis nyob hauv pawg AlCl3 thaum piv rau pawg tswj hwm. Muaj qhov nce siab hauv qib GSK-3 , TAU, A , thiab ACHE thiab qhov poob qis hauv -catenin, BDNF, thiab neurotransmitter (DA, 5HT, thiab NE). Oxidative kev ntxhov siab thiab qhov mob tau pom, pom los ntawm kev txo qis hauv SOD thiab TAC nrog kev nce ntxiv hauv MDA, IL-1 , thiab TNF- . Cov kev tshawb pom no tsis sib haum nrog cov kev tshawb fawb yav dhau los [33-36].
GSK-3 thiab -catenin yog cov cim ntawm Wnt/ -catenin signaling pathway. Wnt/-catenin signaling yog downregulated nyob rau hauv lub laus lub hlwb, ua rau kom tsis muaj zog neurogenesis thiab kev txawj ntse poob [37]. Wnt/-catenin signaling yog ib qho tseem ceeb ntawm kev taw qhia uas tswj tau ntau yam kev ua ub no, suav nrog kev muaj sia nyob ntawm tes. GSK-3 yog xav tias sawv cev rau qhov tseem ceeb ntawm kev sib txuas ntawm cov plaques senile thiab neurofibrillary tangles, ob lub cim histological ntawm AD(Alzheimer tus kab mob). Ob qhov cuam tshuam ua raws li qhov nce hauv GSK-3 , thawj ntawm lawv yog TAU hyperphosphorylation uas ua rau neurofibrillary tangles thiab neuronal tuag; Qhov thib ob nyhuv yog -catenin degradation uas nyob rau hauv lem induces A tsim [38,39].
Tsis tas li ntawd, GSK-3 tau xav tias ua haujlwm hauv choline metabolism, suav nrog kev tswj hwm ntawm ACHE [40]. Kev ua ACHE hauv lub hlwb ua lub luag haujlwm tseem ceeb hauv kev tswj lub hlwb ua haujlwm. Kev cuam tshuam ntev rau AlCl tuaj yeem ua rau lipid peroxidation tshwm sim los ntawm kev tsim dawb radical thiab ROS, ua rau ACHE kev ua haujlwm thiab txo qis acetylcholine, cuam tshuam rau kev paub thiab kev nco [41].
Nws yog tsim los hais tias proinflammatory cytokines, tshwj xeeb tshaj yog IL-1ß, tuaj yeem txo qis BDNF kev qhia hauv cov cheeb tsam ntawm lub hlwb, suav nrog hippocampus [42]. BDNF muaj cov haujlwm tseem ceeb hauv lub cev hauv ob qho tib si peripheral thiab hauv nruab nrab paj hlwb [43]. BDNF tuaj yeem txhawb txoj kev ciaj sia, kev loj hlob, kev sib txawv, thiab kev loj hlob ntawm neurons thiab ua lub luag haujlwm tseem ceeb hauv cov qauv neural thiab kev ua haujlwm zoo. Muaj cov pov thawj txuas ntxiv tias kev hloov pauv hauv cerebral BDNF ntau ntau thiab BDNF-TrkB teeb liab txoj hauv kev tuaj yeem ua lub luag haujlwm hauv etiology ntawm AD (Alzheimer tus kab mob) [44].
Raws li neuroinflammation paub tias cuam tshuam rau ntau yam BDNF-txog kev taw qhia txoj hauv kev, txoj kev xav tam sim no pom tau tias cov qib BDNF qis no tuaj yeem cuam tshuam rau cov mob ntev ntawm lub hlwb hauv AD (Alzheimer tus kab mob). Glia cell activation tuaj yeem ua rau muaj kev tiv thaiv cytokines thiab cov pa oxygen reactive, ua rau muaj kev hloov kho neuronal thiab neurotoxicity, raws li pom nyob rau hauv ntau yam kab mob hlwb [45].
TNF kuj muaj kev puas tsuaj rau kev sib kis ntawm synaptic thiab plasticity, xws li kev ua kom ntev mus ntev thiab kev ua kom pom tseeb, qhov tseem ceeb hauv kev kawm thiab kev nco [46]. Thaum lub hnub nyoog laus, kev raug mob, thiab ntau yam kab mob hauv lub xeev, TNF tuaj yeem ua rau puas tsuaj thiab txawm tias muaj tshuaj lom. TN, zoo li feem ntau cov cytokines, kuj tsawg hauv cov neeg laus lub hlwb noj qab haus huv tab sis siab heev hauv cov hlwb neurodegenerative, thiab neuroinflammation tuaj yeem kuaj tau ntau xyoo ua ntej neuronal cell tuag [47].
Tsis tas li ntawd, aluminium neurotoxicity cuam tshuam cerebrospinal kua tetrahydrobiopterin qib, uas ua rau poob hauv hlwb neurotransmitters qib [36]. Qhov kev poob no yog txuas nrog txo qis BDNF qib, uas muaj cov teebmeem trophic ntawm serotonergic thiab catecholaminergic neurons [48-50].
cistanche txiaj ntsig: txhim kho kev nco ua haujlwm
Ntawm qhov tod tes, qhov tshwm sim ntawm kev noj AlCl3 nyob rau hauv pab pawg neeg sim tau qhia pom tias muaj kev puas tsuaj thiab toxicity nyob rau hauv daim siab thiab lub raum cov ntaub so ntswg. Kev kuaj mob histological tau nthuav tawm ntau qhov kev puas tsuaj morphological txawv txav hauv lub raum thiab cov kab mob siab ntawm pawg AlCl3 hauv kev tshawb nrhiav tam sim no.
Peb cov txiaj ntsig tau pom qhov nce ntxiv hauv cov ntshav ALT, AST, ALP, creatinine, thiab urea qib nrog rau oxidative kev nyuaj siab, inflammatory txheej txheem, thiab apoptosis nyob rau hauv ob lub raum thiab lub raum cov ntaub so ntswg cim los ntawm ib tug tseem ceeb nce nyob rau hauv cov theem ntawm IL{{0} }, TNF- , NF-kB, NO, MDA, thiab caspase 3 kev ua haujlwm nrog qhov txo qis hauv qib SOD, thiab TAC. Tsis tas li ntawd, peb pom qhov nce ntxiv hauv cov ntshav TC thiab TAG qib thiab txo qis hauv qib HDL. Cov kev tshawb pom no tau pom zoo nrog cov kev tshawb fawb yav dhau los [51-55].
Hepatotoxicity thiab nephrotoxicity tuaj yeem tshwm sim los ntawm AlCl; buildup nyob rau hauv cov ntaub so ntswg. Kev ntsuas siab siab thiab lub raum ua haujlwm yog cov cim tseem ceeb ntawm AlCl hepatotoxicity thiab nephrotoxicity [54,56]. Kev raug AlCl3 ua rau daim siab necrosis, cov cellular membrane puas, thiab tom qab tso tawm ntawm intracellular enzymes thiab bilirubin rau hauv cov hlab ntsha [51]. Cov txheej txheem ua tau ntawm lub raum-hlwb crosstalk nyob rau hauv cov nqe lus ntawm inflammatory molecules yog premised nyob rau hauv qhov tseeb hais tias cytokines, xws li IL-1 , IL-6, TNF-c, uas nquag implicated nyob rau hauv lub tsim ntawm CKD, tuaj yeem cuam tshuam cov kabmob nyob deb li lub hlwb [55].
Lwm qhov tseem ceeb ntawm qhov kev xav ntawm inflammatory yog oxidative kev nyuaj siab thiab nws puas thiab pathogenic muaj peev xwm los ntawm distortion ntawm proteins, lipids, nucleic acids, lub cev tsis ua hauj lwm, thiab apoptosis [57]. Aberrant lipid metabolism tau cuam tshuam nrog kev pheej hmoo ntawm kev tsim AD (Alzheimer tus kab mob), raws li daim siab yog lub hauv paus tseem ceeb ntawm lub cev lub luag haujlwm rau lipid metabolism [58].
Hepatotoxicity thiab nephrotoxicity tuaj yeem ua rau AD (Alzheimer tus kab mob) cov xwm txheej los ntawm kev tsis muaj peev xwm tswj tau A homeostasis ntawm qhov chaw ib puag ncig, vim lawv ua lub luag haujlwm tseem ceeb hauv kev tshem tawm A los ntawm kev ncig [15,17].
Peb txoj kev tshawb fawb tau sivfluoxetine, hom qoob mog, thiab lawv cov kev sib xyaw ua ke hauv pab pawg kho mob txhawm rau tshawb nrhiav lawv lub luag haujlwm hauv kev txo qis AD (Alzheimer tus kab mob) Cov tsos mob thiab txo qis nws qhov tshwm sim ntawm daim siab thiab raum cov ntaub so ntswg.
Cov txiaj ntsig ntawm peb txoj haujlwm tau pom qhov txo qis hauv txhua qhov ntsuas lub hlwb biomarkers qhia los ntawm kev txhim kho oxidative kev nyuaj siab thiab inflammatory txheej txheem, kev kuaj tus cwj pwm, kuaj histopathological, thiab lub hlwb Wnt/-catenin pathway markers. Qhov kev txhim kho zoo tshaj plaws tau pom hauv pawg ua ke, ua raws li covfluoxetinepab pawg, thiab tom qab ntawdhom qoob mogpab pawg. Kev txhim kho hauv kev paub thiab kev nco yog nrog los ntawm kev txhim kho daim siab thiab lub raum ua haujlwm oxidative kev nyuaj siab thiab inflammatory txheej xwm.
Fluoxetineyog ib qho kev xaiv serotonin reuptake inhibitor antidepressant uas tuaj yeem txhim kho kev nco thiab kev paub txog kev ua haujlwm thiab txo kev ntxhov siab thiab kev ntxhov siab ntawm AD (Alzheimer tus kab mob) cov neeg mob.Fluoxetinetau pom tias muaj peev xwm inhibit -amyloid ntau lawm thiab tiv thaiv neuronal degeneration raws li nws tuaj yeem rov qab Wnt / -catenin signaling los ntawm kev txhim kho GSK-3 phosphorylation thiab nce qib -catenin [20-22].
Wheatgrasstuaj yeem kho cov qib antioxidant xws li SOD, catalase, thiab txo glutathione [59].Wheatgrasstuaj yeem tiv thaiv thiab kho dawb radical puas rau lub siab hlwb. Chlorophyll zoo li yog qhov tseem ceeb tshaj plaws hauv cov txheej txheem. Chlorophyll yog nqus sai sai rau hauv cov hlab ntsha thiab pab ua kom lub siab huv, cov ntshav qab zib thiab cov ntshav khiav tau zoo, txhim kho lub cev tiv thaiv kab mob, thiab tshem tawm cov tshuaj lom [60].Wheatgrasskua txiv txhim kho lub raum ua haujlwm cim (urea, creatinine, thiab uric acid). Nws muaj vitamin C thiab phenolic compounds, uas ua rau lub siab thiab lub raum detoxification thiab ntshav purification ntawm cov pa phem [61].
TNF- , IL-1, thiab IL-6 yog cov proinflammatory cytokines uas ua rau lub siab puas tsuaj los ntawm kev hloov kho lub xeev oxidative thiab thaum kawg kev puas tsuaj ntawm lub cev [62]. Endotoxin poob siab yog kho los ntawm TNF-, uas tseem txhawb nqa caspase-dependent apoptotic signaling [63]. Kev tsim ntau dhau ntawm ROS pib tsim kev phom sij oxidative, thiab NF-kB activates ntau yam noob caj noob ces cuam tshuam nrog lub xeev oxidative, xws li glutathione peroxidase thiab SOD [64].WheatgrassCheebtsam tau pom tias muaj cov tshuaj tiv thaiv antioxidant thiab tiv thaiv kab mob los ntawm inhibiting NF-kB activation hauv kev tshawb fawb yav dhau los [65]. Wheatgrass ua rau txo qis tiam neeg thiab tso tawm cov inflammatory mediators, raws li peb qhov kev tshawb pom.
Peb qhov kev tshawb pom tau qhia tiashom qoob mogmuaj peev xwm rov qab tau Wnt/-catenin signaling, inhibit GSK3, uas nyob rau hauv lem nce qib ntawm -catenin. Qhov tshwm sim ntawm txoj kev no yog inhibiting qhov tsim ntawm A plaque thiab kev tiv thaiv los ntawm NFTs.
cistanche tubulosa txiaj ntsig
4. Cov ntaub ntawv thiab cov txheej txheem
4.1. Tsiaj
Tsib caug tus txiv neej laus Wistar nas hnyav kwv yees li 280-320 g tau siv rau hauv txoj kev tshawb fawb tam sim no. Cov nas tau txais los ntawm Nile Co. for Pharmaceuticals and Chemical Industries, Cairo, Egypt. Lawv tau nyob hauv lub tawb stainless hlau, peb mus rau plaub rau ib lub tawb, ntawm qhov kub ntawm 25 ± 1 degree nrog 12 h lub teeb thiab tsaus nti. Cov nas tau khaws cia nyob rau hauv tib txoj kev tsim nyog thiab muab nrog lawv cov kev cai noj haus txhua hnub ntawm cov qauv noj pellets (El-Nasr, Abu Zaabal, Cairo, Egypt) uas tsis muaj tsawg dua 20 feem pua ntawm cov protein, 5 feem pua fiber, 3.5 feem pua rog, 6.5 feem pua ash , thiab vitamin sib tov; dej tau muab ad-libitum.
4.2. Nqe lus hais txog kev ncaj ncees
Cov txheej txheem ntawm txoj kev tshawb no tau pom zoo los ntawm "Al-Azhar University-Institutional Animal Care and Use Committee" (297/2020). Txhua qhov kev siv zog tau ua kom txo qis kev ntxhov siab ntawm nas thaum lub sijhawm sim tag nrho.
4.3.DruQs thiab Tshuaj
Wheatgrasshmoov tau yuav los ntawm Bioglan Superfoods (Surrey, England, UK),fluoxetineHCl(CAS#:56296-78-7), thiab txhuas chloride hydrated(AlCl3. 6H2O, CAS#:7784-13-6) tau muas los ntawm Sigma Chemical Co. (St.Louis, MO, USA).Tag nrho lwm yam chemicals thiab cov ntaub ntawv tau raug muag thiab zoo.
Covhom qoob mogKev daws tau npaj los ntawm kev sib tov 1 gm ntawmhom qoob moghmoov hauv 10 mL dej distilled, khaws cia rau 6h, thiab co zoo ua ntej kev tswj qhov ncauj [66]. AlCl tov yog npaj los ntawm dissolving 20 mg AlCl3 nyob rau hauv 1 mL distilled dej thiab raug kho rau pH 7.4 nrog 0.1 M phosphate buffer saline [67].FluoxetineHCl tau yaj nyob rau hauv ib qho distilled sib npaug rau 10 mg / mL [68].
4.4. Kev sim tsim
Cov nas tau muab faib ua tsib pawg (n=10) thiab muab rau kev kho mob sib txawv rau tsib lub lis piam. Pab pawg 1 tau txais kev tswj hwm thiab tau muab cov dej distilled txhua hnub. Pawg 2 tau txhaj tshuaj txhua hnub nrog AlCl3 (70 mg / kg ip)[69].AD(Alzheimer tus kab mob) nas nyob rau hauv pab pawg 3 tau txaisfluoxetine(10 mg/kg, po) [70]. AD(Alzheimer tus kab mob) nas nyob rau hauv pab pawg 4 tau kho nrogWheatgrass(100 mg/kg, po)[71]. AD(Alzheimer tus kab mob) nas nyob rau hauv pab pawg 5 tau txhaj nrog kev sib xyaw ntawm fluoxetine (10 mg / kg, po) thiabhom qoob mog(100 mg/kg, po).
suab puam ginseng: cistanche tubulosa
5. Cov lus xaus
Fluoxetinethiab Triticum muaj cov nyhuv ameliorative ntawm aluminium-induced AD (Alzheimer tus kab mob) hauv nas. Lawv muaj qhov cuam tshuam rau neuroprotective raws li lawv tuaj yeem kho qhov tsis txaus ntseeg, nce acetylcholinesterase enzyme kev ua haujlwm thiab qib monoamine, tiv thaiv neuronal degeneration, thiab txo oxidative kev nyuaj siab thiab mob. Tsis tas li ntawd, lawv txo qhov tsis txaus ntseeg uas tshwm sim hauv daim siab lossis lub raum lub sijhawm no, uas tuaj yeem ua rau lawv qhov tsis zoo rau AD (Alzheimer tus kab mob). Tsis tas li ntawd, kev sib xyaw ua ke ntawmfluoxetinethiab Triticum tau pom cov txiaj ntsig tseem ceeb hauv kev kho AD ntau duafluoxetineib leeg. Txhawm rau kom paub tseeb tias cov txiaj ntsig tau txais txiaj ntsig no, cov kev tshawb fawb soj ntsuam ntxiv hauv cov neeg laus yuav tsum tau txiav txim siab qhov koob tshuaj tiag tiagfluoxetinethiabhom qoob mog.
cistanche ntxiv: txhim kho kev nco
Cov ntaub ntawv
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