Kev Noj Qab Haus Huv Polyphenols Raws li Kev Pabcuam Kho Mob Rau Alzheimer's Disease: Ib Qhov Kev Pom Zoo
Jun 30, 2022
Thov hu rauoscar.xiao@wecistanche.comyog xav paub ntxiv
Abstract:Kev noj zaub mov polyphenols suav nrog ntau yam ntawm cov metabolites theem nrab pom nyob rau hauv cov xwm txheej, xws li txiv hmab txiv ntoo, zaub, tshuaj ntsuab tshuaj yej, cawv, cocoa khoom, thiab lwm yam. Raws li txoj cai, lawv yog cov derivatives lossis isomers ntawm phenol acid, thiab isoflavonoids thiab muaj cov yam ntxwv txhawb kev noj qab haus huv. , xws li tshuaj tiv thaiv oxidative, tiv thaiv kev laus, tiv thaiv qog noj ntshav, thiab ntau ntxiv. Kev siv cov polyphenols zoo li no hauv kev sib ntaus sib tua ntawm kev ua tsov rog neuropathological raging nyob rau tiam no yog tam sim no yog ib lub ntsiab lus kub sib cav. Tsis ntev los no, Alzheimer's disease (AD) tau tshwm sim los ua cov kab mob neuropathological ntau tshaj plaws, ua rau kev ua neej nyob ntawm tsheej lab ntawm ib txoj kev lossis lwm qhov. Ib qho kev cuam tshuam kho mob los txo nws txoj kev nce qib hauv tiam tom ntej yog qhov tsis muaj txiaj ntsig rau hnub no. Kev siv cov khoom noj polyphenols los tsim lub barricade nyob ib ncig ntawm nws yuav yog ib lub tswv yim zoo, coj mus rau hauv tus account lawv cov peev xwm zais cia los tawm tsam ntau yam xwm txheej tshwm sim nyob rau hauv xws li pathology. Dhau li ntawm lawv cov khoom muaj zog antioxidant, ib txwm tshwm sim polyphenols tau tshaj tawm tias muaj cov teebmeem neuroprotective los ntawm kev hloov pauv A biogenesis txoj hauv kev ntawm Alzheimer's disease. Yog li, hauv qhov kev tshuaj xyuas no, kuv tsom mus rau kev qhib qhov zais zais zais ntawm kev noj haus polyphenols thiab lawv cov cuab yeej zoo rau kev sib ntaus sib tua nrog kev sib ntaus sib tua thiab cov kab mob ntsig txog.
Ntsiab lus:amyloid; zoo li curcumin; quercetin; homeostasis; hlau chelation
Thov nias ntawm no kom paub ntxiv
1. Taw qhia
Alzheimer's kab mob poob rau hauv qeb ntawm cov kab mob neurodegenerative ntev thiab suav tias yog qhov ua rau dementia ntau tshaj plaws thoob ntiaj teb. Cov ntaub ntawv pov thawj qhia tias kwv yees li 40 lab tus tib neeg raug kev txom nyem los ntawm hnub nyoog ntsig txog kev puas siab puas ntsws thoob ntiaj teb, thiab tus lej no yuav tsum tau muab ob npaug los ntawm kwv yees li 2050 [1]. Alzheimer's tus kab mob muaj cov ntaub ntawv pov thawj zoo neuropathology, uas yog tus cwj pwm los ntawm kev tsim ntawm extracellular amyloid plaques thiab intracellular Tau neurofibrillary tangles (NFTs) nyob rau hauv nruab nrab ntawm lub cev nqaij daim tawv thiab cov qauv neocortical hauv lub hlwb [2]. Lub amyloid, tseem hu ua senile plaques (SPs), feem ntau yog tsim los ntawm cov proteinaceous Cheebtsam hu ua A peptides, uas yog tsim los ntawm cov cleavage ntawm loj amyloid precursor protein (APP) [3]. APP tau ua ntu zus los ntawm ob lub enzymes, y-secretase thiab -secretase (BACE1), feem ntau pro-ducing A 38, A 40, thiab A 42 raws li qhov sib txawv tshaj plaws. Raws li "amyloid hypothesis", tsub zuj zuj ntawm A nyob rau hauv lub hlwb ua rau ib tug cascade uas tshwm sim nyob rau hauv tsim ntawm neurofibrillary tangles ntawm tau protein hyperphosphorylation thiab kuj pib multifactorial biochemical teb xws li hauv zos o, cytokine tso, oxidative kev nyuaj siab, thiab excitotoxicity [{ {14}}].oteflavonoidYog li ntawd, cov kev hloov pauv hloov pauv nyob rau hauv ib puag ncig cov hlwb neuronal uas yog tus cwj pwm los ntawm kev poob qis, qhov tsis sib xws ntawm cov neurotransmitters (xws li, acetylcholine, dopamine), thiab kev tuag neuron thaum kawg ua rau kev paub tsis meej hauv cov neeg mob AD [3,7-9]. Alzheimer's disease muaj qhov nruab nrab ntev ntawm 10 xyoo. Raws li tus kab mob loj hlob zuj zus, cov neeg mob qhia txog kev nyuaj hauv kev sib txuas lus, kev ua haujlwm, kev paub txog kev coj ua, kev muaj peev xwm kawm, thiab kev txawj ntse [9,10]. Ntau yam tsis xws li caj ces, epigenetic, ib puag ncig yam tseem ceeb, kev ua neej nyob, thiab comorbidities kuj ua rau muaj kev loj hlob ntawm cov kab mob neurodegenerative nyuaj. Hauv kaum xyoo dhau los, kev siv zog loj heev tau ua rau hauv kev tshawb fawb soj ntsuam kom nkag siab txog cov kab mob ntawm Alzheimer's kab mob nrog rau kev txhim kho tshiab Alzheimer's kab mob kho. Txawm li cas los xij, ob peb cov tshuaj uas muaj feem cuam tshuam xws li levodopa thiab tetrabenazine muaj los txo cov tsos mob ntawm Alzheimer's dis-ease thiab ncua kev loj hlob ntawm tus kab mob loj no [11-14]. Alzheimer tus kab mob yog kho nrog acetylcholinesterase inhibitors (AChEI) thiab N-methyl-d-aspartate receptor (NMDAR) antagonist memantine. Cov kev mob tshwm sim tuaj yeem tshwm sim txawm tias muaj cov tshuaj muaj txiaj ntsig zoo xws li AChEls thiab memantine. Qhov no tuaj yeem ua rau txo qis hauv kev ua neej zoo, tsis raug tshuaj xyuas cascades, lossis txawm tias tuag, yog li nws yog ib qho tseem ceeb kom paub txog cov kev mob tshwm sim [15]. Vim muaj kev kho mob tsawg thiab cov kev mob tshwm sim hnyav, muaj qhov yuav tsum tau ua tam sim rau lwm txoj hauv kev, tiv thaiv, thiab kev noj haus uas tuaj yeem txwv qhov tshwm sim thiab kev loj hlob ntawm Alzheimer's disease. Ua raws li qhov no los txiav txim siab, ntau qhov kev tshawb fawb tau ua tiav los piav qhia qhov muaj txiaj ntsig zoo ntawm kev noj zaub mov hauv kev tiv thaiv kev kis kab mob [16-18]. Lub cev loj hlob ntawm cov pov thawj qhia tias kev noj cov vitamins ntau xws li vitamin C, E, flavonoids, PUFA (unsaturated fatty acid), folate, polyphenols, thiab lwm yam kev txwv kev noj haus tau cuam tshuam nrog kev txo qis ntawm Alzheimer's disease [{{12]. }}]. Nyob rau hauv xyoo tas los no, Mediterranean noj zaub mov tau txais kev saib xyuas zoo tsis yog tsuas yog txo qis kev pheej hmoo ntawm cov kab mob neurodegenerative, tab sis kuj vim tias nws qhov kev noj haus tau cuam tshuam nrog kev txo qis ntawm cov kab mob plawv thiab ntau yam mob qog noj ntshav [22]. Ntxiv mus, Washington Heights-Inwood Columbia Aging Project tseem muab cov lus qhia rau lub koom haum zoo ntawm Mediterranean noj zaub mov uas muaj kev pheej hmoo tsawg ntawm Alzheimer's kab mob thiab lwm yam kev paub tsis zoo [23]. Kev noj zaub mov Mediterranean yog cov zaub mov muaj txiaj ntsig zoo nrog cov ntsiab lus ntawm phytochemicals hu ua polyphenols. Polyphenols yog ib yam khoom tshwm sim nyob rau hauv cov nroj tsuag, txiv hmab txiv ntoo, thiab zaub thiab paub tias muaj cov teebmeem neuroprotective. Muaj ntau qhov chaw noj zaub mov tseem ceeb ntawm polyphenols, suav nrog txiv hmab txiv ntoo (apple, berries, cocoa), zaub, tshuaj ntsuab, nplej, liab cawu cub, txiv ntseej, tshuaj yej, dos, thiab noob [22]. Nws tau raug tshaj tawm tias kev noj haus polyphenols tiv thaiv cov kab mob pathological ntawm Alzheimer's tus kab mob vim lawv muaj peev xwm hla cov ntshav-hlwb barrier [24,25]. Cov teebmeem neuroprotective nthuav tawm los ntawm kev noj zaub mov polyphenols tuaj yeem yog vim lawv cov tshuaj tiv thaiv kab mob antioxidant thiab tiv thaiv kab mob, tab sis cov pov thawj tseem ceeb kuj qhia tias lawv lub luag haujlwm tau txais txiaj ntsig yog los ntawm cov kev kho tshiab thiab cov hom phiaj los ntawm kev hloov kho intracellular signaling pathways, gene qhia, thiab enzyme kev ua hauv neurodegenerative. kab mob [26-29]. Qhov kev tshuaj xyuas no qhia txog kev kho lub luag haujlwm ntawm kev noj zaub mov polyphenols hauv kev ua kom muaj kev loj hlob ntawm Alzheimer's disease los ntawm kev tsom mus rau tus kab mob neuro-pathophysiology, raws li cov ntaub ntawv tshawb fawb tsis ntev los no.
Cistanche tuaj yeem tiv thaiv kev laus
2. Molecular Mechanisms thiab Pathology ntawm Alzheimer's Disease
Alzheimer's kab mob yog txhais pathologically los ntawm maj mam synaptic thiab neuronal degeneration thiab cov tsos mob ntawm kev kuaj mob amyloid plaques uas muaj fibril -amyloid peptide aggregates thiab neurofibrillary tangles muaj xws li hyperphosphorylated tau protein filaments. Thaum cov plaques thiab tangles yog thawj zaug xav tias yog thawj tus neeg nruab nrab ntawm neurotoxicity hauv Alzheimer's kab mob, kev tshawb fawb tshiab tau tsim qhov tseem ceeb ntawm soluble-amyloid oligomers thiab tau molecules [30], (Figures 1 thiab 2).
3. Cov tswv yim kho mob raws li cov tsos mob ntawm Alzheimer's Disease
Txawm hais tias Alzheimer's tus kab mob tau lees paub tias yog ib qho teeb meem kev noj qab haus huv rau pej xeem, tsuas yog ob hom tshuaj tau pom zoo los kho nws: cholinesterase enzyme inhibitors thiab N-methyl d-aspartate (NMDA) antagonists [2]. Thaum lub sij hawm kev loj hlob ntawm Alzheimer's kab mob, kev txo qis hauv biosynthesis ntawm acetylcholine raug pom. Acetylcholinesterase inhibitors (AChEls) tshwj xeeb thaiv kev ua haujlwm ntawm cholinesterase enzymes, uas ua rau muaj kev nce qib ACh hauv cov synaptic cleft. Raws li qhov tshwm sim, thaiv kev ua haujlwm ntawm acetylcholinesterase (AChE) yog ib txoj hauv kev zoo tshaj plaws los tawm tsam Alzheimer's cov tsos mob.
Thawj qhov kev pom zoo cholinesterase inhibitor tshuaj yog Tacrine (tetrahydroaminoacri-dine) rau kev kho mob Alzheimer's cov tsos mob, uas ua rau ACh nce hauv cov neurons, tab sis thaum muaj ntau qhov kev sim, nws tau pom tias muaj cov teebmeem hepatotoxic [2,33]. Niaj hnub no, ntau AChEls muaj nyob rau hauv kev ua lag luam, xws li donepezil, rivastigmine, thiab galantamine, thiab tau siv nrov los kho cov tsos mob ntawm Alzheimer's disease [11-14].
Lwm lub tswv yim uas yuav pab tau hauv kev kho mob Alzheimer's yog siv cov antagonist ntawm NMDA. NMDA receptor plays lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm Alzheimer's kab mob. Thaum stimulation ntawm NMDA receptor, Ca2 ntxiv rau influx activates ib qho kev taw qhia txoj kev uas ua rau lub activation ntawm noob koom tes nyob rau hauv tsim ntawm lub sij hawm ntev potentiation (LTP). Overstimulation ntawm NMDARs ua rau muaj qhov txawv txav ntawm Ca2t influx uas ua rau excitotoxicity puas, synaptic tsis ua haujlwm, apoptotic cell tuag, thiab kev txawj ntse poob [34,35]. Ntau yam ntawm NMDAR antagonists, xws li Memantine thiab RL-208, tau raug tsim los kho mob nruab nrab mus rau qhov mob hnyav ntawm Alzheimer's disease [36-38]. Cov tshuaj no yog siv los txo cov neeg mob ntawm Alzheimer's cov tsos mob, tab sis muaj zog heev, xaiv, thiab cov kev siv tau zoo yog tam sim ntawd los kho Alzheimer's kab mob thiab lwm yam kev mob dementia.
4. Cov tswv yim kho mob raws li Targeting txawv Alzheimer's Marker
4.1.Metal Chelation Approach
Cov hlau chelation mus kom ze yog qhov chaw tawm tshiab uas tuaj yeem ua tau zoo hauv kev tswj hwm tus kab mob Alzheimer. Kev txhawb nqa rau qhov no tuaj yeem txiav txim siab los ntawm cov kev tshawb fawb uas lawv tau pom tias thaum muaj kev koom tes nrog cov hlau ions xws li Cu2 ntxiv , Zn2 ntxiv , thiab Fe2 ntxiv , Aggregation propensity nce nrog kev nce ntxiv hauv oxidative kev nyuaj siab teb [39,40] . Twb tau, hlau chelation tau raug txheeb xyuas tias yog ib qho ntawm cov txheej txheem cuam tshuam nrog kev tiv thaiv cov lus teb ntawm ob peb polyphenols [28]. Txawm hais tias cov hlau chelation cuam tshuam rau kev nce qib ntawm Alzheimer's pathology yog nyob rau hauv nws cov theem pib, theem ntawm cov hlau ions muaj qhov sib txawv ntawm cov hnub nyoog sib txawv.
4.2.Amyloid Fiber Disruption Strategy
Qhov tshwj xeeb tshaj plaws uas txhais tau tias Alzheimer's tus kab mob yog tsim ntawm A fiber ntau thiab hyperphosphorylation ntawm au protein [4, A41]. Kev tsom ncaj qha rau cov txheej txheem txuas nrog lawv cov biogenesis yog ib qho kev xav zoo los saib rau hauv. Kev cuam tshuam hauv qhov kev pabcuam tshuaj lom no tuaj yeem ua tiav los ntawm cov chaw molecular uas nthuav tawm cov khoom ntawm adduct tsim nrog A uas txo lawv cov kev sib sau ua ke. Tsis tas li ntawd, kev hloov pauv cov protein uas muaj kuab lom rau hauv daim ntawv tsis sib haum thaum tsim cov khoom siv ntxiv tau pom tias muaj feem cuam tshuam nrog kev txo qis hauv lawv cov tshuaj toxicity teb raws li Alzheimer's tej yam kev mob [42,43].
4.3.Antioxidant Txoj Kev
Nws tau pom tias oxidative kev nyuaj siab yog ib qho tseem ceeb rau kev loj hlob ntawm Alzheimer's'pathology [44]. Txoj hauv kev uas txo cov oxidative lub nra tau zoo hauv kev kho mob ntawm Alzheimer's disease [45,46]. Nyob rau hauv cov kev taw qhia, muaj peev xwm antioxidants tuaj yeem tshawb nrhiav, uas tuaj yeem muaj txiaj ntsig hauv kev tswj hwm tus kab mob Alzheimer.
4.4. Targeting Protein Homeostasis
Kev tsim ntawm A aggregate tshwm sim los ntawm qhov tsis txaus ntawm cov protein homeostasis hauv cov hlwb. Ib qho unfolded protein teb (UPR) yog ib lo lus teb uas tau txais activated nyob rau hauv cov lus teb rau tej yam tsis zoo proteins. Cov tswv yim uas siv qhov kev ua kom sai sai ntawm UPR tau zoo hauv kev kho mob ntawm Alzheimer's kab mob pathology [47]. Tsis tas li ntawd, cov proteins uas tsis muaj teeb meem lossis tsis zoo yog raug rau ubiquitin proteasomal system (UPS) cov txheej txheem kho kom zoo. Cov lus teb tsis zoo UPS cuam tshuam nrog kev ua rau Alzheimer's pathological teb [48,49]. Yog li, kev tswj hwm homeostasis ntawm UPS tuaj yeem yog txoj hauv kev zoo los tawm tsam Alzheimer's kab mob pathological teb.
4.5. Anti-Inflammatory Approach for Alzheimer's Disease
Kev laus-activated inflammatory cascades tau xav tias ua lub luag haujlwm tseem ceeb hauv kev hloov kho cov txheej txheem ntawm kev laus cuam tshuam nrog cov kab mob neurodegenerative [50]. Lub luag haujlwm ntawm inflammatory cascades hauv amplifying Alzheimer's pathology tau tsim nyob rau yav dhau los [51]. Yog li ntawd, tsom rau cov xwm txheej no yog ib txoj hauv kev zoo siv rau kev kho kom zoo dua hauv Alzheimer's disease.
4.6. Dietary Approaches for Alzheimer's Disease
Ntau qhov kev tshawb fawb tau qhia txog kev kho lub luag haujlwm ntawm kev noj haus thiab kev noj haus hauv kev loj hlob thiab kev tswj hwm tus kab mob Alzheimer. Kev noj zaub mov Mediterranean tau txais txiaj ntsig ntawm cov pej xeem vim nws koom nrog kev mob qis thiab kev tuag txuas rau cov kab mob neurodegenerative [16,52].puritans vitamin cKev noj zaub mov Mediterranean paub tias muaj ntau hauv polyphenols vim nws yog tus cwj pwm los ntawm kev noj cov txiv hmab txiv ntoo thiab zaub uas yog nplua nuj ntawm polyphenols. Scarmeas et al., 2007 [53], tau kawm seb puas muaj kev noj ntau ntawm polyphenols hauv daim ntawv ntawm cov txiv hmab txiv ntoo thiab zaub yog txuas nrog txo kev pheej hmoo ntawm Alzheimer's disease. Txawm li cas los xij, muaj ntau qhov kev tshawb fawb qhia tias kev siv cov polyphenols txo qhov tshwm sim ntawm qhov mob, ib qho mob sib txuas nrog ntau yam kab mob thiab kev noj qab haus huv [26,54].
5. Lub hauv paus ntawm Dietary Polyphenols
Kev noj haus polyphenols yog cov chav kawm loj ntawm cov tshuaj tua kab mob antioxidants noj txhua hnub thoob plaws ntiaj teb, thiab lawv siv rau tib neeg kev noj qab haus huv tau txais kev saib xyuas zoo heev. Polyphenols ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv ntau yam kab mob, tshwj xeeb tshaj yog kab mob plawv, mob qog noj ntshav, ntshav qab zib mellitus, thiab cov kab mob neurodegenerative, raws li lub cev loj hlob ntawm cov pov thawj [22,55]. Polyphenols raug suav tias yog cov tshuaj antioxidants uas muaj zog tiv thaiv oxidative kev nyuaj siab los ntawm kev sib sau ntau ntawm cov dawb radicals. Nyob rau hauv xyoo tas los no, qee cov pov thawj kuj tau qhia tias, dhau ntawm lawv cov kev ua haujlwm antioxidant nrov, lawv tuaj yeem ua tiav los ntawm kev hloov pauv ntawm tes taw qhia txoj hauv kev [56,57]. Raws li txoj cai, polyphenols yog ib pawg ntawm cov khoom ntuj tsim uas muaj phenolic rings. Lawv raug tsim los ntawm kev muaj lub nplhaib uas muaj ntxhiab hauv lawv cov qauv, muaj ntau theem ntawm hydroxyl moiety txuas rau lawv. Raws li txoj cai, kwv yees li 8000 tus qauv sib txawv ntawm cov polyphenolic tebchaw tam sim no nyob rau hauv ntau yam khoom noj tau raug txheeb xyuas txog niaj hnub no. Txiv hmab txiv ntoo thiab dej haus sawv cev rau qhov tseem ceeb ntawm kev noj haus polyphenols, ua raws li zaub, cereals, thiab legumes qhuav. Nws tau raug tshaj tawm tias cov pab pawg polyphenol sib txawv yuav muaj kev ruaj ntseg sib txawv, bioavailability, thiab physiological functions [58]. Cov tshuaj polyphenolic no tau muab cais ntxiv raws li diferuloylmethane, stilbenes, flavonoids, phenolic acids, thiab tannins (Daim duab 3).sibNws tau raug tshaj tawm tias cov pab pawg polyphenol sib txawv yuav muaj kev ruaj ntseg sib txawv, bioavailability, thiab kev ua haujlwm ntawm lub cev. Phenolic acid tsim ib feem peb ntawm peb cov khoom noj khoom haus thiab ob feem peb yog pab los ntawm flavonoids. Ib chav kawm loj ntawm phenolic acids muaj hydroxycinnamic acids xws li caffeic acid, uas yog tam sim no nyob rau hauv ib daim ntawv esterified nrog chlorogenic acid. Lawv tau pom tias muaj cov khoom tiv thaiv kab mob los ntawm lawv lub luag haujlwm hauv kev cuam tshuam nrog cov txheej txheem nitrosylation hauv cov kab mob lom. Ntawm qhov tod tes, flavonoids tau muab faib ua anthocyanin (xim xim hauv cov xim & feem ntau muaj xim txiv hmab txiv ntoo thiab zaub) thiab canthaxanthin (tsis muaj xim ntxiv rau hauv flavones, flavanols, flavans, isoflavones). Stilbenes (xws li, trans-resveratrol) muaj cov yam ntxwv 1 , 2- pawg diphenylethylene thiab muaj nyob rau hauv lawv cov ntaub ntawv monomeric thiab oligomeric nyob rau hauv qhov xwm txheej. Tannin yog cov dej-soluble daim ntawv ntawm kev noj haus polyphenol muaj qhov hnyav molecular nyob rau hauv thaj tsam ntawm 500 txog 3000.cistanche yog dab tsiDiferuloylmethane muaj cov nplhaib uas muaj ntxhiab hloov nrog hydroxyl. Lawv txuas ntxiv los ntawm pawg carbonyl uas muaj aliphatic chains. Cov polyphenols no tau yooj yim muaj nyob rau hauv txiv hmab txiv ntoo (apples, grapes, berries), zaub tshuaj ntsuab, nplej, dos, liab cawu cub, thiab lwm yam.
6. Polyphenols Lub luag haujlwm hauv Oxidative Stress thiab Alzheimer's Disease
Alzheimer's disease yog feem ntau ua rau muaj kev tsis taus ntawm cov neeg laus dua 65 xyoo. Lub luag haujlwm ntawm oxidative kev nyuaj siab hauv kev pib lossis txhim kho cov kab mob pathological no zoo li yog qhov tseem ceeb. Feem ntau, oxidative kev nyuaj siab yog lub xeev ntawm kev tsis sib haum xeeb ntawm oxidative thiab antioxidative systems nyob rau hauv txaus siab ntawm oxidative machinery. Lub hauv paus loj ntawm oxidative kev nyuaj siab yog kev hloov pauv ntawm cov pa mus rau ib qho superoxide radical, uas ntxiv, thaum ntxiv ib qho hluav taws xob ntxiv, tau hloov mus rau hydrogen peroxide. Hydrogen peroxide nrog ntxiv oxidation tsim hydroxyl radicals nrog siab oxidative muaj peev xwm. Lawv tau pom oxidize cov proteins, lipids, thiab nucleic acids mus rau qhov zoo, yog li ua rau muaj kev hloov pauv hauv lawv cov kev ua haujlwm lom neeg. Hauv ib lub xov tooj ntawm tes, 98 feem pua ntawm cov pa oxygen yog siv los ntawm cov khoom siv hluav taws xob thauj khoom thiab qhov seem 2 feem pua tau hloov mus rau superoxide uas tau saib xyuas los ntawm cellular antioxidative tiv thaiv kab mob. Txhawm rau tiv thaiv mitochondria los ntawm oxidative puas tsuaj, peb lub cev tau tsim ntau yam txheej txheem. Mn-SOD, uas muaj nyob rau hauv mitochondrial matrix, pab txo cov superoxide uas ua rau lub sijhawm ua pa [59,60]. Lub xub ntiag ntawm Cu-Zn-SOD nyob rau hauv cytosolic qhov chaw ntawm cov hlwb ntxiv mitigates cov teebmeem ntawm superoxide thiab hydrogen peroxide radicals [61]. Nyob rau hauv lub mitochondrial membrane nws tus kheej, Cytochrome C kuj yuav pab tau regenerate molecular oxygen los ntawm superoxide radicals [62]. Tsis tas li ntawd, glutathione peroxidase thiab catalase yog ob kab ntxiv ntawm kev tiv thaiv tsim los ntawm cov cellular system los tawm tsam oxidative kev nyuaj siab [63]. Nrog kev laus, qib ntawm oxidative kev nyuaj siab nce, uas ntxiv hloov cov molecular architecture ntawm cellular ib puag ncig. Qhov kev nce hauv oxidative kev ntxhov siab no yog qhov ua rau muaj kev loj hlob ntawm Alzheimer's tus kab mob, uas yog tshwm sim los ntawm cov lus teb muaj kuab heev uas pom hauv A - tooj liab piv rau A [64]. Tooj liab yog tus neeg nruab nrab ntawm hydroxyl radical-mediated oxidative kev nyuaj siab. Yog li, oxidative kev nyuaj siab plays lub luag haujlwm tseem ceeb hauv kev txhim kho pathology ntawm Alzheimer's kab mob. Tsis tas li ntawd, kev nce qib ntawm zinc nyob rau hauv cov cheeb tsam kev txawj ntse, xws li neocortex, amygdala, thiab hippocampus, ntxiv cov pov thawj ntxiv rau cov hlau-catalyzed oxidative cov tshuaj tiv thaiv thiab lawv lub luag haujlwm hauv Alzheimer's pathologies [65,66]. Yog li ntawd, txhua tus neeg sawv cev lossis lub koom haum molecular uas tuaj yeem nqa qhov sib npaug ntawm cov txheej txheem tiv thaiv oxidative no yuav yog qhov tseem ceeb rau kev tiv thaiv Alzheimer's disease. Kev noj zaub mov polyphenols zoo kawg nkaus haum cov qauv saum toj no. Nws tau raug pom tias polyphenols siv cov tshuaj tiv thaiv oxidative ncaj qha los ntawm kev tshem tawm ntawm cov dawb radicals los yog los ntawm kev ua kom muaj peev xwm ntawm kev tiv thaiv endogenous. Ntawm cov polyphenols, dihydrocaffeic acid tau pom tias muaj peev xwm tshem tawm dawb radicals [66]. Glutathione peroxidase thiab superoxide dismutase tau pom tias raug ntxias tom qab siv curcumin thiab quercetin [67-70]. Hydroxytyrosol kuj tau pom tias muaj kev cuam tshuam rau kev ua haujlwm ntawm catalase thiab superoxide dismutase (SOD) [71,72]. Xws li cov tshuaj tiv thaiv oxidative yog ntxiv los ntawm kev hloov kho ntawm KEAP-ARE axis, uas yog ib qho tseem ceeb tiv thaiv oxidative thiab xenobiotic kev nyuaj siab. Epigallocatechin thiab quercetin tau pom los cuam tshuam rau qhov ARE axis kom txo cov oxidative lub nra [73,74](Daim duab 4). Tsis tas li ntawd, curcumin modulation ntawm ARE axis los ntawm NRF2 kev hloov kho tau pom los ua kom Glutathione S-Transferase P1 functionality [75].
7. Xaiv Polyphenols siv los kho Alzheimer's Disease
7.1.Mechanistic Kev Koom Tes ntawm Curcumin hauv Alzheimer's Disease
Ntawm cov khoom noj polyphenols, curcumin txoj kev siv nyob rau sab qab teb Esxias teb chaws tau raug sau tseg rau ntau pua xyoo. Nws cov tshuaj tiv thaiv kab mob, tshuaj tua kab mob, thiab tshuaj tua kab mob tau ua rau nws siv dav hauv Ayurvedic kev coj ua thiab. Nyob rau hauv natural extracts cais los ntawm turmeric rhizome, ntau hom curcumin, collectively hu ua curcuminoids xws li curcumin (curcumin-I), desmethoxycurcumin (curcumin-Ⅱ), bisdemethoxycurcumin (curcumin-II) [76], tau pom. Lawv qhov kev txiav txim siab yog lub luag haujlwm rau kev tiv thaiv cov txiaj ntsig pom nyob rau hauv rooj plaub ntawm ntau yam pathologies.Anti aging cistancheNyob rau hauv cov ntaub ntawv ntawm Alzheimer's kab mob, ib tug pej xeem-raws li txoj kev tshawb no ua los sib piv qhov tshwm sim ntawm Alzheimer's kab mob tau txheeb xyuas 4.4-fold ntau dua tshwm sim ntawm Alzheimer's kab mob nyob rau hauv Teb Chaws Asmeskas cov pej xeem nyob rau hauv lub 70-79 pawg hnub nyoog thaum piv rau tus nqi ntawm cov xwm txheej hauv Is Nrias teb. Yog vim li cas rau qhov no tau suav hais tias yog kev noj zaub mov zoo ntawm turmeric uas muaj curcumin raws li cov ntsiab lus tseem ceeb [77,78]. Ntau qhov kev tshawb fawb tshawb fawb tau pom tias curcumin cuam tshuam nrog A biogenesis thiab tseem pab txhawm rau tshem tawm nws cov deposits, yog li tiv thaiv kev tsim ntawm A aggregates [21,27,79]. Vim yog lub luag haujlwm ntawm oxidation hauv kev txhim kho Alzheimer's kab mob, curcumin cuam tshuam cov tshuaj tiv thaiv oxidative tuaj yeem ua lub luag haujlwm tseem ceeb hauv cov txiaj ntsig tau pom tom qab siv curcumin hauv Alzheimer's disease. Xws li cov teebmeem ntawm curcumin ntawm qib molecular yog kev sib koom tes los ntawm NF-k, uas yog qhov tseem ceeb ntawm kev hloov pauv uas yog lub luag haujlwm rau kev ua haujlwm ntawm cov kab mob inflammatory [29]. Hauv lub xeev ib txwm, NF-k units raug thaiv los ntawm kev ua kom los ntawm IKB kinase. Txawm li cas los xij, nyob rau hauv inflammatory stimuli, IkB kinase-mediated tswj yog relieved uas directs NF-k rau nuclear ntshuam tshwm sim nyob rau hauv induction ntawm inflammatory mediators 'kev qhia. Ntawm qhov tsis sib xws, kev tswj hwm ntawm Curcumin tau pom tias inhibit NF-k activation uas yog ib qho tseem ceeb contributor rau Curcumin-associated anti-inflammatory teebmeem. Cov teebmeem no tshwm sim los ntawm Curcumin-directed inhibitory kev ua ntawm IKB kinase [80]. Li no, lwm yam kev noj haus polyphenols uas muaj peev xwm hloov kho qhov NF-k-qhia inflammatory teb tuaj yeem raug txiav tawm ntxiv los qhib lawv cov peev xwm kho mob hauv Alzheimer's disease. Lwm yam tshaj li qhov ua kom NRF no -2, nws kuj yog ib qho ntawm cov lus teb ntawm tes pom tom qab Curcumin daim ntawv thov, uas txuas ntxiv ua rau cov tshuaj tiv thaiv kab mob antioxidant (ARE) los txhawb kev qhia ntawm ARE-muaj cov noob xws li catalase, glutathione. peroxidase, thiab superoxide dismutase (SOD) [81]. Tag nrho cov no yog cov ntsiab lus teb cuam tshuam pab lub hlwb kom txo qis oxidative lub nra ntawm lub xov tooj ntawm tes thiab yog li nres qhov kev ua tiav ntawm cov kev pab cuam neurodegenerative.
Ntawm qhov tod tes, ntau qhov kev noj haus polyphenols xws li curcumin thiab quercetin kuj muaj peev xwm los hloov txoj kev A biogenesis. Amyloid Precursor Protein (APP) tau ua tiav los ntawm Amyloidogenic thiab Non-Amyloidogenic txoj hauv kev. Tsis yog --amyloidogenic txoj hauv kev tsim Sapporo thiab p3 fragments, whereas cov amyloidogenic txoj kev tsim sAPP thiab A peptides ua rau amyloid plaques. Ntau yam lwm tus neeg kho kom haum xeeb tau ua tiav ua ntu zus los ntawm a-Secretase, -Secretase, thiab y-Secretase los ua p3, C83, C99, thiab APP Intracellular domain (AICD), uas tau tso tawm rau hauv qhov chaw intracellular lossis extracellular. Nws tau raug tshaj tawm tias curcumin nthuav tawm lub peev xwm los khi rau amyloid peptide (A) thiab inhibit lossis hloov pauv cov amyloid precursor protein (APP) metabolism (Daim duab 5) [82].
Zuag qhia tag nrho, cov txiaj ntsig tau pom tom qab Curcumin hauv Alzheimer's kab mob pathology zoo li tau koom tes los ntawm nws cov teebmeem ntawm kev tswj oxidative, tiv thaiv kev mob thiab A biogenesis txoj hauv kev hauv Alzheimer's kab mob pathology.
7.2. Quercetin: Flavonoid rau Alzheimer's Disease
Quercetin, polyphenol categorized nyob rau hauv flavonoids, muaj nyob rau hauv cov nroj tsuag siab dua, txiv hmab txiv ntoo, thiab zaub uas tau noj txhua hnub, xws li dos, txiv apples, berries, asparagus, thiab lwm yam., [68,83]. Lawv inflammatory thiab anti-oxidative zog yog lub luag hauj lwm rau feem ntau ntawm cov teebmeem pom nyob rau hauv ntau yam mob [17]. Lawv lub peev xwm los tiv thaiv oxidative yog vim muaj ob lub pharmacophores, piv txwv li, hydroxyl ntawm C-3 txoj haujlwm thiab catechol uas pab kom tsis txhob muaj cov pa oxygen reactive (ROS). Ib qho kev cuam tshuam ncaj qha rau AMPK cov dej num kuj tseem pab cuam tshuam rau NADPH oxidase-qhia oxidative lub nra. Lwm cov teebmeem antioxidant yog pab los ntawm kev ua haujlwm ntawm NRF2-ARE axis [18,68]. Nyob rau hauv tej yam kev mob xws li Alzheimer's kab mob, xws li ib tug antioxidative muaj nuj nqi ua ke nrog nws cov nyhuv ntawm A ntau lawm yog txuam nrog neuroprotective teebmeem pom nyob rau hauv tej yam kev mob. Kev cuam tshuam hauv A biogenesis yog ua tiav los ntawm kev cuam tshuam amyloid precursor protein (APP) ua los ntawm inhibition ntawm -Secretase (BACE) kev ua haujlwm [84]. Thib ob, los ntawm inhibition ntawm NFk, quercetin kuj hloov kho APP ua (Daim duab 5) [85]. Lwm cov teebmeem pom tom qab kev tswj hwm quercetin yog kev sib tw inhibition ntawm acetylcholinesterase (AChE) thiab butyrylcholinesterase (BuChE) uas yuav pab kom nce qib ntawm acetylcholine uas yog lub luag haujlwm rau kev txhim kho kev txawj ntse hauv qab me me lossis nruab nrab Alzheimer tus mob [86]. Ua tsaug rau cov haujlwm neuroprotective pom nyob rau hauv kev kho mob quercetin, tsuas yog qhov teeb meem uas tsim teeb meem hauv nws daim ntawv thov kev kho mob yog qhov teeb meem ntawm bioavailability tsawg uas tshwm sim vim kev hloov kho (methylation, sulfation) ntawm quercetin hauv plab uas txo nws cov concentration [24. 87, 88] ib. Txawm hais tias cov koob tshuaj ntau ntawm quercetin tuaj yeem siv los ua kom muaj txiaj ntsig zoo, nyob rau hauv kev sim hauv vitro, cov koob tshuaj ntau tau pom tias muaj tshuaj lom, thaum cov tshuaj tiv thaiv oxidative thiab cov tshuaj tiv thaiv tau pom nyob rau hauv cov koob tshuaj tsawg [89]. Lwm qhov kev txhawj xeeb txog kev siv quercetin los ua tus neeg saib xyuas neuroprotective yog nws cov hlab ntsha tsis zoo (BBB) kev nkag mus rau cov khoom [90]. Kev tswj hwm ncaj qha ntawm quercetin los ntawm txoj hlab ntshav thiab intraperitoneal txoj kev tau siv los ua kom muaj txiaj ntsig zoo neuro-tiv thaiv concentration [19]. Yog li, yuav tsum tau ua haujlwm ntawm bioavailability kev txhawj xeeb txog kev siv quercetin hauv chaw kho mob.
7.3.Tannic Acid: Ib tug Buster
Tannic acid yog cov nroj tsuag-derived polyphenol (strawberries, kua, barley, kas fes, tshuaj yej, cranberries) belongs rau hydrolyzable tannin chav kawm ntawv uas tau pom muaj ntau yam kev pab cuam txog kev noj qab haus huv [91]. Qib ntawm polymerization hauv tannin txiav txim siab lawv cov bioavailability thiab kho cov txiaj ntsig zoo, Cov qauv tsim, tannic acid muaj feem xyuam rau EGCG thiab xav tias yuav muaj cov qauv kev ua haujlwm. Hauv Alzheimer's kab mob, lawv tau pom tias muaj kev cuam tshuam rau kev ua haujlwm ntawm Amyloid Precursor Protein (APP) los ntawm inhibiting qhov cleavage ntawm -site los ntawm lawv cov inhibitory kev ua ntawm -Secretase kev ua (Daim duab 5). Cov xwm txheej no thaum kawg ua rau txo qis hauv kev sib txuas ntawm A thiab pom tias muaj kev koom tes nrog kev paub txog kev ua haujlwm hauv Alzheimer's disease [92]. Lwm cov khoom siv sab hauv, xws li tshuaj tiv thaiv kab mob, tiv thaiv oxidative, tshuaj tiv thaiv kab mob, thiab tshuaj tua kab mob [93], yuav tsum muaj cov teebmeem ntxiv los ntawm kev txhim kho nws cov teebmeem neuroprotective. Txawm li cas los xij, qhov tsis tshua muaj ntshav-hlwb nkag mus ntawm tannic acid xav tau kev txhim kho ntawm txoj hauv kev kom nws cov bioavailability. Lub encapsulation ntawm tannic acid nyob rau hauv liposomes yog ib tug zoo xws li txoj kev uas tau pom tias yuav ua tau zoo nyob rau hauv ua kom lub BBB nkag mus efficiency ntawm tannic acid [94]. Lwm cov thev naus laus zis uas tuaj yeem ua rau kom muaj tannic acid bioavailability nrog rau kev txo qis hauv toxicity tuaj yeem pab ua kom muaj txiaj ntsig ntawm kev noj zaub mov polyphenol hauv cov kab mob neurodegenerative.
7.4.Mechanistic Kev Koom Tes ntawm Epigallocatechin-3-Gallate (EGCG) hauv Alzheimer's Disease
EGCG yog polyphenolic compound muaj nyob rau hauv cov tshuaj yej ntsuab. Nws lub peev xwm zoo tshaj plaws los ua tus A fibril cuam tshuam ua rau nws muaj txiaj ntsig zoo rau kev siv hauv Alzheimer's kab mob kho 【95,96】. Mechanistically, EGCG tau txais kev sib cuam tshuam ionic nrog Aß fiber ntau raws li kev sib txuas ntawm hydrogen nrog rau kev sib cuam tshuam uas tsis yog-polar los tsim ib qho adduct [95,97]. Xws li ib qho adduct tsim txo cov kev sib sau ua ke ntawm cov fibers thiab yog li txo cov txheej txheem neurodegenerative uas pom hauv Alzheimer's kab mob pathology. Adduct tsim nrog lwm cov proteins amyloidogenic kuj tau pom [98]. Qhov no qhia tau hais tias qhov cuam tshuam ncaj qha ntawm EGCG ntawm A kinetics zoo li yog qhov tseem ceeb rau nws txoj kev kho mob tawm tsam Alzheimer's kab mob pathology. Ntxiv mus, EGCG-qhia kev hloov pauv ntawm kev ua haujlwm zais cia txo qis kev tsim ntawm amyloid precursor protein, uas tom qab suppresses A aggregation [99]. Tsis tas li ntawd, EGCG-txuas nrog cov tshuaj tiv thaiv kab mob tuaj yeem tshwm sim los ntawm nws lub luag haujlwm hauv kev tawm tsam microglia ua kom muaj peev xwm hloov kho cov kab mob Alzheimer [99,100].
7.5. Trans-Resveratrol (RV), Protein Homeostasis Regulator hauv Alzheimer's Disease
Protein homeostasis yog qhov yuav tsum tau ua ua ntej rau qhov kev xav tau ntawm cov cell hauv lub cev. Ntau yam txheej txheem yog ua si los tswj qhov chaw ua haujlwm kom zoo rau cov protein. Ib qho ntawm lawv yog cov lus teb tsis muaj protein ntau (UPR) uas tau qhib thaum twg muaj qhov tsis xws luag thaum lub sijhawm cov txheej txheem protein folding hauv ER thiab mitochondria. Cov proteins uas tsis zoo yog raug rau degradation, thiab cov ntaub ntawv tshwm sim tau rov ua dua tshiab rau qhov kev tshwm sim tom ntej ntawm cov protein synthesis. Txawm li cas los xij, UPR sai sai ua rau muaj qhov tshwm sim tsis tau pom dua. Nyob rau hauv cov ntaub ntawv ntawm Alzheimer's kab mob, ib qho exaggerated UPR yog txuam nrog kev loj hlob ntawm pathology. Kev noj zaub mov polyphenols xws li Trans-resveratrol (RV) tau pom los ua kom lub UPR no cuam tshuam rau Alzheimer's kab mob pathogenesis [101]. UPR ua tus neeg nruab nrab tseem ceeb ntawm RV tuaj yeem suav tau los ntawm qhov yuav tsum tau ua ntawm UBL-5 thiab XBP-1(lub ntsiab UPR cov ntsiab lus cuam tshuam nrog cov proteins hauv mitochondria thiab ER, raws li) rau RV-kev taw qhia downstream teebmeem [ 102] ib. Cov lus teb tseem ceeb pom tom qab kev kho RV nyob rau hauv rooj plaub ntawm Alzheimer's disease yog 2.5-fold txo qis hauv A plaque deposition[103] uas tau cuam tshuam nrog kev cuam tshuam ntawm RV ntawm kev nce tus nqi ntawm A secretion nrog rau kev txhawb nqa. lub ubiquitin-proteasome system (UPS), uas pab kom tshem tawm qhov teeb meem A thiab yog li cuam tshuam nrog kev txhim kho qhov tshwm sim ntawm Alzheimer's disease [104]. Ntau yam xwm txheej molecular xws li kev ua kom SIRT1 los ntawm AMPK ua rau muaj feem cuam tshuam rau kev sib haum xeeb ntawm RV [105] .SIRT1, siv nws qhov kev ua haujlwm ntawm de-acetylation, kho cov de-acetylation ntawm p-tau protein uas pab nws tshem tawm los ntawm UPS [ 106] ib. Yog li, kev txheeb xyuas ntawm cov khoom noj muaj feem xyuam nrog polyphenols uas tuaj yeem cuam tshuam cov protein homeostasis cov xwm txheej yuav tsum tau tshawb nrhiav hauv cov ntsiab lus ntawm kev kho lub tswv yim txhim kho los tswj cov kab mob Alzheimer. Raws li Capiralla li al., [107| resveratrol kuj nthuav tawm cov haujlwm tiv thaiv kab mob tiv thaiv A -evoked microglial ua kom dhau los ntawm TLR4 / NF-k B / STAT signaling cascade.
8. Kev kho mob thiab Preclinical Aspects ntawm Dietary Polyphenols
Hauv 2 lub xyoo dhau los, kev siv zog loj heev tau ua los nthuav tawm cov txiaj ntsig ntawm kev noj zaub mov polyphenols hauv ntau yam kab mob. Los ntawm kev tshawb nrhiav PUBMED nrog cov lus tshawb fawb "polyphenols", 10,718 cov kev tshawb fawb ntawm kev noj haus polyphenols tau luam tawm thaum xyoo 2001 thiab 2010, uas tau loj hlob mus rau 31,452 ntawm 2011 thiab 2020. Qhov no yog kwv yees li 3-fold nce hauv kev txaus siab ntawm cov kws tshawb fawb hauv uncovering lub luag hauj lwm ntawm kev noj haus polyphenols nyob rau hauv ntau yam kab mob modalities. Txog tam sim no, tsuas yog 2 xyoo dhau los, 5725 kev tshawb fawb tau luam tawm. Yog li ntawd, kev tshawb fawb txog kev noj zaub mov polyphenol yog ib txoj hauv kev nthuav dav uas tuaj yeem tshawb xyuas kom zoo dua rau kev kho mob. Ntawm qhov chaw kho mob, raws li txoj hauv kev tau tshaj tawm yav dhau los [108, thaum siv https://clinicaltrials.gov/( nkag mus rau 4 Lub Ib Hlis 2022) tshawb nrhiav portal los txheeb xyuas cov kev tshawb fawb soj ntsuam ntsig txog polyphenols siv cov lus tshawb fawb: Kab mob: "Alzheimer's dis-ease "Cov ntsiab lus ntxiv: "polyphenols LOSSIS flavonoids LOSSIS flavanols LOSSIS anthocyanidins LOSSIS anthocyanins LOSSIS isoflavones LOSSIS flavones LOS OR flavonols LOSSIS flavanones LOSSIS flavanonols LOSSIS nonflavonoids LOSSIS phenolic acids los yog lignans's muaj kwv yees li kev tshawb fawb. Ib qho kev tshawb fawb tau ua tiav plaub txoj kev tshawb fawb thiab peb qhov ntxiv tseem nyob rau theem kev nrhiav neeg ua haujlwm. Flavonoids tau kawm ntau tshaj plaws rau kev sim tshuaj kho tau zoo. Ib txoj kev tshawb fawb tau siv cov kua isoflavone rau kev sim nws cov kev kho mob. Txhim kho kev txawj ntse hauv cov neeg laus [109]. Saib ntawm qhov kev pom zoo li no, cov kua isoflavone tau soj ntsuam ntxiv rau nws cov teebmeem ntawm impr oving Alzheimer's disease cov neeg mob kev paub txog kev ua yeeb yam hauv cov neeg laus (txiv neej thiab poj niam). Txawm hais tias txoj kev tshawb no ntawm cov neeg mob Alzheimer's tsis pom muaj txiaj ntsig tseem ceeb ntawm Soy Isoflavone rau kev txhim kho Alzheimer's dis-ease cov neeg mob kev paub txog kev ua tau zoo, lawv tau pom muaj kev sib koom ua ke ntawm kev hais lus zoo dua qub thiab kev ua kom nrawm nrawm nrog kev sib npaug (ib qho metabolite ntawm cov kua isoflavone. )[109] Ntau yam yuav cuam tshuam nrog cov lus teb sib txawv pom raws li qhov xav tau pib. Txoj kev tshawb no tau ua tiav rau cov neeg mob Alzheimer's laus heev (nruab nrab hnub nyoog ntawm 76.3). Txij li thaum Alzheimer's kab mob cuam tshuam los ntawm lub hnub nyoog, kev tshawb fawb ntau ntxiv nrog rau cov hnub nyoog qis dua tuaj yeem muab kev pom ntxiv ntawm kev siv cov kua isoflavone hauv kev kho mob Alzheimer's kab mob pathology. Ntawm cov kab zoo sib xws, lwm qhov kev sim ntsuas ib qho ntawm cov isoflavones pom hauv cov kua txiv hmab txiv ntoo, piv txwv li, Genistein, tau sim tsis ntev los no rau nws txoj kev cuam tshuam rau kev kho Alzheimer's kab mob (ClinicalTrials.gov Identifier: NCT01982578). Txoj kev tshawb no yog raws li kev tshawb fawb pom tseeb tias hauv kev tshawb fawb tsiaj, Genistein muaj peev xwm nce qib ntawm PPARg (peroxisome proliferator-activated receptor-gamma) uas tsim dimmers nrog Retinoid X receptor kom qhib apolipoprotein (ApoE) uas pab kom degrade amyloid. - beta peptides. Xws li Alzheimer's tus kab mob attenuating zog ntawm Genistein tau xav tias yuav ua rau muaj feem cuam tshuam rau kev txo qis ntawm amyloid-beta protein. Cov txiaj ntsig zoo sib xws yog xav tau los ntawm qhov kev sim tshuaj ntsuam xyuas uas tsis ntev los no tau xaus thiab cov kev tshawb fawb soj ntsuam los ntawm txoj kev tshawb fawb no yuav xav tau sai dua. Ob qhov kev tshawb fawb saum toj no qhia txog cov txiaj ntsig zoo ntawm cov khoom noj khoom haus soy hauv kev txhim kho kev txawj ntse thiab yog li yuav tsum tau sim ntxiv rau hauv thaj chaw sib txawv thiab haiv neeg.
Kev siv cov khoom noj muaj txiaj ntsig yog lwm txoj hauv kev rau kev cuam tshuam tshuaj ncaj qha los daws cov kab mob Alzheimer. Ib txoj kev tshawb fawb no siv cov khoom noj khoom haus sib xyaw ua ke muaj cov tshuaj yej ntsuab polyphenols, ginsenoside thiab marine collagen peptides kuaj rau lawv cov teebmeem ntawm kev tiv thaiv kab mob Alzheimer's kab mob pathological. Txoj kev tshawb no nyuam qhuav ua tiav thaum lub Kaum Ob Hlis 2019 thiab cov txiaj ntsig tau los ntawm nws tseem tsis tau muaj nyob rau hauv pej xeem sau (ClinicalTrials.gov Identifier: NCT04279418). Tsis tas li ntawd, ntau txoj hauv kev tshiab tau ua haujlwm tsis ntev los no rau kev sim tshuaj xyuas ntawm polyphenols. Ntawm lawv, kev sim siv cov ntawv xa mus rau kev xa cov cocoa flavonols thiab multivitamins rau cov neeg koom thiab tom qab ntawd soj ntsuam lawv cov kev txawj ntse siv cov lus nug hauv xov tooj tau tshawb fawb los kawm txog cov hlab plawv thiab kev txawj ntse txhawb cov khoom ntawm cocoa flavonols hauv kev sib xyaw nrog multivitamin supplementation [110].
Hauv kev tshawb nrhiav ntxiv, txog tam sim no tsuas yog siv cov ntsiab lus ntxiv tau hais los saum toj no, muaj nyob ib puag ncig 793 kev tshawb fawb tiav. Nyob rau hauv feem ntau ntawm cov kev tshawb fawb tau ua kom deb li deb, haye muab polyphenols nyob rau hauv xws li ib tug extract, ib tug ntshiab compound, los yog ib tug nplua nuj zaub mov. Ntawm cov polyphenols, cov khoom noj khoom haus nplua nuj (berries, cocoa, thiab tsaus chocolates, txiv kab ntxwv, kua txiv kab ntxwv, cereals, liab cawu cub, txiv roj roj, tshuaj yej ntsuab, kua, pomegranates, txiv apples, kas fes, qos yaj ywm, pulses, npias, hazelnuts, almonds, artichokes. , thiab mangos) tau txaus siab rau ntau xyoo dhau los ntawm kev tshawb fawb soj ntsuam. Hauv ib daim ntawv ntshiab, flavonols tau kawm ntau tshaj plaws, ua raws li anthocyanidins. Tseem, muaj ib tug loj repertoire ntawm kev noj haus polyphenols uas yuav siv tau kom tau txais kev kho kom zoo nyob rau hauv cov kab mob neurodegenerative.
9. Cov lus qhia yav tom ntej hauv Kev Tshawb Fawb Kev Noj Qab Haus Huv Polyphenol rau Alzheimer's Disease
Nyob rau hauv xyoo tas los no, ntau cov kev tshawb fawb tau ua tiav los piav qhia cov txiaj ntsig ntawm cov nroj tsuag tau los ntawm polyphenols hauv kev kho cov kab mob neuropathological, suav nrog Alzheimer's dis-ease. Muaj qee yam pov thawj uas qhia tau hais tias cov teebmeem pathophysiological ntawm metabolic syndrome tau hloov pauv zoo los ntawm kev noj zaub mov noj ntawm polyphenols [20,107,111.112. Rau txhua tus kws kho mob yuav tsum tau tshawb nrhiav los kho cov kab mob neurodegenerative, nws yuav tsum muaj peev xwm hla cov ntshav-hlwb teeb meem. Ntawm cov khoom noj polyphenols, curcumin [113] thiab resveratrol [55] tau pom tias hla BBB architecture, uas ua rau lawv cov neeg sib tw zoo tshaj plaws rau kev txhim kho neuroprotective. Lwm qhov kev txiav txim siab tseem ceeb rau lawv siv yog lawv cov bioavailability hauv lub cev tom qab kev tswj hwm. Nws tau pom tias curcumin nce mus txog qhov siab tshaj plaws hauv 48 teev hauv lub hlwb tom qab kev tswj hwm qhov ncauj [113]. Lwm txoj hauv kev ntawm kev tswj hwm, xws li intraperitoneal (ip), qhov ncauj gavage, thiab intramuscular, kuj tau ua tiav hauv kev nce bioavailability ntawm curcumin [114]. Lub neej luv luv kuj yog lwm qhov kev txhawj xeeb txog kev siv curcumin. Nws tau pom tias curcumin tau dhau los ua glucuronidation (los tsim curcumin glucuronides) thiab hloov kho los ntawm sulfates hauv plab hnyuv thiab daim siab milieu uas txo lawv cov bioavailability. Lwm cov khoom noj polyphenols, xws li resveratrol, thiab lwm yam, kuj raug kev txom nyem los ntawm qhov teeb meem bioavailability. Yog li ntawd, ntau yam tswv yim uas siv cov inhibition ntawm cov txheej txheem ntawm glucuronidation yog li yuav ua tau zoo nyob rau hauv ua kom cov concentration ntawm curcumin. Piperine yog ib qho chaw muaj nyob hauv cov kua txob dub (piper nigrum) uas pom tau tias yog ib qho zoo inhibitor ntawm cov txheej txheem glucuronidation. Kev siv Piperine ua ke nrog curcumin tau pom tias muaj txiaj ntsig zoo txhawm rau txhawm rau txhim kho bioavailability ntawm curcumin [115]. Lwm yam tshaj li qhov ua kom muaj bioavailability, tshuaj lom cov lus teb nyob rau hauv daim ntawv ntawm ulcers, hyperkeratosis, thiab lwm yam, tau pom nyob rau hauv cov kev kho mob ntev ntawm curcumin rau lub sij hawm ntev ntawm 2 xyoo (National Toxicological Program, 1993). Txawm hais tias qhov kev kho mob ntev npaum li cas siv nyob rau hauv txoj kev tshawb no ntau dua li qhov kev pom zoo, nws tseem ceeb rau qhov yuav tsum tau tshuaj xyuas curcumin txoj kev siv nyab xeeb hauv kev txwv. Tsis zoo li qhov no, lwm lub tswv yim uas tuaj yeem siv los ua kom cov txiaj ntsig kho tau zoo ntawm curcumin yog siv cov tswv yim sib xyaw ua ke, piv txwv li, ascorbic acid ua ke nrog curcumin tau pom los ua kom cov tshuaj tiv thaiv kab mob [116]. Lwm cov tshuaj tiv thaiv neuroprotective, xws li resveratrol thiab epigallocatechin [117], kuj tau siv rau qhov kev sib koom ua ke no. Qhov txiaj ntsig zoo ntawm cov kev sib koom ua ke zoo li no qhia tau hais tias yuav tsum tau nthuav dav lub qab ntug thiab qhov kev nthuav dav ntawm txoj hauv kev no txhawm rau txhawm rau tiv thaiv tus mob Alzheimer's.
Kab lus no yog muab rho tawm los ntawm Antioxidants 2022, 11, 554. https://doi.org/10.3390/antiox11030554 https://www.mdpi.com/journal/antioxidants