Lub Xeev Ntawm Kev Ua Yeeb Yam Ntawm Antioxidant Cov Khoom Ntawm Curcuminoids hauv Cov Kab Mob Neurodegenerative Part 1

Abstract:

Cov kab mob neurodegenerative sawv cev rau cov kab mob pathologies uas tshwm sim los ntawm kev hloov pauv tsis tau thiab nce zuj zus, thiab poob ntawm cov hlwb neuronal hauv qee thaj chaw ntawm lub hlwb. Oxidative phosphorylation yog ib qhov chaw ntawm lub zog tsim los ntawm ntau lub hlwb, xws li cov hlwb neuronal, ua tau raws li lawv cov kev xav tau.

Cov kab mob neurodegenerative yog ib hom kab mob ntawm cov neeg laus, xws li Alzheimer's disease, Alzheimer's disease, thiab lwm yam. Raws li cov neeg laus laus zuj zus tuaj, qhov cuam tshuam ntawm cov kab mob no rau peb lub neej thiab lub neej yog qhov hnyav dua.

Cov kab mob neurodegenerative yog ze rau kev nco. Cov kab mob no feem ntau ua rau lub hlwb hloov pauv, y cuam tshuam rau lub hlwb ua haujlwm, nrog rau kev nco ua haujlwm. Cov neeg mob yuav hnov ​​​​qab lossis muaj amnesia thaum ntxov. Txawm li cas los xij, yog tias lawv tau ceeb toom tas li thiab saib xyuas, lawv tuaj yeem tswj hwm lawv lub peev xwm los saib xyuas lawv tus kheej thiab tswj hwm kev ua haujlwm siab.

Peb yuav tsum ua li cas thaum muaj tus kab mob no? Ua ntej tshaj plaws, peb yuav tsum ua kom muaj kev tiv thaiv zoo, xws li kev tawm dag zog ntau dua, tsis txhob qaug zog ntau dhau, thiab ua raws li kev noj zaub mov zoo. Cov kev ntsuas no tuaj yeem ua rau qeeb ntawm kev loj hlob ntawm tus kab mob. Nyob rau tib lub sijhawm, peb tseem yuav tsum tau kawm txuas ntxiv thiab nkag siab txog kev paub txog tus kabmob no thiab txhim kho kev kho mob thiab kev tshaj lij ntawm cov neeg ua haujlwm saib xyuas neeg laus kom muab kev pabcuam zoo dua rau cov neeg mob.

Tsis tas li ntawd, peb kuj yuav tsum pib nrog kev tawm dag zog kom tsim nyog, kev sib raug zoo hauv zej zog, kev kho cov pa oxygen, thiab lwm yam los txhim kho cov neeg mob lub neej zoo thiab kev hwm tus kheej thiab txhawb lawv txoj kev hlub thiab kev ntseeg siab hauv lub neej. Cov yam ntxwv zoo no tuaj yeem ua lub luag haujlwm zoo hauv kev txo cov neeg mob lub siab lub ntsws thiab kev ntxhov siab, ua rau lawv zoo siab rau lub neej.

Nyob rau hauv luv luv, txawm hais tias cov kab mob neurodegenerative tuaj yeem cuam tshuam rau kev nco, peb yuav tsum tau ntsib qhov xwm txheej no, ua kev ntsuas kom txo qis kev loj hlob ntawm tus kab mob, txhim kho lub neej zoo, thiab ua cov tswv yim coj los ua kom sov thiab pab rau cov neeg mob thiab lawv tsev neeg. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj hauv Suav teb uas muaj ntau yam teebmeem, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm Cistanche deserticola los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog tannic acid, polysaccharides, flavonoid glycosides, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv los ntawm ntau txoj hauv kev.

Nyem Paub Short-term Nco yuav ua li cas txhim kho

Dysregulations ntawm oxidative phosphorylation induce oxidative kev nyuaj siab, uas plays lub luag hauj lwm tseem ceeb nyob rau hauv lub pib ntawm neurodegenerative kab mob xws li Alzheimer's kab mob (AD), Parkinson's kab mob (PD), thiab amyotrophic lateral sclerosis (ALS).

Txog niaj hnub no, rau feem ntau cov kab mob neurodegenerative, muaj cov kev kho mob noresolute, tab sis tsuas yog cov kev cuam tshuam uas muaj peev xwm txo tau cov tsos mob los yog ua rau qeeb ntawm cov kab mob. Yog li ntawd, cov tswv yim zoo neuroprotection yog xav tau.

Nyob rau hauv xyoo tas los no, naturalproducts, xws li curcuminoids, tau tshawb nrhiav thiab kawm txog lawv cov peev xwm kho mob hauv ntau yam kab mob neurodegenerative. Curcuminoids yog nutraceutical compounds, uas muaj ntau yam kev kho mob xws li antioxidant, anti-inflammatory, thiab neuroprotectiveeffects.

Nyob rau hauv cov ntsiab lus no, qhov kev tshuaj xyuas no tsom los muab cov ntsiab lus ntawm preclinical thiab clinicalevidence tsom los qhia txog cov teebmeem antioxidant ntawm curcuminoids hauv cov kab mob neurodegenerative. Cov txiaj ntsig tau los ntawm kev tshawb fawb ua ntej txhawb kev siv curcuminoids rau neurodegenerationprevention thiab kev kho mob.

Ntsiab lus: kab mob neurodegenerative; curcuminoids; anti-oxidant zog.

1. Taw qhia

Cov kab mob neurological cuam tshuam ntau lab tus tib neeg thoob ntiaj teb [1]. Kev hloov pauv ib puag ncig hauv lub hauv nruab nrab lub paj hlwb (CNS) ua rau kev ua kom cov microglia thiab astrocytes, cov hlwb koom nrog kev tswj hwm homeostasis ntawm CNS.

Tom qab kev puas tsuaj, cov cell no qhib cov lus teb uas ua rau kev tso tawm cov cytokines pro-inflammatory lub luag haujlwm rau cov tshuaj tiv thaiv hauv zos [2]. Tsis tas li ntawd, ib zaug ua haujlwm, microglia thiab astrocytescan tsim cov pa oxygen reactive (ROS).

Txawm li cas los xij, lub hlwb, txawm tias suav txog 2% ntawm tag nrho lub cev qhov hnyav, siv li 20% ntawm lub cev oxygen (O2); Yog li, itis nplua nuj nyob rau hauv cov antioxidants koom nrog hauv kev tiv thaiv kev tsim ntawm ROS. Kev tsim ntau dhau ROS, yog tias tsis muaj txiaj ntsig zoo los ntawm cov khoom siv cellular, ua rau muaj kab mob xws li cov kab mob neurodegenerative [3-5].

Qhov no yog tshwj xeeb tshaj yog muaj feem xyuam rau cov kab mob neurodegenerative xws li Alzheimer's disease (AD), Parkinson's disease (PD), andamyotrophic lateral sclerosis (ALS). Tseeb neuroinflammation thiab oxidative kev nyuaj siab yog cov yam ntxwv ntawm cov kab mob neurodegenerative [6,7].

Txawm hais tias cov kev kho mob uas ncua sij hawm lossis tswj cov tsos mob muaj rau cov teeb meem no, tam sim no tsis muaj kev kho mob zoo. Yog li ntawd, muaj kev txaus siab nyob rau hauv tej yam ntuj tso tebchaw uas muaj antioxidant thiab anti-inflammatory zog [8,9].Curcuma yog ib tug txuj lom muab rho tawm los ntawm rhizomes ntawm Curcuma Longa, teej tug mus rau lub Zingiberaceae tsev neeg, cultivated nyob rau hauv Is Nrias teb thiab Southeast Asia [10].

Cov ntsiab lus tseem ceeb ntawm Curcuma yog curcumin, cov xim daj feem ntau siv los ua cov txuj lom thiab zaub mov xim. Tseeb, curcumin yog ib qho khoom noj khoom haus uas muaj ntau yam kev kho mob tiv thaiv ntau yam kab mob, suav nrog cov kab mob neurodegenerative [12].

Ntawm ob peb lub zog ntawm curcuminoids [13-15], cov tshuaj tiv thaiv kab mob [16,17] thiab cov haujlwm antioxidant [18,19] yog qhov kev tshawb nrhiav ntau tshaj plaws vim lawv lub luag haujlwm hauv pathogenesis ntawm cov kab mob neurodegenerative [20].

Qhov tseeb, curcuminoids ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv cov enzymes xws li p38 Mitogen-activated protein kinase (MAPK) thiab c-Jun N-terminal kinase (c-JNK) thiab cov ntsiab lus hloov pauv (xws li nuclear factor-κB, NF-κB) muaj feem xyuam rau cov txheej txheem inflammatory.

Tsis tas li ntawd, lawv txo qhov kev qhia ntawm ntau yam pro-inflammatorycytokines [21,22]. Ntxiv mus, ntau yam ntawm curcumin cov txiaj ntsig tuaj yeem cuam tshuam nrog nws cov khoom antioxidant [23].

Txij li thaum oxidative kev nyuaj siab, tshwm sim los ntawm ntau ntau lawm ntawm reactive oxygen hom, lipid peroxidation, thiab oxidative kev puas tsuaj rau DNA thiab cov proteins, yog lub luag hauj lwm rau ntau yam pathological teeb meem xws li neurodegenerative kab mob, curcumin tuaj yeem ua lub luag haujlwm tseem ceeb hauv cov xwm txheej no.Curcumin tau tshawb xyuas ntau ntxiv. rau nws cov khoom muaj txiaj ntsig tiv thaiv ntau yam kab mob neurological xws li PD [24], AD [25], thiab ALS [26].

Lub hom phiaj ntawm qhov kev tshuaj xyuas no yog piav qhia txog cov khoom antioxidant ntawm curcuminoids koom nrog lawv cov kev ua tau zoo hauv cov kab mob neurological. Hauv kev tshuaj xyuas tam sim no, cov pov thawj preclinical thiab cov ntaub ntawv pov thawj qhia txog cov curcuminoids 'cov tshuaj tiv thaiv antioxidant hauv cov kab mob neurological tau sau tseg.

2. Curcumin

Curcuminoids yog cov tshuaj nquag muaj nyob hauv turmeric thiab suav nrog curcumin (diferuloylmethane), demethoxycurcumin, thiab bisdemethoxycurcumin (Daim duab 1). Ntau cov pov thawj hauv vitro thiab hauv vivo piav qhia txog cov tshuaj tiv thaiv kab mob [27] thiab antioxidantproperties [28] ntawm curcuminoids.

Ntawm cov curcuminoids, curcumin ua li 90% ntawm curcuminoids tam sim no nyob rau hauv turmeric. Curcumin yog ib qho polyphenol, nrog rau molecularformula C21H20O6, tus yam ntxwv thawj zaug hauv xyoo 1910 [29].

Ntawm lawv, curcumin paub tias muaj cov teebmeem neuroprotective, thiab nws lub zog antioxidant thiab tiv thaiv kab mob yog dav kawm. Cov pab pawg diketone thiab ob lub phenolic ringsin nws cov qauv tshuaj ua raws li cov cuab yeej hluav taws xob, yog li tiv thaiv kev tsim cov hydrogenperoxide (H2O2), hydroxyl radical (OH·), thiab superoxide anion (O2−·).

Ntxiv mus, theb-diketone feem thiab hydroxyl pawg ntawm curcumin muaj peev xwm ua kom cov hlau tsis zoo, xws li tooj liab (Cu2+) zinc (Zn2+), thiab ferrous hlau (Fe2+) [30]. Fe2+ yog qhov tsim nyog rau Fenton cov tshuaj tiv thaiv uas tsim OH· radicals; yog li, curcumin los ntawm chelating Fe2+ tiv thaiv cov hlau-xws li toxicity.

Qhov tseeb, nws paub zoo tias curcumin muaj cov khoom tiv thaiv oxidant thiab nws zoo nkaus li kaum npaug zog dua li cov vitamin E raws li ib tug freeradical scavenger [31]. Vim muaj peev xwm ntawm curcumin hla cov ntshav-hlwb thaiv teeb meem [32], nws kuj txo qis ROS qib [33], tiv thaiv lub hlwb los ntawm lipid peroxidation, thiab txo cov neuron tuag vim yog oxidative insults [34].

Tsis tas li ntawd, curcumin, ntxiv rau kev ua raws li kev tshem tawm ncaj qha ntawm ROS, siv nws cov khoom antioxidant los ntawm kev nce glutathione (GSH) qib [35], txhim kho cov haujlwm ntawm glutathione peroxidase (GSHPx), glutathione reductase (GR), catalase (CAT) thiab superoxide dismutase. (SOD) [36] .Tsis tas li ntawd, curcumin txo mitochondrial puas thiab apoptosis kho los ntawm lipidperoxidation [37].

Curcumin tuaj yeem tiv thaiv kev ua kom muaj ntau yam kev hloov pauv xws li NF-κB [38], activated protein-1 (AP-1) [39], Notch-1 [40], -catenin [41] ], thiab peroxisome proliferator-activated receptor-gamma (PPAR-) [42], tag nrho cov koom nrog hauv cov txheej txheem lom neeg sib txawv, suav nrog kev mob.

NF-κB yog nyob rau hauv lub cytosol-tom qab ua kom, nws yog translocated mus rau lub nucleus, qhov uas nws txhawb cov kev qhia ntawm txawv genes koom tes nyob rau hauv cellproliferation thiab o [43]. Cov kev ua haujlwm dysregulated ntawm NF-κB underlies ob peb inflammatory kab mob, xws li cov kab mob neurodegenerative [44]. Curcumin inhibits NF-κB ua kom los ntawm kev txwv kev hloov pauv ntawm p65 thiab inhibitor κB (IκB) mus rau hauv lub nucleus [45].

Nyob rau hauv txoj kev no, nws inhibits kev ua kom muaj ntau cov noob uas koom nrog hauv kev muaj sia nyob, suav nrog Bcl-2, Bcl-xL, cyclin D1, cyclooxygenase 2 (COX-2), thiab matrixmetallopeptidase (MMP){{5} }, yog li txhawb kev ntes cell voj voog, inhibiting proliferationand inducing apoptosis [46].

Ntau yam ntawm curcumin cov teebmeem kuj tau kho los ntawm nws lub peev xwm los inhibit ntau cov protein kinases (PKs) koom nrog ntau cov txheej txheem ntawm tes, xws li autophosphorylation activated(AK) protein kinase [47], Ca2+-dependent protein kinase (CDPK) [ 48], Januskinase (JAK) [49], mitogen-activated protein kinase (MAPK) [50,51], mammalian target of rapamycin (mTOR) [52,53], phosphorylase kinase (PhK) [47], cytosolic protein kinase (cPPK [47], PKA [47], PKB/Akt [54], PKC [47].

Tsis tas li ntawd, qhov inhibitory kev ua ntawm txoj kev MAPK thiab inhibition ntawm phosphorylation ntawm extracellular receptorkinase (ERK), c-JNKs, thiab p38 MAPKs yog lub luag hauj lwm rau cov haib anti-inflammatory nyhuv ntawm curcumin [55].

Qhov tseeb, qhov inhibition ntawm NF-κB thiab MAPK txoj hauv kev txo cov kev qhia ntawm ntau cov kab mob inflammatory interleukins (ILs) xws li IL-1 , IL-6, Tumornecrosis factor-alpha (TNF- ) [56], IL -2 [57], IL-5 [58], IL-8 [59], IL-12 [60], IL-18 [61] and signal transducer thiab activator ntawm transcription (STAT) proteins [49]. Yog li ntawd, curcumin los ntawm kev tswj hwm cov ntsiab lus hloov pauv, xws li NF-κB, inhibits zus tau tej cov pro-inflammatorycytokines, yog li nthuav tawm lub zog tiv thaiv kab mob [62].

Cov yam ntxwv ntawm curcumin no ua rau nws siv tau cov tshuaj tiv thaiv kab mob neuroprotective.Qhov tseeb, kev tshawb fawb txog kab mob tshwm sim qhia tau tias nyob rau hauv cov pej xeem Indian, kev noj cov tshuaj tsw qab zoo sib xws nrog cov kab mob qis qis xws li AD thiab PD, piv rau cov neeg Caucasian [63,64] ].

3. Txoj kev

Cov ntawv sau no yog npaj los muab cov ntsiab lus ntawm kev sim thiab kev tshawb fawb soj ntsuam uas qhia txog cov teebmeem antioxidant ntawm curcuminoids hauv cov kab mob neurodegenerative, xws li PD, AD, thiab ALS.

Txhawm rau sau qhov kev tshuaj xyuas no, kev tshawb fawb tau ua nyob rau hauv PubMedusing cov ntsiab lus hauv qab no: "Curcuminoids", "antioxidant teebmeem", "Parkinson's Disease", "Alzheimer's Disease", "thiab Amyotrophic Lateral Sclerosis".

Peb tau txiav txim siab cov ntawv luam tawm ntawm xyoo 2015 thiab 2021 qhia txog lub luag haujlwm neuroprotective ntawm curcuminoids.Nyob rau hauv qhov kev tshawb fawb no, 65 kab lus tau pom, raws li qhia hauv Prisma flow diagram (Daim duab 2).Nyob rau hauv seem "Cov ntaub ntawv soj ntsuam", 20 kab lus raug tshem tawm; ntawm lawv, 12 tsis tau txiav txim siab vim lawv txawv ntawm qhov tseem ceeb ntawm peb qhov kev tshuaj xyuas.

Ob tsab xov xwm raug tshem tawm vim lawv tsom mus rau lub luag haujlwm antioxidant ntawm lwm cov tebchaw. Ntxiv mus, txij li thaum peb tsom ntsoov rau curcuminoids, peb kuj tsis suav nrog rau 6 tsab xov xwm uas ntsuas cov txiaj ntsig ntawm curcumin ua ke nrog lwm cov tshuaj.

Raws li qhov kev tshuaj xyuas no yog npaj los muab cov ntsiab lus ntawm cov kev tshawb fawb soj ntsuam, hauv "Cov ntawv sau tag nrho ntsuas rau kev tsim nyog" ntu, 13 kab lus raug tshem tawm vim lawv yog kev tshuaj xyuas.

Thaum kawg, phau ntawv no tau txiav txim siab 27 cov kev tshawb fawb uas ntsuas cov txheej txheem biochemical thiab molecular hauv qab cov tshuaj tiv thaiv antioxidant ntawm curcuminoids thiab lawv cov kev siv tshuaj kho mob hauv lub cev.

Hauv kev txhawb nqa ntawm qhov kev tshawb pom ntawm kev tshawb fawb ua ntej, peb kuj muab cov ntsiab lus ntawm cov kev sim tshuaj ntsuam xyuas tam sim no sau tseg rau ntawm ClinicalTrial.gov (https://clinicaltrials.gov/ nkag mus rau 12 Lub Ob Hlis 2021), siv cov lus tseem ceeb hauv qab no: "Curcumin", "Parkinson's Kab mob" lossis "Alzheimer's In Disease" Hauv lossis Hauv "Amyotrophic Lateral Sclerosis".

4. Tus kab mob Parkinson

y lub luag hauj lwm hauv kev pab txhawb los yog exacerbating nigrostriatal degeneration [68]. Cov yam ntxwv tshwj xeeb ntawm PD yog tremors, bradykinesia, rigidity, thiab tshuav nyiaj li cas cuam tshuam. Tsis tas li ntawd, hauv cov neeg mob PD kuj tshwm sim tsis muaj lub cev muaj zog xws li kev ntxhov siab, dementia, kev nyuaj siab, pw tsaug zog, thiab kev puas siab puas ntsws uas ua rau lub neej tsis zoo [69] ].

Ntxiv mus, lub ntsiab lus ntawm PD yog tsim los ntawm Lewy lub cev, uas yog cytoplasmic inclusions ntawm alpha-synuclein (-syn) [70]. Txawm li cas los xij, oxidative kev nyuaj siab thiab o ua lub luag haujlwm tseem ceeb hauv PD. Hauv 90% ntawm cov neeg mob, PD tshwm sim nyob rau hauv ib daim ntawv sporadic; tsuas yog 10% ntawm cov ntaub ntawv tam sim no raws li tsev neeg.

Cov ntaub ntawv tsev neeg ntawm PD koom nrog -synuclein gene mutations (SNCA), ubiquitin C-terminal hydrolase L1 (UCHL-1), phosphatase thiab tensin homolog induced putative kinase 1 (PINK1), Parkin (PRKN), protein delicate (DJ{ {6}}), thiab leucine-nplua nuj rov kinase 2 (LRRK2) [71].Daim duab 2.

Prisma flow diagram qhia txog kev xaiv cov txheej txheem ntawm cov kev tshawb fawb preclinical siv rau kev sau ntawv ntawm kev tshuaj xyuas. Cov ntawv luam tawm raug cais tawm ntawm tag nrho cov kev tshawb fawb tau sau tseg.

Hloov chaw, lawv tau suav hais tias yog cov khoom uas ntsuas cov teebmeem antioxidant ntawm curcuminoidin neurological kab mob. PRISMA Tsab Ntawv Tshaj Tawm tau tshaj tawm nyob rau hauv [65].Tau txhawb qhov kev tshawb pom ntawm kev tshawb fawb ua ntej, peb kuj muab cov ntsiab lus ntawm cov kev sim tshuaj ntsuam xyuas tam sim no sau tseg rau ntawm ClinicalTrial.gov (https://clinicaltrials.gov/ nkag mus rau 12 Lub Ob Hlis 2021), siv lub Cov lus tseem ceeb hauv qab no: "Curcumin", "Parkinson's Disease" lossis "Alzheimer's Disease" lossis "Amyotrophic Lateral Sclerosis".

Parkinson's DiseasePD yog ib yam kab mob loj thiab cov kab mob neurodegenerative tshwm sim los ntawm kev poob ntawm cov neurons nyob rau hauv substantia nigra, tom qab los ntawm kev txo qis hauv dopamine qib hauv thestriatum [66].

Cov xwm txheej no ua rau muaj qhov tsis zoo ntawm txoj kev nigrostriatal uas ua rau muaj kev cuam tshuam ntawm kev txav mus los [67]. Lub oxidative kev nyuaj siab thiab inflammatory teb playa lub luag hauj lwm tseem ceeb hauv kev pab los yog exacerbating nigrostriatal degeneration [68]. Cov tsos mob tshwj xeeb ntawm PD yog tremors, bradykinesia, rigidity, thiab tshuav nyiaj li cas.

Tsis tas li ntawd, hauv cov neeg mob PD kuj tshwm sim tsis muaj lub cev muaj zog xws li kev ntxhov siab, dementia, kev nyuaj siab, pw tsaug zog, thiab kev puas siab puas ntsws uas ua rau lub neej tsis zoo [69]. Ntxiv mus, lub ntsiab lus ntawm PD yog tsim los ntawm Lewy lub cev, uas yog cytoplasmic inclusions ntawm alpha-synuclein (-syn) [70]. Txawm li cas los xij, oxidative kev nyuaj siab thiab mob ua rau lub luag haujlwm tseem ceeb hauv PD.

Hauv 90% ntawm cov neeg mob, PD tshwm sim nyob rau hauv ib daim ntawv sporadic; tsuas yog 10% ntawm cov neeg mob tam sim no ua ib daim ntawv ntawm tsev neeg. Cov ntaub ntawv tsev neeg ntawm PD koom nrog -synuclein genemutations (SNCA), ubiquitin C-terminal hydrolase L1 (UCHL-1), phosphatase thiab tensinhomolog-induced putative kinase 1 (PINK1), Parkin (PRKN), protein ntau (DJ{{ 9}}), andleucine-nplua nuj rov kinase 2 (LRRK2) [71].

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