Tshiab Kev cog lus kho Avenues ntawm Curcumin nyob rau hauv mob hlwb

Thov hu rauoscar.xiao@wecistanche.comyog xav paub ntxiv

Abstract:Curcumin, kev noj haus polyphenol cais los ntawm Curcuma longa (turmeric), feem ntau yog siv los ua tshuaj ntsuab thiab txuj lom thoob ntiaj teb. Vim tias nws cov teebmeem bio-pharmacological, curcumin tseem hu ua "spice of life", qhov tseeb, nws tau lees paub tias curcumin muaj cov khoom tseem ceeb xws li tshuaj tiv thaiv oxidant, tiv thaiv kev mob, tiv thaiv kab mob, tshuaj tiv thaiv kab mob, tiv thaiv qog, thiab anti-aging. Cov kab mob neurodegenerative xws li Alzheimer's Diseases, Parkinson's Diseases, thiab Ntau Sclerosis yog ib pawg ntawm cov kab mob uas tshwm sim los ntawm kev loj hlob ntawm lub hlwb cov qauv thiab kev ua haujlwm vim kev tuag neuronal; tam sim no, tsis muaj kev kho mob zoo los kho cov kab mob no. Cov nyhuv tiv thaiv ntawm curcumin tiv thaiv qee cov kab mob neurodegenerative tau raug pov thawj los ntawm kev tshawb fawb hauv vivo thiab hauv vitro.cistanche noov lojKev tshuaj xyuas tam sim no qhia txog qhov kev tshawb pom tshiab tshaj plaws ntawm cov teebmeem neuroprotective ntawm curcumin, nws cov bioavailability, nws cov txheej txheem ntawm kev ua, thiab nws muaj peev xwm thov rau kev tiv thaiv lossis kho cov kab mob neurodegenerative.

Thov nias ntawm no kom paub ntxiv

Ntsiab lus:curcumin; ntuj flavonoid; neuroinflamation; anti-inflammatory; kab mob neurodegenerative; Cov kab mob Alzheimer; Cov kab mob Parkinson; ntau yam sclerosis; glioblastoma ntau hom; epilepSy

1. Taw qhia

Cov pov thawj tsis ntev los no qhia tau hais tias kev siv cov nutraceuticals thiab cov khoom noj khoom haus tuaj yeem coj kev tiv thaiv rau lub hauv paus paj hlwb (CNS) los ntawm kev khaws cov neurons tiv thaiv kev ntxhov siab vim kev puas tsuaj, suppressing neuroinflammation, thiab ua kom muaj kev paub txog kev ua haujlwm.

Curcumin yog ib qho ntawm curcuminoid constituents tam sim no nyob rau hauv turmeric (Curcuma longa Limn) thiab yog ib tug perennial tshuaj ntsuab ntawm tsev neeg Zingiberaceae. Turmeric, tseem hu ua "golden spice" yog siv los ua cov tshuaj hauv cov tshuaj ib txwm siv thiab tseem siv dav hauv Asian cuisine raws li cov khoom noj ntxiv thiab ua cov xim xim hauv kev lag luam dej haus [1].

Cov (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3, 5-dione yog IU-PAC lub npe ntawm curcumin, nws cov tshuaj formula yog CanHzoOg thiab nws muaj molecular hnyav ntawm 368.38g/mol. Ntau yam kev ua si lom neeg thiab cov khoom kho mob ntawm curcumin yog vim nws cov chemistry, tshwj xeeb tshaj yog phenolic hydroxyl pawg, lub hauv paus bis- , -unsaturated -diketone, ob-conjugated bonds, thiab methoxy pawg yog lub luag hauj lwm rau nws bio-pharmacological teebmeem. Curcumin yog lipophilic molecule, uas tsis zoo solubility nyob rau hauv dej los yog hydrophilic daws, es tsis txhob, nws yog yooj yim soluble nyob rau hauv organic solvents xws li methanol, ethanol, acetone, thiab dimethyl sulfoxide, chloroform [2].

Curcuminoid complex muaj curcumin, demethoxycurcumin thiab bis-deme thoxycurcumin [3].

Cistanche tuaj yeem tiv thaiv kev laus

Curcumin, zoo li lwm yam phytochemicals, muaj pleiotropic kev ua haujlwm ntawm cov hlwb, qhov tseeb, vim nws muaj peev xwm cuam tshuam nrog ntau cov proteins, curcumin tuaj yeem ua rau cov cellular teb rau sab nraud stimuli. Tsis tas li ntawd, curcumin nce-thiab qis- tswj ntau yam miRNA thiab tuaj yeem ua rau muaj kev hloov pauv hauv cov hlwb. Ob peb hauv vitro, hauv vivo thiab kev sim tshuaj ntsuam xyuas tau tsom mus rau qhov muaj peev xwm kho tau ntawm curcumin suav nrog antioxidant [4], immunomodulatory, cardio-protective [5], nephroprotective [6], hepatoprotective [7,8], anti-neoplastic [9] ,10], anti-microbial, anti-diabetic [11] anti-rheumatic [12] anti-aging [13], anti-inflammatory tshwj xeeb tshaj yog anti-neuroinflammatory [14] as well as inhibiting properties for microglia [15].

Txawm hais tias nws cov txiaj ntsig kho tau zoo heev, cov khoom siv bioactive no muaj qhov tsis zoo bioavailability vim kev nqus tsis txaus, tshuaj tsis ruaj khov, thiab cov metabolism hauv lub cev sai.

Txhawm rau ua kom bioavailability ntawm curcumin, nanocarriers tau raug pov thawj los ua ib lub tswv yim zoo, los txhim kho nws cov txiaj ntsig kho.

Vim lawv cov nanometric loj thiab cov cuab yeej tshuaj, nanoparticles [16], liposomes [17,18] micelles, phospholipid vesicles [19], thiab polymeric nanoparticles [20,21] muaj peev xwm ua kom cov txiaj ntsig ntawm curcumin.

Ntawm cov natural nanocarriers, extracellular vesicles, tshwj xeeb tshaj yog exosomes, yog siv raws li ib tug system rau kev xa tshuaj.cistanche hmoovExosomes raug tso tawm los ntawm cov hlwb los ntawm exocytosis tom qab maturation ntawm multivesicular lub cev.

Exosomes muaj peev xwm kho kom haum xeeb kev sib txuas lus ntawm tes nrog lawv cov protein, lipid, thiab nucleic acid muaj pes tsawg leeg [22]. Lub lipid membrane ntawm exosome muaj curcumin los ntawm kev sib cuam tshuam ntawm hydrophobic tails thiab hydrophobic active ingredient. Qhov tso rau hauv lipid bilayer lav kev tiv thaiv ntawm curcumin los ntawm degradation [23]. Qhov tseeb, curcumin nrog ib qho exosomal formulation yog zoo dua nrog rau liposomal curcumin thiab dawb curcumin [23].

Zhang et al. tau ua pov thawj tias intranasal tswj curcumin-loaded ex los ntawm cov kab mob sib kis, xws li Lipopolysaccharide (LPS)-induced hlwb mob qauv, sim autoimmune encephalitis, thiab GL26 hlwb qog qauv, induce neuroprotection los ntawm kev txo cov neuroinflammation los yog qog loj [24 ].

Hauv ischemia-reperfusion (I / R) kev raug mob, curcumin-loaded exosomes muaj peev xwm txo qis-tswj cov pa oxygen hom (ROS) ntau lawm hauv qhov txhab, txo cov ntshav-hlwb barrier (BBB) ​​kev puas tsuaj, thiab suppress mitochondria-mediated neuronal apoptosis [25] ]. Liposomes yog nanovesicles ua los ntawm ib leeg lossis ntau lub bilayers ntawm phospholipids uas kaw cov hydrophilic, lipophilic, thiab amphiphilic molecules [26], uas tuaj yeem siv los xa cov tshuaj mus rau qhov chaw.

Mohajeri et al. tau pom cov tshuaj tiv thaiv thiab tiv thaiv oxidant los ntawm polymerized nano-curcumin uas muaj cov txiaj ntsig zoo ntawm kev sim autoimmune encephalomyelitis qauv ntawm ntau yam sclerosis, thiab induced myelin kho mechanisms [27].

Nano-curcumin muaj cov tshuaj tiv thaiv neuroprotective ntawm kev raug mob ntawm lub hlwb thaum ntxov, nws yog qhov tseeb muaj peev xwm txo qis BBB ua haujlwm tsis zoo tom qab subarachnoid hemorrhage los ntawm kev tiv thaiv kev puas tsuaj ntawm cov protein sib txuas (ZO-1, occludin, thiab claudin-5) . Tsis tas li ntawd, nano-curcumin up-regulates glutamate transporter-1 uas txo cov glutamate concentration hauv Cerebrospinal kua (CSF) tom qab subarachnoid hemorrhage thiab inhibits kev ua kom microglia [28]. Kev sib xyaw ua ke ntawm w-3 fatty acids thiab nano-curcumin txo qhov zaus ntawm migraine tawm tsam los ntawm kev hloov pauv ntawm IL-6gene qhia thiab C-Reactive Protein qib, raws li muaj pov thawj hauv cov txheej txheem kuaj mob [29 ]. CUR-loaded liposomes txo cov angiotensin-hloov enzyme kev ua haujlwm nyob rau hauv lub hom phiaj cheeb tsam ntawm lub hlwb thiab potentiate nco rov qab nyob rau hauv nas nrog Alzheimer's kab mob (AD) [30].

Raws li lub neej expectancy nce thoob ntiaj teb, cov kab mob neurodegenerative nce thiab qhov no ua rau lub nra hnyav dua ntawm kev lag luam kev lag luam tsis zoo rau cov neeg mob, tsev neeg, thiab cov zej zog [31]. Cov kab mob Neurodegenerative yog tus cwj pwm los ntawm cov kab mob uas ua rau muaj kev cuam tshuam loj ntawm cov qauv thiab / lossis kev ua haujlwm ntawm cov neurons thiab ntawm lawv cov synaptic network thaum kawg ua rau lub hlwb tsis ua haujlwm.

AD, Parkinson's disease (PD), Huntington's disease (HD), Multiple Sclerosis (MS), thiab amyotrophic lateral sclerosis (ALS) yog cov kab mob neurodegenerative uas tshwm sim hauv cov neeg laus.

Cov yam ntxwv uas ua rau cov kab mob neurodegenerative muaj xws li genetic polymorphisms, nce hnub nyoog, poj niam txiv neej, kev kawm tsis zoo, kab mob endocrine, oxidative kev nyuaj siab, o, mob stroke, kub siab, ntshav qab zib, haus luam yeeb, mob taub hau, kev nyuaj siab, kab mob, qog, vitamin tsis txaus, tiv thaiv kab mob thiab metabolic. , thiab raug tshuaj lom neeg [32].

Cov inflammatory teb nyob rau hauv lub hlwb los yog txha caj qaum yog hu ua neuroinflamation. Neuroinflammation yog tshwm sim hauv ntau cov kab mob hauv hlwb, suav nrog AD, PD, MS, thiab ntau lwm tus. Cov txheej txheem no yog kho los ntawm kev tsim cov cytokines, chemokines, reactive oxygen hom, thiab cov tub txib theem nrab, uas tuaj yeem rhuav tshem BBB, ua rau muaj kev puas tsuaj ntawm tes thiab poob ntawm cov haujlwm neuronal [33]. Glia, cov hlwb endothelial, thiab peripheral derived lub cev tiv thaiv kab mob ua rau cov neeg nruab nrab. Ntawm cov hlwb glial, microglia thiab astrocytes ua lub luag haujlwm tseem ceeb hauv kev kho mob ntawm cov kab mob neurodegenerative. Astrocytes ua hauj lwm ua ke los tswj CNS homeostasis thiab txhawb nqa neuronal ciaj sia los ntawm kev tswj cov metabolite khiav thiab ntshav khiav. Microglial hlwb pom qhov cuam tshuam ntawm lub hlwb cov ntaub so ntswg homeostasis thiab ua haujlwm li CNS phago-cytes [34,35]. Lub hom phiaj ntawm qhov kev tshuaj xyuas no yog hais txog qhov tseem ceeb ntawm curcumin hauv kev kho mob ntawm AD, PD, MS glioblastoma, thiab qaug dab peg tsom rau nws cov peev txheej ntawm kev ua haujlwm hauv kev txhim kho lawv cov kev kawm.

2. Curcumin thiab AD

AD sawv cev rau qhov laj thawj tseem ceeb ntawm dementia thoob ntiaj teb, suav txog 60-80 feem pua ​​​​ntawm cov neeg mob uas tau kuaj pom tias muaj dementia [36]. Clinically, AD feem ntau tshwm sim los ntawm kev nco tsis tau, kev paub tsis meej zuj zus, thiab kev ua haujlwm tsis zoo ntawm qib dhau los ntawm kev ua haujlwm thiab kev ua haujlwm ntawm kev ua haujlwm lossis kev ua haujlwm ib txwm muaj. Neurodegeneration tau raug ntaus nqi thiab yog tsav los ntawm extracellular aggregates ntawm amyloid (A) plaques thiab intracellular neurofibrillary tangles (NFIs) ua los ntawm hyperphosphorylated tau protein nyob rau hauv cortical thiab limbic cheeb tsam ntawm tib neeg lub hlwb [37l. Kev tsim ntawm A plaques pib los ntawm kev ua haujlwm tsis zoo ntawm amyloid precursor protein (APP) los ntawm -secretases (BACE1) thiab -secretases, ua rau kev tsim ntau hom A monomers, ntawm cov A 40 thiab A 42 (zoo heev insoluble thiab aggregation. -ntseeg). Yog li ntawd, A monomers txuas ntxiv oligomerize thiab sib sau ua ke rau hauv cov quav hniav. NFTs yog lub cim thib ob ntawm AD thiab muaj cov hyperphosphorylated tau nyob hauv cytoplasm ntawm neurons [38]. Tau muaj microtubule-binding domain thiab sib sau ua ke nrog tubulin, uas ua rau tsim cov microtubules ruaj khov. A tuaj yeem qhib ntau kinases, suav nrog glycogen synthase kinase 3 (GSK-3), cyclin-dependent kinase 5 (CDK5), thiab lwm yam xws li Protein Kinase C, Protein Kinase A, extracellular signal-regulated kinase 2 (ERK2), serine/threonine kinase, uas phosphorylates tau, ua rau nws oligomerization [39. Raws li qhov tshwm sim, microtubules ua tsis ruaj khov, thiab lawv cov subunits hloov mus rau hauv cov chunks loj ntawm tau filaments, uas txuas ntxiv mus rau hauv NFIs. NFIs yog insoluble heev thiab ua rau ib qho txawv txav ntawm kev sib txuas lus ntawm neurons thiab teeb liab mus rau txheej txheem thiab thaum kawg apoptosis nyob rau hauv neurons [40]. Raws li amyloid hypothesis, pathological hloov pauv ntawm tau raug suav tias yog cov xwm txheej hauv qab ntawm A deposition. Txawm li cas los xij, nws kuj tau pom tias A thiab tau ua nyob rau hauv txoj kev sib txuas uas ua rau AD thiab ua kom muaj kev sib haum xeeb rau ib leeg [41]. Muab qhov cuam tshuam rau kev noj qab haus huv thiab kev lag luam, nws yog ib qho tseem ceeb kom nkag siab txog qhov muaj feem cuam tshuam dab tsi tuaj yeem cuam tshuam rau txoj kev loj hlob ntawm AD thiab tseem nrhiav cov tshuaj uas tuaj yeem tiv thaiv qhov pib lossis nres cov kab mob, Ntawm lub xeev kos duab, muaj cov tshuaj tsawg tsawg uas yog muaj rau kev kho mob ntawm AD, xws li acetylcholinesterase inhibitors (donepezil, rivastigmine, thiab galantamine) thiab glutamate antagonist memantine, uas tsis muaj txiaj ntsig hauv kev txwv tsis pub tus kab mob mus rau chav kawm 42].cistanche salsa extractTsis ntev los no, FDA tau pom zoo siv cov tshuaj thawj zaug nrog cov kab mob hloov pauv hloov pauv, Aducanumab, uas yog tib neeg monoclonal antibody uas xaiv cov tshuaj tiv thaiv nrog A aggregates thiab txo A plaques hauv lub hlwb, yog li kwv yees cov txiaj ntsig tseem ceeb hauv kev kho mob. Txawm li cas los xij, kev sim tshuaj tom qab kev pom zoo yog xav tau los txheeb xyuas cov tshuaj tiag tiag cov txiaj ntsig kho mob [43]. Ob peb lub tebchaw ntuj tau raug tshawb nrhiav tsis ntev los no kom nkag siab zoo dua lawv cov txiaj ntsig zoo hauv "kev kho mob" ntawm AD [44]. Kev tshawb fawb tam sim no yog tsom rau curcumin cov txheej txheem ntawm kev ua thiab nws lub luag haujlwm hauv kev hloov pauv ntawm AD kev nce qib.

Curcumin cov txheej txheem ntawm kev txiav txim yog pleiotropic (Table S1) [45] thiab lub hom phiaj A thiab tau (saib daim duab 1). Tsis tas li ntawd, nws hloov pauv lwm yam ntawm cov txheej txheem kab mob: nws kuj khi tooj liab, txo qis cov roj cholesterol, hloov cov kev ua ntawm microglial, inhibits acetylcholinesterase, txhim kho txoj hauv kev ntawm cov tshuaj insulin, thiab ua raws li antioxidant [45]. Curcumin zoo li lub hom phiaj A ntawm qib sib txawv. Qhov tseeb, nws tau piav qhia tias nws inhibits A ntau lawm; Ntxiv mus, curcumin inhibits kev sib sau ua ke hauv vitro thiab hauv cov qauv nas yog li tiv thaiv kev tsim cov plaques thiab nws txhawb kev sib cais ntawm daim ntawv fibrillar [46].

Txog A ntau lawm, kev tshawb fawb hauv vitro tau pom tias curcumin ua raws li inhibitor ntawm BACE1, uas koom nrog hauv kev sib cais ntawm APP [47l. Cov txiaj ntsig no tau lees paub hauv cov qauv nas ntawm AD, ua kom pom tias curcumin downregulates qhov kev qhia ntawm BACE1, yog li txo A tsim [48].

Tsis tas li ntawd, curcumin zoo nkaus li inhibit GSK-3 -dependent presenilin 1(PS1) ua kom thiab ua rau txo A ntau lawm Qhov tseeb, neuroblastoma SHSY5Y hlwb kho nrog curcumin pom qhov txo qis hauv PS1 thiab GSK{5}} qib thiab ib qho kev txo qis ntawm A ntau lawm nyob rau hauv ib koob- thiab lub sij hawm-dependent yam [49]. GSK-3 tau qhib thaum nws dephosphorylated ntawm Ser9 qhov chaw. Nws cov dej num yog tswj hwm los ntawm Akt, ib qho serine / threonine tshwj xeeb protein kinase. Phosphatidylinositol (PIP) thiab PDK-mediated phosphorylation ntawm Akt ntawm Ser473 thiab Thr308 qhov chaw ua rau Akt qhib thiab ua rau phosphorylation thiab inhibition ntawm GSK-3 . Akt kev ua tsis zoo yog tswj hwm tsis zoo los ntawm PTEN, uas catalyzes phosphoinositide rau dephosphorylate deactivating PIP3 teeb liab-ing. PI3K/Akt/GSK-3 txoj kev taw qhia tseem cuam tshuam ncaj qha los ntawm A raug [50], qhov tseeb, oligomers nquag GSK-3 los ntawm dephosphorylation ntawm Ser9 site. Ntxiv mus, A induces downregulation ntawm phosphorylation ntawm Akt thiab kuj overexpression ntawm PTEN, nws tsis zoo regulator, uas ua rau downstream activation ntawm GSK-3 . Curcumin inhibits ob qho tib si overexpression ntawm PTEN mRNA, downregulation ntawm phosphorylation-mediated activation ntawm Akt, thiab kuj A -mediated GSK -3 ua kom [51,52], yog li txo A ntau lawm thiab tsim-up ntawm plaques (Daim duab 2) .

Hais txog lub luag haujlwm ntawm curcumin hauv inhibiting aggregation ntawm A, nws tau pom tias curcumin destabilizes lub zog txaus nyiam xav tau rau kev tsim ntawm -cov ntawv hauv amyloid plaques los ntawm nws cov hydrophobicity lossis nws kev cuam tshuam ntawm keto lossis enol rings thiab aromatic nplhaib ntawm A dimers. [53]. Lub destabilization ntawm -sheets kuj cuam tshuam los ntawm kev sib cuam tshuam ntawm curcumin's hydroxyl pawg ntawm cov nplhaib uas muaj ntxhiab thiab cov hnab tshos polar ntawm A [54].

Interestingly, tsis ntev los no hauv vitro kev tshawb fawb tau tsom rau curcumin lub luag haujlwm hauv kev tiv thaiv A neurotoxicity. Thapa et al. qhia tias curcumin txo tus nqi ntawm A nkag mus rau hauv cov ntshav plasma thiab yog li ua raws li kev tiv thaiv tiv thaiv A membrane toxicity. Hauv kev nthuav dav ntxiv, curcumin txo qhov cuam tshuam ntawm plasmatic daim nyias nyias vim A, yog li zam kom tsis txhob nce calcium influx thiab cell tuag [55]. Cov nyhuv neuroprotective ntawm curcumin, tej zaum daim nyias nyias-mediated, zoo li ua los ntawm kev txo cov toxicity tshwm sim los ntawm ntau yam A conformers, xws li monomeric, oligomeric, pre-fibrillary, thiab fibrillary A [56]. Interestingly, nws kuj tau piav qhia tias curcumin txhawb kev tsim ntawm "off-pathway" soluble oligomers thiab pre-fibrillar aggregates uas tsis muaj tshuaj lom [56]. Lwm txoj kev tshawb fawb los ntawm Huang et al. qhia tau tias curcumin muaj peev xwm ua kom A-mediated activation ntawm NMDA receptor glutamate thiab yog li inhibits intracellular nce hauv Ca² ntxiv, uas koom nrog hauv glutamate toxicity. Cov nyhuv ntawm curcumin ntawm kev nyuaj siab ntawm NMDA receptor / Ca2 ntxiv rau txoj hauv kev zoo li tiv thaiv kev puas tsuaj ntawm tes los ntawm A [57]. Txawm hais tias cov txiaj ntsig zoo li no, hauv vivo cov kev tshawb fawb tseem tsim nyog los txhais cov kev tshawb pom no thiab nrhiav kev siv tshuaj kho mob. Hais txog NFIs, GSK{11}} tswj cov phosphorylation ntawm tau los ntawm kev ntxiv phosphate pawg ntawm serine thiab threonine amino acid residues. Curcumin tau pom tias tiv thaiv hyperphosphorylation ntawm tau ua raws li GSK{12}} inhibitor [45,47]. Hauv kev nthuav dav ntxiv, Huang et al.[51] qhia tau tias curcumin inhibits A -induced tau hyperphosphorylation nrog PTEN/Akt/GSK{17}} txoj hauv kev hauv tib neeg cov kab lis kev cai ntawm tes thiab yog li cuam tshuam rau inhibition ntawm tau hyperphosphorylation tiv thaiv kev sib sau hauv NFIs.

Curcumin kuj tseem tuaj yeem ua lub luag haujlwm hauv NFTs tshem tawm nrog qhov txo qis hauv tau-induced toxicity. Tseeb, nyob rau hauv nas neuron kab lis kev cai ntawm tes, curcumin, nyob rau hauv tsawg concentration, upregulates qhov kev qhia ntawm BCL2 txuam athanogene 2 (BAG2), ib tug molecular chaperone uas xa tau mus rau proteasome rau degradation [58].cistanche qiaTxawm li cas los xij, txij li txoj kev tshawb no tsis tau ua tiav ntawm cov kab mob pathological, cov txiaj ntsig no yuav tsum tau lees paub. Lwm txoj kev tshawb fawb los ntawm Miyasaka et al. piav qhia txog cov theem ntawm acetylated -tubulin, qhov taw qhia ntawm microtubule stabilization, tau ntau dua hauv curcumin-kho nematodes, qhia tias curcumin tuaj yeem txo tau-mediated neurotoxicity los ntawm kev txhim kho microtubule stabilization [59]. Dhau li ntawm A thiab NFTs, lwm yam yuav tsum tau coj mus rau hauv tus account hauv AD pathogenesis. Microglia muaj lub luag haujlwm tseem ceeb hauv kev tiv thaiv kab mob hauv lub cev ntawm CNS thiab tuaj yeem raug cais tawm hauv M1 (uas zais cov kab mob neurotoxic cytokines, prostaglandins, ROS, thiab nitric oxide) thiab M2 phenotype (uas tso tawm neuroprotective thiab anti-inflammatory mediators thiab phagocyte toxic protein aggregates. ). Lub luag haujlwm ntawm microglia hauv AD tau kawm tob [60]. Ib deviates microglia los ntawm neuroprotective M2 rau neurotoxic M1 phenotype [61]. Tsis tas li ntawd, A accumululation activates microglia, uas ua rau inflammatory mediators yog li txhawb ntxiv A tsub zuj zuj, uas ua rau lub voj kev tawm tswv yim zoo. Curcumin zoo li ua lub luag haujlwm hauv kev txo cov neurotoxicity vim A-induced microglia activation [62]. Hauv qhov no, nws tau tshaj tawm tias curcumin blocks ERK1/2 thiab p38 kinase signaling hauv A -activated microglia yog li txo qhov tsim ntawm TNF- x, IL-1 , thiab IL-6 [63] thiab, Tsis tas li ntawd, attenuates qhov tso tawm ntawm nitric oxide [64]. Tsis tas li ntawd, curcumin suppresses phosphoinositide 2 kinases (PI3K) / Akt phosphorylation thiab ua kom muaj zog ntawm nuclear factor-kB (NF-kB), uas ua rau microglia activation thiab neuroinflammation pathways [64]. Interestingly, curcumin induces qhov nce ntawm peroxisome proliferator-activated receptor y (PPARy) protein ntau ntau, yog li pab txhawb PPARy anti-inflammatory kev ua nyob rau hauv lub downregulation ntawm NF-kB thiab ERK txoj kev. Ntawm qhov tod tes, curcumin tuaj yeem txhim kho cov txiaj ntsig neuroprotective ntawm M2 microglia: qhov tseeb, A phagocytosis zoo li nce hauv microglia hauv AD cov neeg mob kho nrog curcuminoids hauv vitro [65].

Kev txo qis hauv neurogenesis tau piav qhia dav dav hauv AD thiab lwm yam kab mob neurodegenerative [66]. Cov hauj lwm yav dhau los pom tias curcumin tswj cov neurogenesis los ntawm kev ua kom Wnt txoj hauv kev hauv vitro thiab hauv hippocampus thiab subventricular cheeb tsam ntawm cov neeg laus nas. Wnt cuam tshuam nrog 7-transmembrane Frizzled receptor thiab phosphorylated co-receptor low-density lipoprotein (LRP-5/6), yog li ua rau kom ua kom cov cytoplasmic disheveled (Dvl) protein. Thaum ua haujlwm, Dvl protein cuam tshuam nrog Axin/APC/GSK-3 kev puas tsuaj complex thiab inhibits GSK-3 . Qhov inhibition ntawm GSK -3 ua rau tsub zuj zuj ntawm cytoplasmic -catenin thiab nws translocation mus rau hauv lub cell nucleus. Hauv cov nucleus, -catenin cuam tshuam nrog TCF / LEF tus txhawb nqa txoj haujlwm, ua rau kev ua kom lub hom phiaj cov noob uas koom nrog hauv kev loj hlob thiab kev sib txawv ntawm CNS. Curcumin zoo li cuam tshuam txoj hauv kev no ntawm ntau qib. Hauv kev nthuav dav ntxiv, curcumin cuam tshuam nrog Wif-1 thiab Dkk-1, uas yog Wnt inhibitory molecules, yog li nce qib Wnt. Ntxiv mus, curcumin tej zaum yuav cuam tshuam nrog GSK-3, yog li txhim kho cov theem ntawm cytoplasmic -catenin, thiab txhim kho -catenin nuclear translocation, ua rau txhim kho TCF/LEF thiab cyclin-D1 txhawb kev ua haujlwm thiab nce neurogenesis. Interestingly, nws tau pom tias txawm tias tsis tshua muaj hlwb concentration ntawm curcumin (500 nM) stimulated neurogenesis, siab lub hlwb concentrations (10 μM) inhibited neurogenesis thiab neuroplasticity [67]. Yog li ntawd, kev xaiv ntawm cov concentration ntawm curcumin yuav tsum tau ua tib zoo xaiv. Cov qauv kev kho mob feem ntau tau pom muaj txiaj ntsig zoo ntawm curcumin ntawm AD, txawm li cas los xij, tsuas yog qee qhov kev tshawb fawb soj ntsuam tau tshuaj xyuas curcumin qhov cuam tshuam rau tib neeg kev paub txog kev ua haujlwm hauv AD thiab cov txiaj ntsig tsis sib xws. Cov kev tshawb pom ntawm Kev txo qis yog qhov tsis meej vim tias tsis muaj kev hloov pauv tseem ceeb hauv A lossis tau qib hauv plasma lossis CSF tau pom ntawm curcumin thiab placebo [68,69]. Ntawm qhov tod tes, neuroimaging txhawb kom curcumin txo A deposits nyob rau hauv lub hlwb ntawm 2-(1-{6-[(2-[F-18] fluoroethyl)) (methyl)amino-2-naphthyl}ethylidene) malononitrile positron emission tomography(FDDNP-PET) hauv cov neeg mob uas tsis muaj demented [70]. Cov kev tsis sib haum no yuav cuam tshuam txog qhov sib txawv ntawm cov txheej txheem thiab cov pej xeem suav nrog |71. Ntxiv mus, curcumin qhia tau hais tias tsis muaj bioavailability thiab nws cov teebmeem ntawm antioxidant pathways thiab neurogenesis tej zaum yuav xav tau ntau lub sij hawm los induce ib tug tseem ceeb kev txhim kho nyob rau hauv kev txawj ntse muaj peev xwm thiab nyob rau hauv A txo. Yog li, cov teebmeem me me uas tau piav qhia yav dhau los kuj tuaj yeem yog vim lub sijhawm luv luv ntawm kev kho mob. Cov kev tshawb fawb ntxiv yog xav tau los txhim kho curcumin's bioavailability thiab kom zoo dua tshawb nrhiav curcumin qhov cuam tshuam ntawm A thiab NFTs, txhawm rau nkag siab yog tias curcumin tuaj yeem yog qhov muaj peev xwm tshiab rau kev tiv thaiv thiab kho AD.

3. Cov teebmeem ntawm Curcumin hauv PD

PD yog tus kab mob neurodegenerative thib ob tshaj plaws tom qab AD. Kwv yees li ntawm 10 lab tus tib neeg raug kev txom nyem los ntawm PD thoob ntiaj teb xyoo 2020 (https://www.epda.eu.com/, nkag rau 27 Lub Kaum Hli 2021)[72]. PD feem ntau cuam tshuam rau dopamine-tsim neurons nyob rau hauv substantia nigra ntawm midbrain ua rau lub cev muaj zog thiab kev txawj ntse tsis zoo. Hauv idiopathic PD, cov txheej txheem pathophysiological suav nrog kev tsim cov -synuclein thiab mitochondrial respiratory dysfunction-ffecting complex, tshwm sim los ntawm ROS [73]. Nws kuj yog tus cwj pwm los ntawm kev sib sau ntawm cov protein sib sau ua ke, suav nrog feem ntau ntawm -synuclein, vim tsis ua haujlwm ntawm cov protein degradation mechanisms xws li lysosomal system [74,75]. Feem ntau ntawm cov kev kho mob uas twb muaj lawm tsuas yog cov tsos mob. Qhov no suav nrog cov tshuaj dopamine ntxiv uas ib ntus tswj lub cev muaj zog ua haujlwm tsis zoo tshwm sim los ntawm degeneration ntawm dopaminergic nigrostriatal system. Kev sib sib zog nqus hlwb stimulation (DBS) yog siv nyob rau hauv tshuaj-resistant PD.

Txhawm rau tiv thaiv oxidative kev nyuaj siab thiab txo cov kab mob, kev siv cov tshuaj antioxidants ntuj tseem yog lwm txoj kev kho mob. Muab cov neuroprotective, anti-neuroinflammatory, thiab anti-oxidant los tiv thaiv kev ntxhov siab vim neurodegeneration ntawm curcumin, ntawm no peb tham txog cov kev tshawb pom tsis ntev los no hais txog cov txiaj ntsig zoo ntawm curcumin hauv kev txo qis PD kev loj hlob thiab kev tiv thaiv [12].

Txawm hais tias lub pathogenesis ntawm PD tseem tsis tau paub meej, ntau lub tswv yim tau npaj thiab ntau daim ntawv pov thawj txhawb nqa lub luag haujlwm tseem ceeb ntawm mitochondrial dysfunction hauv PD pathogenesis [76].

Ib txoj kev tshawb fawb tsis ntev los no qhia txog kev tiv thaiv ntawm curcumin tiv thaiv mitochondrial dysfunction thiab cell tuag nyob rau hauv ib tug siRNA-mediated PINK1 knock-down qauv ntawm PD [77]. Lwm txoj kev tshawb fawb piav qhia txog qhov cuam tshuam ntawm curcumin ntawm mitochondrial dysfunction nyob rau hauv paraquat-induced toxicity qauv ntawm PD, nyob rau hauv fibroblasts muab los ntawm LRRK2-mutation-positive PD thiab tswj kev noj qab haus huv. Qhov tseeb, ua ntej kho cov qauv ntawm tes nrog curcumin ua ntej kev kho paraquat, txhim kho kev ua pa siab tshaj plaws thiab kev ua pa ntawm ATP tsis cuam tshuam rau kev ua pa. Tom qab kev kho mob paraquat, tom qab kev kho mob ntawm fibroblasts nrog curcumin tsis tau txhim kho mitochondrial ua pa hla peb qhov tsis zoo (qhov siab tshaj plaws ua pa, ATP-txuas ua pa, thiab lub peev xwm ua pa seem), yog li qhia txog kev tiv thaiv ntawm curcumin ua ntej pib ntawm PD [ 78] ib.

Kev tshawb fawb tsis ntev los no los ntawm Motawi et al. [79] tshawb xyuas qhov cuam tshuam ntawm curcumin thiab kev noj zaub mov ntxiv ntawm rotenone nas qauv ntawm PD tau pom tias muaj kev txhim kho tag nrho. Tseeb, kev tswj hwm ntawm curcumin nyob rau hauv cov nas kho rotenone txhim kho -synuclein qib thiab txo cov Lewy lub cev. Tus cwj pwm ntawm cov tsiaj kuj tau txhim kho thiab cov qib ntawm cov neeg kho mob inflammatory tau txo qis hauv cov nas uas kho curcumin thaum piv rau pawg tswj hwm. Cov no suav nrog IL-6, CRP, thiab Ang Il, yav dhau los qhia nrog cov teebmeem pro-inflammatory thiab pro-fibrotic uas ua rau muaj kev cuam tshuam loj ntawm cov kabmob hauv nruab nrog cev hauv PD[80]. Thaum soj ntsuam cov cim PD, qhov txo qis hauv adenosine A2AR noob qhia qib tau pom nyob rau hauv nas kho nrog curcumin piv rau pawg rotenone. Lwm qhov kev txhim kho tseem ceeb hauv qib dopamine thiab serotonin tau raug sau tseg hauv curcumin-kho nas qauv ntawm PD. Tsis tas li ntawd, kev kho mob nrog curcumin ua rau txo qis oxidative kev nyuaj siab hauv PD nas qauv [79]. Lwm cov pov thawj txhawb nqa qhia tau hais tias cov txiaj ntsig zoo sib xws ntawm cov qauv nas ntawm PD nrog cov lus teb ntau dua ntawm cov nas rau kev kho curcumin hais txog oxidative kev nyuaj siab thiab lub zog indices. Yog li ntawd, curcumin txo qis qhov cuam tshuam loj ntawm PD hauv cov qauv nas thiab tuaj yeem pom tias yog cov khoom noj muaj peev xwm ntxiv [81].

Cov ntaub ntawv pov thawj los ntawm cov ntaub ntawv tau pom tias qhov tsis zoo ntawm txoj kev autophagy-lysosome (ALP) ua lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob PD. Ib txoj kev tshawb fawb tsis ntev los no tau tsom mus rau cov txiaj ntsig ntawm curcumin ntawm alpha-synuclein (S) oligomer los ntawm kev simulation molecular dynamics pom tias curcumin txo cov qauv kev ruaj ntseg ntawm S-oligomer los ntawm kev cuam tshuam nws cov khoom siv dav dav. Tsis tas li ntawd, kev sib sau ua ke ntawm -synuclein oligomers tau tiv thaiv thiab kev tsim cov fibril tsim tau inhibited los ntawm curcumin [82].

Vim tias muaj peev xwm ntawm curcumin hauv kev txo qis misfolded -synuclein los ntawm kev txhawb nqa autophagy, cov kev tshawb fawb tsis ntev los no tau tshawb xyuas nws cov teebmeem ntawm kev tswj autophagy. Yog li, kev kho mob ntawm cov qauv cellular rau PD tau pom tias muaj kev nthuav qhia ntau ntxiv ntawm microtubule-associated protein 1 lub teeb saw 3 (LC3-}II), kev txiav txim siab ntawm nuclear plasma protein ntawm nuclear transcription factor EB (TFEB), thiab autophagy- Muaj feem xyuam rau cov protein lysosome membrane protein 2 (ALAMP2A). Qhov no ua rau kev txhawb nqa autophagy-lysosome synthesis thiab autophagic clearance ntawm -synuclein [83,84].

TFEB tau raug txheeb xyuas tias yog ib qho tseem ceeb ntawm kev tswj hwm ntawm autophagy thiab lysosome biogenesis [8586]. Qhov no tau txhawb qhov kev xav tias TFEBcan yog suav tias yog lub hom phiaj kho tshiab rau PD. Qhov tseeb, curcumin derivative, hu ua E4 (curcumin analog), muaj peev xwm qhib thiab txhawb kev hloov pauv ntawm TFEB los ntawm cytoplasm mus rau hauv lub nucleus. Qhov no translocation yog nrog los ntawm stimulation ntawm autophagy thiab lysosomal biogenesis. Mechanistically, compound E4 activated TFEB ntawm inhibition ntawm AKT-MTORC1 txoj kev. Tsis tas li ntawd, hauv PD cell qauv, E4 tau pom tias txo qis -synuclein qib thiab tiv thaiv cytotoxicity ntawm MPP ntxiv (1-methyl-4-phenylpyridinium ion) hauv cov hlwb neural. Cov ntaub ntawv cog lus no qhia txog kev tiv thaiv hauv vitro ntawm E4 txawm li cas los xij tseem xav tau ntxiv hauv vivo kev sim ntsuas txij li lub hlwb bioavailability ntawm E4 tseem tsis paub. Kev tiv thaiv neuroprotective ntawm E4 yuav tsum tau tshawb nrhiav ntxiv hauv PD tsiaj qauv [87].

Tsis tas li ntawd, nyob rau hauv vivo intraperitoneal txhaj ntawm curcumin txhawb LC 3-II protein qhia thiab inhibited P62 qhia nyob rau hauv txaus siab ntawm autophagy. Curcumin inhibited a-synuclein qhia thiab apoptosis ntawm dopamine neurons nyob rau hauv MPTP-induced PD nas qauv (curcumin 80mg / kg rau 14 hnub) thiab txhim kho kev txav mus los hauv nas 33]. Nws tau raug pom tias kev siv tshuaj loog sevoflurane ua rau muaj kev puas siab puas ntsws los ntawm kev ua kom autophagy hauv hippocampus ntawm cov nas hluas [88]. Interestingly, curcumin muaj peev xwm hloov kho autophagy ntawm 300 mg / kg rau rau hnub thiab inhibit qhov tsis nco qab hauv cov nas vim yog sevoflurane [89]. Cov kev tiv thaiv ntawm curcumin tau tshawb xyuas hauv kev tswj hwm qhov ncauj hauv 6-hydroxy dopamine (6-OHDA)-tus qauv tsiaj ntawm PD.cistanche tubulosa cov txiaj ntsig thiab kev phivCov teebmeem neuroprotective ntawm curcumin ntawm (200 mg / kg) 2 lub lis piam ua ntej thiab tom qab kev phais raug soj ntsuam los ntawm kev soj ntsuam morphological thiab kev coj cwj pwm. Lub cev muaj zog ua haujlwm tau raug ntsuas peb lub lis piam tom qab kev phais. Curcumin tau txhim kho tus cwj pwm tsis zoo ntawm lub cev muaj zog thiab tau pom tias tiv thaiv qhov txo qis dopaminergic neurons hauv substantia nigra thiab caudate-putamen nucleus raws li tau pom los ntawm tyrosine hydroxylase (TH) immunoreactivity.

Kev tswj hwm intraperitoneal ntawm 7-nAChR-xaiv antagonist methyl-aconitine thim rov qab cov teebmeem neuroprotective. Qhov no tau lees paub qhov cuam tshuam ntawm 7-nAChRs hauv curcumin-mediated teebmeem. Hauv txoj kev tshawb no, nws tau pom tias curcumin muaj cov nyhuv neuroprotective hauv 6-hydroxy dopamine(6-OHDA)rat qauv ntawm PD ntawm ib qho 7-nAChR-mediated mechanism [90]. Zhang et al. tau pom tias qhov kev qhia ntawm G2385R-LRRK2 induced neurodegeneration hauv tib neeg neuroblastoma SH-SY5Y thiab nas thawj neurons. Qhov no neurotoxicity kho los ntawm oxidative kev nyuaj siab tshwm sim nyob rau hauv lub activation ntawm apoptotic txoj kev. Curcumin, uas nthuav tawm cov haujlwm antioxidant, tau tiv thaiv kev sib koom ua ke G2385R-LRRK2-induced neurodegeneration los ntawm attenuating mitochondrial ROS theem, caspase-3/7 ua kom, thiab PARP cleavage thiab txo cov cellular ib puag ncig stressor H , O, (Daim duab 2). Cov txiaj ntsig no muab kev pom tshiab rau hauv cov txheej txheem ntawm G2385R-LRRK2- cuam tshuam txog neurodegeneration thiab muaj peev xwm kho cov nyhuv curcumin hauv PD cov neeg mob nqa G2385R [91].

Ntxiv rau qhov kev sib tham saum toj no-curcumin-neuroprotective mechanisms tawm tsam PD, qhov kev txaus siab tshiab ntawm lub plab-hlwb hauv PD tuaj yeem piav qhia txog cov txiaj ntsig zoo ntawm curcumin txawm tias nws muaj kev txwv tsis pub muaj. Qhov tseeb, curcumin tuaj yeem ua tsis ncaj rau CNS ntawm microbiota-gut axis. Lub complex bidirectional system uas plays lub luag hauj lwm tseem ceeb nyob rau hauv lub hlwb kev noj qab haus huv tseem tsis to taub tag nrho.

Cov kev tshawb fawb tsis ntev los no tau pom tias curcumin restores dysbiosis ntawm plab microbiome. Dysbiosis yog txhais tau tias yog ib qho kev ruaj ntseg microbial hauv zej zog uas ua haujlwm tau zoo rau etiology, kuaj mob, lossis kho kab mob [92]. Txawm li cas los xij, kev hloov pauv ntawm curcumin los ntawm cov kab mob tsis tsim cov metabolites ntau dua ntawm curcumin [93]. Qhov kev sib koom ua ke no tuaj yeem tswj hwm kev ua haujlwm ntawm lub cev muaj zog thiab ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv neuroprotection thiab tiv thaiv kev txhim kho PD thiab kev loj hlob. Txawm hais tias muaj kev nce ntxiv, kev tshawb fawb txaus siab rau PD-txuas nrog cov tsos mob tsis yog lub cev muaj zog xws li kev nyuaj siab, olfactory tsis txaus, cem quav, pw tsaug zog, thiab kev coj tus cwj pwm tsis zoo rau cov teebmeem ntawm curcumin ntawm PD xav tau kev tshawb nrhiav ntxiv.

Noj ua ke, curcumin tau pom muaj txiaj ntsig zoo hauv kev kho mob ntawm PD (Table S1) (saib daim duab 1). Txawm li cas los xij, tshawb nrhiav ntau curcumin formulations hauv vivo qauv thiab hauv kev sim tshuaj yuav muab kev nce qib ntxiv hauv kev siv curcumin raws li kev tiv thaiv kev kho mob los thaiv lossis qeeb qhov pib ntawm PD.

4. Curcumin ua tus kws kho mob sib tw hauv MS

MS yog ib tug mob ntev, neuroinflammatory, autoimmune demyelinating kab mob ntawm CNS nyob rau hauv cov hluas uas muaj feem xyuam rau ntau lab tus tib neeg [94]. MS cuam tshuam nrog ntau cov txheej txheem pathophysiological suav nrog kev mob ntev, hloov pauv lub cev tsis muaj zog, ua txhaum BBB raws li rov qab-remitting (RR) ntu, infiltration ntawm ntau cov leukocytes, oxidative kev nyuaj siab, demyelination uas ua rau axonal thiab neuronal puas, remyelin. thiab kho tshuab ua kom [95-98]. Txawm hais tias qhov laj thawj ntawm MS tseem tsis tau paub, cov kws tshawb fawb ntseeg tias MS yog kab mob ntau yam uas cuam tshuam nrog kev sib txuas ntawm caj ces, ib puag ncig, thiab autoimmunological yam uas ua rau muaj kev pheej hmoo ntawm kev tsim MS [99]. Thawj theem ntawm o yog tus cwj pwm los ntawm kev koom tes ntawm IL-22, IL-17, thiab T hlwb ua rau muaj kev ua kom muaj kab mob inflammatory thiab lwm yam kab mob MS, uas yog qhov ua rau demyelination thiab axonal kev puas tsuaj [100]

Txog niaj hnub no, tsuas yog muaj kev kho mob rau MS, uas tsom mus rau kev kho mob rov qab thiab tshem tawm cov mob rov qab. Kev kho MS tam sim no yog hu ua kab mob-hloov kho kho (DMT) uas muaj ntau yam sib txuas tau tsim. Feem ntau ntawm cov kev kho mob no yog cov tshuaj immunomodulatory, pom zoo rau kev kho mob ntawm ntau hom MS thiab lub hom phiaj sib txawv pathophysiological pathways [101,102]. Lwm cov tswv yim kho mob tau siv nrog kev siv cov qia cell kho xws li autologous hematopoietic qia cell transplantation (HSCT) thiab B-cell depleting monoclonal kho [102]. Relapses yog qhov tseem ceeb ntawm kev kho mob ntawm RRMS, tab sis kuj tshwm sim nyob rau hauv thawj theem ntawm theem nrab MS [103]. Qhov kev xaiv ntawm txoj kev kho mob rau kev rov qab los thiab tshem tawm MS(RRMS), tam sim no nyob rau hauv 85-90 feem pua ​​​​ntawm cov neeg mob MS, tseem muaj teeb meem [104]Qhov no yog vim muaj qhov sib txawv ntawm cov tsos mob cuam tshuam nrog MS rau txhua tus neeg. Txawm hais tias muaj ntau txoj kev kho mob muaj, cov kev cov nyom tshiab tau raug tsa hais txog kev txheeb xyuas cov tswv yim kho mob uas tsim nyog rau txhua tus neeg mob. Tsis tas li ntawd, kev nyab xeeb thiab kev ua tau zoo profile rau cov khoom sib xyaw no, nrog rau kev nkag siab txog cov kev mob tshwm sim tshwm sim tseem nyuaj. Cov kev mob tshwm sim, kev kho tsis ua haujlwm, cov ntawv ceeb toom toxicity, thiab tus nqi siab ntawm cov tshuaj siv tshuaj tam sim no yog yam uas txaus siab rau kev txiav txim siab ntawm cov nroj tsuag tshuaj, suav nrog curcumin, rau kev kho mob. Ob peb lub zog ntawm curcumin tsis ntev los no tau raug txheeb xyuas, qee qhov uas yuav ua tau zoo hauv kev kho MS, tshwj xeeb tshaj yog nws cov khoom tiv thaiv kab mob los ntawm inhibiting qhov tso tawm ntawm pro-inflammatory cytokines (Daim duab 1) [103]. Ntawm no, peb yuav tshuaj xyuas ntau yam khoom thiab cov txiaj ntsig tseem ceeb ntawm curcumin rau kev kho MS (Table S1). Muab lub luag haujlwm tseem ceeb ntawm astrocytes hauv kev txhim kho thiab rov qab los ntawm MS, tib neeg astrocyte cell kab (U373-MG) tau siv los ua tus qauv cellular ntawm MS hauv kev kawm ua ntej [105]. Hauv cov hlwb pretreated hlwb nrog LPS, curcumin txo qis kev tso tawm ntawm ob qho tib si IL6 thiab MMP9 kev ua haujlwm, txawm hais tias nws tsis cuam tshuam rau insulin zoo li kev loj hlob (IGF)-1 lossis neurotrophin{19}} mRNA qib. Qhov no txhawb cov nyhuv anti-inflammatory ntawm curcumin ntawm astrocytes hauv CNS [106]. Qhov kev sim autoimmune encephalomyelitis (EAE) ua los ntawm kev txhaj tshuaj myelin rau cov nas tau siv los ua tus qauv sim los kawm MS. Kev txaus siab hauv curcumin raws li tus neeg tuaj yeem kho mob rau MS kuj tseem loj tuaj. Interestingly, kev tshawb pom tsis ntev los no ntawm cov teebmeem ntawm curcumin ntawm Lewis nas qauv ntawm EAE tau pom tias polymerized nanoCUR (PNC) noj ntawm ib koob ntawm 12.5 mg / kg tau txais kev kho mob zoo nrog cov txiaj ntsig tseem ceeb ntawm EAE cov qhab nia thiab pom cov txheej txheem kho myelin. Qhov tseeb, PNC nce myelination los ntawm kev kho kom zoo dua qub uas ua rau muaj kev txhim kho neurotrophic. Tsis tas li ntawd, nws thim rov qab EAE-induced neuroinflammation los ntawm inhibiting cov pro-inflammatory gene qhia NF-kB, IL-1, IL-17, TNF-, MCP-1 thiab nce cov tshuaj tiv thaiv. gene expression IL-4, IL-10, FOXP3, thiab TGF- .Tsis tas li ntawd, PNC tau hloov kho qhov kev qhia ntawm oxidative stress markers. Ntau qhov nthuav, kev kho ua ntej nrog PNChas tau nce cov cim ntawm cov kab mob progenitor thiab ncua EAE txoj kev loj hlob [27,107,108]. Muab qhov tseem ceeb ntawm oligodendrocytes thiab lawv cov tsis paub tab, uas yog lub hom phiaj tseem ceeb rau cov tswv yim kho mob rau kev kho cov kab mob demyelinating, cov txiaj ntsig ntawm curcumin ntawm oligodendrocytes tau kawm. Kev soj ntsuam ntawm qhov cuam tshuam ntawm curcumin ntawm qhov sib txawv ntawm oligodendrocyte progenitor (OP), tshwj xeeb tshaj yog nyob rau hauv cov kab mob inflammatory, tau pom tias curcumin txhim kho qhov sib txawv ntawm OPs los ntawm kev nthuav qhia ntawm cov cim cuam tshuam nrog ntau theem kev loj hlob. Curcumin muaj peev xwm qhib PPAR-y hauv OPs los ntawm kev qhia txog curcumin-dependent nuclear translocation ntawm PPAR- 【109】. Lub peev xwm ntawm curcumin los txhawb kev sib txawv ntawm OPs rau hauv (tsis paub tab oligodendrocytes) OLs koom nrog ntau lub tswv yim, suav nrog PPAR-y thiab ERK1/2 ua kom thiab tiv thaiv TNF- -induced deleterious teebmeem. Kev tshawb fawb tsis ntev los no tau lees paub qhov ua tau zoo ntawm nanoformulation ntawm curcumin ntawm cov yam ntxwv inflammatory hauv cov neeg mob MS. Tseeb tiag, curcumin txo qis qhov kev qhia ntawm miRNAs suav nrog miR-145, miR-132, thiab miR-16, nrog rau cov tshuaj kho mob xws li STAT-1, NF-kB, AP-1, IL-1, IL-6, IFN-y, CCL2, CCL5, TNF- .Ntawm qhov tod tes, nanoCUR tau ua rau muaj kev nce qib hauv kev qhia ntawm Sox2, Sirtuin -1, Foxp3, thiab PDCD1. Tsis tas li ntawd, cov qib secretion ntawm IFN- , CCL2, thiab CCL5 tau txo qis hauv pawg neeg mob kho nrog curcumin piv rau pawg placebo [110]. T helper 1 (Th1) thiab T helper 17 (Th17) hlwb koom nrog hauv MS pathogenesis thiab ntseeg tau tias yog cov hom phiaj kho mob [111](saib daim duab 2). Kev tshawb fawb tsis ntev los no ntawm EAE cov qauv thiab cov neeg mob MS tau hais txog lub luag haujlwm tseem ceeb rau Th17 hlwb hauv kev kho autoimmune neuroinflamation. Th17, cov kab mob pro-inflammatory ntawm effector Th hlwb ntseeg tau tias yog qhov tseem ceeb tshaj plaws cytokines tsim tawm ntawm IL17 [112]. Yog li, cov hlwb no koom nrog hauv demyelination thiab axonal / neuronal degeneration. Interestingly, thaum piv rau cov pab pawg neeg placebo, qhov kev faib ua feem ntawm Th17 hlwb thiab qhia theem ntawm RORyt thiab IL-17 tau txo qis hauv cov neeg mob MS uas tau txais kev txhaj tshuaj interferon -1a (Actovex) txhua lub lim tiam thiab ntxiv nrog. NanoCUR rau 6 lub hlis [113]. Feem ntau, EDSS cov qhab nia hauv pawg MS cov neeg mob uas tau ntxiv nrog nanoCUR qhia tau tias muaj txiaj ntsig zoo dua piv rau pawg placebo. Zuag qhia tag nrho, nanoCUR tuaj yeem cuam tshuam kev kis kab mob hauv MSpatients. Hauv kev xaus, nanoCUR tuaj yeem raug saib raws li tus neeg saib xyuas neuroprotective tiv thaiv kev loj hlob ntawm MS, feem ntau tsom rau cov khoom inflammatory ntawm MS. Lwm cov kev tshawb fawb siv EAE qauv tau qhia txog lub luag haujlwm tseem ceeb ntawm CD4 ntxiv rau kev tswj hwm T (Treg) cell hauv MS pathogenesis thiab exacerbation [114-117]. Nws yog ib qho tseem ceeb uas yuav tsum tau hais tias qhov zaus thiab kev ua haujlwm ntawm Treg hlwb tsis zoo rau cov neeg mob MS[118,119]. Lwm qhov kev tshawb fawb tsis ntev los no los ntawm Dolati li al. piav txog cov teebmeem nanoCUR ntawm Treg muaj nuj nqi thiab zaus hauv cov neeg mob MS. Ib pawg ntawm lawv tau txais cov tshuaj nanoCUR tshuaj ntsiav tsawg kawg rau lub hlis, lwm pab pawg tau txais cov placebo ua pawg tswj hwm. Kev nce zaus ntawm kev ncig Treg nrog kev qhia ntau dua ntawm FoxP3 tau pom hauv cov neeg mob MS. Zuag qhia tag nrho, nano-formulation ntawm curcumin muaj peev xwm txo tus qhab nia EDSS hauv MS cov neeg mob piv rau cov hauv paus, qhia txog kev rov qab los ntawm cov xwm txheej rov ua dua dua li kev txhim kho tiag tiag. Raws li cov txiaj ntsig saum toj no, nws pom tias nanoCUR suav tias yog tus neeg sawv cev tiv thaiv kab mob los ntawm kev tswj hwm kev ua haujlwm ntawm lub cev tiv thaiv kab mob thiab tiv thaiv autoreactivity los ntawm kev hloov pauv qhov kev faib ua feem thiab kev ua haujlwm ntawm Treg hlwb hauv MSpatients [120]. Cov kev soj ntsuam no qhia tau hais tias nanoCUR muaj peev xwm los ntawm kev kho qhov zaus thiab kev ua haujlwm ntawm Treg hlwb hauv MS cov neeg mob, qhia txog cov txheej txheem kho mob uas tshwm sim ntawm curcumin hauv MS kev kho mob raws li lub tswv yim los txhawb cov remyelination.

5. Cov teebmeem ntawm Curcumin hauv Glioblastoma Multiforme

Glioblastoma (GBM) yog qhov mob hnyav tshaj plaws ntawm cov kab mob astrocytic thiab raug cais raws li qib IV glioma raws li WHO kev faib tawm [121]. GBM yog qhov mob qog nqaij hlav loj tshaj plaws hauv lub hlwb thiab suav txog 54 feem pua ​​​​ntawm tag nrho cov gliomas thiab 16 feem pua ​​​​ntawm tag nrho cov kab mob hauv lub hlwb [122]. GBM tseem yog cov qog uas kho tsis tau nrog qhov muaj sia nyob ntawm 14-15 hli tom qab kuaj pom [123,124]. Txawm hais tias muaj kev nce qib hauv kev phais mob, qhov kev cia siab rau cov neeg mob GBM tseem tsis zoo thiab tsis txaus siab [125]. Cov txheej txheem rau kev kho GBM yog qhov kev phais mob siab tshaj plaws ua raws li kev siv hluav taws xob txhua hnub thiab kev siv tshuaj khomob. Temozolomide, tus neeg sawv cev ntawm qhov ncauj alkylating tuaj yeem hla BBB, yog thawj kab kev kho mob tshaj plaws rau GBM tom qab phais. Nws yog siv ua ke nrog kev kho hluav taws xob [126].

Muab qhov tshwm sim ntawm qhov muaj peev xwm metastatic ntawm GBM, ua tiav qhov kev txiav tawm ntawm cov qog yog qhov nyuaj. Ntau yam tuaj yeem cuam tshuam cov txiaj ntsig ntawm cov kev kho mob sib xyaw ua ke, suav nrog kev ua haujlwm tsis zoo ntawm lub hlwb thiab cov tshuaj tiv thaiv ntau yam (MDR), uas ua rau GBM hlwb ua rau pom cov lus teb tsis zoo ntawm monotherapy txawm tias rov qab los ntawm cov kab noj hniav tsis zoo 127. Qhov tseeb, qhov ua tau zoo. ntawm cov tshuaj chemotherapy tshuaj temozolomide (TMZ) feem ntau yog txwv los ntawm kev siv tshuaj tiv thaiv thiab qhov cuam tshuam ntau ntxiv [128,129]. Yog li, kev kho mob GBM tseem nyuaj thaum muaj qhov xav tau ceev los txhim kho cov txiaj ntsig ntawm kev kho mob thiab txheeb xyuas cov phiaj xwm tshiab rau kev kho GBM.

Cov kev tshawb fawb tsis ntev los no tau pom tias curcumin tsis tsuas yog ua haujlwm los tiv thaiv mob qog noj ntshav hauv lub ntsws, qhov quav, thiab mob qog noj ntshav, feem ntau yog vim nws cov tshuaj tiv thaiv kab mob antioxidant thiab tiv thaiv kab mob, tab sis kuj vim tias nws ua rau muaj txiaj ntsig ntawm hluav taws xob thiab tshuaj tua kab mob, ua rau muaj kev txhim kho hauv lub cev. kev muaj sia nyob nrog rau kev qhia txog cov tshuaj tiv thaiv metastatic[130], thiab txo qis, tib lub sijhawm, lawv cov kev mob tshwm sim[131-134]. Interestingly, curcumin txhim kho thiab ua rau cov kev ua haujlwm apoptotic tawm tsam cov qog hlwb uas cuam tshuam nrog cov txheej txheem sab hauv thiab sab nrauv raws li tau piav qhia yav dhau los [10,135]. Yog li ntawd, kev sib xyaw ua ke ntawm curcumin nrog kev kho tshuaj khomob lossis kev khomob hluav taws xob tuaj yeem ua rau muaj kev cuam tshuam ntawm cov qog nqaij hlav cancer rau kev khomob lossis kev kho hluav taws xob thiab txhim kho kev ua haujlwm ntawm cov tshuaj khomob. Tseeb, qhov kev qhia ntawm caspase-3 thiab Bax tau nce, tab sis kev qhia ntawm Bcl-2 thiab HIF1in U251 hlwb tau txo qis tom qab kev kho mob nrog 20 thiab 30 μM curcumin. Ob leeg HIF-1 thiab ENO1 qhia hauv U251 hlwb txo. Hauv cov xwm txheej hypoxic, HIF-1 tuaj yeem ua raws li qhov tseem ceeb ntawm kev hloov pauv mus ua kom cov encoded glycolytic enzymes suav nrog ENO1.

Nws tau raug sau tseg zoo tias nce glycolysis yog suav tias yog ib qho ntawm cov khoom metabolic ntawm GBM [136]. Enolase yog ib qho tseem ceeb glycolytic enzyme thiab ENO1 yog nws cov isoform loj, uas tau qhia hauv GBM. Hauv tib txoj kev tshawb fawb, ENO1 tau txo qis uas ua rau muaj kev cuam tshuam ntawm kev loj hlob, kev tsiv teb tsaws, thiab cuam tshuam kev loj hlob ntawm glioma hlwb. Hauv kev xaus, ENO1 tuaj yeem yog lub hom phiaj muaj peev xwm rau curcumin thiab nws cov tshuaj tiv thaiv kab mob qog noj ntshav tuaj yeem cuam tshuam nrog glycolytic thiab apoptotic txoj hauv kev [137]. Cov kev tshawb pom no tau lees paub los ntawm cov ntaub ntawv tshawb fawb tsis ntev los no qhia tias ob qho tib si nanomicelle-curcumin thiab curcumin hauv kev sib xyaw nrog Erlotinib txo qis kev muaj peev xwm, kev tsiv teb tsaws, thiab kev cuam tshuam ntawm tib neeg glioblastoma hlwb U87 hauv vitro. Ob leeg ntxeem tau thiab tsiv teb tsaws ua lub luag haujlwm tseem ceeb hauv kev mob qog noj ntshav metastasis. Interestingly, qhov kev qhia ntawm angiogenesis-nrog rau cov yam ntxwv xws li VEGF, HIF-1 , bFGF, thiab Cox{10}} tau txo qis hauv U87 tib neeg glioblastoma hlwb. Ntawm qhov tod tes, curcumin ib leeg lossis ua ke nrog Erlotinib nce qhov kev qhia ntawm autophagy-associated proteins (LC3-I, LC3-}I, thiab Beclin1) thiab hloov kho qhov kev qhia ntawm pro-apoptotic yam. Bax, Caspase 8, thiab Bcl-2 nrog cov pro-inflammatory NF-kB (saib daim duab 2) [138].

Tsis tas li ntawd, kev qhia ntawm cov noob muaj feem xyuam nrog Wnt txoj hauv kev xws li cyclin D1, ZEB1, -catenin, thiab Twist tshwm sim los ntawm curcumin [139]. Nyob rau theem molecular, curcumin tau pom tias inhibit qhov kev loj hlob ntawm GBM cell proliferation ntawm AKT / mTOR signaling txoj kev thiab kom nce PTEN qhia. Cov kev sim hauv vitro ntawm txoj kev tshawb fawb no tau lees paub tsis tu ncua tias curcumin inhibits kev tsiv teb tsaws thiab kev cuam tshuam ntawm U251 hlwb tau los ntawm tib neeg malignant Glioblastoma multiforme thiab txhawb nqa apoptosis [140].

Ntau txoj hauv kev tau thov kom ua tiav kev nkag mus rau BBB zoo dua thiab tso tawm cov tshuaj intracephalic zoo thiab muab cov tshuaj tiv thaiv zoo rau GBM. Hauv cov txheej txheem no, curcumin tau encapsulated nyob rau hauv qhov chaw-hloov kho polyamidoamine (PAMAM) dendrimers ntawm plaub tiam. Qhov tseem ceeb, hauv vitro siv cov encapsulated curcumin ntawm cov tshuaj kho tau txo qis kev muaj peev xwm ntawm ntau lub hlwb glioblastoma los ntawm peb hom sib txawv (U98, F98, thiab GL261) [141]. Nws paub tias cov qog nqaij hlav cancer yuav tsum muaj lub xeev oxidative siab kom tswj tau lawv txoj kev loj hlob thiab kev loj hlob. Raws li tau piav qhia saum toj no, curcumin yog ib qho nutraceutical compound paub txog nws cov kev tiv thaiv kab mob thiab cov tshuaj tua kab mob antioxidant thiab yog li ntawd tuaj yeem yog lwm txoj hauv kev zoo rau kev kho mob ntawm GBM kev puas tsuaj. Txawm li cas los xij, qhov kev ntsuam xyuas ntawm lub peev xwm ntawm curcumin rau GBM yog txuas rau lwm cov kev kho mob uas twb muaj lawm tab sis yuav tsum muaj kev kawm yav tom ntej hauv vivo nrog cov nas ua qauv ntawm glioblastoma. Txhawm rau txhim kho BBB nkag mus thiab kom ua tiav cov tshuaj xa mus rau nas glioblastoma, tus kab mob rabies glycoprotein polypeptide derivative (RVG) peptide-directed, doxorubicin-loaded thiab curcumin-pab txo rhiab heev nanomicelle (DOX/RVG-CSC) tau siv. Kev tsim nyog ntawm curcumin txhawb nqa tag nrho cov repolarization ntawm microglia, uas nyob rau hauv lem txhawb kev hloov ntawm GBM hlwb los ntawm lub xeev immunosuppressive M2 mus rau ib tug raug phenotype M1 [142]. Vim nws qhov tshwj xeeb microenvironmental compatibility thiab affinity rau intracerebral gliomas, chondroitin sulfate (CHS) tau siv los ua ntu hydrophilic [143] thiab conjugated rau curcumin ntawm disulfide bonds. Qhov no ua rau nws tus kheej sib sau ua ke cov tub ntxhais-plhaub polymeric micelles hauv dej. RVG-mediated DOX/RVG-CSC nkag mus rau BBB, mus txog lub hom phiaj thaj tsam ntawm cov qog cell thiab tom qab ntawd, tom qab stimulation los ntawm siab glutathione concentration hauv GBM, tso tawm cov tshuaj nquag [144]. Tsis tas li ntawd, kev tshawb pom tsis ntev los no qhia tau hais tias curcumin tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev tshem tawm GMB hlwb los ntawm kev txhawb lub cev tiv thaiv kab mob [145,146].

Lub luag haujlwm tam sim no ntawm curcumin nyob rau hauv cov ntsiab lus ntawm GBM tau tshawb fawb los ntawm cov kev tshawb fawb txog kev ua haujlwm hauv nas qauv ntawm GBM. Tsis ntev los no, Baidoo et al. tau kawm txog kev siv lub cev tiv thaiv kab mob hauv lub cev hauv kev kho mob rau kev tshem tawm cov qog nqaij hlav cancer. Lawv pom tias cov qog muaj cov macrophages thiab microglia hauv lawv cov niches, tab sis feem ntau nyob rau hauv lub xeev ntawm qog-txhim M2 nyob rau hauv kev tswj ntawm qog-tso cytokines. Qhov tseem ceeb tshaj plaws pom tshwm sim los ntawm lawv cov txiaj ntsig yog tias curcumin induced repolarization ntawm cov qog-koom nrog macrophages (TAM) rau hauv nitric oxide (NO)-ua qog nqaij hlav M1 phenotype. Qhov no M2 → M1 hloov koom nrog cov curcumin-mediated suppression ntawm STAT-3 thiab induction thiab ua kom STAT-1. Qhov no recruits lub activated natural killer cells (NK) thiab cytotoxic T (Tc) rau hauv cov qog thiab thiaj li tshem tawm cov qog nqaij hlav cancer thiab cov qog nqaij hlav cancer. Yog li, txoj hauv kev no tuaj yeem muab cov tswv yim dav dav rau kev sib ntaus sib tua GBM, tab sis xav tau kev tshawb fawb ntxiv kom nkag siab zoo dua qhov cuam tshuam ntawm ntau yam cuam tshuam rau curcumin-anticancer txoj hauv kev [147-150]. Tsis tas li ntawd, qhov no tau qhib qhov kev cia siab ntawm Phase I / II kev sim tshuaj hauv cov neeg mob GBM los tshawb xyuas qhov ua tau zoo ntawm lawv cov curcumin-based therapy kom induce repolarization ntawm TAMs.

Hauv cov ntsiab lus, curcumin tuaj yeem hloov kho GBM-txuas txoj hauv kev. Piv txwv li, curcumin inhibits qog loj hlob los ntawm kev thaiv cov qog-txhim kho txoj hauv kev NF-kB, PI3k / Akt / mammalian lub hom phiaj ntawm rapamycin (PI3K / Akt / mTOR), Janus kinase / signal transducers, thiab activators ntawm transcription (JAK / STAT3) thiab mitogen. -activated protein kinase txoj hauv kev, thaum lub qog loj-tshuaj noob caj noob ces (piv txwv li, p53 thiab p21, thiab caspase) tau nce- tswj [151].

Raws li tag nrho cov kev tshawb pom hauv vitro ntawm curcumin, lwm yam txiaj ntsig hauv vivo cuam tshuam ntawm curcumin ntawm GBM tau tshaj tawm (Table S1), suav nrog inhibition ntawm matrix metalloproteinases (MMP)-nyob ntawm cell migration thiab invasive cell proliferation, uas tom qab ntawd coj mus rau txo cov qog ntim thiab, tib lub sijhawm, lub sijhawm muaj sia nyob ntev dua [137].

Txhua qhov kev sib tham curcumin qhia tau hais tias kev ua haujlwm / kev ua haujlwm ntawm glioblastoma hlwb raug hloov kho, thiab lawv txoj kev loj hlob qeeb (Daim duab 1). Txawm li cas los xij, genome profiling ntawm glioblastoma cov qog thiab kev txheeb xyuas cov hom phiaj tshwj xeeb ntawm curcumin rau kev kho mob GBM tseem yog ib qho tseem ceeb hauv kev nkag siab txog nws cov tshuaj siv tshuaj thiab, qhov tseem ceeb tshaj, tuaj yeem muab lub hauv paus theoretical rau kev siv curcumin hauv kev kho mob. Kev tshawb fawb ntxiv yuav tsum raug txiav txim siab rau daim ntawv tshaj tawm kawg ntawm kev kho mob ntawm curcumin hauv kev kho mob ib leeg lossis ua ke nrog cov khoom siv tshuaj. Qhov muaj feem cuam tshuam ncaj qha rau lub hlwb kev noj qab haus huv thiab kev tiv thaiv glioblastoma los ntawm lub plab-hlwb axis yuav tsum tau tshawb xyuas ntxiv.

6. Curcumin thiab Epilepsy

Cov kab mob ntawm CNSare tam sim no yog ib qho teeb meem loj ntawm kev sib raug zoo thiab tus kheej. Tshwj xeeb, cov ntaub ntawv pov thawj kis kabmob tshiab tshiab qhia tau hais tias kev mob qaug dab peg yog ib pab pawg neeg coob zuj zus tuaj thoob ntiaj teb. Vim li no, ntau xyoo, ntau thiab ntau cov tshuaj thiab kev kho mob tau tsim los tiv thaiv cov tsos mob thiab zaus ntawm qaug dab peg; Txawm li cas los xij, ntau yam ntawm cov tshuaj no tau pom tias muaj txiaj ntsig zoo, tab sis lawv kuj muaj lub luag haujlwm rau kev mob tshwm sim hnyav thiab nquag. Qhov tseeb, ntau cov nroj tsuag tshuaj tau kawm tsis ntev los no, thiab curcumin yog ib qho ntawm cov no. Curcumin zoo li ua lub luag haujlwm hauv kev tswj hwm ntawm lub hlwb monoamine ntau ntau thiab qhov no yuav qhia tau tias muaj peev xwm tiv thaiv kev qaug dab peg thiab kev paub tsis meej (tshwj xeeb yog hais txog kev puas hlwb). Curcumin tau pom tias muaj cov nyhuv antioxidant 10 npaug ntau dua li cov vitamin E thiab sawv cev rau lwm txoj hauv kev rau vitamin E nws tus kheej [152].

Curcumin yeej muaj peev xwm inhibiting NF-kB mediated transcription, inflammatory cytokines, inducible iNOS, thiab Cox -2 ua rau nws cov antioxidant thiab anti-inflammatory zog [153]. Cov khoom no qhia nws lub luag haujlwm hauv neuroprotection thiab neuromodulation hauv cov txheej txheem epileptogenesis tau piav qhia (Table S1) (Daim duab 1).

Cov tshuaj tiv thaiv kab mob vwm ntawm curcumin kuj tuaj yeem ua tiav los ntawm kev tswj hwm ntawm cov tshuaj tiv thaiv kab mob xws li Interleukin -10 receptor subunit beta gene, thiab chemokine ligand16 (CXCL16), CXCL17, thiab NCSTN [154]. Tsis ntev los no cov kev tshawb fawb preclinical tau pom tias curcumin tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev qaug dab peg thiab nws cov kab mob cuam tshuam nrog tsis muaj kev phiv lossis tsis zoo [155,156]. Qee qhov kev sim kev tshawb fawb raws li tus qauv ua rau qaug dab peg tau tshaj tawm cov txiaj ntsig ntawm curcumin hauv kev ncua lossis cuam tshuam tag nrho qhov pib ntawm qaug dab peg [157].

Curcumin kuj tau pom zoo los ua lub luag haujlwm hauv kev txiav txim siab txo qis ntawm qee cov channel proteins (CACNA1A thiab GABRD), uas ua rau muaj kev cuam tshuam tom qab ntawm FeClg-induced qaug dab peg (Daim duab 2). Kev tswj hwm ntawm curcumin reproduces tib neeg qauv ntawm post-traumatic epilepsy [158]. Micronized curcumin tau pom tias muaj txiaj ntsig zoo piv rau cov tshuaj tiv thaiv kab mob vwm valproate hauv inhibiting tonic-clonic qaug dab peg hauv PTZ-induced qauv ntawm qaug dab peg nyob rau hauv ob qho tib si larvae thiab neeg laus zebrafish [159]. Hauv lwm txoj kev tshawb fawb, kev soj ntsuam ntawm cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob ntawm curcumin tom qab koob tshuaj ntau ntawm FeCl; noj nrog kev noj zaub mov thiab ntsuas hauv qhov chaw ntawm ib lab (1500 ppm) tau pom tias muaj txiaj ntsig zoo hauv kev tiv thaiv kev qaug dab peg piv rau cov koob tshuaj tsawg (500 ppm) [160].

Nyob rau hauv tus qauv ntawm kev nce-voltage electroshock test nyob rau hauv nas, curcumin ntawm ib koob ntawm 100 mg / kg ntawm qhov ncauj nce qhov qaug dab peg nyob rau hauv ob qho tib si mob thiab mob vwm (rau 21 hnub) [161]. Cov nyhuv no yog piv rau kev tswj hwm ntawm phenytoin (25 mg / kg PO) [161]. Hauv txoj kev tshawb no, kev txo qis hauv kev tuag tau pom txawm tias muaj kev tswj hwm curcumin ntev, piav qhia txog cov nyhuv anticonvulsant ntawm cov tshuaj no. Cov kev tshawb fawb ua ntej ua ntej tau lees paub nws cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob. Tsis tas li ntawd, curcumin tau pom los ua lub luag haujlwm tiv thaiv hauv kev hloov pauv ntau yam kev ntxhov siab oxidative cuam tshuam nrog pilocarpine stimulation [162]. Cov ntaub ntawv no kuj tau lees paub los ntawm lwm txoj kev tshawb fawb uas tau soj ntsuam cov koob tshuaj curcumin ntawm 10 thiab 300 mg / kg uas tau pom tias muaj txiaj ntsig zoo hauv kev txo qis pilocarpine vim qaug dab peg [163]

Curcumin kuj tau qhia nws cov teebmeem hauv lub xeev mob vwm. Tseeb tiag, txoj kev tshawb fawb los ntawm Gupta li al.[164], kwv yees kev tswj hwm ntawm curcumin nyob rau hauv ib koob ntawm 50-200mg / kg kwv yees li 30 min ua ntej stimulation nrog kainic acid. Cov kws sau ntawv ntawm txoj kev tshawb fawb no tau pom qhov kev tiv thaiv ntawm curcumin hauv kev ua kom lub latency ntawm qhov pib ntawm qaug dab peg thaum noj tshuaj ntawm 100 thiab 200 mg / kg. Tib pab pawg tau pom qhov txo qis hauv qhov tshwm sim ntawm qaug dab peg [164]. Cov koob tshuaj qis dua tsis pom muaj txiaj ntsig zoo. Kev soj ntsuam ntawm cov tsiaj hlwb tom qab ntawd pom tias kev qaug dab peg ntev npaum li cas nce MDA qib thiab txo qis glutathione. Cov nyhuv no tsuas yog thim rov qab nrog koob tshuaj 100 thiab 200 mg / kg ntawm curcumin. Cov koob tshuaj qis dua tsis muaj txiaj ntsig zoo [164].

Curcumin kuj tau pom tias muaj txiaj ntsig zoo hauv kev txo qis kev xav thiab oxidative kev nyuaj siab los ntawm kev siv cov tshuaj tiv thaiv kab mob ntev xws li phenobarbital thiab carbamazepine uas tau siv dav hauv kev kho mob [165].

Tsis tas li ntawd, qhov ua tau zoo ntawm curcumin nyob rau hauv cov kab mob vwm uas muaj feem cuam tshuam tau raug lees paub los ntawm kev tshawb fawb nrog txiv neej Wistar nas hauv PTZ-vim txoj kev. Hauv txoj kev tshawb no, kev tswj hwm ntawm 300 mg / kg ntawm curcumin ua rau ob qho tib si txhim kho qhov pib ntawm PTZ-vim qaug dab peg thiab txo qis hauv oxidative kev nyuaj siab, thiab txo qis hauv kev txawj ntse [165].

Raws li paub, kev tswj hwm ntev ntawm qee cov tshuaj tiv thaiv kab mob xws li carbamazepine thiab phenobarbital tuaj yeem ua rau muaj kev paub tsis meej uas tau ntseeg tias yog los ntawm oxidative kev nyuaj siab. Curcumin, thaum noj ua ke nrog cov tshuaj tiv thaiv kab mob no tau pom tias yuav thim rov qab qhov kev paub txog kev poob qis nrog rau oxidative kev ntxhov siab tsis zoo [165]

Lwm cov kev tshawb fawb, tshuaj xyuas qhov ua tau zoo ntawm curcumin hauv cov kab mob hauv lub paj hlwb thiab kev puas siab puas ntsws nrog rau kev paub tsis meej, tau pom tias tsis muaj kev paub txog kev poob qis hauv cov nas uas tau noj curcumin piv rau kev paub poob qis hauv cov nas uas noj phenytoin [166]. Kev txhaj tshuaj ntawm piperine ua ke nrog curcumin tuaj yeem txhim kho nws cov bioavailability thiab ua rau nws cov tshuaj tiv thaiv kab mob vwm ntau dua [167].

Cov kev tshawb fawb no muaj kev txhawb zog heev thiab sawv cev rau lub hauv paus rau kev tshawb fawb yav tom ntej txawm tias muaj kev txwv ob qho tib si hais txog qhov nyuaj ntawm kev tsim tawm ntawm tib neeg epileptogenic networks pib los ntawm cov qauv kev sim thiab qhov nyuaj ntawm kev hloov cov koob tshuaj hauv cov qauv sim rau hauv koob tshuaj rau tib neeg.

7. Cov lus xaus

Lub ntuj tsim Curcumin muaj cov tshuaj tiv thaiv oxidant, thiab cov khoom tiv thaiv kab mob, thiab muaj kev tiv thaiv los ntawm kev ua ntawm ntau txoj hauv kev ntawm tes. Hauv qhov kev tshuaj xyuas no, peb tsom ntsoov rau peb cov kev mob siab rau kev kho mob ntawm curcumin hauv cov kab mob neurodegenerative xws li AD, PD, MS, glioblastoma, thiab qaug dab peg los ntawm kev hloov pauv ntau txoj hauv kev molecular hauv hlwb hlwb (saib Table S1 thiab Daim duab 2). Extracellular vesicles los yog nanovesicles yuav txhim kho cov solubility thiab bioavailability ntawm curcumin nyob rau hauv lub hlwb, tab sis txog rau tam sim no, daim ntawv thov ntawm cov tshiab txoj kev ntawm curcumin xa yog tsis tau tag nrho tshawb fawb nyob rau hauv cov kab mob neurodegenerative. Yog li, kev tshawb fawb ntau ntxiv siv cov tshuaj biomolecules no tuaj yeem ua rau muaj txiaj ntsig zoo rau kev tiv thaiv kab mob. Cov kev tshawb fawb tshiab no yuav raug focalized rau (1) txhim kho cov kev xa tshuaj los txhim kho bioavailability thiab BBB permeability ntawm curcumin; (2) kev tshawb fawb soj ntsuam ntxiv los tsim cov koob tshuaj zoo dua ntawm cov biomolecules thauj curcumin rau kev kho mob neurodegenerative ntshawv siab;(3 ) tshawb xyuas cov kev taw qhia txoj hauv kev uas kho biomolecules siv los ua kom muaj kev tiv thaiv neuroprotection. Cov txiaj ntsig tau piav qhia hauv qhov kev tshuaj xyuas no tau txhawb nqa tab sis kev tshawb fawb ntxiv yog xav tau los txhim kho kev siv curcumin hauv kev tiv thaiv thiab kho cov kab mob neurodegenerative.

Kab lus no yog muab rho tawm los ntawm Molecules 2022, 27, 236. https://doi.org/10.3390/molecules27010236 https://www.mdpi.com/journal/molecules