Punicic Acid Thiab Nws Lub Luag Haujlwm Hauv Kev Tiv Thaiv Cov Kab Mob Neurological: Kev Ntsuam Xyuas Ntu 3

3.2. Punicic Acid cuam tshuam rau Kab Mob Neurodegenerative

Punicic acid tuaj yeem cuam tshuam txog kev tiv thaiv neurodegeneration los ntawm ntau txoj kev sib txawv, suav nrog (1) cov txheej txheem intracellular ntsig txog oxidative puas tsuaj los ntawm peroxisome proliferator-activated receptor (PPAR)s thiab high-density lipoprotein (HDL) txuam nrog paraoxonase 1 (PON1); (2) cov ntaub so ntswg hauv cheeb tsam xws li synaptic functionvia calpains, thiab (3) ib puag ncig zoo xws li mob thiab lipid metabolism viaPPARs thiab cov piam thaj metabolism nrog cov piam thaj transporter hom 4 (GLUT4) (Table 1).

Exosomes yog cov khoom nyob rau hauv cov hlwb uas ua lub luag haujlwm tseem ceeb hauv kev tswj cov kev ua haujlwm ntawm lub cev ntawm cov hlwb. Kev tshawb fawb nyob rau hauv xyoo tas los no tau pom tias peroxisomes muaj feem xyuam nrog tib neeg kev nco thiab ua lub luag haujlwm tseem ceeb hauv kev txhim kho tib neeg kev txawj ntse.

Ua ntej, exosomes tuaj yeem txhawb lub zog metabolism hauv cov hlwb thiab nce lub cev lub zog. Qhov no yog tshwj xeeb tshaj yog pom nyob rau hauv tib neeg lub hlwb vim hais tias lub hlwb yog ib tug ntawm cov complex kab mob nyob rau hauv tib neeg lub cev thiab yuav tsum tau ib tug loj npaum li cas ntawm lub zog los pab txhawb tib neeg txoj kev xav, nco, thiab lwm yam dej num. Yog tias qib ntawm peroxisomes hauv lub cev tuaj yeem tswj tau zoo, tib neeg lub cim xeeb yuav ruaj khov thiab kav ntev.

Qhov thib ob, exosomes tuaj yeem txhawb kev tshem tawm cov dawb radicals hauv lub cev thiab tiv thaiv cov hlwb los ntawm kev puas tsuaj los ntawm kev tawm tsam dawb radicals. Dawb radicals yog cov khoom ntawm cell metabolism. Lawv muaj nyob rau hauv cov nyiaj loj hauv tib neeg lub cev thiab tuaj yeem ua rau cov qauv thiab kev ua haujlwm ntawm cov molecules hauv cov hlwb. Yog tias peroxisomes hauv lub cev tuaj yeem tshem tawm cov dawb radicals zoo, kev noj qab haus huv thiab kev ruaj ntseg ntawm cov hlwb tuaj yeem tswj tau, yog li txhim kho tib neeg kev nco thiab kev txawj ntse.

Thaum kawg, oxisomes kuj tuaj yeem txhim kho tib neeg lub peev xwm antioxidant, yog li tiv thaiv lub cev los ntawm kab mob. Tib neeg txoj kev noj qab haus huv muaj feem xyuam nrog kev nco. Yog tias lub cev muaj kev noj qab haus huv, tib neeg lub cim xeeb thiab kev txawj ntse kuj yuav muaj zog dua. Oxisosomes yog cov antioxidants zoo uas tiv thaiv lub cev los ntawm cov dawb radicals thiab tiv thaiv lub cev tsis muaj zog vim muaj kab mob.

Hauv luv luv, exosomes muaj qhov cuam tshuam loj heev rau tib neeg kev nco thiab kev txawj ntse. Lawv tuaj yeem tswj cov metabolism hauv cov hlwb, tiv thaiv cov hlwb los ntawm cov dawb radicals, thiab txhim kho tib neeg lub peev xwm antioxidant. Yog li ntawd, peb yuav tsum nquag tswj cov qib ntawm peroxisomes hauv lub cev kom ntxiv dag zog rau peb lub cim xeeb thiab kev txawj ntse. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov neurotransmitters, xws li nce qib ntawm acetylcholine thiab kev loj hlob. Cov khoom no tseem ceeb heev rau kev nco thiab kev kawm. Tsis tas li ntawd, Cistanche deserticola kuj tseem tuaj yeem txhim kho cov ntshav khiav thiab txhawb nqa cov pa oxygen, uas tuaj yeem ua kom lub hlwb tau txais cov as-ham txaus thiab lub zog, yog li txhim kho lub hlwb tseem ceeb thiab kev ua siab ntev.

Nyem paub 10 txoj hauv kev los txhim kho kev nco

Punicicacid tuaj yeem ua tus agonist ntawm PPAR, nce mRNA qhia ntawm PPAR-, PPAR-, PPAR-, thiab PPAR-, thiab khi rau ob qho tib si PPAR- thiab PPAR- [83,84]. Nws nce GLUT4protein qhia [85] thiab ua kom cov khoom tiv thaiv oxidative ntawm HDL thiab PON1 kev ua [86,87].

Thaum kawg, punicic acid tuaj yeem ua tus inhibitor ntawm calpain, uas ua lub luag haujlwm tseem ceeb hauv ROS tiam, thiab calpain tuaj yeem ua lub luag haujlwm hauv mitochondrial ROS tiam thiab HDL degradation [88].

3.2.1. Punicic Acid nce kev nthuav qhia ntawm Peroxisome Proliferators Activated Receptors (PPARs)
Muaj kev sib raug zoo ntawm lub luag haujlwm ntawm PPARs xws li PPAR-, PPAR- / δ, thiab PPAR- thiab cov kab mob neurodegenerative, tshwj xeeb yog Alzheimer's. Hauv lub hlwb, kev ua ub ua no los ntawm PPAR- suav nrog txo qis hauv oxidative kev nyuaj siab, neuroinflammation, tauhyperphosphorylation, tsawg A tsim thiab sib sau ua ke, qabzib metabolism, autophagy, neurotransmission, thiab yam ntawm lipid metabolism xws li fatty acyl-CoA -oxidation thiab PUFA biosynthesis.

Ib yam li ntawd, PPAR- / δ tswj lub hauv paus paj hlwb myelinationprocess, thaum PPAR- koom nrog hauv neuron biogenesis, neuroinflammation, thiab neurodegeneration [89,90]. Hauv cov neeg mob uas muaj kab mob hauv lub paj hlwb, PPARs raug txo qis [91].

Cov teebmeem ntawm punic acid ntawm PPARs tau kawm dhau sijhawm. Cov pov thawj qhia tau hais tias punicic acid txo qhov mob tshwm sim los ntawm pro-inflammatory cytokinesTumor Necrosis Factor Alpha (TNF- ) thiab Interleukin 6 (IL-6) ntawm 3T3-L1 pre-adipocytes.

Ib yam li ntawd, punicic acid-enhanced protein qhia ntawm PPAR- abates transcriptional kev ua ntawm Nuclear Factor Kappa B (NFκB) p65 subunit, txo mRNA qhia ntawm suppressorof cytokine signaling 3 (SOCS3), thiab attenuates protein tyrosine phosphatase 1B (PTP1B) hauv [83, 84].

Ib txoj kev tshawb fawb tsis ntev los no hauv nas lub siab tau noj cov zaub mov muaj roj ntau ntxiv nrog PSO nanoemulsions pom tias punicic acid nce qhov kev qhia ntawm lipidmetabolism ntsig txog cov noob PPAR-, PPAR- thiab PPAR-, fatty acid synthase (Fasn), andsterol regulatory element-binding. transcription factor (Srbp1), nrog rau cov tshuaj antioxidant (aldehyde oxidase 1 (Aox1), glutathione S-transferase A4 (Gst4), NAD(P)H quinone dehydrogenase 1 (Nqo1), Nrf2, thiab peroxiredoxin 1 (Prdx1), thiab txo qis. qib IL-6 thiab TNF- [12].

Cov nyhuv Punicic acid tshaj PPARs kuj muaj feem xyuam rau HDL metabolism. Rabbitssupplemented nrog microencapsulated pomegranate pom qhov hloov lipid muaj pes tsawg leeg ntawm HDL hais. PPAR thiab PPAR tuaj yeem hloov kho HDL cov qauv los ntawm kev tswj hwm kev qhia ntawm cov noob ntsig txog HDL metabolism [86].

3.2.2. Punicic Acid Kev Koom Tes hauv Calpain Hyperactivation Inhibition

Calpains yog calcium-dependent cysteine ​​proteases uas tau cuam tshuam rau ntau yam kab mob neurodegenerative xws li Alzheimer's thiab Huntington's Disease. Calpains yog qhov tseem ceeb rau kev ua haujlwm ntawm synaptic thiab neuroplasticity, raws li lawv siv cov nyhuv neuroprotective ntawm lub hauv paus qhia, thaum overactivation ua rau neurotoxicity. Calpain-1 thiab calpain-2 muaj ntau nyob rau hauv lub hlwb, thiab lawv cov hyperactivation cuam tshuam rau theem lig ntawm cov kab mob neurodegenerative [92].

Calpain -1 yog overexpressed nyob rau hauv lub lig theem ntawm Alzheimer's, tsim tshuaj lom fragments ntawm tau nyob rau hauv teb rau A aggregate kev kho mob. Calpain-2, ntawm qhov tod tes, tau pom pom tias muaj kev nce ntxiv thaum ntxov hauv pathogenesis ntawm Alzheimer's hauv tus qauv nas thiab tau cuam tshuam nrog kev paub tsis meej thiab nce A hauv cov ntaub so ntswg neocortical los ntawm Alzheimer's cov neeg mob [92,93].

Cov nas uas induced Machado-Joseph Disease (MJD) phenology tau nthuav tawm ib qho overactivated calpain system hauv paus thiab ua rau nce cell tuag nyob rau hauv lub cerebellum. Kev tshem tawm ntawm calpain -2 hauv cov nas nrog induced MJD phenology ua rau txo qis neurotoxicity thiab nce kev ciaj sia ntawm cov nas [94].

Calpain inhibitors paub tias muaj cov teebmeem neuroprotective; Yog li ntawd, cov tuam txhab tshuaj tau tsim cov tshuaj calpain inhibitors ua cov tshuaj kho mob rau Alzheimer's, ntawm lwm cov NDs [95].

Calpain inhibition cov teebmeem tau pab txhawb rau cov teebmeem neuroprotective nthuav tawm los ntawm PSO-nanoformulation kev lag luam raws li cov khoom lag luam GranaGard®. Cov txheej txheem muaj cov qib siab ntawm cov kua qaub punicic thiab ua rau raug kaw ntawm tus kab mob Creutzfeldt-Jakob (CJD) rau 60-80 hnub, ua raws li cov kab mob qeeb qeeb [88]. Qhov no tib formulation tau pom los txo A tsim, cyclin-dependent kinase 5 (cdk5) tsub zuj zuj, thiab tseem ceeb mitochondrial enzyme Cytochrome c oxidase nyob rau hauv cov nas transgenic [43].

Tsis tas li ntawd, cov kev tshawb fawb ducking tau lees paub tias punicic acid's metabolite, CLA, inhibits qhov chaw nquag ntawm µ-calpain, ua rau cov teebmeem neuroprotective tiv thaiv H2O2 thiab induced A degradation inhuman neuroblastoma cell kab [96].

3.2.3. Punicic Acid Induced Higher Expression of GLUT4

Lwm qhov tshwm sim rau ntau yam kab mob neurodegenerative yog kev cuam tshuam inglucose metabolism thiab kev ua haujlwm thiab kev qhia ntawm cov piam thaj thauj khoom. Piv txwv li, hypometabolism ntawm cov piam thaj vim qhov txo qis ntawm cov piam thaj thauj mus rau hauv lub hlwb tshwm sim hauv Alzheimer's disease [97].

Ib yam li ntawd, lub zog thiab cov piam thaj metabolism cuam tshuam tau pom zoo los ua lub luag haujlwm hauv kev txhim kho Huntington's diseasepathology [98]. Tib neeg lub hlwb qhia txog kaum qhov sib txawv ntawm sodium-yeeb yaj kiab glucosetransporters (GLUTs), uas ua ke nrog sodium-dependent glucose cotransporters (SGLTs) thiab uniporter SWEET protein, yog lub luag haujlwm rau kev noj qab haus huv.

GLUT4 yog aninsulin-sensitive qabzib thauj mus rau hauv hypothalamus, sensorimotor cortex, cerebellum, hippocampus, thiab pituitary. Nws lub luag haujlwm physiological tsis paub, tab sis qee qhov ntawm nws cov haujlwm tau pom zoo yog nws txoj kev koom tes hauv kev kuaj ntshav qabzib, insulin hloov pauv cov piam thaj hauv cov hlwb sib txawv, thiab kev thauj cov piam thaj, thaum muaj kev xav tau siab, mus rau lub cev muaj zog neurons [97,98].

Hauv Alzheimer's, nrog rau kev txo qis cov piam thaj hauv cov chaw ua haujlwm ntawm lub hlwb xws li cortex, hippocampus, thiab cerebral microvessels, glucose transporters (GLUT) txo [98,99]. Kev tsis pom zoo ntawm GLUT-4 hauv hippocampal neurons tuaj yeem cuam tshuam nrog lub sijhawm luv luv nco thiab tsis txaus ntseeg hauv Alzheimer's cov neeg mob [100].

Kev ntxiv nrog peb lub ntsiav tshuaj txhua hnub ntawm PSO hauv 52 cov neeg mob rog rog nrog hom 2 mob ntshav qab zib tau pom tias muaj kev nce ntxiv ntawm GLUT-4 noob thiab txo qis hauv cov ntshav qab zib sai sai [85]. Ib yam li ntawd, kev nce hauv mRNA thiab cov protein qhia ntawm GLUT4 tau soj ntsuam 3T3-L1 adipocytes kho nrog punic acid [83].

3.2.4. Cov nyhuv ntawm Punicic Acid tshaj HDL thiab PON1

Lwm cov txheej txheem cuam tshuam nrog cov kab mob oxidative kev ntxhov siab yog kev hloov pauv ntawm paraoxonase 1 (PON1) hauv cov ntshav ntshav. Paraoxonase (PON) tsev neeg ntawm enzymesis ib pawg ntawm polymorphic lactonases nrog dav substrate tshwj xeeb uas muaj potentantioxidant, anti-inflammatory, thiab anti-apoptotic zog.

Lawv pom muaj ntau hauv HDLs, thiab PON1 cuam tshuam nrog HDL pab tiv thaiv LDL oxidation [101,102]. Cov qib qis ntawm PON1 thiab HDL cov roj cholesterol yog cuam tshuam nrog qhov muaj peev xwm ua rau oxidative puas tsuaj ntawm lipids, proteins, thiab DNA thiab txhawb kev tiv thaiv kab mob.

Cov ntsiab lus txo qis PON1 kuj tseem cuam tshuam txog cov teebmeem neurotoxic ntawm lub cev tiv thaiv kab mob thiab nitro-oxidative txoj hauv kev hauv cov neeg uas raug kev txom nyem los ntawm cov kab mob neuroprogressive xws li kev nyuaj siab loj, kev puas siab puas ntsws bipolar, thiab schizophrenia [103]. Hauv NDs, kev hloov pauv ntawm cov ntshav ntshav PON1 tau tshaj tawm [101]. Tsis tas li ntawd, kev txo qis hauv PON1 qib yog tshwm sim hauv cov neeg mob PD piv rau cov neeg noj qab haus huv [104].

Pomegranate induces kev hloov kho ntawm high-density lipoproteins (HDL) lipid muaj pes tsawg leeg thiab kev ua haujlwm. Cov luav tau ntxiv rau lub sijhawm 30 hnub nrog microencapsulatedpomegranate, uas ua rau muaj kev nce hauv HDL cholesterol thiab HDL phospholipids, txo qis cov qib non-HDL sphingomyelin, thiab txo cov ntsiab lus ntawm triglycerides-phospholipids piv. Muaj kev nce qib hauv HDL kev ua haujlwm thiab txhim kho oxidationresistance, feem ntau yuav ua rau txo qis triglyceride theem ntawm HDL thiab nce PON1 kev ua haujlwm [86].

Hauv ib txoj kev tshawb fawb zoo sib xws, cov poj niam uas muaj tus mob coronary syndrome tau ntxiv nrog microencapsulated pomegranate rau 30 hnub, uas tau hloov pauv kev faib tawm los ntawm HDL loj mus rau qhov nruab nrab thiab me me, thiab txo qis cov txiaj ntsig intriglyceride thiab nce hauv PON1 kev ua haujlwm tau pom. HDL remodeling tsis hloov qhov kev sib raug zoo ntawm lipoprotein rau PON1 txij li thaum PON1 kev ua haujlwm tseem nyob tas li ua ntej lossis tom qab ntxiv.

Qhov no txhais tau hais tias ntau dua PON1 kev ua tom qab pomegranatesupplementation yog vim nws cov synthesis ntau dua [87]. Tsis tas li ntawd, CLA isomers, tshwj xeeb tshaj yog c9, thiab t11, pab tiv thaiv PON1 los ntawm oxidative oxidation thiab stabilization nyob rau hauv ib tug concentration-dependent yam los ntawm kev khi rau ib tug tshwj xeeb binding site ntawm PON1 molecule [102].

Vim tias microencapsulated pomegranate yog tsim los ntawm ntau cov txiaj ntsig nutraceutical Cheebtsam, suav nrog cov kua qaub punicic, cov kev tshawb fawb tshiab yuav tsum tau ua los tshawb nrhiav cov nyhuv ncaj qha ntawm PON1 thiab HDL.Nyob rau hauv cov ntsiab lus, punicic acid (PuA) tuaj yeem ua raws li (1) agonist ntawm PPARs. , uas txo cov neuroinflammation thiab tau hyperphosphorylation thiab ua tsawg A tsim thiab aggregation.

Punicic acid txo qhov tsim A los ntawm (2) inhibiting ua kom calpain thiab cyclin-dependent kinase 5 (cdk5), txwv qhov hyperphosphorylation ntawm tau protein ntau. Ib yam li ntawd, (3) PuA nce GLUT4 protein qhia tswj cov piam thaj hauv lub hlwb metabolism, txo cov insulin tsis kam, thiab txo cov hyperphosphorylation ntawm tau proteins. Asa ib feem ntawm nws cov teebmeem antioxidant muaj zog, (4) PuA nce cov tshuaj tiv thaiv oxidative ntawm HDL thiab PON1 kev ua, txo ROS tiam thiab lipids peroxidation (Daim duab 6).

4. Cov lus xaus thiab cov kev xav yav tom ntej

Punicic acid yog ib qho tseem ceeb nutraceutical compound hauv kev tiv thaiv thiab kho cov kab mob neurodegenerative xws li Alzheimer's, Parkinson's, thiab Huntington's disease.

Punicic acid tuaj yeem txo oxidative kev puas tsuaj thiab o los ntawm kev ua kom pom cov peroxisome proliferator-activated receptors. Tsis tas li ntawd, nws tuaj yeem txo qis beta-amyloiddeposit tsim thiab tau hyperphosphorylation los ntawm kev ua kom cov lus qhia ntawm GLUT4protein thiab inhibition ntawm calpain hyperactivation. Microencapsulated pomegranate, nrog rau qib siab ntawm punicic acid, nce PON1 antioxidant kev ua haujlwm hauv HDL.

Ib yam li ntawd, encapsulated pomegranate formulations nrog qib siab ntawm punicic acid tau pom tias muaj kev nce ntxiv hauv PON1 antioxidant kev ua hauv HDL. Txawm li cas los xij, punicic acid qhia tau hais tias muaj kev cuam tshuam tsawg heev thoob plaws cov ntshav-hlwb hauv hlwb, ua rau muaj kev cuam tshuam tsis zoo rau cov kab mob neurological.

Txhawm rau kov yeej qhov kev sib tw no, cov qauv tsim lub hlwb uas hla BBB tau zoo dua ntawm kev txo qis ND cov tsos mob, xws li txo qis amyloidprecursor protein noob qhia, oxidative kev nyuaj siab, thiab neuroinflammation. Cov kev tshawb fawb yav tom ntej uas tsom mus rau cov nyhuv ntawm punicic acid rau neurodegeneration yuav tsum nco ntsoov txog qhov cuam tshuam ntawm BBB ntawm lub hlwb bioavailability ntawm bioactive molecule thiab sim tsim cov txheej txheem xa khoom tshwj xeeb uas tso cai rau kev tawm dag zog ntawm cov teebmeem hauv zos.

Sau Kev Koom Tes: Conceptualization, MA-R. thiab DG-F.; kev tshawb nrhiav, CMG-V.; kev sau ntawv-kev npaj ua ntej, CMG-V.; sau-saib thiab kho, MA-R., MM-Á., DG-F. thiab C.MG-V.; Visualization, MA-R., DG-F. thiab MM-A. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.

Cov Nyiaj Txiag: Txoj haujlwm no tau txais kev txhawb nqa los ntawm Consejo Nacional de Ciencia y Tecnología (CONACYT) [CVU1078786] Claudia Melissa Guerra Vázquez scholarship, thiab Lub Tsev Kawm Ntawv ntawm Engineering thiab Sciences ntawm Tecnológico de Monterrey.

Institutional Review Board Statement: Tsis siv tau.

Cov Lus Qhia Txog Kev Pom Zoo: Tsis siv tau.

Kev lees paub: Cov kws sau ntawv ua tsaug rau Consejo Nacional de Ciencia y Tecnología (CONACYT), rau Claudia Melissa Guerra Vázquez scholarship [CVU 1078786] thiab Nutriomics thiab EmergingTechnologies, thiab Bioprocess Research Chairs of Tecnológico de Monter. Cov duab tau tsim nrog BioRender.com.

Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.

Cov ntaub ntawv

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