Lub luag haujlwm ntawm Neuroprotective ntawm Polydatin: Neuropharmacological Mechanisms, Molecular Targets, Therapeutic Potentials, Thiab Clinical Perspective

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Abstract

Cov kab mob neurodegenerative (NDDs) yog ib qho ntawm cov ua rau kev tuag thiab kev tsis taus ntawm tib neeg. Los ntawm kev xav txog kev siv tshuab, qhov nyuaj ntawm cov txheej txheem pathophysiological pab txhawb rau NDDs. Yog li, muaj qhov xwm txheej ceev los muab cov neeg sawv cev tshiab ntau lub hom phiaj rau kev hloov kho ib txhij ntawm dysregulated txoj hauv kev tawm tsam NDDs. Tsis tas li ntawd, lawv qhov tsis muaj txiaj ntsig thiab cov kev mob tshwm sim cuam tshuam tau ua rau tsis muaj cov kev kho mob raws li cov neeg ua haujlwm kho mob tsim nyog. Cov ntawv ceeb toom tam sim no tau qhia txog cov nroj tsuag thib ob metabolites uas tau cog lus ntau tus neeg sawv cev hauv kev tawm tsam NDDs. Polydatin yog lub ntuj phenolic compound, uas siv cov cuab yeej muaj peev xwm hauv kev sib ntaus NDDs. Nws raug suav hais tias yog cov khoom noj muaj txiaj ntsig zoo hauv kev hloov pauv neuroinflammatory / apoptotic / autophagy / oxidative kev ntxhov siab cov teeb meem sib tham xws li nuclear factor-κB (NF-κB), NF-E2-txog yam 2 (Nrf2) / antioxidant teb cov ntsiab lus (ARE), matrix metalloproteinase ( MMPs), interleukins (ILs), phosphoinositide 3-kinases (PI3K) / protein kinase B (Akt), thiab extracellular regulated kinase (ERK) / mitogen-activated protein kinase (MAPK). Yog li, polydatin muaj peev xwm tiv thaivAlzheimer tus kab mob, kev paub / nco tsis ua haujlwm,Tus kab mob Parkinson, mob hlwb / txha caj qaum, ischemic stroke, thiab lwm yam neuronal dysfunctionalities. Txoj kev tshawb no muab tag nrho cov neuroprotective mechanisms ntawm polydatin nyob rau hauv ntau yam NDDs. Tsis tas li ntawd, cov txheej txheem xa tawm tshiab ntawm polydatin tau muab hais txog kev nce nws txoj kev nyab xeeb, solubility, bioavailability, thiab kev ua tau zoo, nrog rau kev txhim kho kev kho mob ntev ntev ntawm polydatin nyob rau hauv lub hauv nruab nrab lub paj hlwb, muaj kev phiv tsawg.

Ntsiab lus:polydatin; neurodegeneration; neuroprotection; cov hom phiaj kho mob; kws tshuaj; tshiab xa system

Sajad Fakhri 1, Mohammad Mehdi Gravandi 2, Sadaf Abdian 2, Esra Küpeli Akkol 3, Mohammad Hosein Farzaei 1,* thiab Eduardo Sobarzo-Sánchez 4,5,*

1 Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran; sajad.fakhri@kums.ac.ir

2 Pawg Neeg Tshawb Fawb Tub Ntxhais Kawm, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran

3 Department of Pharmacognosy, Kws qhia ntawv ntawm Pharmacy, Gazi University, 06330 Ankara, Qaib ntxhw

4 Department of Organic Chemistry, Kws Qhia Ntawv ntawm Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

5 Instituto de Investigación thiab Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8330507, Chile

1 Kev Taw Qhia

Cov kab mob neurodegenerative(NDDs) yog ib qho ntawm feem ntau ntawm kev xiam oob khab thiab kev tuag ntawm tib neeg, uas yog xa mus rau qhov maj mam, symmetrical, thiab tshwj xeeb txo qis hauv kev hnov ​​​​lus, lub cev muaj zog, thiab kev puas siab puas ntsws ua rau kev tuag ntawm neurons [1,2]. Nerve death accounts rau ntau yam cim qhia ntawm neurological dysregulations, ob qho tib si ntev thiab mob, muaj xws li Parkinson's disease (PD), Alzheimer's disease (AD), central nervous system (Brain/Spinal Cord) raug mob, thiab mob stroke [3]. Tsis tas li ntawd, autism, mob neuropathic, kev laus, thiab kev nyuaj siab yog lwm yam NDDs uas tshwm sim los ntawm paj hlwb tuag [4,5]. Los ntawm kev xav txog kev siv tshuab, ntau yam ua rau muaj teeb meem hauv lub paj hlwb, xws li oxidative stress [6], o [7], thiab apoptosis [5,8]. Cov kab mob pathological uas tau hais tseg saum toj no ua lub luag haujlwm tsis zoo hauv cov txheej txheem neuronal cell tuag.

Cov kev ua ntawm microglia, inflammatory cytokines, reactive oxygen hom (ROS), thiab cuam tshuam mitochondrial cuam tshuam ntawm oxidative txoj kev tau qhia tsis zoo rau cov txheej txheem ntawm paj hlwb degeneration uas nws thiaj li ua rau cell tuag [9,10]. Txawm hais tias muaj kev nce qib hauv kev kho mob hauv tsev kho mob, cov tshuaj tiv thaiv neuroprotective tseem muaj kev sib tw hauv cov hlab ntsha puas tsuaj thiab NDDs. Yog li, muaj ib qho kev xav tau los tsim kho tshiab ntau lub hom phiaj uas pab ntxiv kom txo qis cov teeb meem tsis raug cai hauv NDDs [11–13]. Ob peb lub ntuj sib xyaws cais los ntawm cov khoom siv tau thiab tshuaj ntsuab uas muaj cov tshuaj tiv thaiv kab mob tau raug tshawb xyuas rau daim ntawv thov muaj peev xwm ua cov kws tshuaj [14]. Cov khoom ntuj yog cov nplua nuj ntawm cov tshuaj polyphenolic, suav nrog stilbenoids, uas yog ib pawg loj ntawm resveratrol tshuaj xws li monomers, dimers, thiab oligomers. Stilbenoids yog ib txwm tshwm sim nyob rau hauv ntau yam nroj tsuag tsev neeg, xws li Vitaceae, Gnetaceae, Cyperaceae, thiab Rocarpaceae. Yog li ntawd, cov txiv hmab txiv ntoo, Vitis vinifera L., yog suav tias yog thawj qhov khoom noj khoom haus ntawm cov tebchaw [15].

suab puam cistanche cov txiaj ntsigrauhlwb

Polydatin yog ib tug stilbenoid uas passively penetrates hlwb. Nws kuj tso rau hauv cov hlwb los ntawm kev ua haujlwm los ntawm cov neeg nqa cov piam thaj. Cov piam thaj moiety ntawm polydatin ua rau muaj kev tiv thaiv ntau dua rau enzymatic oxidation dua li resveratrol thiab muaj dej solubility zoo dua [16,17]. Polydatin tau pom tias yuav txwv tsis pub oxidative kev nyuaj siab, o, thiab apoptosis ua txoj hauv kev tseem ceeb rau kev tsim cov paj hlwb. Kev ua haujlwm lom neeg ntawm polydatin thiab qee yam derivatives entails tiv thaiv lossis cuam tshuam nrog ntau lub tshuab neurodegenerative [18]. Hauv kev tshawb fawb yav dhau los, cov txheej txheem tiv thaiv ntawm polydatin tau ua pov thawj hauv cerebral ischemia [19]. Tsis ntev los no, cov teeb meem ntsig txog dementia kuj tau tsom los ntawm polydatin [20]. Tsis tas li ntawd, cov kws kho mob dav dav thiab cov tshuaj pharmacokinetic ntawm polydatin tau tsim los ntawm Du et al. [21]. Txog tam sim no, tsis muaj tsab xov xwm tshuaj xyuas tau tham txog tag nrho cov txheej txheem neuroprotective ntawm polydatin. Qhov kev tshuaj xyuas no tsom mus rau cov hom phiaj tshuaj, cov txheej txheem molecular, cov peev txheej kho mob, thiab kev soj ntsuam saib xyuas ntawm polydatin hauv NDDs. Cov tshuaj pharmacological ntawm kev ua ntawm polydatin hauv kev kho lossis tiv thaiv NDDs tau muab.

2. Polydatin: Chemical Structure, Sources, thiab Pharmacokinetic Properties

Ntau cov kev tshawb fawb txog cov tshuaj lom neeg tus yam ntxwv ntawm stilbenoids tau mob siab los ntawm lawv cov kev cog lus lom zem ntau, tshwj xeeb tshaj yog cov polydatin. Polydatin (3,40,5-trihydroxystilbene-3- -}D-glucoside) yog ib qho ntuj resveratrol glucoside hu ua resveratrol-3- -mono-D-glucoside, ib qho khoom siv los ntawm Polygonum cuspidatum Sieb. thiab Zucc cov hauv paus hniav (Daim duab 1). Txawm li cas los xij, nws tseem pom muaj nyob rau hauv txiv hmab txiv ntoo, cawv liab, hop cones, txiv laum huab xeeb, cocoa / chocolate khoom, thiab ntau lwm yam zaub mov [21]. Ob hom isomeric (cis thiab trans) ntawm polydatin muaj nyob hauv qhov xwm txheej. Cis-polydatin feem ntau pom nyob rau hauv qis dua. Ntxiv mus, lawv tsis tshua muaj roj ntsha ua haujlwm ntau dua li kev hloov pauv [22]. Feem ntau qhov chaw ntawm polydatin yog kua txiv hmab txiv ntoo thiab liab / dawb wines. Cis-polydatin yog qhov tseem ceeb tshaj plaws isoform hauv carbonated wines thiab rosé, thaum lub trans isomer muaj ntau nyob rau hauv txiv laum huab xeeb, txiv laum huab xeeb, thiab pistachios [23].

Lub hauv paus loj ntawm polydatin isomers yog cov rhizomes thiab cov hauv paus hniav ntawm Fallopia japonica (Houtt.) Ronse Decraene (Polygonaceae), tau ntev tau siv nyob rau hauv tsoos suav thiab Japanese tshuaj raws li ib tug anticancer, diuretic, analgesic, antipyretic, thiab expectorant tus neeg saib xyuas nyob rau hauv kev tswj. Kev kho mob ntawm atherosclerosis [24] Txawm li cas los xij, cov khoom no muaj nyob rau hauv ntau lwm yam xws li Rumex, Picea, Rosa, Quercus, thiab Malus. Polydatin tau txais qhov kev xav zoo sib xws rau resveratrol vim tias qhov concentration ntawm glucoside feem ntau siab dua aglycone hauv cov cawv liab thiab lwm yam khoom txiv hmab. Qhov sib piv ntawm glycosylated cov ntaub ntawv rau aglycones hauv cawv yog nyob ntawm ntau yam xws li txoj kev fermentation thiab ecological tej yam kev mob nyob rau hauv lub vineyards [25].

Kev tshawb fawb Pharmacokinetic feem ntau xav tau rau kev siv tshuaj zoo thiab nyab xeeb. Kev nqus, kev faib tawm, thiab cov metabolism hauv polydatin txuas nrog nws cov bioactivity. Polydatin tej zaum yuav muaj bioavailability ntau dua thiab muaj txiaj ntsig zoo antioxidant piv rau resveratrol. Tsis tas li ntawd, plab hnyuv nqus ntawm polydatin yog siab dua resveratrol ua los ntawm cov piam thaj hauv pawg [26]. Polydatin nkag mus rau hauv lub cell los ntawm kev ua haujlwm ntawm cov kua nplaum uas muaj cov txheej txheem ua haujlwm thiab kev ua kom tsis muaj zog, thaum resveratrol tsuas yog nkag mus rau hauv cell membranes [27]. Kev thauj mus los ntawm polydatin feem ntau dhau los ntawm sodium-dependent glucose transporter 1 (SGLT1), feem ntau tshwm sim hauv cov hnyuv thiab plab [16]. Txij li thaum cov ntsiab lus ntawm tes ntawm polydatin tsis tsawg heev, nws qhia tau hais tias muaj kev hloov pauv ntawm polydatin los ntawm SGLT1 [21,27].

Polydatin siv ob txoj hauv kev kom deglycosylated los ntawm trans-resveratrol. Txoj hauv kev tseem ceeb yog cleavage los ntawm cytosolic- -glucosidase tom qab SGLT1 kho kom haum los ntawm kev hla ntawm txhuam-border membrane. Qhov thib ob mechanism, uas tshwm sim nyob rau sab luminal ntawm lub epithelium, yog deglycosylation los ntawm daim nyias nyias enzyme lactase-phlorizin hydrolase. Qhov no mechanism yog ua raws li passive diffusion ntawm tso tawm aglycone thiab ntxiv glucuronoconjugation [17]. Txawm hais tias resveratrol ntau ntxiv thiab tawm ntau qhov seem hauv cov hlwb dua li polydatin, ib nrab-lub neej ntawm polydatin yog kwv yees li plaub teev nrog qib siab ntawm resveratrol Cmax ntawm tib koob [27]. Txawm li cas los xij, ntau txoj kev tshuaj ntsuam xyuas yuav tsum tau tshawb xyuas rau kev txiav txim siab ntawm trans-stilbene glycoside thaum kev tshawb fawb pharmacokinetic [28]. Raws li, polydatin li glycosylated resveratrol tuaj yeem yog tus neeg sawv cev kho mob nrog tsawg dua cov kev txwv pharmacokinetic hauv kev sib piv rau resveratrol.

3. Polydatin tiv thaiv NDDs

Polydatin tau pom ntau yam teebmeem lom neeg / tshuaj noj, xws li tshuaj tiv thaiv kab mob [29], anti-apoptotic [30], thiab antioxidant [31], tiv thaiv NDDs [32]. Txhawm rau tiv thaiv oxidative kev nyuaj siab, polydatin nce antioxidant muaj peev xwm los ntawm kev cuam tshuam cov tshuaj tiv thaiv antioxidant, nuclear factor erythroid 2-txog yam 2 (Nrf2) thiab sirtuin 1 (Sirt1), thiab cov ntsiab lus teb antioxidant (AREs) [18]. Polydatin suppresses oxidative kev nyuaj siab los ntawm phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt)-interconnected mediators [33]. Nws tseem thaiv cov kev ntxhov siab oxidative thiab txo cov microglial apoptosis los ntawm Nrf2/heme oxygenase (HO{17}}) txoj kev [34]. Los ntawm qhov pom ntawm qhov mob, los ntawm kev ua kom muaj zog ntawm cov khoom siv nuclear kappa B (NF-κB), polydatin tuaj yeem nres intercellular adhesion molecule -1 (ICAM-1) protein / mRNA ntau lawm. Polydatin kuj tau pom tias yuav txo tau cov cytokines pro-inflammatory (IL-1 , TNF- , thiab IL-6) los ntawm down-regulating hu-like receptor-2 (TLR{29}} ) thiab NF-κB p65 txoj kev [35]. Raws li mitochondria yog lub hauv paus loj ntawm ROS nyob rau hauv cov hlwb, thaum lub intracellular mitochondria puas lawm, electron hloov mus rau qhov txawv txav, thiab ROS ntau lawm, uas thaum kawg accelerates qhov pib ntawm apoptosis [36].

Ntau qhov kev tshawb fawb tau pom tias muaj txiaj ntsig zoo ntawm polydatin ntawm mitochondria los ntawm qhov kev xav tshiab. Polydatin tau raug txiav txim siab los tawm tsam mitochondria-txog cytochrome c tso tawm, ntxiv rau kev tshem tawm caspase -9 thiab caspase -3 [37]. Polydatin tau xav tias yuav txo qis ROS tso tawm thiab txhim kho mitochondrial kev ua haujlwm los ntawm kev hloov kho Sirt3 / superoxide dismutase 2 (SOD2) txoj hauv kev. SOD2 yog ib qho mitochondrial antioxidant enzyme uas nws cov haujlwm yog kho los ntawm Sirt3 [38]. Zuag qhia tag nrho, los ntawm kev hloov kho ntau tus neeg nruab nrab hauv inflammatory / apoptotic / autophagy / oxidative stress pathways, polydatin tuaj yeem yog tus neeg sib tw muaj kev cia siab hauv kev tawm tsam NDDs.

3.1. Polydatin tiv thaiv AD, thiab Cognition / Memory Dysfunction

Raws li feem ntau ntawm NDDs, AD yog tus cwj pwm los ntawm kev poob qis hauv kev nco thiab kev puas siab puas ntsws hauv txhua yam ntawm tus neeg muaj peev xwm ua haujlwm txhua hnub, nrog rau qhov tsis paub [39]. Cov kev tshawb fawb tau pom tias cov pob txha ntawm cov laus cov plaques, feem ntau muaj cov amyloid beta-peptide (A) thiab intracellular fiber nodules uas muaj cov hyperphosphorylated proteins, plays lub luag haujlwm tseem ceeb hauv neuropathology ntawm AD [40-42]. Tsis tas li ntawd, ob peb txoj hauv kev inflammatory, apoptotic, thiab oxidative txoj kev yog qab lub pathogenesis ntawm AD. Vim muaj ntau cov txheej txheem pathophysiological rau AD, kev kho mob tseem tsis tau tsim. Cov khoom ntuj tsim tau pom muaj txiaj ntsig zoo rau AD [43]. Ntawm cov koom haum ntuj tsim, kev tswj hwm qhov ncauj ntawm polydatin tuaj yeem txo qis kev tsim cov malondialdehyde (MDA) thiab ua kom cov haujlwm ntawm cov antioxidants SOD thiab catalase (CAT) los tiv thaiv kev kawm thiab kev nco tsis zoo hauv vivo. Tsis tas li ntawd, nws txo qis qhov kev puas tsuaj los ntawm qhov tsis muaj oxygen-glucose hauv kab lis kev cai neurons [44]. Tong et al. tshawb xyuas cov txiaj ntsig tiv thaiv ntawm polydatin hauv cov neeg mob qog noj ntshav uas tau txais tshuaj kho mob, feem ntau ntawm cov neeg muaj kev paub tsis meej vim yog siv cov tshuaj khomob.

Hauv lawv txoj kev tshawb fawb, polydatin, ntawm ib koob tshuaj txhua hnub ntawm 50 mg / kg, txo qis doxorubicin-vim kev paub tsis meej thiab kho cov qauv hippocampal ntawm hippocampus. Tsis tas li ntawd, polydatin txo qis doxorubicin-vim kev ntxhov siab los ntawm kev tswj hwm Nrf2, ua kom txoj hauv kev NF-κB, thiab txo qis apoptosis [45,46]. Hauv lwm txoj kev tshawb fawb, polydatin tau tshaj tawm los tiv thaiv kev kawm thiab kev nco tsis ua haujlwm hauv cov nas me me nrog hypoxic-ischemic hlwb raug mob (HIBI) los ntawm unilateral carotid artery ligation. Tsis tas li ntawd, polydatin txo qis kev nco tsis txaus thiab nce qhov kev qhia ntawm hippocampal hlwb-derived neurotrophic factor (BDNF) hauv nas nrog HIBI [47]. Ntxiv mus, nyob rau hauv ib txoj kev tshawb no ntawm nas 'kev txawj ntse muaj nuj nqi raug rau ethanol ntev, polydatin nce cell ciaj sia taus thaum txo cov qhia theem ntawm cyclin-dependent kinase 5 (cdk5), thiab thim rov qab functional defects nyob rau hauv ethanol-kho nas ntsuas los ntawm Morris dej kuaj [ 48] ib. Hauv lwm txoj kev tshawb fawb tsis ntev los no, polydatin tau qhia txog kev tiv thaiv lub luag haujlwm tiv thaiv kev puas siab puas ntsws los ntawm kev txo qis ntau txoj hauv kev dysregulated, suav nrog suppressing neuroapoptosis, oxidative stress, N-methyl D-aspartate receptor subtype 2B (NR2B), senile plaques, neurofibrillary tangles, thiab cholinergics. [20].

Polydatin-mediated in vitro inhibition ntawm A 25-35 polymerization thiab txuam fibrils / oligomers kuj tau tshaj tawm los ntawm Rivière li al. [49,50]. Raws li lwm txoj kev tiv thaiv AD ntawm polydatin, qhov nce hauv vitro hauv 3 thiab 7 nicotinic acetylcholine receptors (nAChRs) tuaj yeem pab tiv thaiv NDDs [51]. Thaum lub sijhawm kawm hauv vivo, kev hloov pauv ntawm NR2B los ntawm polydatin hauv nas 'prefrontal cortex txo kev kawm thiab kev nco tsis zoo [52]. Yog li ntawd, polydatin tuaj yeem yog tus neeg sib tw pabcuam hauv kev tiv thaiv AD thiab kev paub / nco tsis zoo nyob rau ntau qhov xwm txheej. Xws li cov nyhuv yog exerted los ntawm kev hloov kho ntawm ntau lub dysregulated mechanisms, xws li neurological deficit qhab nia, oxidative kev nyuaj siab (xws li, Nrf2, SOD, CAT), o (xws li, NF-κB), as well as A , BDNF, thiab nAChRs.

3.2. Polydatin tiv thaiv PD

PD yog ib qho mob uas muaj feem cuam tshuam txog kev laus thiab qhov tseem ceeb thib ob yog vim li cas rau NDDs [53]. PD yog lub npe hu rau midbrain dopaminergic neuronal poob thiab tsub zuj zuj ntawm -synucleins hu ua Lewy lub cev. Tsis tas li ntawd, kev puas tsuaj rau txoj hauv kev uas tsis yog dopaminergic ua rau tsis muaj lub cev muaj zog thiab lub cev muaj zog [54]. Raws li lawv cov txiaj ntsig tsis zoo thiab cov kev mob tshwm sim tsis zoo, cov kev kho mob ib txwm muaj rau PD yog qhov nyuaj rau kev siv, thiab kev tsim cov tshuaj tshiab tshiab thiab kev nyab xeeb tam sim no xav tau. Oxidative stress thiab neuroinflammation ua lub luag haujlwm tseem ceeb hauv PD pathogenesis [55]. Yog li ntawd, kev tiv thaiv cov dysregulated mediators ntawm txoj kev no muaj lub luag haujlwm tseem ceeb hauv kev txwv tsis pub tshaj tawm ntawm PD. Los ntawm txoj kev xav ntawm pathophysiological, qhov degradation ntawm substantia nigra dopaminergic neurons yog tshwm sim los ntawm kev hloov pauv hloov pauv thiab cov lus teb rau cov teeb meem ib puag ncig stimuli [56]. Bai et al. qhia tias polydatin tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev tawm tsam PD. Tsis tas li ntawd, polydatin muaj nuj nqis txo qis apoptosis thiab mitochondrial dysfunction thaum lub sij hawm rotenone / Parkin deficiency induced nyob rau hauv tib neeg dopaminergic neuronal cell kab, SH-SY5Y. Hauv lawv txoj kev kawm, polydatin suppressed rotenone-induced cell tuag, mitochondrial membrane muaj peev xwm (MMP), Sirt 1, DJ1, thiab ROS ntau lawm. Lawv txoj kev tshawb fawb pom tias thaum autophagy-txog noob 5 (Atg5) yog tshuaj lom neeg inhibited, cov txiaj ntsig zoo ntawm polydatin yog ib feem inhibited, implying Atg5-mediated neuroprotection [57]. Parkin knockdown-induced oxidative stress, mitochondrial malfunction autophagy deficiency, thiab mitochondrial fusion expansion tau alleviated los ntawm polydatin [58]. Kev kho polydatin kuj tseem tuaj yeem thim rov qab qhov txawv txav hauv mitochondrial morphology thiab lub cev muaj zog ua haujlwm tsis zoo hauv Drosophila qauv ntawm PD los ntawm Parkin insufficiency [57]. Hauv pathogenicity ntawm PD, neuroinflammation hyperactivates microglia thiab ua rau kev puas tsuaj ntawm dopaminergic neurons. Yog li ntawd, kev txo qis microglial kev ua haujlwm tuaj yeem pab hauv kev tswj hwm ntawm PD [59].

Polydatin hla cov ntshav-hlwb thaiv kev tiv thaiv lub cev muaj zog ntawm substantia nigra thiab khaws cia dopaminergic neurons thiab lub cev muaj zog ua haujlwm los ntawm suppressing pro-inflammatory mediators thiab microglia [60,61]. Huang et al. qhia tias polydatin ua rau muaj kev nce hauv Nrf2, p-Akt, thiab p-glycogen synthase kinase-3 (GSK-3 ) Ser9, activated microglial BV-2 hlwb thiab suppressed NF-κB thiab proinflammatory Cov neeg kho kom haum xeeb hauv substantia nigra ntawm PD rat-induced los ntawm lipopolysaccharide (LPS). Polydatin kuj inhibited dopaminergic neurodegeneration tshwm sim los ntawm microglial activation los ntawm modulating Akt/GSK{13}} /Nrf2/NF-κB signaling pathway [62]. Nws tsim nyog sau cia qhov tsis sib xws hauv cov tshuaj tiv thaiv / pro-inflammatory cytokines tom qab ua kom microglia. Nws nthuav tawm qhov nyuaj ntawm lub hlwb microglial txoj cai, suav nrog qhov tseem ceeb M1 (inflammatory microglia) thiab M2 (anti-inflammatory microglia).

Microglia activations, tshwj xeeb tshaj yog hom M1, tau raug suav hais tias yog tus kws kho mob tseem ceeb hauv kev ua rau cov lus teb inflammatory thaum NDDs. Txawm li cas los xij, kev tsim khoom / tso tawm ntawm cov kab mob cytokines tau raug qhia tias yog ib qho kev cuam tshuam nrog cov lus teb microglial, uas yog ze rau qhov tsis muaj protein ntau homeostasis hauv NDDs [63]. Yog li, modulating microglia activation tuaj yeem yog lub tswv yim zoo rau polydatin hauv kev tawm tsam NDDs. Kev cuam tshuam ntawm glycolysis thiab txo qis hauv ATP ntau lawm yog lwm yam cuam tshuam rau kev ua haujlwm ntawm dopaminergic neurons thiab tsim PD [64]. Zhang et al. pom tias polydatin tuaj yeem txhim kho glycolysis, qabzib metabolism, ATP ntau lawm, thiab lub cev muaj zog ua haujlwm tsis zoo hauv cov nas nrog 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced thaum ntxov dopaminergic neuronal degeneration. Hauv lawv txoj kev tshawb fawb, polydatin tiv thaiv kev poob ntawm dopaminergic neurons hauv striatum thiab substantia nigra, yog li suppressing neural apoptosis (Bax thiab cleaved caspase-3) thiab txhim kho lub cev muaj zog hauv nas [65].

Kev tshem tawm txoj haujlwm I ntawm cov saw hlau thauj hluav taws xob thiab qhov siab oxidative kev nyuaj siab yog ib qho ntawm thawj qhov tshwm sim hauv cov kab mob ntawm PD [66]. Hauv kev tshawb fawb hauv vitro, txo qis lipid peroxidation, inhibiting apoptosis, thiab ua kom cov mitogen-activated protein kinase (MAPK) tau qhia ua thawj cov txheej txheem neuroprotective ntawm polydatin ntawm dopaminergic neurons [67]. Kev kawm los ntawm Ahmed et al. pom tau tias polydatin (3 mg / kg, intraperitoneally) muaj cov nyhuv neuroprotective hauv attenuating degeneration ntawm dopaminergic neurons nyob rau hauv nigrostriatal cheeb tsam ntawm lub hlwb. Lawv kuj tau qhia tias polydatin txhim kho tus cwj pwm neuromotor hauv tus qauv nas ntawm rotenone-induced PD. Yog li, cov nyhuv tiv thaiv ntawm polydatin tiv thaiv striatal degeneration yog nthuav tawm hauv lawv daim ntawv qhia [68]. Hauv daim ntawv tshaj tawm zoo sib xws, polydatin muaj txiaj ntsig tiv thaiv rotenone-induced dysregulations ntawm MDA, manganese SOD, glutathione, thiab thioredoxin hauv striatum. Tsis tas li ntawd, polydatin inhibited rotenone-induced neurodegeneration ntawm dopaminergic neurons hauv substantia nigra [61]. Polydatin, raws li kev sib npaug, tuaj yeem yog qhov kev kho mob hauv PD los ntawm kev txo qis oxidative kev nyuaj siab, nrog rau kev tswj cov txheej txheem autophagic thiab mitochondrial fusion.

Sprague-Dawley nas tau txais 30 mg / kg polydatin intraperitoneally tom qab TBI txo qis hauv ROS thiab thaiv TBI-induced MDA qhia thaum nce SOD qib hauv cov cortices puas. Hauv lawv txoj kev tshawb fawb, polydatin tiv thaiv MMP lub cev qhuav dej thiab yav dhau los mitochondrial hloov pore los ntawm kev qhib TBI thiab txo cov endoplasmic reticulum kev nyuaj siab teb tom qab TBI [69]. Raws li qhov tshwm sim, polydatin tseem ceeb txo qis endoplasmic reticulum kev ntxhov siab cuam tshuam txog kev nthuav tawm cov protein ua kom muaj zog, muaj cov blocked p-extracellular regulated kinase (ERK) phosphorylation, tsis kam spliced ​​XBP-1, thiab cleaved activating transcription factor 6 (ATF6) ntau lawm, Kev nthuav qhia ntawm cov protein uas tswj cov piam thaj (GRP78). Dhau li ntawd, polydatin tswj txoj kev p38MAPK signaling pathway thiab mitochondrial apoptotic txoj kev (xws li, caspase-3/9) thiab txhim kho cov qhab nia neurological thiab qhov ntev ntawm kev ciaj sia nyob hauv TBI nas [69].

Hauv lwm daim ntawv tshaj tawm, polydatin tiv thaiv SCI los ntawm kev tawm tsam oxidative kev nyuaj siab thiab apoptosis dhau los ntawm Nrf2/HO-1 taw qhia hauv vitro thiab hauv vivo [34]. Polydatin kuj tseem muaj zog neuronal viability thiab tiv thaiv cov pa oxygen-qabzib deprivation / re-oxygenation-induced mitochondrial raug mob thiab apoptosis raws li koob tshuaj. Tsis tas li ntawd, polydatin modulated cov kev ua ntawm neuronal mitochondria, nrog rau MMP, intracellular calcium theem, qhib lub mitochondrial permeability hloov pore (mPTP), ROS tiam, thiab adenosine triphosphate theem. Los ntawm kev xav txog kev siv tshuab, polydatin suppressed Keap1 thiab upregulated Nrf2/HO-1 thiab NAD(P)H Quinone Dehydrogenase 1 (NQO-1) nyob rau hauv oxygen-glucose deprivation/re-oxygenation-kho spinal cord motor neurons . Tsis tas li ntawd, polydatin thim rov qab mitochondrial thiab neuronal kev puas tsuaj tshwm sim los ntawm tus txha caj qaum ischemia / reperfusion hauv tus qauv nas, ib feem cuam tshuam los ntawm Nrf2 inhibitor. Qhov no sawv cev tias cov teebmeem neuroprotective ntawm polydatin dhau los ntawm Nrf2/ARE txoj kev [73].

Kev koom tes ntawm Nrf2 ntawm kev sib txawv neuronal hauv ob qho tib si hauv vivo thiab hauv vitro kev tshawb fawb kuj yog muab los ntawm Zhan li al. [74]. Kev koom tes ntawm Nrf2/ARE hauv kev tiv thaiv cov teebmeem ntawm polydatin kuj tau nthuav tawm hauv lwm cov ntaub ntawv [75]. Hauv kab no, cov nyhuv inhibitory ntawm polydatin ntawm ferroptosis tau pom ob qho tib si hauv vitro thiab hauv TBI nas. Cov lus teb no tau siv los ntawm kev tiv thaiv kev sib sau ntawm cov dawb Fe2 ntxiv, nce MDA, thiab txo qis glutathione peroxidase (GPx) [76]. Feem ntau ua rau muaj mob txha caj qaum (SCI) yog lub cev muaj zog / tsheb sib tsoo, tsim txom, thiab ntog [77]. Tsis tau xav txog, kev sim tshuaj tiv thaiv kab mob tau tshawb pom tias SCI feem ntau muaj nyob rau hauv cov txiv neej hluas thiab ua rau muaj kev paub tsis meej txog lub neej uas ua rau txo lawv lub neej zoo [78]. SCI yog tus cwj pwm los ntawm ntau yam tsos mob, suav nrog limb tuag tes tuag taw, tsis hnov ​​​​tsw hauv qis qis, thiab uracratia lossis prosthesis. Ib lub cev loj hlob ntawm kev tshawb fawb qhia txog kev sib sau ntawm cov kab mob cytokines thoob plaws tus txha caj qaum yog qhov tseem ceeb ntawm kev pheej hmoo rau SCI cov tsos mob [10,11].

Cov kev tshawb pom tau qhia tias ntau yam pro-inflammatory cytokines, suav nrog cov macrophage migration inhibitory factor (MIF), interleukin-1 (IL-1), IL-6, thiab qog necrosis factor-, yog intensified tsis tu ncua. Tom qab compression-induced SCI [9]. Txhawm rau hloov cov txheej txheem no, polydatin tau txhaj rau hauv cov txiv neej laus Sprague-Dawley nas nyob rau hauv ib koob tshuaj intraperitoneal. Nyob rau hauv cov kab no, polydatin tseem ceeb txo tus txha caj qaum edema thiab morphological hloov hauv vivo. Nws kuj tseem txo cov nitric oxide (NO) hauv cov ntaub so ntswg txha caj qaum ntawm SCI nas, uas yog raws li cov qauv ntawm inducible nitric oxide synthase (iNOS) ntau lawm.

Raws li, LPS nce protein ntau thiab mRNA qib ntawm iNOS hauv BV2 hlwb, thiab polydatin thim rov qab cov kev hloov no [78]. Yog li ntawd, polydatin txo qis LPS-induced nce nyob rau hauv NO thiab teb rau inflammatory microglia. Polydatin kuj tseem txo qis IL-6, IL-1, thiab TNF- tom qab ib qho kev txhaj tshuaj thiab inhibited kev loj hlob ntawm inflammatory cytokines nyob rau hauv cov ntaub so ntswg qaum tom qab SCI. Dhau li ntawd, polydatin thaiv LPS-induced NF-κB ua rau hauv BV2 microglia thiab inhibited kev ua ntawm NLRP3 inflammasomes [78]. Qhov no stilbene attenuated TBI-induced mob ntsws raug mob los ntawm suppressing S100B-mediated tsim ntawm neutrophil extracellular ntxiab [79]. Polydatin kuj txhais tau tias txo MDA thaum nce SOD, GPx, CAT, thiab qib ntawm tag nrho cov antioxidant muaj peev xwm hauv lub hlwb thiab daim siab. Tsis tas li ntawd, polydatin txo cov inflammatory mediators ntawm cov ntshav, xws li IL-6, IL-1 , thiab TNF- . Nws kuj tau hloov kho D-galactose-induced caspase{20}} thiab Bcl{21}}/Bax piv nce siab hauv daim siab thiab hlwb [30]. Ua ke, lub luag haujlwm tseem ceeb ntawm polydatin hauv kev hloov kho ntawm Nrf2 / ARE, ERK / MAPK, thiab kev sib txuas ntawm apoptotic / inflammatory pathways tuaj yeem ua txoj hauv kev hauv kev hloov pauv ntawm lub hlwb / SCI raug mob.

3.4. Polydatin tiv thaiv Stroke: Raws li Coupled Complication rau NDDs

Stroke yog ib qho mob cerebrovascular mob hnyav tshaj plaws, cuam tshuam rau cov neeg mob lub neej zoo [80]. Ntxiv cov ntaub ntawv pov thawj thiab cov txheej txheem ntawm polydatin tiv thaiv cerebral ischemia. Ob qhov sib txawv ntawm cov pov thawj tau hais, uas yog qhov inhibition ntawm cov qhab nia neurological deficit thiab txwv lub hlwb infarction ntim hauv nas nrog nruab nrab cerebral hlab ntsha occlusion tom qab tau kho nrog polydatin. Ob peb lub tswv yim tau muab rau ob qhov teebmeem ntawm polydatin [81]. Ischemic stroke nce neuroinflamation thiab ROS. Shah et al. tshawb xyuas cov kev tiv thaiv neuroprotective ntawm polydatin tiv thaiv ischemic hlwb puas nyob rau hauv ib tug nas qauv ntawm chronic nruab nrab cerebral artery occlusion (MCAO). Lawv cov txiaj ntsig tau qhia tias polydatin txo qis qhov ntim ntawm infarction thiab txo cov kev tsis zoo ntawm cov neurobehavioral los ntawm kev txwv qhov ua kom p38MAPK thiab c-Jun N-terminal kinase, yog li suppressing neuroinflammation thiab ROS.

Lawv kuj tau pom tias polydatin upregulated endogenous antioxidants Nrf2, HO-1, thiab txoj kev thioredoxin, thiab txo qhov mob thiab ROS hauv cov ntaub so ntswg cortical [82]. Raws li tau hais dhau los, kev mob o thiab oxidative kev nyuaj siab yog ob yam tseem ceeb hauv cerebral ischemic pathogenesis. Hauv kab no, NF-κB ua kom muaj lub luag haujlwm tseem ceeb hauv kev ua rau mob. Tsis tas li ntawd, cov qib qis ntawm glioma-sociated oncogene Patched-1 (Ptch1), homolog1 (Gli1), thiab SOD1 yuav ua rau oxidative stress. Ji et al. pom tau tias polydatin tuaj yeem tiv thaiv lub hlwb ntawm nas nrog MCAO mus tas li. Cov teebmeem zoo li no tau ua los ntawm kev hloov pauv ntawm qhov mob ntawm qhov txo qis NF-κB thiab txo qis ntawm oxidative kev nyuaj siab los ntawm kev nce Ptch1, Gli1, SOD1 qhia, nrog rau ameliorating ntshav-hlwb barrier permeability [83].

Tsis tas li ntawd, cov teebmeem neuroprotective ntawm polydatin ntawm kev ua haujlwm ntawm lub paj hlwb thiab Nrf2 txoj hauv kev ntawm cov nas uas muaj lub hlwb hemorrhage tau txheeb xyuas. Lawv txoj kev tshawb fawb tau pom tias polydatin txhim kho kev ua haujlwm ntawm lub paj hlwb thiab txo qis oxidative kev nyuaj siab hauv cov nas los ntawm kev tswj cov Nrf2/ARE txoj hauv kev thiab cov noob qoob loo qis [84]. Mitochondrial dysfunction thiab apoptosis yog koom nrog hauv cov txheej txheem ntawm ischemic stroke. Hauv kev tshawb fawb ntawm Gao li al., cov nyhuv neuroprotective ntawm polydatin tau raug soj ntsuam. Lawv cov txiaj ntsig tau pom tias muaj cov nyhuv anti-apoptotic ntawm polydatin thiab txhim kho mitochondrial dysfunction vim yog ischemic / reperfusion raug mob hauv tus nas MCAO qauv. Kev nce Bcl-2 thiab txo cytochrome c, Bax, thiab caspases-3/9 yog cov txheej txheem tiv thaiv hauv nruab nrab [37].

Xav txog lub luag haujlwm ntawm cell adhesion molecules (CAMs) hauv kev tsim cov ischemia / reperfusion-induced cerebrovascular kab mob hauv tus nas MCAO qauv, Cheng et al. pom tias polydatin tuaj yeem txo qhov ntim ntawm lub hlwb infarction los ntawm kev txo qis ntawm CAMs hauv kev sib piv rau pawg tswj hwm, nrog rau kev koom tes ntawm E-selectin, L-selectin, integrins, ICAM-1, thiab vascular cell adhesion molecule-1 (VCAM-1) [85]. Metastasis-associated ntsws adenocarcinoma transcript 1 (MALAT1) yog ib qho tsis-coding RNA uas muaj lub luag haujlwm los tiv thaiv cov ntshav-hlwb thaiv kab mob tom qab muaj kev tshwm sim ischemic. Hauv kev tshawb fawb ntawm Ruan li al., nws tau pom tias polydatin tuaj yeem txhim kho qhov kev qhia ntawm MALAT1. Polydatin pib MALAT1/CREB/PGC{14}} / PPAR cascade uas thaum kawg ua rau kev tiv thaiv cerebrovascular endothelium thiab ntshav-hlwb barrier kev ncaj ncees los ntawm ischemia [81]. Tsis tas li ntawd, Chen et al. tshawb pom tias cov koob tshuaj ntau ntawm polydatin tuaj yeem txo qis edema, o, thiab apoptosis tom qab ib qho kev tshwm sim ischemic nyob rau hauv lub hlwb cov ntaub so ntswg ntawm nas qauv nrog MCAO los ntawm kev tswj cov kev qhia ntawm p53 thiab Notch1. Cov qhab nia rau kev ua haujlwm ntawm lub paj hlwb thiab cov qhab nia coj tus cwj pwm kuj tau txhim kho hauv cov qauv no [86]. Thaum lub sijhawm kawm hauv vitro, kev tiv thaiv cov teebmeem ntawm polydatin kuj tau pom tias muaj kev cuam tshuam rau kev tswj hwm ntawm neuroglobin (Ngb) txhawb kev ua haujlwm thiab mRNA qhia [87].

Polydatin kuj tseem tuaj yeem tswj cov noob qhia ntawm Ngb los ntawm kev txo qis ntawm CREB, HIF-1 , p56, thiab cov lus teb thaum ntxov ntawm cov protein 1 (Egr1). Tsis tas li ntawd, kev txo qis hauv polydatin hauv NO kuj tseem cuam tshuam nrog Ngb up-regulation [88,89]. Los ntawm lwm qhov kev pom, polydatin txhais tau tias inhibited cerebral edema hauv cerebral hemorrhage nas los ntawm suppressing excitatory amino acids [90]. Tshaj li mob stroke, polydatin tau pom ob peb lwm cov teebmeem neuroprotective. Piv txwv li, hauv txoj kev tshawb fawb ntawm Guan li al., polydatin muaj peev xwm pom tau tias muaj kev cuam tshuam rau anxiolytic thiab suppressed neuroinflammation hauv tus qauv nas mob ntev los ntawm kev txo qis pro-inflammatory cytokines, suav nrog TNF- thiab IL-1 hauv amygdala [91].

Cov txheej txheem sib txawv yog ua haujlwm los ntawm polydatin los tiv thaiv kev mob stroke thiab kev ntxhov siab, suav nrog Nrf2/HO-1/ARE, Bax/caspases, Egr1/Ngb, CREB, thiab PGC-1. Tsis tas li ntawd, kev ua haujlwm antioxidant, kev txhim kho hauv mitochondrial noj qab haus huv, dawb-radical scavenging, anti-apoptotic / anti-inflammatory kev ua ub no, up-regulation ntawm BDNF / Shh / Ngb txoj kev, thiab down-regulation ntawm CAMs yog lwm yam kev tiv thaiv mechanisms ntawm polydatin [19] , 92] ib. Tag nrho cov txheej txheem ntawm neuropharmacological yam ntxwv ntawm polydatin tiv thaiv AD, PD, TBI / SCI, thiab mob hlab ntsha tawg tau nthuav tawm hauv Table 1. Zuag qhia tag nrho, los ntawm kev siv ntau lub tswv yim thiab kev hloov kho ntawm ntau txoj hauv kev dysregulated, polydatin tuaj yeem yog ib qho kev cog lus neuroprotective phytochemical tiv thaiv PD, AD. , TBI/SCI, thiab mob stroke (Daim duab 2).

4. Polydatin Novel Delivery Systems: Nanoformulations, thiab Targeted

Kev kho Nanomedicine yog kev siv tshuaj kho mob ntawm nanotechnology uas ntiav biocompatible, low-toxicity nanomaterials thiab nanoparticles los tswj cov tshuaj pharmacokinetics, kev tswj hwm tus nqi, thiab bioavailability [96]. Tsis tas li ntawd, polydatin tuaj yeem tiv thaiv lub hlwb raug mob, teeb meem rau lub raum, lub plawv tsis ua haujlwm, thiab txhim kho cov piam thaj thiab lipid metabolism [97,98]. Txawm li cas los xij, kev ua haujlwm kho mob ntawm polydatin raug txwv vim tsis muaj dej solubility, cov tshuaj tsis txaus ntseeg hauv cov dej alkaline nruab nrab, thiab cov metabolism hauv thawj zaug. Txhawm rau hais txog cov kev txwv no, cov khoom siv rov ua dua nano tau ua rau muaj kev xav dav vim tias lawv muaj peev xwm xa cov tshuaj thiab ua tiav kev tshem tawm ntawm lub cev [11].

Nyob rau hauv txoj kev no, chitosan-loaded nanoparticles tswj txhua hnub los ntawm gastric intubation li ib hlis txhim kho cov nyhuv ntawm polydatin nyob rau hauv txiv neej Wistar albino nas [99]. Hauv ntshav qab zib mellitus (DM), polydatin tau siv vim nws ntau yam kev kho mob uas muaj xws li kev tswj cov dawb-radical ntau lawm thiab mitochondrial kev ua, nrog rau kev tswj ntawm qhov mob thiab oxidative kev nyuaj siab [97,98]. Kev tiv thaiv hyperglycemic thiab antioxidant cuam tshuam ntawm polydatin ua rau txo qis hauv hemoglobin A1C hauv cov nas mob ntshav qab zib, thiab kev kho mob ua rau muaj qhov nce siab hauv cov qib siab glycogen, uas tej zaum yuav yog theem nrab ntawm kev txhim kho cov tshuaj insulin thiab kev cuam tshuam [98]. Sib nrug los ntawm nws cov dej solubility tsawg, qhov txo cov txiaj ntsig thiab kev nyab xeeb ntawm polydatin yuav tsum tau hais ua ntej siv hauv kev sim tshuaj.

Nyob rau hauv txoj kev no, microenvironment-sensitive nanoparticles tau pom cov lus cog tseg hauv kev ua kom bioavailability ntawm lipophilic tshuaj [100]. Lub depletion ntawm daim siab fibrosis nyob rau hauv nas tau muab ib tug polydatin loaded micelle (PD-MC) tau txheeb xyuas los ntawm kev ntsuas hydroxyproline thiab fibrotic tsis, xws li collagen hom 1 (Col1), cov ntaub so ntswg inhibitor ntawm metalloproteinases 1 (TIMP-1), transforming kev loj hlob. factor-beta (TGF- ), thiab PD-MC, uas tsis tsuas yog inhibited hepatocyte apoptotic cell tuag tab sis kuj pom cov khoom tiv thaiv kab mob. Kev tiv thaiv kev ua haujlwm ntawm PD-MC tau txuas nrog nws lub peev xwm los tiv thaiv ROS thiab TLR4 / NF-B p65 txoj kev taw qhia. Cov nas uas kho nrog PD-MC muaj qhov tsis tshua muaj siab oxidative hauv siab vim qhov qis dua ntawm 4-Hydroxynonenal (4-HNE) [101].

Polydatin muaj qhov cuam tshuam meej rau ntawm lub plawv, ua haujlwm ua cov tshuaj tiv thaiv coagulant, tiv thaiv kev mob, tiv thaiv atherosclerotic, tiv thaiv hypercholesterolemic, thiab cov tshuaj tiv thaiv ischemic. Nws txo cov platelet tsub zuj zuj, nce microcirculation, ntxiv dag zog rau endothelium thiab paj hlwb, thiab txo cov hnoos thiab hawb pob, uas tuaj yeem pom los tswj kev poob siab [21]. Txawm li cas los xij, qhov txwv qhov ncauj bioavailability (ib nrab-lub neej 8-14 min) thiab solubility tsawg (qhov siab tshaj solubility kwv yees yog 30 g / mL hauv dej ntawm 25 ◦C) ntawm polydatin tau txwv nws cov kev tswj hwm [21,102]. Raws li, liposomes tau pom muaj zog solubilization thiab stabilization thaum tseem muab cov tshuaj zoo rau cov dej-soluble thiab lipid-soluble tshuaj. Cov kab mob polydatin-loaded liposomes (10 mg / kg) tau sib npaug hauv Sprague-Dawley nas. Cov yam ntxwv ntev ntawm polydatin-loaded liposomal system tuaj yeem txhim kho qhov nqus ntawm polydatin hauv lub plab zom mov, tab sis tsis muaj kev hloov pauv hauv lub cev tom qab kho nrog polydatin-loaded liposome [102].

Hauv kev mob qog noj ntshav, cov kev kho mob ib txwm muaj, xws li kev phais, tshuaj khomob, xov tooj cua, tshuaj tiv thaiv kab mob, thiab kev kho tshuaj hormonal tsis txaus rau kev tswj kev mob qog noj ntshav [103]. Nyob rau hauv txoj kev no, polydatin muaj ntau yam khoom xws li tshuaj tiv thaiv proliferative, antioxidant, anti-o, thiab immunomodulatory. Rau kev txhim kho cov tshuaj tiv thaiv kab mob ntawm polydatin thiab lwm yam kev kho tshiab, kev tsim cov nanoparticles tau txais kev saib xyuas ntau [104]. Yog li, kev tswj hwm qhov ncauj ntawm polydatin-loaded poly (lactic-co-glycolic acid) [PLGA] nanoparticles (polydatin-PLGA-NPS) hauv Syrian hamsters ua rau qis qis ntawm lipid peroxidative byproducts. Polydatin-PLGA-NP therapy txo cov qog histological cov tsos mob los ntawm huab mus rau me me thiab thaiv kev loj hlob ntawm squamous cell carcinoma. Tsis tas li ntawd, kev tswj hwm ntawm polydatin-PLGA-NPs tau coj mus rau qhov txo qis hauv cov qog ntim thiab tshwm sim. Polydatin-PLGA-NPs tseem ceeb nce enzymatic antioxidant tus nqi xws li SOD, CAT, thiab GPx, thaum txo tus nqi ntawm cytochrome (Cyt) p450, Cyt b5, glutathione S-transferase, gamma-glutamyl transferase, thiab glutathione reductase cov dej num, uas yog Ntawm cov metabolizing enzymes ntawm theem I thiab II. Polydatin-PLGA-NPS kev kho mob tshwm sim los ntawm apoptosis ntawm sheared caspase-3 overexpression thiab kev tiv thaiv ntawm dimethyl benzyl anthracene-induced mutant p53 thiab cyclin-D1 ntau lawm nyob rau hauv ib koob tshuaj-dependent yam [105].

Raws li lwm qhov kev tsis sib haum xeeb, kev chim siab plob tsis so tswj yog tam sim no xav tias yuav tshwm sim los ntawm kev ua haujlwm tsis zoo hauv lub hlwb-lub plab axis, suav nrog ob qho tib si hauv nruab nrab thiab sab hauv txoj kev txhawj xeeb, thiab tshwj xeeb, koom nrog cannabinoid receptors thiab cuam tshuam rau kev ua haujlwm ntawm cov hlwb feem ntau. Txhawm rau hloov kho cov txheej txheem dysregulated no, cov txiaj ntsig ntawm daim ntawv co-micronized ntawm palmitoylethanolamide / polydatin tau tshuaj xyuas hauv 157 cov neeg mob uas muaj mob plab plob tsis so tswj [106]. Ua ke, ntxiv rau nws cov txiaj ntsig zoo thiab cov yam ntxwv ntawm cov tshuaj pharmacokinetic zoo dua ntawm polydatin, kev siv cov tshuab xa tawm tshiab rau cov txheej txheem metabolite no tuaj yeem ua rau muaj kev cuam tshuam thiab txo qee qhov kev txwv ntawm phytochemicals, los ntawm kev nce solubility / bioavailability thiab txo kev pheej hmoo ntawm kev nyab xeeb. Daim duab 3 qhia txog kev xa khoom tshiab ntawm polydatin.

5. Cov lus xaus

Polydatin yog ntau lub hom phiaj stilbenoid theem nrab metabolite muab rho tawm los ntawm cov tshuaj ntsuab. Raws li polydatin yog glycosylated daim ntawv ntawm resveratrol, ntau yam kev ua ub no lom neeg thiab cov txiaj ntsig kev noj qab haus huv tau txuas nrog kev tswj hwm ntawm polydatin, suav nrog cardioprotective, hepatoprotective, thiab neuroprotective yam. Cov kev tshawb fawb tam sim no tsom mus rau cov peev txheej neuroprotective ntawm polydatin los ntawm kev siv ntau lub tshuab, suav nrog Nrf2/Keap1/ARE, PI3K/Akt, ERK/MAPK, TLR/NF-κB/TNF- /ILs, thiab Bax/Bcl-2/ caspases (Daim duab 4). Nyob rau hauv kab no, polydatin critically modulates inflammatory, apoptotic, thiab oxidative mediators rau combating AD, PD, stroke, CNS raug mob, thiab lwm yam neuroprotective teb.

Ntawm qhov tod tes, pharmacokinetic drawbacks ntawm polydatin, nrog rau lawv cov bioavailability tsis zoo, tsis tshua muaj solubility/selectivity, tsis tshua muaj ntshav plasma concentration, sai metabolism, thiab tshuaj degradation, txwv tsis pub siv cov tshuaj kho mob. Nws nthuav tawm qhov tseem ceeb ntawm kev xa tshuaj tshiab los txo cov kev txwv hauv kev hloov kho qog cell senescence. Nws tseem tsim nyog sau cia tias kev muab cov txheej txheem xa tawm tshiab tuaj yeem pab tau cov polydatin kom dhau los ntawm cov hlab ntsha-hlwb thiab txhim kho kev kho mob ntev ntev ntawm cov tshuaj hauv CNS thaum muaj kev phiv tsawg dua [107–109]. Hauv txoj kev tshawb fawb tam sim no, lub hom phiaj tshuaj kho mob, cov txheej txheem molecular, thiab cov peev txheej kho mob ntawm polydatin tau qhia los ntawm kev txo qis ntawm inflammatory / apoptotic / oxidative txoj hauv kev los daws ntau txoj hauv kev dysregulated hauv NDDs. Qhov xav tau los muab cov txheej txheem xa tawm tshiab ntawm polydatin, suav nrog nanoformulations thiab kev kho cov phiaj xwm kuj raug txiav txim siab. Cov kev tshawb fawb ua ntej kev kho mob ntxiv yog xav tau los piav qhia meej cov txheej txheem neuroprotective ntawm polydatin ua raws los ntawm kev tswj xyuas kev soj ntsuam zoo.

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