Muaj peev xwm Neuroprotection Los Ntawm Dendrobium Nobile Lindl Alkaloid hauv Alzheimer's Kab Mob Qauv Ntu 2

Dendrobium nobile Lindl alkaloid hauv Tauhyperphosphorylation

Tau yog unfolded, soluble heev, thiab multifaceted neuronalprotein stabilizes microtubules, yog li txhawb kev ua haujlwm ntawm neurons (Duan li al., 2017). Nyob rau hauv AD, hyperphosphorylated tau protein aggregation ua rau NFTs uas yog postulated ua raws li los ntawm qhov tsis sib xws ntawm A ntau lawm thiab clearance (Chong et al., 2018; Twohig etal., 2018; Shi et al., 2020).

Neuronal protein yog ib qho tseem ceeb neuronal molecule uas ua lub luag haujlwm tseem ceeb hauv peb lub cim xeeb. Neuronal proteins ua rau kev sib kis ntawm cov ntaub ntawv ntawm cov neurons hauv peb lub hlwb sai dua thiab ua haujlwm tau zoo, yog li pab peb nco qab thiab kawm tau zoo dua.

Kev tshawb fawb txog keeb kwm niaj hnub no qhia tau hais tias neuronal proteins tuaj yeem tsim kev sib txuas synaptic ruaj khov hauv lub hlwb thiab tswj kev sib txuas lus ntawm neurons. Synaptic kev sib txuas yog lub hauv paus rau khaws cia nco hauv peb lub hlwb. Neuronal proteins txhawb kev nco txog cov ntaub ntawv tshiab thiab tsim kom muaj kev nco mus ntev. Hauv cov txheej txheem nco, neuronal proteins ua lub luag haujlwm tseem ceeb hauv kev txhawb nqa kev ruaj ntseg ntawm kev sib txuas ntawm cov neurons, yog li tswj xyuas qhov kev kawm ib txwm muaj thiab kev nco ua haujlwm ntawm lub hlwb.

Tsis tas li ntawd, txoj kev tshawb no kuj pom tau hais tias nyob rau hauv cov neeg laus, kev nco poob yog ze ze rau kev txo cov proteins ntawm neuronal. Yog li ntawd, nce neuronal protein cov ntsiab lus tuaj yeem yog txoj hauv kev zoo los txhim kho kev nco poob. Nyob rau tib lub sijhawm, kev txhim kho kev tsim khoom thiab kev saib xyuas cov proteins neuronal los ntawm kev noj zaub mov kom tsim nyog thiab kev ua neej nyob kuj tuaj yeem txhim kho kev nco thiab txo cov kab mob.

Hauv luv luv, neuronal proteins ua lub luag haujlwm tseem ceeb hauv peb lub hlwb thiab kev nco. Txhim kho kev tsim khoom thiab kev saib xyuas cov proteins neuronal los ntawm kev tshawb fawb thiab kev noj zaub mov kom tsim nyog thiab kev ua neej nyob tuaj yeem pab txhim kho peb lub cim xeeb thiab kev txawj ntse, thiab ua rau peb muaj kev noj qab haus huv, lub neej zoo dua. 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 ntxiv los txhim kho kev nco

Thaum tau yog hyperphosphorylated, phosphorylation ntawm tau induces ib tug nqi them mus rau lub conformation ntawm lub microtubule-binding cheeb tsam, yog li ua rau tsim NFTs nyob rau hauv lub hlwb (Chong li al., 2018).In contrast to A plaques, tau pathology tau qhia. Ib qho kev sib raug zoo nrog kev poob qis ntawm kev paub txog kev ua tau zoo raws li kev tshawb fawb txog kab mob ntev thiab cov duab (Aschenbrenneret al., 2018; Vergallo et al., 2018).

Cov teebmeem ntawm DNLA ntawm kev tawm tsam hyperphosphorylatedtau protein aggregation tau raug tshawb xyuas. DNLA (40mg / kg) kev kho mob rau 6 lub hlis downregulated endoplasmicreticulum stress-related protein kinase RNA-like endoplasmicreticulum kinase (PERK) signaling pathway, sequentialinhibition of calpain1, glycogen synthase kinase-3 beta (GSK3 depend ) thiab cyclinase 5. kev ua ub no, thiab nws thiaj li txo qhov hyperphosphorylation ntawm tau hauv SAMP8 nas (Liu li al., 2020a).

Tnws txoj kev tshawb fawb tau tshaj tawm tias DNLA tau txo qis tau hyperphosphorylation, txo qis qis hauv cov hlab ntsha, thiab txhim kho kev nco ua haujlwm tom qab.

Dendrobium nobile Lindl alkaloid hauv neuroinflamation
Lwm qhov kev lees paub txog kab mob ntawm AD isneuroinflammation (Sofroniew, 2014; Fakhoury, 2018).Microglia thiab astrocytes yog lub ntsiab glial hlwb koom nrog kev tiv thaiv kab mob ntawm lub hauv nruab nrab paj hlwb thiab hnov ​​​​mob rau ntau hom kev tiv thaiv thiab tshuaj tiv thaiv (Zilka et al., 2006).

Ntau qhov kev tshawb fawb tau pom tias cov txheej txheem inflammatory yuav txhawb nqa neuronal poob thiab kev paub tsis meej (Cai li al., 2014; Webers li al., 2020).Microglia ua lub luag haujlwm tseem ceeb hauv A homeostasis. Activatedmicroglia pib phagocytosis kom tshem A tawm ntawm lub hlwb.Txawm li cas los xij, hauv AD, A tsub zuj zuj tau pom tias ua rau mob plab (Calsolaro thiab Edison, 2016).

Microglia yog qhib los ntawm A thiab APP, ua rau microglial activation ncig A plaques (Regen li al., 2017). Kev ua kom microglia txhawb nqa kev tso tawm ntawm cov teeb meem proinflammatory, xws li qog nqaij hlav- (TNF- ), interleukin -1 (IL-1 ), thiab IL-6(Chen thiab Zhong, 2017; Rajendran thiab Paolicelli, 2018). Kev sib sau ntawm cov inflammatory yam tseem ceeb ntxiv txhawb kev tiv thaiv kab mob thiab ua rau cov degeneration ntawm neurons, suav nrog kev poob ntawm cov neurons, uas ua rau kev txawj ntse poob thiab dementia.

LPS, tus kab mob inducer, tau tshaj tawm rau influenceA deposition. LPS txhaj rau hauv nas lub hlwb ventricle tuaj yeem ua rau kev nco tsis txaus thiab A tsub zuj zuj. DNLAtreatment tau raug tshaj tawm los tiv thaiv nas lub hlwb tawm tsam LPS-induced neuroinflammation thiab kev paub tsis meej; cov nyhuv no tau tshwm sim los ntawm kev tawm tsam ntawm LPSinduced overexpression ntawm qog necrosis factor receptor1, thiab inhibition ntawm phosphorylated p38 mitogen-activatedprotein kinases (MPO) Zhang et al., 2011).

Tsis tas li ntawd, DNLA tau pom tias yuav txo qis LPS-induced microglial activation thiab txo cov nuclearfactor-Κb (NF-κB) p65, ib qho inhibitor ntawm NF-κB (IκB) thiab lawv cov khoom phosphorylative hauv cellular nucleus thiab cytosolof BV2 microglia, thiab kev qhia ntawm Tus xov tooj hu-zoo li receptor 4(TLR4), NLR tsev neeg pyrin domain-muaj protein ntau 3 (NLRP3), apoptosis-associated Speck-zoo li protein uas muaj CARDand caspase-1 (Liu li al., 2020c).

Ua ke, cov kev tshawb pom no qhia tias DNLA tiv thaiv cov neurons tiv thaiv LPS-inducedneuroinflammation los ntawm kev txo qis ntawm glial cell activation, txo cov proinflammatory factor ntau lawm, thiab inhibition ofp-p38 MAPK thiab downstream NF-κB thiab NLRP3 signalingpathway.

Dendrobium nobile Lindl alkaloid hauv apoptosis

Lwm cov txheej txheem ntawm AD yog apoptosis (Obulesuand Lakshmi, 2014). Apoptosis yog preprogrammed cell tuag (Fleisher, 1997). Programmed cell tuag yog ib qho tseem ceeb ntawm cov txheej txheem bioological hauv kev txhim kho thiab kev ua haujlwm ntawm tib neeg lub cev (Tower, 2015).

Pathologicalapoptosis yog txuam nrog ntau yam kab mob, nrog rau cov kab mob neurodegenerative thiab mob qog noj ntshav. Apoptosis tuaj yeem ua rau neurodegeneration thiab tuaj yeem ua rau AD (Radi etal., 2014). Apoptosis yog qhib los ntawm ntau tus neeg nruab nrab, xws li caspases 2, 3, 8, thiab 9 (Friedlander, 2003), MAPK (Sunet al., 2015; Aghaei et al., 2020), p53 (Wang et al., 2015), Bax (Aghaei et al., 2020) thiab A.

Txawm hais tias A pab txhawb txoj kev loj hlob ntawm AD thiab induces neuronal apoptosis, lub hauv paus mechanisms yog elusive (Li li al., 2018). Ib qho induced synthesis ntawm GD3 tau tshaj tawm los pab txhawb toapoptosis hauv cortical neurons (Kim li al., 2010). Yog li ntawd, qhov inhibition ntawm apoptosis yog suav tias yog ib qho kev cog lus los tiv thaiv AD.A txoj kev tshawb fawb dhau los tau tshaj tawm tias DNLA nthuav tawm cov txiaj ntsig tiv thaiv PC12 cell raug mob los ntawm A 25-35 throughattenuating apoptosis, raws li muaj pov thawj los ntawm kev nce cell viability thiab txo qis cell morphology impairment hauv vitro ( Zhanget al., 2015).

Tsis tas li ntawd, DNLA (2.5 mg / mL) tau pom cov teebmeem neuroprotective tiv thaiv cov pa oxygen-glucose deprivation / reperfusion (OGD / RP)-induced neuronal puas nyob rau hauv ratprimary neuron kab lis kev cai los ntawm stabilizing lub mitochondrialmembrane muaj peev xwm, inhibiting intracellular free calciumoverload, thiab txo qis kev tawm tsam. kev qhia ntawm caspase-3 andcaspase-12 (Wang et al., 2010).

Tsis tas li ntawd, DNLA tau tshwm sim los txo qis LPS-vim kev paub tsis txaus ntseeg hauv nas, thiab cov txiaj ntsig yuav cuam tshuam nrog kev txo qis ntawm caspase 3/8 mRNA qhia thiab txo qis ntawm A 1-42 hauv hippocampus (Chen li al., 2008). DNLA inhibited neuronalapoptosis thiab ntxiv ameliorated cov tsos mob dementia hauv AD qauv, uas tej zaum yuav cuam tshuam nrog inhibition of hyperphosphorylation ntawm tau protein.

Tsis tas li ntawd, DNLAameliorated LPS-induced nco thiab kev paub tsis meej hauv nas; Cov txheej txheem tau zoo sib xws nrog txo qis ntawm cov hlwb apoptotic, txo qis kev qhia ntawm hyperphosphorylated tau protein ntawm serine 396 (Ser396), Ser 199-202, Ser404, tyrosine 231 (Tyr231), Thr205 sitesand nce kev qhia ntawm GSK-3 ( Yang et al., 2014).

Insummary, luam tawm cov ntaub ntawv qhia hais tias DNLA muaj txiaj ntsig zoo rau cov tsos mob dementia hauv AD qauv los ntawm kev txo qis A tsub zuj zuj thiab inhibiting hyperphosphorylation ntawm tauprotein. Cov txheej txheem hauv qab no tuaj yeem cuam tshuam txog kev txhawb nqa neural apoptosis.

Dendrobium nobile Lindl alkaloid hauv autophagy

Txoj kev basal autophagy yog qhov tseem ceeb rau neuronaldegradation (Funderburk li al., 2010). Activated autophagy koom nrog ntau yam txheej txheem physiological thiab pathological mob, suav nrog kev tuag ntawm tes, tshem tawm cov kab mob hauv lub cell, thiab qog nqaij hlav (Glick li al., 2010).Kev tshawb fawb tsis ntev los no tau pom tias autophagy yog ze rau kev laus (Madalina li al., 20). .

Ntau yam autophagydysfunctions tuaj yeem ua rau muaj kev cuam tshuam rau cov neurodegeneration, suav nrog kev txwv tsis pub autophagosome-lysosome fusion (Tammineniand Cai, 2017), txo qis lysosomal acidification (Tanakaet al., 2013) lossis tsub zuj zuj ntawm cov proteins hauv cov hlwb neuronal (Menzies et 207). Nyob rau hauv parallel, autophagy yog ib qho tseem ceeb regulatorof A tsub zuj zuj thiab clearance (Li li al., 2017).

Nyob rau hauv AD, autophagosome fusion nrog lysosomes thiab lawv retrogradepassage mus rau lub cev neuronal yog hindered (Uddin li al., 2018). Cov ntawv ceeb toom no qhia tias cov txheej txheem autophagy yog qhov tseem ceeb rau kev nce qib ntawm AD.DNLA tau kawm txog nws cov kev tiv thaiv ntawm autophagys uas muaj peev xwm koom nrog AD. DNLA txhim kho kev kawm thiab kev nco tsis zoo hauv APP / PS1 nas, thiab cov txiaj ntsig tau tshaj tawm los ntawm kev sib kho los ntawm kev txhawb nqa ntawm intracellular A degradation los ntawm kev nce qib v-ATPase A1protein thiab tom qab ntawd txhim kho autolysosomal acidification thiab proteolysis (Nie li al., 2018). 

Tsis tas li ntawd, nyob rau hauv tus qauv SAMP8, tom qab 6 lub hlis ntawm kev kho mob, DNLA txhim kho kev ua haujlwm autophagy los ntawm kev nce qhov kev qhia ntawm autophagymarker lub teeb saw 3 (LC3), autophagy-related proteinBeclin1 thiab Klotho, thiab txo cov nucleoporin p62 hauv thehippocampus thiab cortex (Lv et al. ). Hauv kev tshawb fawb hauv vitro, cov txiaj ntsig zoo sib xws ntawm DNLA tau pom hauv thawj hippocampalneurons.

DNLA pretreatment txo qis axonaldegeneration induced los ntawm A 25-35 cytotoxicity; Cov kws sau ntawv tau tshaj tawm tias cov txiaj ntsig yuav cuam tshuam nrog kev txhim kho autophagic flux los ntawm kev txhawb kev tsim thiab degradation ntawm autophagosomes hauv axonal degeneration ntawm hippocampalneurons (Li et al., 2016). Raws li cov kev tshawb pom no, peb kos cov lus xaus uas ntseeg tau tias DNLA tiv thaiv cov neuronaldegeneration los ntawm kev ua kom lub cev tsis muaj zog.

Dendrobium nobile Lindl alkaloid nyob rau hauv neuronal synapticconnection

Hmoov tsis zoo, ntau cov tshuaj kho tshiab tau npaj raws li cov kev xav ib txwm muaj tau ntsib cov txiaj ntsig tsis txaus siab hauv kev sim tshuaj; lawv tsis tuaj yeem tiv thaiv kev kis kab mob los yog txhawb nqa neuronalregeneration (Alipour li al., 2019). Cov neeg laus neurogenesis nqa lub peev xwm ntawm lub hlwb kho tus kheej los ntawm qhov endogenous tsim ntawm cov neurons tshiab hauv cov neeg laus lub hlwb. Txawm li cas los xij, nws kuj txo qis nrog hnub nyoog. Pharmacological cov tswv yim los txhim kho cov tsos mob ntawm AD tau suav nrog ntau txoj hauv kev los txhawb cov neurogenesis. Yog li ntawd, kev nkag siab tob dua ntawm cov txheej txheem tswj hwm hauv qab qia cell neurogenesis lossis kev sib koom ua haujlwm ntawm cov menyuam yug tshiab neurons tuaj yeem pab txhawb kev tsim kho tshiab thiab zoo AD (Vasic etal., 2019).

Peb cov kev tshawb fawb yav dhau los tau pom tias DNLA tiv thaiv cov kab mob cortical neurons tiv thaiv A 25–35-induced neurotoxicity thiab synaptic puas. DNLA thim rov qab A 25–35-induceddecreses hauv synaptophysin (SYP) thiab postsynaptic ntom ntom 95 (PSD-95) (Zhang li al., 2017). SYP, PSD-95, thiab lwm yam synapse-associated proteins yog qhov tseem ceeb rau kev tswj xyuas kev ua haujlwm ntawm synaptic morphology thiab kev ua haujlwm. DNLA tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev txhawb nqa neurogenesis ntsig txog synapse-associatedproteins txhawm rau txhim kho kev sib kis hauv cov hlab ntsha.

Xaus

Nutraceuticals tau dhau los ua cov lus cog tseg tshiab los tiv thaiv lossis kho AD. Raws li tau tshaj tawm, cov kev tshawb fawb tseem ceeb tshaj plaws qhia tau hais tias DNLA yog ib qho kev cog lus molecule los tawm tsam cov txheej txheem pathophysiological ntawm AD, yog li txhim kho kev paub txog kev ua haujlwm thiab inhibiting neurodegeneration. Qhia hauv daim duab 1.

Cov txheej txheem hauv qab DNLA cov teebmeem yuav cuam tshuam rau inhibiting A plaque ntau lawm thiab tau proteinhyperphosphorylation, txo cov neuroinflammation andapoptosis, ua kom autophagy, thiab txhim kho synapticconnections. Cov kev tshawb fawb tshawb xyuas cov txheej txheem ntawm DNLAare tsis tu ncua hauv cov qauv kab mob tsiaj. Lub sijhawm no, kev tshawb fawb soj ntsuam tsis tau ua. Yog li ntawd, kev tshawb nrhiav kev kho mob dav dav yuav tsum tau ua kom paub meej txog cov teeb meem ntau yam thiab theoretical ntawm DNLA-mediatedneuroprotection hauv AD.

Sau cov nyiaj pab: JSS tau xeeb thiab tsim qhov kev tshuaj xyuas. DDLand CQZ tau tshawb nrhiav cov ntaub ntawv. DDL sau cov ntawv sau. FZsubstantially edited and improved the manuscript. Txhua tus kws sau ntawv tau txhawb nqa cov lus tseem ceeb thiab cov ntawv sau kho dua tshiab thiab pom zoo cov ntawv kawg.
Kev tsis sib haum xeeb: Cov neeg sau ntawv tshaj tawm tias tsis muaj kev tsis sib haum xeeb ntawm kev txaus siab cuam tshuam nrog cov ntawv sau no.

Kev txhawb nqa nyiaj txiag: Txoj haujlwm no tau txhawb nqa los ntawm Shijingshan Tus Kws Qhia Ntawv Studioof Pharmacology, No. GZS-2016-07 (rau JSS); Kev tsim kho ntawm NationalFirst Class Pharmacy Discipline, No. GESR-2017-85 (rau JSS); MasterStart Foundation ntawm Zunyi Medical University, No. F-839 (rau DDL); thiab kev pom zoo los ntawm Guizhou Chinese Medicine Administration, No. QZYY-2018-025(rau DDL). Cov peev nyiaj tsis muaj lub luag haujlwm hauv kev kawm txog kev xav thiab tsim qauv, kev tshuaj xyuas cov ntaub ntawv lossis kev txhais lus, sau ntawv, lossis txiav txim siab xa daim ntawv no rau kev tshaj tawm.

Daim ntawv tso cai daim ntawv tso cai: Daim Ntawv Pom Zoo Daim Ntawv Tso Cai Tso Cai tau raug kos npe los ntawm txhua tus kws sau ntawv ua ntej tshaj tawm.

Cov ntaub ntawv sib qhia: Cov ntaub ntawv txheeb xyuas thaum lub sijhawm kawm tam sim no muaj los ntawm tus kws sau ntawv raws li kev thov tsim nyog.

Plagiarism check: Tshawb xyuas ob zaug los ntawm iThenticate.

Kev tshuaj xyuas cov phooj ywg: Sab nraud cov neeg txheeb xyuas.

Qhib cov lus qhia nkag: Qhov no yog ib phau ntawv xov xwm qhib, thiab cov ntawv tau muab faib raws li cov ntsiab lus ntawm Creative Commons AttributionNonCommercial-ShareAlike 4.0 Daim ntawv tso cai, uas tso cai rau lwm tus los remix, tweak, thiab tsim los ntawm kev ua haujlwm tsis yog lag luam, ntev npaum li qhov tsim nyog tau txais credit thiab cov kev tsim tshiab tau tso cai raws li cov ntsiab lus zoo ib yam.

Qhib cov neeg saib xyuas: Hans-Gert Bernstein, Otto-von-Guericke University, Lub Tebchaws Yelemees; Paulina Carriba, Cardiff University, UK.

Cov ntaub ntawv ntxiv: Qhib cov ntaub ntawv txheeb xyuas cov phooj ywg 1 thiab 2.

Cov ntaub ntawv

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