Anti-aging Effects Of Ribes Meyeri Anthocyanins On Neural Stem Cells And Aging Muas Part 1

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

Abstract:Kev laus yog txuam nrog kev puas hlwb neurological thiab kev txawj ntse poob. Flavonoids tau zoo heev hauv kev tshawb fawb los tiv thaiv kev laus hauv cov qauv nas. Ribes Meyer anthocyanins yog nplua nuj nyob rau hauv ntau flavonoids, tab sis lawv cov kev tiv thaiv kev laus kev lom zem tseem tsis tau paub. Hauv txoj kev tshawb no, peb tau npaj ib qho R. Meyer anthocyanin extract thiab tshuaj xyuas nws cov teebmeem ntawm neural stem cell (NSC) senescence hauv vivo thiab hauv vitro. Peb cais nas NSCs thiab siv cov khoom siv ntawm tes suav -8(CCK-8), cell cycle, reactive oxygen hom (ROS), thiab immunofluorescence txoj kev los tshuaj xyuas cov kev tiv thaiv kev laus ntawm R. Meyer anthocyanins ib yam nkaus. raws li naringenin (Nar), uas tsom xam metabolic qhia raws li ib qho tseem ceeb flavonoid nyob rau hauv R. Meyer anthocyanins. RNA-sequencing (RNA-seq) thiab enzyme-linked immunosorbent assay (ELISA) txoj kev kuj tau siv los tshawb xyuas Nar-specific mechanisms ntawm kev tiv thaiv kev laus. Tom qab R. Meyer anthocyanin kev kho mob, NSC proliferation accelerated, thiab NSCs tau txo cov cim senescence thiab txo P16ink4 qhia. R. Meyer anthocyanin kev kho mob kuj thim rov qab lub hnub nyoog-dependent neuronal poob hauv vivo thiab hauv vitro. Nar thaiv mNSC kev laus hauv vitro thiab txhim kho spatial nco thiab kev txawj ntse hauv cov nas laus los ntawm kev txo qis ntawm cov ntshav TNF- protein.Citrus bioflavonoidsCov kev tshawb pom no qhia tias R. Meyer anthocyanins nce NSC proliferation thiab txhim kho neurogenesis nrog kev laus ntawm Nar-induced txo qis hauv TNF- protein ntau hauv vivo.

Taw qhia

Ribes Meyer (tseem hu ua R. Meyer Maxim) belongs rau tsev neeg Saxifragaceae [1, 2]. Cov hauv paus hniav thiab nplooj ntawm R. Meyer yog nplua nuj nyob rau hauv ib chav kawm ntawm cov nroj tsuag theem nrab metabolite flavonoids [1-6] nrog ntau lub zog, nrog rau cov tshuaj tiv thaiv kab mob thiab tiv thaiv qog noj ntshav [7-9]. Zhou et al. thawj cais naringenin (Nar) los ntawm R. Meyer anthocyanins [1]. Nar yog lub ntsiab ntawm R. sativum; Txawm li cas los xij, kev tiv thaiv kev laus ntawm cov tshuaj lom neeg ntawm Nar thiab R. Meyer anthocyanins tseem tsis paub. Stem cell qaug zog yog qhov cim tseem ceeb ntawm kev laus [10] Lub hnub nyoog-raws li kev poob ntawm neural stem cells (NSCs) yog txuam nrog kev txawj ntse poob, thiab NSCs koom nrog cov kab mob cuam tshuam nrog kev nco tsis tau [11, 12]. Muaj qhov cim poob hauv NSC thiab cov lej neuronal hauv cov laus murine hlwb [13].cov txiaj ntsig cynomoriumUa rau muaj kev laus hauv cov qia hlwb suav nrog luv telomeres, nce qib ntawm cov pa oxygen reactive (ROS), ua kom lub cev muaj zog P16ink4a, thiab cell voj voog ntes [14-16]. Cov yam tseem ceeb no thaum kawg ua rau lub paj hlwb puas, metabolic ntshawv siab, thiab kev paub tsis meej [17].

Thov nias ntawm no kom paub ntxiv

Xav txog tias cov kev hloov pauv no cuam tshuam txog kev laus, kev ua haujlwm ntawm R. Meyer anthocyanins tsis tau kawm zoo. Raws li, peb tau tshawb xyuas cov teebmeem ntawm R. Meyer anthocyanins ntawm NSCs hauv cov nas laus. Peb cov txiaj ntsig tau pom tias R. Meyer anthocyanins txhim kho cov neeg laus phenotype los ntawm kev thim rov qab cov txiaj ntsig ntawm NPCs hauv vitro, nrog rau kev txhim kho kev txawj ntse thiab txhim kho NSC kev loj hlob thiab cov lej neuronal hauv cov nas laus. Peb kuj tau qhia tias cov flavonoid Nar, uas yog enriched ntawm R. Meyer anthocyanins, reverses aging nyob rau hauv NSCs thiab txhim kho kev txawj ntse theem nyob rau hauv cov laus nas los ntawm inhibiting lub qog necrosis factor (TNF) signaling pathway.

TSEEM CEEB

Cov teebmeem ntawm R. Meyer anthocyanins ntawm cov hnub nyoog hloov pauv hauv MNCs

Txhawm rau txiav txim siab qhov cuam tshuam ntawm R.Meyer anthocyanins ntawm cell senescence, peb siv NSCs los ntawm 23-cov nas hnub nyoog (23M-mNSCs). Xav tias R. Meyer anthocyanins tuaj yeem ua rau cytotoxic lossis tiv thaiv cov hlwb nyob ntawm lawv qhov kev xav, peb thawj zaug xav tau kom paub tseeb tias muaj kev nyab xeeb ntawm R. Meyer anthocyanins los kho 23M-mNSCs. Kev muaj peev xwm ntawm cov hlwb uas kho nrog R. Meyer anthocyanins tau kuaj pom siv cov khoom siv ntawm tes suav -8 (CCK-8) assay.At concentrations txog 100 pg/mL,R. Meyer anthocyanin kev kho mob rau 48 lossis 72 h nce 23M-NSC cell viability (Ntxiv daim duab 1A). Kev sib sau ntawm ROS thaum laus ua lub luag haujlwm tseem ceeb hauv kev puas tsuaj mitochondrial [16,18]. Txhawm rau txiav txim siab seb R. Meyer anthocyanins tuaj yeem cuam tshuam oxidative puas tsuaj, peb tau ua ROS kev soj ntsuam. R. Meyer anthocyanins inhibited oxidative kev puas tsuaj ntawm ib tug concentration ntawm 100 pg/mL (Ntxiv daim duab 1B). Piv nrog rau kev tswj hwm, peb pom cov cim kev hloov pauv hauv kev loj hlob thiab ROS qib hauv R. Meyer anthocyanin-kho hlwb, ua kom pom tias 100 pg / mL ntawm R. Meyer anthocyanins txhawb nqa 23M-NSC proliferation thiab inhibit oxidative puas. Txhawm rau txiav txim siab qhov cuam tshuam ntawm R. Meyer anthocyanins ntawm kev tsim cov neurosphere, peb cais NSCs los ntawm lub hlwb ntawm 3-lub lim tiam (3W-mNSCs) thiab 23-hli (23M-mNSCs) nas. Cov NSCs tau subcultured thiab kho nrog 100 pg/mL R. Meyer anthocyanins (Daim duab 1A). Piv nrog rau 23M-mNSCs, tus naj npawb ntawm cov neurospheres hauv 3W-NYC pawg tau nce, thiab cov duab ntawm cov neurospheres tau zoo ib yam thiab sib npaug, nrog rau txoj kab uas hla ntawm 20-50 μm (Daim duab 1B{{38}) }D). Tsis tas li ntawd, cov neurospheres tau muab los ntawm 23M-mNSCs tom qab 5 hnub yog qhov me me (20 um), thiab qhov kev tshawb pom no tau ua raws li cov txiaj ntsig ntawm kev tshawb fawb yav dhau los [19,20]. Thaum kho nrog R. Meyer anthocyanins, kev tsim cov neurosphere tau nce ntxiv hauv 3W-mNSCs thiab 23M-mNSCs (Daim duab 1E). Senescence yog ze ze rau lub voj voog ntawm tes raug ntes, luv telomeres, thiab nce kev qhia ntawm senescence noob pl6mk4a. R. Meyer anthocyanin-kho 23M-NSCs tau txo qis p16mk4a noob qhia, muaj ntau lub hlwb nyob rau theem S, thiab lengthened telomeres piv nrog cov hlwb tsis kho (Daim duab 1F-1H). Ntxiv mus, peb paub tias kev laus txo qhov kev loj hlob ntawm NSCs thiab txo lawv cov peev xwm sib txawv rau kev tsim cov neuronal [13,21]. Raws li kev sib txawv ntawm 23M-mNSCs, muaj qhov nce ntxiv ntawm TuJ1-cov neurons zoo tom qab R. Meyer anthocyanin kev kho mob (Daim duab lI-1J), qhia tias R. Meyer anthocyanin kev kho mob txhawb nqa cov sib txawv ntawm NSCs rau hauv neurons. Cov txiaj ntsig no qhia tau tias R. Meyer anthocyanins muaj txiaj ntsig zoo rau cov laus NSCs hauv Vitro.

Cistanche tuaj yeem tiv thaiv kev laus

R. Meyer anthocyanin kev kho mob txhim kho kev kawm thiab kev nco muaj peev xwm ntawm cov nas laus

Kev laus yog txuam nrog kev paub tsis meej [22,23]. Yog li ntawd, peb tau soj ntsuam cov teebmeem ntawm R. Meyer anthocyanins ntawm kev kawm thiab kev nco txog cov nas. Morris dej maze (MWM) kuaj tau qhia tias, thaum cov neeg laus C57BL / 6 nas (12 lub hlis) tau muab 100 mg / kg R. Meyer anthocyanins rau 2 lub hlis, qhov nruab nrab lub sij hawm mus txog lub platform tau txo qis piv nrog cov tswj (Daim duab 2 A). Peb kuj tau tshuaj xyuas lub sijhawm ua ntej mus txog lub platform (Daim duab 2B). Pawg R. Meyer anthocyanin-kho tau siv sijhawm tsawg dua li pawg tswj hwm, txawm hais tias qhov nruab nrab ceev tsis sib txawv ntawm ob pawg (Daim duab 2C), qhia tias R. Meyer anthocyanins muaj kev cuam tshuam me ntsis rau lub zog ntawm cov nas. Tsis tas li ntawd, nyob rau hauv pab pawg kho mob, cov nas ua luam dej luv luv ua ntej mus txog thaj chaw platform piv nrog cov pab pawg tsis kho (Daim duab 2D). Cov txiaj ntsig no qhia tau hais tias R. Meyer anthocyanins tuaj yeem txhim kho kev paub thiab kev nco txog kev muaj peev xwm ntawm cov nas laus.suab puam hyacinthKev laus kev paub txog kev poob qis tau txuas nrog txo NSC tus lej [11, 24]. Raws li, peb cais thiab kab lis kev cai NSCs los ntawm nas hlwb e (SVZ) tom qab intragastric subventricular z ZOne kev tswj hwm ntawm 100 mg / kg R. Meyer anthocyanins (Daim duab 2E). Cov naj npawb ntawm cov neurospheres tau raug ntsuas, thiab muaj ntau ntau cov neurospheres hauv R. Meyer anthocyanin-kho pawg piv nrog pawg tswj hwm (Daim duab 2F). Tom ntej no, peb tsom xam neurosphere loj faib.R. Meyer anthocyanin-kho nas neurospheres feem ntau nyob rau hauv qhov loj me (50-100 um inch),

Daim duab 1. Ribes Meyer anthocyanins cawm lub senescence phenotype ntawm nas neural qia hlwb (MNCs). (A) Neurospheres clonally muab tau los ntawm 23-hli (23M-NSC) thiab 3-lub lim tiam (3W-NSC) nas hlwb thiab kho nrog 100 pg/mL R, txhua txhua anthocyanin. (B) Qhov sib txawv ntawm cov naj npawb neurosphere ntawm 23M-NSC thiab 3W-NSC.(C) Cov duab ntawm 3W-NSC neurospheres tau zoo ib yam, nrog cov lej thiab qhov loj me (20-50 um) piv nrog 23M-NSC neurospheres . (D. E) Kev kho mob nrog R. txhua txhua anthocyanin nce tus lej ntawm ob qho tib si 3W-NSC- thiab 23M-NSC-derived neurospheres piv nrog cov tswj. (FH) Hauv 23M-NSCs kho nrog 100 pg/mL R. Meyer anthocyanins rau 48 h, p16ink4a mRNA qhia, cell voj voog, thiab cov txheeb ze telomere lengths raug ntsuas. (F) Cell senescence marker p16ink4a mRNA qhia pom los ntawm qRT-PCR. (G) Cov voj voog ntawm tes tau txiav txim siab siv cov cytometry ntws. (H) qRT-PCR tshawb pom ntawm qhov txheeb ze telomere ntev. (I) Immunofluorescence staining ntawm TuJ1 thiab GFAP hauv 23M-NSCs kho nrog R.Flavonoid extraction method pdfMeyer anthocyanins thiab tswj. (J) Quantification ntawm (I). Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab ± SD ntawm peb qhov kev sim ywj pheej. *P<0.05,><0.01, and="">< 0.0001="" compared="" with="" untreated="" cells.="" whereas="" control="" neurospheres="" were="" more="" common="" in="" the="" lower="" range="" （20-50="" μm="" diameter）（figure="">

Txhawm rau txheeb xyuas qhov cuam tshuam ntawm R. Meyer anthocyanin kev kho mob ntawm NSCs thiab neurons hauv vivo, immunofluorescence staining ntawm hippocampus tau ua thiab feem pua ​​​​ntawm cov hlwb immunopositive tau txheeb xyuas. Siv cov NSC cov cim uas paub zoo nestin thiab Ki67 [25, 26], peb tau nthuav tawm qhov nce hauv nestin- thiab Ki67-cov hlwb zoo hauv thaj av hippocampal (Cov duab ntxiv 2A, 2B) ntawm R. Meyer anthocyanin-kho nas. Tsis tas li ntawd, tus naj npawb ntawm TuJ1- cov hlwb zoo (ib qho cim ntawm cov neurons paub tab) kuj tau nce ntxiv hauv cov nas no (Cov duab ntxiv 2C, 2D).flavonoidsUa ke, cov txiaj ntsig no qhia tau tias 100 mg / kg R. Meyer anthocyanins tuaj yeem txhim kho kev nco qab thiab kev txawj ntse hauv cov nas laus los ntawm kev txhawb nqa NSC kev loj hlob thiab nce cov lej neuronal.

Kab lus no yog muab rho tawm los ntawm www.aging-us.com AGING 2020, Vol. 12, nr 17

www.aging-us.comAGING 2020, Vol. 12, nr 17www.aging-us.comAGING 2020, Vol. 12, nr 17