Molecular Pathways Muaj feem xyuam rau Kev Txhim Kho Lub Neej Ntev Thiab Kev Txhim Kho Kev Paub Ntawm Cistanche Tubulosa hauv Drosophila
Mar 14, 2022
Yog xav paub ntxiv:ali.ma@wecistanche.com
Wei-Yong Lin et al
Abstract:
Keeb kwm:Cov txheej txheem kev laus, suav nrog kev ua haujlwm tsis zoo ntawm lub cev thiab lub hnub nyoog ntsig txog kev nco tsis zoo (AMI), raug suav tias muaj feem cuam tshuam nrog kev sib xyaw oxidative puas tsuaj thiab insulin / IGF-1 txoj kev taw qhia.Lub hom phiaj: Txoj kev tshawb fawb tam sim no yog los piav qhia hauv vivo. cuam tshuam rau ncua kev laus thiab ameliorating AMIand hauv qab molecular mechanisms ntawmCistanche tubulosa(CT), tshuaj ntsuab siv hauv tshuaj suav tshuaj los txhim kho kev sib deev thiab kho lub raum tsis ua haujlwm
Txoj kev:Cov yoov, kho thiab tsis kho nrog CT(Cistanche Tubulosa), raug soj ntsuam rau lifespan, tiv thaiv oxidativestress nrog H2O2 los yog paraquat, kev tshaib kev nqhis kev soj ntsuam, kev txawj ntse tus cwj pwm nrog T-maze, thiab transcript theem ntawm lub hom phiaj genes nrog ntau RT-PCR.
Cov txiaj ntsig:Kev tswj hwm CT(Cistanche Tubulosa)ncua qhov nruab nrab thiab qhov siab tshaj plaws lifespan thiab nce oxidativestress nyob rau hauv yoov. CT(Cistanche Tubulosa)supplementation kuj txhim khu kev nco tsim nyob rau hauv cov me nyuam yoov thiab suppressed AMIupon laus. Ob peb lub noob thiab cov kev taw qhia, suav nrog lub hom phiaj ntawm lub hom phiaj ntawm rapamycin (mTOR) thiab Notch tes hauj lwm, tau raug txheeb xyuas tias ua rau cov tshuaj siv tshuaj no thiab kev hloov pauv hauv cov noob qhia ntawm glutamate receptors.
Xaus:Peb cov txiaj ntsig qhia tias CT(Cistanche Tubulosa)supplementation tej zaum yuav ua rau kom qeeb aging phenotypesand alleviating kev txawj ntse-kev coj cwj pwm poob rau yoov, qhia tau hais tias muaj peev xwm siv tau los txhim kho tib neeg kev noj qab haus huv thiab txo cov kev pheej hmoo ntawm hnub nyoog txog kev mob.
Ntsiab lus:Kev laus,Tubulosa,Cognitive cwj pwm, Tshuaj ntsuab
Nyem rau Cistanche qia cov khoom
Taw qhia
Raws li cov neeg laus muaj hnub nyoog nce thoob ntiaj teb, kev txhawb nqa kev noj qab haus huv thiab kev noj qab haus huv yog qhov tseem ceeb ntxiv rau pej xeem kev noj qab haus huv rau kev tshawb fawb, zej zog, thiab kev kho mob. Cov txheej txheem aging tau raug npaj raws li kev tswj hwm los ntawm cov txheej txheem nyuaj, uas tau tsav los ntawm kev sib tshuam dav ntawm cov caj ces thiab ib puag ncig. Vim tias kev puas tsuaj zuj zus ntawm cov cellular thiab cov ntaub so ntswg, hnub nyoog yog qhov muaj feem cuam tshuam rau thiab muaj feem cuam tshuam nrog rau cov kab mob ntev xws li mob qog noj ntshav nrog rau cov kab mob plawv thiab cov kab mob neurodegenerative (Kenyon, 2005). Agingals kuj txo cov kev ua haujlwm synaptic, cov protein synthesis tshiab, thiab kev txawj ntse. Cov kev hloov pauv no ua rau muaj kev cuam tshuam txog kev nco txog hnub nyoog (AMI) (Burke and Barnes, 2010; Schimanski and Barnes, 2010). Yog li ntawd, kev tsim tshuaj rau ncua sij hawm muaj hnub nyoog ntsig txog kab mob thiab kev paub txog kev laus tej zaum yuav muaj txiaj ntsig zoo rau tib neeg lub neej. Nyob rau hauv txoj kev tshawb no, peb siv Drosophila melanogaster, uas yog ib qho zoo tagnrho kab mob rau hauv vivo aging kev tshawb fawb vim hais tias ntawm nws shortlifespan, los soj ntsuam cov tshuaj ua tau zoo thiab tshawb cov molecular mechanisms nyob rau hauv lub amelioration ntawm kev laus thiab AMI.
Herbacistanche, tseem paub los ntawm nws lub npe Suav Rou CongRong, yog cov kab mob cab uas feem ntau muab faib rau hauv cov suab puam ntawm Northwest China. Ob hom Cistanche, Cistanche deserticolaY. C. Ma thiabCistanchetubulosa(Schrenk) Wight tau suav nrog hauv Suav Pharmacopoeia (2005 tsab) rau lawv cov khoom xyaw tshuaj zoo sib xws thiab kev ua haujlwm tshuaj. Lawv cov qia extract tau dav siv ntau txhiab xyoo los ua cov tshuaj tonic, feem ntau yog kho ntau yam tsos mob, suav nrog rau lub raum tsis ua haujlwm, impotence, infertility, thiab pab txhawb catharsis, raws li tau piav qhia hauv phau ntawv kho mob Suav thaum ub. Ntau cov khoom siv tshuaj, suav nrog cov roj tseem ceeb, phenylethanoid glycosides (PhGs), iridoids, lignans, thiab saccharides, tau raug cais tawm los ntawmCistanchehom, thiab ob yam tseem ceeb PhG, acteoside, andechinacoside feem ntau raug xaiv los ua cov cim rau kev ntsuam xyuas zoo ntawm Herba cistanche vim lawv cov tshuaj tseem ceeb (Wang li al., 2012).
Cistanche tubulosa(CT) extracts muaj ntau yam kev ua haujlwm lom neeg uas suav nrog kev hloov pauv kev tiv thaiv kab mob, txhim kho kev sib deev, txhawb cov plaub hau kev loj hlob, thiab lwm yam txiaj ntsig ntawm kev tiv thaiv oxidation, hepatoprotection, antiosteoporotic kev ua, thiab kev tiv thaiv qog (Li et al., 2016; Seok et al., 2015 ; Wang et al., 2012). Tsis tas li ntawd, hauv vitro txoj kev tshawb fawb, qhia tias Herbacistancheextract tuaj yeem tiv thaiv cov neurons zoo li ntawm H2O2-induced oxidative kev puas tsuaj thiab ua rau muaj kev cuam tshuam ntawm cov paj hlwb thiab cov paj hlwb-derived neurotrophic (Lin li al., 2013). Echinacoside tiv thaiv dopamine neuron tuag hauv MPTP-lesioned nas qauv ntawm Parkinson tus kab mob (Zhao li al., 2010). Tsis tas li ntawd, CT(Cistanche Tubulosa)extract ameliorated qhov kev paub tsis meej los ntawm kev txo qis amyloid deposition thiab nce acetylcholine thiab dopamine ntau ntau hauv ratmodel ntawm Alzheimer's kab mob (AD) (Wu li al., 2014). Txawm hais tias cov nyhuv kho mob ntawm Herbacistanchetseem yuav tsum tau lees paub, qhov loj me me, tsis yog cov tshuaj placebo-tswj tshuaj ntsuam xyuas ntawm CT(Cistanche Tubulosa)glycoside extracts tau pom tias cov tshuaj muaj peev xwm kho tau cov neeg mob me me mus rau nruab nrab AD thiab muaj cov tshuaj tiv thaiv me me, txawm tias tom qab kev tswj hwm mus ntev (Guo et al., 2013). Cov ntaub ntawv no qhia tias glycoside extracts hauv Herbacistanchemuaj cov teebmeem neuroprotective thiab anti-dementia. Txawm tias muaj ntau yam txiaj ntsig ntawm CT(Cistanche Tubulosa), nws cov txheej txheem molecular thiab cov teebmeem ntawm ncua kev laus thiab ameliorating AMI tsis tau piav qhia. Hauv qhov kev tshawb fawb no, cov teebmeem ntawm CT(Cistanche Tubulosa)ntawm qhov tseem ceeb txuas ntxiv ntawm kev ua neej tau txhim kho kev tiv thaiv ib puag ncig kev ntxhov siab, thiab txo qis hnub nyoog ntsig txog kev paub tsis meej tau raug tshuaj xyuas los txiav txim siab qhov ua tau zoo ntawm CT.(Cistanche Tubulosa)nyob rau hauv slowing cov txheej txheem aging.
Cov ntaub ntawv thiab txoj kev
Tshuaj ntsuab
Keeb kwm kev txheeb xyuas ntawmCistanche tubulosa(Schrenk) Wight (Orobanchaceae) (CT) tau txheeb xyuas hauv Ko Da PharmaceuticalCo. Ltd. (Taoyuan, Taiwan), qhov chaw daim ntawv pov thawj (10,603,205) tau khaws cia thiab CT concentrated tshuaj ntsuab yog tsim. Luv luv, cov tawv nqaij qhuav ntawm CT tau muab rho tawm hauv 12- quav dej rau 1 h tom qab pom. Cov filtrates tau sau thiab raug rau lub tshuab nqus tsev thiab txo qis siab rau 1 h kom tau txais cov khoom rho tawm. Cov CT extracts tau tov nrog starch ntawm 1: 1 piv (w / w) thiab raug tshuaj tsuag granulation forobtaining CT hmoov.
Fly Tshuag tu thiab ntsuas lifespan
Cov kab tsiaj qus uas siv hauv txoj kev tshawb no yog ntawm CantonS, tau los ntawm Bloomington Drosophila Stock Center. Cov yoov tau tsa thiab khaws cia hauv pob kws cov txheej txheem xov xwm ntawm 25 degree hauv 50-60 feem pua ntawm cov av noo nyob rau hauv 12-h lub voj voog-tsaus. Cov yoov tshaj tawm tshiab tau sau hauv 24 teev thiab sib cais los ntawm kev sib deev.Los ntawm thaum ntxov laus, yoov tau ntxiv nrog CT. CT(Cistanche Tubulosa)hmoov tau yaj nyob rau hauv dej thiab ntxiv rau pob kws xov xwm ntawm 5.4,10.8, thiab 21.6 mg / ml concentrations, uas yog proportional tothe zoo noj txhua hnub rau tib neeg lub qhov ncauj. Hauv kev soj ntsuam kev ua neej nyob, nees nkaum mus rau peb caug yoov tau tsa hauv lub raj mis nrog lossis tsis muaj CT.(Cistanche Tubulosa); Tsawg kawg yog 250 yoov tau ua rau txhua qhov kev kho mob. Cov zaub mov vials raug hloov txhua 3 mus rau 4 hnub, thiab cov yoov tuag raug suav rau lub sijhawm ntawd
Kev ntsuam xyuas kev ntxhov siab
Cov neeg laus yoov tau sau, thiab tom qab ntawd pretreated nrog kev tswj kev noj zaub mov tsis muaj CT(Cistanche Tubulosa)thiab kev sim noj zaub mov ntxiv nrog 5.4, 10.8, thiab 21.6 mg / ml ntawm CT rau 20 hnub ntawm 25 degree . Rau kev tshaib kev nqhis, yoov tau khaws cia rau hauv vials nrog cov ntawv ntub dej nkaus xwb thiab ntsuas lawv lub zog tiv thaiv kev tshaib plab-induced oxidative kev nyuaj siab. Rau kev soj ntsuam oxidative kev nyuaj siab, cov yoov tau raug xa mus rau cov zaub mov tsis muaj vials uas muaj cov ntawv lim nrog hydrogen peroxide (H2O2) (Sigma Aldrich) hauv 5 feem pua qabzib los ntsuas cov yoov tiv thaiv H2O2-induced hydroxyl radical (OH -) kev nyuaj siab. Ib yam li ntawd, yoov tau pauv mus rau vials uas muaj cov ntawv lim dej saturated nrog 10 mM paraquat (Sigma-Aldrich), uas tsim cov superoxide anions (O2 −) uas ua rau oxidative puas tsuaj rau tsiaj. Cov yoov tau raug ntaus kom tuag tsawg kawg peb zaug ib hnub kom txog thaum tag nrho cov neeg tuag. Tsawg kawg yog 250 yoov ib qho kev kho mob. Rau kev nce toj raws li hais, yoov raug rau paraquat rau 0 thiab 16 h tau muab tso rau hauv lub raj mis yas thiab maj mam rub mus rau hauv qab. Tus naj npawb ntawm yoov nyob rau saum lub vial tau suav tom qab 18 feeb ntawm kev nce toj.
Kev ntsuas Fecundity
Ob leeg txiv neej thiab poj niam noj 5.4 thiab 10.8 mg / ml ntawm CT(Cistanche Tubulosa)rau 20 hnub ua haujlwm ua pab pawg sim. Kaum tus poj niam sim sim tau sib yuav nrog tus lej sib npaug ntawm cov txiv neej nkauj xwb, uas yog 9- hnub nyoog thiab tsis tau txais CT. Ib yam li ntawd, cov txiv neej sim tau sib raug zoo nrog cov poj niam nkauj xwb nyob rau tib lub sijhawm. Cov yoov matedfemale tau raug xa mus rau lub vial tshiab rau lub qe tso rau 24 teev, thiab tag nrho cov qe nteg nyob rau hauv lub vials raug suav manually. Anindex ntawm fecundity tau xam raws li qhov nruab nrab hnub qe qe tsim poj niam. Yam tsawg kawg yog tsib vials rau ib qho kev kho mob, thiab tag nrho cov yoov n=50–80.
Olfactory associative kawm thiab nco
Cov yoov tau sau tom qab eclosion thiab pretreated nrog 5.4, 10.8, thiab 21.6 mg / ml ntawm CT(Cistanche Tubulosa)tau txais kev pab raws li kev sim pab pawg, thiab tswj yoov tsis tau txais CT(Cistanche Tubulosa)rau 5 thiab 20 hnub ntawm 25 degree . Ib qho kev cob qhia ib leeg tau ua raws li kev kawm dhau los (Dubnau li al., 2001). Luv luv, kwv yees li ntawm 100 yoov raug nthuav tawm los ntawm ob qhov tsw, xws li 3-octanol (OCT, Sigma-Aldrich) lossis 4-methyl cyclohexanol (MCH, Sigma-Aldrich). Cov yoov tshaj tawm rau thawj tus ntxhiab (cov tshuaj tiv thaiv kab mob, CS ntxiv) tau ua ke nrog 80 V hluav taws xob shocks thiab tom qab ntawd tau txais cov ntxhiab tsw thib ob (CS-) yam tsis muaj kev poob siab. Kev kawm muaj peev xwm raug txiav txim siab tam sim tom qab kev cob qhia thiab kev muaj peev xwm ntawm 3- thiab {{ 12}}h nco tau ua qhov kev sim tom qab kev cob qhia rau 3 thiab 24 teev, raws li. Txhawm rau ua qhov kev sim, cov yoov kawm tau raug kaw rau hauv qhov chaw xaiv ntawm T-maze uas lawv tau nthuav tawm ib txhij rau OCT thiab MCH. Ib qho Performance index (PI) raug xam los sawv cev rau qhov kev zam ntawm kev zam txim. Ib qho PI ntawm xoom qhia txog 50: 50 kev faib tawm, thiab aPI ntawm 100 pom qhov 0: 100 faib tawm ntawm CS ntxiv rau tsw.
Kev ntsuas ntawm cov ntawv sau los ntawm lub sijhawm tiag tiag ntawm PCR (qPCR)
Cov yoov tau sau tom qab eclosion thiab pretreated nrog 5.4 thiab 10.8 mg / ml ntawm CT(Cistanche Tubulosa)rau 20 hnub ntawm 25 degree tau txais kev pabcuam raws li pawg sim, thiab cov yoov tswj tsis tau txais CT. Tag nrho RNAwas muab rho tawm siv cov khoom siv RNeasy Mini (Qiagen), thiab cDNA raug tsim los ntawm tag nrho RNA los ntawm kev rov qab cov tshuaj tiv thaiv los ntawm kev siv lub peev xwm siab cDNA Reverse Transcription (Thermo Fisher Scientific). Cov ntawv sau tseg ntawm cov noob caj noob ces tau txheeb xyuas los ntawm lub sijhawm muaj nuj nqis ntawm polymerase chainreaction (Applied Biosystems ViiATM 7 Real-Time PCR System) los ntawm kev siv FastStart SYBR Green Master (Roche) raws li cov chaw tsim khoom cov lus qhia. Cov txheeb ze cov ntaub ntawv sau tseg tau zoo li qub siv txoj kev sib piv ntawm lub voj voog pib nrog ahousekeeping gene, RpLP0, raws li tus qauv sab hauv. Qhov sib txawv ntawm qhov sib txawv ntawm cov hom phiaj ntawm cov pab pawg sim tau normalized rau cov pab pawg tswj thiab nthuav tawm raws li kev hloov pauv. Cov primers rau lub hom phiaj noob tau teev nyob rau hauv Ntxiv Table 1.
Kev tsim kho network thiab kev txheeb xyuas
Txhawm rau txheeb xyuas qhov kev ua haujlwm txhais lus thiab cov txheej txheem lom neeg sib haum xeeb los ntawm cov noob caj noob ces peb txheeb xyuas, Database for Annotation, Visualization thiab Integrated Discovery (DAVID) tau siv los piav qhia thiab txheeb xyuas qhov kev txhawb nqa ntawm Kyoto Encyclopedia ntawm Genes thiab Genome (KEGG) txoj hauv kev thiab Gene. Ontology rau cov noob no (Jiao li al., 2012). Txhawm rau txheeb xyuas qhov sib cuam tshuam ncaj qha thiab tsis ncaj ntawm qhov sib txawv ntawm cov noob tau hais tseg, cov npe noob kuj tau muab tso rau hauv Kev Tshawb Fawb Txog Kev Tshawb Fawb Txog Kev Sib Cuam Tshuam / Cov Proteins (STRING) txhawm rau khaws cov ntaub ntawv sib cuam tshuam thiab tsim cov kev sib cuam tshuam cov protein (Franceschini li al., 2013).
Kev txheeb cais
Txhua qhov kev sim tau ua nrog tsawg kawg peb qhov kev ywj pheej rov ua dua, thiab kev txheeb xyuas cov ntaub ntawv tau ua nrog SigmaStat v3.5 software (Systat Software, Inc., IL). Cov ntaub ntawv rau lifespanextension thiab oxidative kev nyuaj siab nyuaj siab tau ua nrog rau tag nrho cov yoov xws li 250-350, thiab cov log-rank test raug soj ntsuam rau txawv analyses. Kev sib piv pab pawg rau kev ntsuas fecundity thiab kev ntsuam xyuas kev txawj ntse tau soj ntsuam los ntawm ib txoj kev ntsuas qhov sib txawv (ANOVA), tom qab los ntawm Dunnett's post-hoc test.Lwm qhov kev sim sib piv tau ua los ntawm kev ua tub ntxhais kawm qhov t-test piv nrog pawg tswj hwm. Cov ntaub ntawv tau sawv cev raws li qhov nruab nrab ± SEM, thiab p-tus nqi ntawm <0.05 tau="" suav="" tias="" yog="" qhov="" tseem="">
Cov txiaj ntsig
CT (Cistanche Tubulosa) supplementation nce ya lifespan
Txhawm rau tshuaj xyuas seb CT(Cistanche Tubulosa)Kev noj tshuaj ntxiv tuaj yeem txuas ntxiv ya davhlau, yoov tau ntxiv nrog 5.4, 10.8, thiab 21.6 mg / ml ntawm CT tam sim tom qab eclosion ntawm 25 degree thoob plaws hauv cov txheej txheem sim. Peb cov ntaub ntawv qhia tias CT(Cistanche Tubulosa)supplementation canextens lifespan ntawm ob leeg txiv neej thiab poj niam yoov. Raws li qhia hauv Fig. 1A, lub neej ntawm tus txiv neej yoov tau txuas ntxiv los ntawm tag nrho cov koob tshuaj CT(Cistanche Tubulosa). Qhov nruab nrab lub neej ntawm cov pab pawg ntxiv nrog 5.4,10.8, thiab 21.6 mg / ml ntawm CT tau nce 18.9 feem pua, 10.3 feem pua, thiab 9.9 feem pua, feem. CT(Cistanche Tubulosa)kuj tseem ua rau kom lub neej ntev tshaj plaws ntawm txhua pawg CT piv nrog rau pawg tswj hwm ntawm 88 txog 102, 98, thiab 102 hnub tom qab kev kho mob nrog 5.4, 10.8, thiab 21.6 mg / ml ntawm CT.(Cistanche Tubulosa), raws. Hauv cov poj niam, CT(Cistanche Tubulosa)nce qhov nruab nrab lub neej ntawm pawg CT piv nrog pawg tswj hwm (Daim duab 1B). Qhov nruab nrab lub neej nce mus txog 18.8 feem pua nrog 5.4 mg / ml ntawm CT(Cistanche Tubulosa)thiab 5.5 feem pua thiab 6.7 feem pua nrog 10.8 thiab 21.6 mg/mlof CT, feem. Peb kuj tau pom tias qhov siab tshaj plaws lub neej tau txuas ntxiv los ntawm 91 hnub (tswj) mus rau 109, 98, thiab 102 hnub tom qab kev kho mob nrog 5.4, 10.8, thiab 21.6 mg / ml ntawm CT.(Cistanche Tubulosa), raws li; qhov siab tshaj plaws ntawm kev nce hauv qhov siab tshaj plaws yog 19.8 feem pua ntawm 5.4 mg / ml ntawm CT(Cistanche Tubulosa). Peb cov txiaj ntsig qhia tias CT(Cistanche Tubulosa)kev noj zaub mov ntxiv ua kom ntev lub neej ntawm ob tus txiv neej thiab poj niam yoov. Curcumin (10 μM) tau siv los ua kev tswj xyuas qhov zoo thiab ua haujlwm tau zoo hauv kev ua neej ntev, raws li qhia hauv Daim Duab Ntxiv 1.
CT supplementation tsub kom tsis txhob tshaib plab thiab oxidativestress
Lifespan txuas ntxiv feem ntau cuam tshuam nrog kev txhim kho kev tiv thaiv oxidative kev nyuaj siab thaum lub sij hawm kev laus. Peb soj ntsuam seb CT(Cistanche Tubulosa)supplementation tsub kom tiv thaiv oxidative kev nyuaj siab. Txiv neej thiab poj niam yoov tau pretreated nrog sib txawv koob tshuaj CT(Cistanche Tubulosa)rau 20 hnub thiab ntsuas rau lawv txoj sia nyob tom qab kev tshaib kev nqhis (Fig. 2A).Lub sijhawm muaj sia nyob nruab nrab thiab lub neej ntev tshaj plaws ntawm ob leeg poj niam txiv neej, piv nrog cov pab pawg tswj hwm, pom muaj qhov nce ntxiv hauv 5.4 thiab 10.8 mg / ml CT pawg tab sis tsis nyob hauv 21. .6 mg/ml CT(Cistanche Tubulosa)pab pawg. Cov yoov pretreated kuj tau soj ntsuam rau lawv txoj sia nyob tom qab muaj kev sib tw nrog H2O2 thiab paraquat, uas ua rau cov pa oxygen reactive (ROS) ua rau cellular senescence thiab cell tuag. Peb pom tias CT(Cistanche Tubulosa)tiv thaiv ob leeg txiv neej thiab poj niam yoov tawm tsam H2O2 toxicity thiab txuas ntxiv lawv lub neej ntev (Daim duab 2B, p < 0.01 thiab 0.001, ntawm 5.4 thiab 10.8 mg / ml ntawm CT(Cistanche Tubulosa), raws). Ib qho piv txwv zoo sib xws uas qhia tias muaj kev tiv thaiv ntxiv rau qhov kev sib tw paraquat kuj tau pom. Txiv neej yoov yoov nrog tag nrho cov koob tshuaj CT, thiab poj niam, tshwj xeeb tshaj yog cov ntxiv nrog 5.4 mg / ml ntawm CT(Cistanche Tubulosa) (Cistanche Tubulosa), muaj sia nyob ntev dua li kev tswj hwm (Daim duab 3A, p < 0.001).="" hais="" txog="" kev="" nce="" siab,="" ob="" tus="" txiv="" neej="" thiab="" poj="" niam="" yoov="" tau="" tswj="" hwm="" 10.8="" mg="" ml="" ntawm="">(Cistanche Tubulosa)nthuav tawm attenuatedparaquat-induced locomotor dysfunction ntawm 16 h tom qab paraquaatchallenge (Fig. 3B, tag nrho p < 0.05).="" cov="" txiaj="" ntsig="" no="" qhia="" tau="" tias="" ct="" ntxiv="" txhim="" kho="" kev="" tiv="" thaiv="" rau="" qee="" qhov="" kev="" ntxhov="" siab="" oxidative,="" qhia="" tias="">(Cistanche Tubulosa)-induced lifespan extension yog txuam nrog ntxiv antioxidative tiv thaiv.
Qhov cuam tshuam ntawm CT (Cistanche Tubulosa) ntawm kev muaj peev xwm ua me nyuam
Vim hais tias txoj kev xav ntawm kev laus qhia tau hais tias cov txheej txheem kev laus tsis zoo cuam tshuam rau kev yug me nyuam, peb tau tshuaj xyuas seb CT(Cistanche Tubulosa)cuam tshuam kev ua kom muaj kev noj qab haus huv los ntawm kev txheeb xyuas lub peev xwm ntawm lub qe ntawm cov neeg laus. Cov neeg laus yoov tau sau tom qab eclosion, sib cais los ntawm kev sib deev, thiab tswj hwm 5.4 thiab 10.8 mg / ml ntawm CT.(Cistanche Tubulosa)rau 20 hnub. Virgin txiv neej poj niam yoov tswj CT(Cistanche Tubulosa)tau sib raug zoo nrog 9-hnub-laus yoov tsis tswj CT(Cistanche Tubulosa). Peb tau pom cov koob tshuaj nce ntxiv nyob rau niaj hnub cov qe tso rau ib tus poj niam, uas yog 30.3 feem pua thiab 57.2 feem pua tsis muaj yoov yoov kho nrog 5.4 thiab 10.8 mg / ml ntawm CT.(Cistanche Tubulosa), ntsig txog, piv nrog cov tswj (Daim duab 4, p < 0.05).="" cov="" ntaub="" ntawv="" no="" qhia="" tias="">(Cistanche Tubulosa)Kev noj tshuaj ntxiv tuaj yeem pab txhawb kev muaj peev xwm ntawm cov menyuam yaus uas muaj hnub nyoog tab sis yuav tsis nyob hauv cov txiv neej laus.
CT (Cistanche Tubulosa) ntxiv txhim kho kev txawj ntse
Peb txiav txim siab seb CT(Cistanche Tubulosa)supplementation muaj txiaj ntsig zoo rau kev kawm thiab kev nco muaj peev xwm, ib lub voj voog ntawm kev cob qhia olfactoryassociative tau ua. Peb ntsuas kev kawm tau zoo li 3- thiab 24-h nco, uas tau raug suav tias yog lub cim xeeb nruab nrab thiab lub cim xeeb ntev, raws li. Ua ntej, yoov tau ntxiv nrog ntau yam tshuaj CT(Cistanche Tubulosa)rau 5day. Kev muaj peev xwm kawm tau zoo ib yam hauv CT thiab pawg tswj hwm (Daim duab 5A). Hais txog 3-h nco, 10.8 mg/ml CT(Cistanche Tubulosa)pab pawg tended kom muaj qhov Performance index siab dua (PI) dua li dothe tswj (Fig. 5B, 51.5 ± 3.2 piv rau 42.6 ± 2.1), txawm tias tsis muaj qhov sib txawv tseem ceeb. Ntxiv mus, 5.4 thiab 10.8 mg / ml ntawm CT(Cistanche Tubulosa)txhim kho qhov zoo ntawm {{0}}h nco yoov piv nrog cov tswj (Daim duab 5C, PI=41.6 ± 3.6 thiab 45.9 ± 3.0 piv rau 29.6 ± 2.9, raws li , p < 0.05="" thiab="" 0.01).="" cov="" txiaj="" ntsig="" no="" tau="" qhia="" tias="" ctsupplementation="" txhim="" kho="" kev="" nco="" tsim="" hauv="" cov="" yoov="" hluas.="" thib="" ob,="" thaum="">(Cistanche Tubulosa)supplementation ua kom lub neej ntev thiab oxidative tsis kam ntawm yoov, peb txiav txim siab ntxiv seb qhov supplementation tseem tuaj yeem txhim kho kev paub tus cwj pwm hauv cov hnub nyoog yoov.Flies tau muab cov zaub mov txheem nrog lossis tsis muaj 5.4, 10.8, thiab 21.6 mg / ml ntawm CT.(Cistanche Tubulosa)rau 20 hnub los ua kev laus; cov yoov ntxiv nrog cov koob tshuaj CT no(Cistanche Tubulosa)muaj ntau dua PIs oflearning (67.6 ± 1.9, 72.5 ± 0.5, thiab 75.2 ± 1.3, raws li) dua li cov tswj (58.0 ± 2.0; Fig. 5D , p < 0.001), qhia tias CT(Cistanche Tubulosa)muaj txiaj ntsig zoo rau kev ncua sij hawm qhov kev poob qis hauv kev kawm hauv lub hnub nyoog.Cov txiaj ntsig zoo sib xws kuj tau qhia tias 5.4 mg / ml CT(Cistanche Tubulosa)pab pawg tau txais kev nco zoo dua hauv {{{0}}}h (Fig. 5E, 47.5 ± 1.9 tiv thaiv kev tswj hwm 37.{{10}} ± 2.9, p < 0.05)="" thiab="" 24-="" h="" kev="" ntsuam="" xyuas="" nco="" (fig.="" 5f,="" 31.8="" ±="" 3.8="" tiv="" thaiv="" kev="" tswj="" 19.3="" ±="" 2.4,="" p="">< 0.01).="" cov="" txiaj="" ntsig="" no="" qhia="" tias="">(Cistanche Tubulosa)supplementation tsis tau tsuas yog txhim khu kev nco tsim nyob rau hauv cov me nyuam yoov tab sis kuj ncua kev paub txog tus cwj pwm tsis zoo thiab tswj kev kawm ntau dua thiab nco muaj peev xwm nrog lub hnub nyoog.
Txoj hauv kev molecular cuam tshuam nrog kev txhawb nqa lub neej ntev thiab kev paub txog kev txhim kho ntawm CT supplementation
CT(Cistanche Tubulosa)supplementation ob leeg suppresses AMI thiab ncua lifespan. Yog li ntawd, peb tau txiav txim siab tias AMI- thiab lub neej ntev ntawm cov noob caj noob ces yuav txiav txim siab los ntawm kev ntsuas qhov sib txawv ntawm kev tswj thiab 5.4 thiab 10.8 mg / ml CT pawg los ntawm qPCR. Cov kev hloov pauv ntawm cov noob qhia ntawm CT-kho yoov tau muab piv nrog cov pab pawg tswj tau pom hauv daim duab 6A. Qhov kev qhia tawm ntawm ntau lub hom phiaj, suav nrog Sirt6, Sir2, Sod, p38b, thiab Sirt2, tuaj yeem koom nrog hauv kev laus. Cov ntawv sau tseg ntawm S6k, raptor, Psn, Rpd3, thiab N kuj nce ntxiv, qhia tias CT(Cistanche Tubulosa)supplementation hloov lub teeb liab transduction ntawm themTOR thiab Notch txoj kev. Tsis tas li ntawd, CT supplementation cuam tshuam rau mRNA qhia ntawm Nmdar1, Nmdar2, thiabSkpA. Txhawm rau qhia txog CT-txuas ntsig txog cov protein sib cuam tshuam uas txuas ntxiv lub neej thiab txhim kho kev kawm thiab kev nco, cov ntaub ntawv-raws li kev sib cuam tshuam ntawm cov noob caj noob ces qPCR tau tsim (Fig. 6B). Txhua qhov sawv cev rau ib qho protein, thaum txhua qhov edgedenotes ib qho kev sib cuam tshuam ntawm cov ntaub ntawv. Cov nodes yog pawg raws li KEGG txoj kev thiab noob caj noob ces ontology biological txheej txheem (GOBP). Raws li pom nyob rau hauv daim duab 6B, GOBP neuroactive ligand-receptor interaction, uas cuam tshuam rau kev kawm thiab kev nco, thiab lwm tus GOBPof aging, uas yog correlates nrog lifespan, yog ob qho tib si txuas nrog lub Notch signaling pathway. Tsis tas li ntawd, GOBP ntawm kev laus yog cuam tshuam los ntawm mTOR kev taw qhia txoj hauv kev. Qhov tseem ceeb ntawm CT-induced gene overexpression ntawm GOBPs thiab txoj hauv kev tau piav qhia hauv ntu Kev Sib Tham.
Fig. 6. Kev txheeb xyuas cov noob caj noob ces sib txawv. yoov pretreated nrog 5.4 thiab 10.8 mg / ml ntawm CT(Cistanche Tubulosa)thiab tswj kev noj zaub mov ntawm 25 degree rau 20 hnub tau sau rau kev ntsuas qhov sib txawv ntawm cov noob. (A) Cov ntaub ntawv txheeb xyuas qib ntawm cov hom phiaj rau kev tswj tau raug ntsuas los ntawm qPCR. n=4 rau txhua pab pawg. (B) Upregulated genes koom nrog hauv cell signal transduction thiab lawv cov kev sib tshuam network. Nodes sawv cev cov noob. Genes nrog overexpression yog voj voog nyob rau hauv ntsuab. Edges sawv cev kev sib cuam tshuam ntawm cov khoom siv noob. Hom kev sib cuam tshuam yog qhia los ntawm cov xim sib txawv hauv daim duab. (Rau kev txhais cov lus hais txog xim hauv cov lus dab neeg no, tus nyeem ntawv raug xa mus rau lub vev xaib ntawm kab lus no.)
Kev sib tham
Kev tsis sib haum xeeb ntawm tiam thiab kev tshem tawm ntawm cov dawb radicals los ntawm endogenous antioxidative tiv thaiv kab mob yuav ua rau oxidative puas tsuaj rau cov ntaub so ntswg nrog lub hnub nyoog; Yog li, cov dawb radicals tau kwv yees los ua lub luag haujlwm tseem ceeb hauv kev laus (Dato li al., 2013). Ntawm no, peb pom tias CT(Cistanche Tubulosa)supplementation nyob rau hauv yoov ncua lifespan thiab ua rau ib tug siab kam rau oxidative puas los ntawm H2O2 thiab paraquat nyob rau hauv ob qho tib si poj niam txiv neej. Cov kev tshawb fawb, cuam tshuam nrog CT(Cistanche Tubulosa)andantiaging, tsis tshua muaj kev tshawb nrhiav, tab sis cov extracts los ntawm C. deserticola, tuaj yeem txuas lub neej ntev hauv cov nas-accelerated nas prone 8 (SAM-P8) nas (Zhang li al., 2014) thiab echinacoside, ib qho ntawm cov ntsiab lus tseem ceeb uas muaj nyob hauv CT. , muaj txiaj ntsig zoo rau lub neej ncua ntev thiab kev ntxhov siab ntev hauv C. elegans (Wang li al., 2015).
Cov kev tshawb fawb tsiaj tsis ntev los no tau pom tias echinacoside muaj kev tiv thaiv tiv thaiv bisphenol A-induced testicular toxicity thiab txhim kho testosterone biosynthesis los ntawm induction ntawm testicularsteroidgenic enzymes, xws li CYP11A1, 3 -HSD, thiab CYP17A1(Jiang li al., 201). CT(Cistanche Tubulosa)ethanol extract kuj txhawb kev muaj peev xwm thiab zoo ntawm cov phev hauv nas (Wang li al., 2016). Txawm hais tias kev sib raug zoo ntawm CT(Cistanche Tubulosa)thiab tshuaj estrogen tseem xav tau tshawb nrhiav, ib qho kev tshawb fawb tau tshaj tawm tias echinacoside nce qhov kev nthuav tawm ntawm cov tshuaj estrogen receptors, zoo ib yam li estradiol-kho pab pawg hauv ovariectomized nas (Li et al., 2013). Vim tias qhov muaj peev xwm yug me nyuam tshwm sim tsis zoo cuam tshuam nrog lub hnub nyoog (Kenyon, 2005), peb tau tshuaj xyuas seb CT puas muaj txiaj ntsig rau cov yoov hnub nyoog. Kev yug me nyuam muaj zog cuam tshuam los ntawm CT(Cistanche Tubulosa)tsuas yog pom nyob rau hauv cov poj niam, qhia tias cov poj niam yoov tshaj cum yuav teb tau ntau dua rau CT(Cistanche Tubulosa)kev pab ntxiv. Cov txiaj ntsig no qhia tau hais tias CT tuaj yeem muaj cov tshuaj hormones zoo li kev sib deev thiab ncua kev yug me nyuam, raws li kev siv tshuaj CT.(Cistanche Tubulosa)rau kev kho mob dysfunction nyob rau hauv tib neeg.
Acteoside tuaj yeem piav qhia txog kev tiv thaiv los txo cov neuron apoptosis thiab kev nco poob hauv cov qauv nas senescent vim yog kev sib xyaw ntawm D-galactose thiab AlCl3, qhia tias CT tej zaum yuav muaj peev xwm muaj cov tshuaj tiv thaiv kab mob thiab kev nco (Gao li al., 2015; Peng et al., 2015). Peb cov ntaub ntawv qhia tau hais tias kev tsim cov cim xeeb tau txhim kho nyob rau hauv CT-supplementedyoung yoov. Yog li ntawd, peb tau soj ntsuam seb CT(Cistanche Tubulosa)supplementation muaj txiaj ntsig zoo rau kev nco khaws cia thaum laus vim tias kev paub txog kev ua haujlwm tau paub tias yuav poob qis hauv kev laus li qub. Peb cov txiaj ntsig tau qhia tias ntau hom AMIs, suav nrog kev kawm, 3- thiab 24-hmemory, tuaj yeem ua kom zoo dua los ntawm CT(Cistanche Tubulosa)ntxiv rau 20 hnub.Raws li cov txiaj ntsig tau hais tseg, CT(Cistanche Tubulosa)Kev noj tshuaj ntxiv tuaj yeem muaj txiaj ntsig zoo rau kev ua neej ntev thiab txhim kho kev nco qab ntxiv nrog rau kev ncua txaus AMI.
Siv cov qauv tsiaj ua kom yooj yim rau kev txheeb xyuas cov txheej txheem muaj peev xwm thiab txoj hauv kev nyob ntawm CT(Cistanche Tubulosa)kom decelerate hlwb aging thiab ncua AMI ntawm cellular theem. Peb tsom mus rau cov txheej txheem molecular hauv qab kev laus, kev sib kis ntawm neuronal, thiab oxidative kev nyuaj siab thiab xav tias AMI- thiab cov noob caj noob ces ntev yuav raug txheeb xyuas los ntawm kev tshuaj xyuas qhov sib txawv ntawm kev tswj hwm thiab CT pawg los ntawm qPCR. Lub Notch signaling txoj kev tau txais txiaj ntsig zoo ntawm cov tsiaj los ntawm Drosophila rau tib neeg; nws qhia nyob rau hauv cov neeg laus hauv nruab nrab lub paj hlwb rau neural plasticity thiab tswj neural sib txawv nrog rau nws cov inhibitornumb thaum lub sij hawm kev loj hlob (Presente li al., 2001). Cov nas nqa cov kabmob heterozygous hloov pauv ntawm Notch yog qhov tsis txaus hauv kev kawm spatial thiab nco (Costa li al., 2003). Presenilin (Psn) yog qhov yuav tsum tau ua rau kev ua kom lub cleavage ntawm Notch rau hauv Notch intracellulardomain thiab knockout ntawm Psn ua rau kev puas tsuaj ntawm synapticplasticity thiab nco tsim (Saura li al., 2004). Peb cov ntaub ntawv tau tshaj tawm qhov kev tswj hwm ntawm koob tshuaj ntawm Notch thiab Psn hauv CT(Cistanche Tubulosa)ntxiv yoov, nrog rau qhov tsis hloov pauv theem ntawm loog, uas txhais tau hais tias lub Notch signaling txoj hauv kev ua lub zog muaj zog ntawm kev nco txhim kho los ntawm CT supplementation. Ntxiv nrog rau kev taw qhia tsis zoo, N-methyl-D-aspartate receptor (NMDAR), glutamate- thiab D-serine-driven ion channel hauv cov neurons, tswj cov txheej txheem yas thiab nco ua haujlwm (Furukawa li al., 2005).Drosophila genome muaj ob. NMDAR subunits, Nmdar1 thiab Nmdar2, thiab ob qho tib si tseem ceeb hauv kev nco ua haujlwm. Nmdar1 knockdown hauv Drosophila impairs kev kawm thiab kev nco (Xia li al., 2005), whereas Nmdar2 overexpression nyob rau hauv nas txhim khu kev kawm thiab nco (Tang li al., 2001). Peb cov ntaub ntawv tau pom qhov koob tshuaj-dependentincrease hauv Nmdar1 thiab Nmdar2 upregulation hauv CT-supplementedflies, tawm tswv yim rau lwm lub peev xwm ntawm kev txhim kho kev nco los ntawm CT(Cistanche Tubulosa)kev pab ntxiv.
Cov chav kawm O ntawm lub forkhead box transcription factor (FoxO) txoj kev yog kev txuag ntawm cov tsiaj thiab tseem ceeb hauv cov metabolism, kev nyuaj siab, thiab kev ncua ntawm lifespan (Lehtinen li al.,2006). Posttranslational hloov kho, suav nrog phosphorylation, acetylation, thiab ubiquitylation, tswj cov kev ua ntawm FoxOs (van der Horst thiab Burgering, 2007). Cov ntaub ntawv ntsiag to regulator 2 (Sir2; homolog nyob rau hauv cov tsiaj nyeg hu ua SIRT1) tswj cov kev ua ntawm FoxO los ntawm kev deacetylation thiab cuam tshuam rau tsiaj lub neej muaj feem xyuam rau txoj kev loj hlob zoo li insulin (IGF) (Lemieux li al., 2005). Sirt6 dephosphorylates FoxO kom ua rau lub neej ntev ntev hauv cov txiv neej nas (Kanfi li al., 2012). Peb cov ntaub ntawv tau nthuav tawm Sir2 thiab Sirt6 upregulation nyob rau hauv CT-ntxiv yoov, hais tias FoxO kev cai los ntawm Shirts yuav yog ib tug muaj zog mechanism ntawm kev ncua ntawm lifespan los ntawm CT.(Cistanche Tubulosa)kev pab ntxiv. Dawb radicalsproduced thaum lub sij hawm metabolic dab ua rau kev puas tsuaj rau DNA thiab proteins, yog li ua rau ib tug luv luv lifespan. Sir2 kuj yog ib qho oxidative kev nyuaj siab teb cov noob (Whitaker li al., 2013), thiab overexpressed superoxide dismutase (SOD), uas converts O2− rau H2O2 thiab thaum kawg rau H2O los ntawm kev siv catalase thiab glutathione peroxidase, tau raug tshaj tawm kom ntev lifespan nyob rau hauv yoov ( Le Bourg, 2001). Ourdata tau nthuav tawm koob tshuaj-raws li Sod thiab Sir2 upregulation hauv CT-ntxiv yoov, tawm tswv yim tias txoj hauv kev tiv thaiv oxidative yuav ua rau lub zog muaj zog ntawm kev txuas ntxiv ntawm kev ua neej los ntawm CT.(Cistanche Tubulosa)kev pab ntxiv.
Lwm txoj hauv kev tseem ceeb hauv kev laus yog tswj hwm los ntawm mTOR complexes mTORC1 thiab mTORC2, ob qho tib si ntawm kev txhawb nqa lub cev nyob rau hauv evolutionary conservative yam. Cov teeb liab los ntawm theinsulin receptor qhib mTORC1 los ntawm phosphoinositide3-kinase-Akt txoj hauv kev los txhawb cov protein synthesis thiab o thiab inhibit autophagy thiab glycolysis los ntawm kev siv cov protein sib txawv (Johnson li al., 2013). Protein synthesis yog qhib los ntawm ribosomal protein S6 kinase (S6K), uas ua rau lub voj voog tsis zoo rau inhibit insulin receptor signaling (Hands et al., 2009). Ib lub hom phiaj inhibitory ntawm mTORC1 yog Drosophila protein zoo sib xws (sima), uas nws homolog nyob rau hauv cov tsiaj yog hu ua hypoxia-inducible factor 1 alpha (HIF1). HIF1 playsa lub luag haujlwm tiv thaiv lub hnub nyoog ntawm kev puas tsuaj rau cov hlab ntsha thiab lub cev muaj zog neurons (Oosthuyse li al., 2001; Rivard li al., 2000).Peb cov ntaub ntawv qhia txog qhov tsis hloov pauv ntawm mTOR complex subunits, suav nrog Tor, rictor, thiab raptor, hos CT(Cistanche Tubulosa)supplementation koob tshuaj-nyob ntawm upregulated S6K thiab sima, implying aprotective luag hauj lwm ntawm CT(Cistanche Tubulosa)tawm tsam mTOR kev ua.
Cov lus xaus
Txawm hais tias qee qhov kev cuam tshuam tau raug txheeb xyuas, kev ua neej ntev thiab kev txawj ntse tau pab los ntawm CT(Cistanche Tubulosa)Kev cuam tshuam tej zaum yuav yog qhov zoo ntawm apolygenic cuam tshuam los ntawm kev sib cuam tshuam ntawm ntau cov noob, thiab lwm yam genetic yam uas peb tsis tau piav qhia kuj tseem tuaj yeem hloov kho cov txheej txheem kev laus. Rau cov neeg laus, kev tswj hwm lub cev muaj zog thiab kev txawj ntse kom ncua lossis tiv thaiv kev dementia thiab cov kab mob ntev yuav tsum yog qhov tseem ceeb ntawm kev tshawb fawb txog kev laus. vim CT(Cistanche Tubulosa), lub npe hu ua "ginseng ntawm cov suab puam," muaj cov txiaj ntsig zoo ntawm kev txhawb nqa lub raum yang, uas txhawb nqa tag nrho cov kabmob thiab ntxiv cov ntsiab lus tseem ceeb hauv cov tshuaj suav tshuaj, peb ntseeg tias peb txoj kev tshawb fawb muab pov thawj txhawb kev kho mob ntawm CT.(Cistanche Tubulosa)thiab tej zaum yuav muab kev pom muaj txiaj ntsig zoo rau kev tsim cov tshuaj tshiab lossis cov khoom noj ntxiv kom tsis txhob ncua kev laus thiab cov kab mob uas muaj hnub nyoog tab sis kuj los txhim kho tib neeg lub neej zoo.
Kev tsis sib haum xeeb
Cov kws sau ntawv tshaj tawm tias lawv tsis muaj kev tsis sib haum xeeb.
Kev lees paub
Txoj haujlwm no tau txais kev txhawb nqa los ntawm Tuam Tshoj Medical University (CMU103-S-25); Tuam Tshoj Medical University Tsev Kho Mob (DMR-101-065, DMR-103-099); Ministry of Science thiab Technology hauv Taiwan (NSC 102-2632-B-039-001-MY3, MOST 104-2632-B-039-002), thiab ib feem los ntawm Taiwan Ministry of Health thiab Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019).
Cov khoom siv ntxiv
Cov ntaub ntawv ntxiv uas cuam tshuam nrog tsab xov xwm no tuaj yeem pom, hauv online version, ntawm doi: 10.1016/j.phymed.2017.01.006.
Los ntawm: 'Molecular pathways ntsig txog kev txhawb nqa lub neej ntev thiab kev paub txog kev txhim kho ntawmCistanche tubulosahauv DrosophilaWei-Yong Lin et al
--W.-Y. Lin et al. / Phytomedicine 26 (2017) 37–44
Cov ntaub ntawv
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