Glochidion Littorale Nplooj Extract Exhibits Neuroprotective Effects hauv Caenorhabditis Elegans Ntawm DAF-16 Ua kom

Yog xav paub ntxiv hu rau emailtina.xiang@wecistanche.com 
Abstract:Ib tug xov tooj ntawm cov nroj tsuag siv nyob rau hauv pej xeem tshuaj nyob rau hauv Thaib teb thiab Eastern Asia yog attracting txaus siab vim lub siab bioactivities ntawm lawv cov extracts. Lub hom phiaj ntawm txoj kev tshawb no yog txhawm rau tshuaj xyuas cov nplooj ntoo uas tau txais txiaj ntsig ntawm 20 cov nroj tsuag pom hauv Thaib teb thiab tshawb xyuas cov txiaj ntsig neuroprotective ntawm cov qauv bioactive tshaj plaws. Tag nrho cov ntsiab lus phenol thiab flavonoid thiab 2,2-diphenyl-1-picrylhydrazylradical-scavenging kev ua haujlwm tau txiav txim siab rau tag nrho 20 nplooj extracts. Raws li cov kev ntsuam xyuas no, Glochidionlittorale nplooj extract (GLE), uas tau pom tias muaj txiaj ntsig zoo hauv txhua qhov kev sim ntsuas, tau siv hauv kev sim ntxiv los ntsuas nws cov teebmeem ntawm neurodegeneration hauvCaenorhabditis elegans. GLE kev kho mob ameliorated H2O2-induced oxidative stress los ntawm attenuating lub tsub zuj zuj ntawm reactive oxygen hom thiab tiv thaiv cov cab tawm tsam 1-methyl-4-phenylpyridinium-induced neurodegeneration. Cov teebmeem neuroprotective pom tuaj yeem cuam tshuam nrog kev ua haujlwm ntawm qhov kev hloov pauv DAF-16. Tus cwj pwm ntawm cov extract no los ntawm LC-MS tau txheeb xyuas ntau cov phenolic tebchaw, suav nrog myricetin, coumestrin, chlorogenic acid, thiab hesperidin, uas tuaj yeem ua lub luag haujlwm tseem ceeb hauvneurotiv thaiv. Txoj kev tshawb no qhia txog cov haujlwm tshiab neuroprotective ntawm GLE, uas tuaj yeem siv los tsim kho cov kab mob neurodegenerative xws li Parkinson's syndrome.

Ntsiab lus: Caenorhabditis elegans; nplooj extract;neurotiv thaiv; kev ua haujlwm antioxidant; DAF-16

1. Taw qhia 

Cov kab mob neurodegenerative xws li Alzheimer's disease thiab Parkinson's disease (PD) ua rau muaj kev txhawj xeeb loj txog kev noj qab haus huv thiab nyiaj txiag rau cov koom haum saib xyuas kev noj qab haus huv thoob ntiaj teb [1]. Txawm hais tias tib neeg txoj sia nyob tau nce nyob rau ob peb lub xyoo dhau los hauv cov teb chaws uas muaj kev lag luam, feem ntau ntawm cov kab mob muaj hnub nyoog kuj tau nce ntxiv. Qhov tshwm sim ntawm cov teeb meem tshwm sim lig xws li kev cuam tshuam ntawm cov paj hlwb xav tias yuav nce nrawm dua li ob peb xyoos tom ntej no. Yog li ntawd, nws yog ib qho tseem ceeb los txhawb kev tshawb fawb thiab ua cov kev sim tshuaj ntsuam xyuas ntawm cov tebchaw uas yuav muaj peev xwm kho tau, tiv thaiv, lossis tsawg kawg ncua qhov pib ntawm cov kab mob neurodegenerative [2]. Ib qho ntawm cov yam ntxwv ntawm PD yog qhov nce zuj zus ntawm dopaminergic (DA) neurons hauv substantia nigra [3]. Hauv PD pathogenesis, nce kev tsim cov pa oxygen reactive (ROS) ua lub luag haujlwm tseem ceeb hauv kev poob ntawm DA hlwb [4]. Yog li ntawd, qhov txo qis hauv oxidative kev nyuaj siab yog suav tias yog ib qho kev cog lus kho mob hauv kev kho PD [5]. Cov 1-methyl-4-phenylpyridinium (MPP ntxiv), uas inhibits mitochondrial complex I kev ua, tuaj yeem ua rau cov tsos mob zoo li PD hauv tib neeg thiab tsiaj qauv [6].

Kev siv ntawmCaenorhabditis elegansraws li tus qauv hauv vivo muab qee qhov zoo hauv kev kawm ntawm PD [7]. Lub nematode yog qhov yooj yim, pheej yig, thiab muaj lub neej luv luv. Nws txhawb nqa cov kev tshawb fawb uas suav nrog kev ntsuas loj. Ntxiv mus, lub neuronal network ntawm C. elegans tau mapped kiag li. Nws muaj 8 DA neurons thiab PD-txog homologous genes [8]. Neurodegeneration, uas ua raws li cov tsos mob ntawm tus mob parkinsonian, tuaj yeem raug ntxias hauv C. elegans ntawm kev kho mob nrog neurotoxins xws li MPP ntxiv [9].
Ntuj antioxidant tebchaw sawv cev rau qhov txaus nyiam rau kev tsim tshuaj los kho cov kab mob neurodegenerative vim lawv cov teebmeem neuroprotective hauv cov qauv tsiaj thiab tsis muaj tshuaj lom [3]. Polyphenols paub tias yog cov antioxidants ntau tshaj plaws hauv tib neeg noj [10]. Nws kuj tau tsim muaj cov txheej txheem oxidative koom nrog ntau yam pathologies, suav nrog neurodegeneration, mob qog noj ntshav, ntshav qab zib, kab mob plawv thiab tshuaj tiv thaiv kab mob. Yog li ntawd, nrhiav polyphenols uas muaj cov tshuaj tiv thaiv antioxidant los ntawm tej yam ntuj tso tuaj yeem pab tiv thaiv lossis kho cov kab mob no. Txoj kev tshawb no tau tsom mus rau kev rho tawm los ntawm cov nplooj tuaj yeem ntawm cov nroj tsuag pom hauv Thaib teb. Feem ntau ntau hom cog qoob loo nyob rau sab qaum teb thiab yav qab teb Thaib tau siv los ua cov tshuaj pej xeem tiv thaiv kev raug mob thiab kab mob; Txawm li cas los xij, muaj ob peb tsab ntawv ceeb toom txog lawv cov teebmeem neuroprotective.
Nyob rau hauv txoj kev tshawb no, peb thawj zaug tshuaj ntsuam cov extracts ntawm edible nplooj los ntawm 20 nroj tsuag cultivated nyob rau hauv Thaib teb thiab ntsuam xyuas lawv phenolic thiab flavonoid cov ntsiab lus thiab lawv 2, 2-diphenyl-1- picrylhydrazyl (DPPH) radical-scavenging kev ua. Cov teebmeem ntawm Glochidion littorale nplooj extract (GLE), uas tau pom tias muaj txiaj ntsig zoo hauv txhua qhov kev sim ntsuas, tau soj ntsuam ntawm C. elegans nrog neurodegeneration. Tsis tas li ntawd, txoj hauv kev muaj peev xwm koom nrog cov txiaj ntsig neuroprotective ntawm GLE tau kuaj xyuas, nrog rau kev txheeb xyuas cov khoom tseem ceeb hauv GLE.
Raws li qhov kev hloov pauv ntawm DAF-16 paub tias ua lub luag haujlwm tseem ceeb hauv kev tswj oxidative kev nyuaj siab [11], nws tau xav tias GLE tuaj yeem tsom DAF-16. C. elegans strain CF1038, uas yog DAF-16 poob-of-function mutant strain, tau siv los txiav txim qhov muaj sia nyob ntawm cov kab mob uas tau kho nrog thiab tsis muaj GLE. Hauv H2O2-induced oxidative stress, GLE kev kho mob tsis ua rau kom muaj sia nyob ntawm transgenic worms (Daim duab 1C).

2. Cov txiaj ntsig

2.1. Kev tshuaj xyuas cov nplooj ntoo Thaib

Crude extracts ntawm edible nplooj los ntawm cov nroj tsuag cultivated nyob rau hauv Thaib teb tau npaj los ntawm ultrasonication. Cov nplooj rho tawm ntawm 20 cov nroj tsuag tau tshuaj xyuas rau lawv cov ntsiab lus phenolic thiab flavonoid thiab kev ua haujlwm antioxidant los ntawm DPPH radical-scavenging assay. Ob peb ntawm cov qauv kuaj, xws li Glochidion sphaerogynum thiab Mentha piperita, tau pom tias muaj kev ua haujlwm siab radical-scavenging nrog cov ntsiab lus phenolic thiab flavonoid qis, qee qhov piv txwv, xws li Clinacanthus nutans thiab Ocimum × citriodorum, nthuav tawm qhov sib txawv (Table 1 ). Cov nplooj extract ntawm G. littorale qhia siab DPPH radical-scavenging kev ua si nrog rau siab phenolic thiab flavonoid cov ntsiab lus. Yog li ntawd, cov bioactivities txuam nrog G. littorale tau tshawb xyuas ntxiv.

2.2. GLE Enhanced Resistance tiv thaiv Oxidative Stress ntawm DAF-16 hauv C. Elegans

Cov nyhuv ntawm GLE ntawm kev muaj sia nyob ntawm N2 worms nyob rau hauv oxidative kev nyuaj siab tau tshawb xyuas. Kev kho mob nrog H2O2 (5 mM) ua rau 75 feem pua ​​​​ntawm kev tuag hauv pawg tswj hwm, qhov kev kho nrog 50 µg/mL thiab siab dua ntawm GLE tau cuam tshuam nrog kev muaj sia nyob siab (Daim duab 1A). Ntawm qhov kev sim siab ntawm GLE, 100 µg / mL thiab 200 µg / mL tau cuam tshuam nrog cov neeg muaj sia nyob siab tshaj (82.0 feem pua ​​thiab 88.2 feem pua). Yog li ntawd, ob qhov concentrations no tau siv rau hauv kev sim tom ntej. Txhawm rau ntsuas cov nyhuv antioxidant ntawm GLE hauv vivo, cov qib ROS intracellular tau ntsuas hauv cov tsiaj qus nematodes siv 2',7'-dichlorodihydroflfluorescein diacetate (H2DCF-DA), uas paub zoo txog kev sojntsuam fluorescence rau kev kuaj xyuas intracellular ROS ntau lawm. Qhov tseem ceeb txo qis hauv cov fluorescence intensities nyob rau hauv cov pab pawg neeg kho GLE raug soj ntsuam piv rau cov nyob rau hauv cov pab pawg neeg uas tsis kho (Daim duab 1B), paub meej tias cov khoom antioxidant ntawm GLE.

2.3. GLE Treatment Txo qhov Lethality ntawm MPP ntxiv -Induced DA Neurotoxicity ntawm DAF-16 hauv C. Elegans C. elegans muaj 8 DA neurons [8]. Kev xaiv degeneration ntawm cov DA neurons no tau raug soj ntsuam tom qab raug rau MPP ntxiv. Kev kho cov kab mob qus-hom N2 nrog 0.75 mM MPP ntxiv ua rau muaj kev muaj sia nyob tsawg zuj zus (Daim duab 2). Txawm li cas los xij, kev kho mob nrog GLE ua rau muaj kev vam meej ntawm cov cab. Cov txiaj ntsig ntawm kev kho GLE ntawm daf-16 cov kab mob mutant tau tshawb xyuas. Raws li pom nyob rau hauv daim duab 3 thiab Table 2, GLE kev kho mob tsis ua rau kom muaj sia nyob ntawm cov cab no tom qab raug rau MPP ntxiv rau qhov piv rau hauv pawg tswj hwm. Cov txiaj ntsig no qhia tias DAF-16 tej zaum yuav xav tau rau kev kho kom haum xeeb rau cov nyhuv neuroprotective ntawm GLE hauv C. elegans. Tom ntej no, DAF -2 poob-ntawm-function mutant strain, CB1370, tau siv los txiav txim seb DAF-2 puas tau koom nrog hauv cov teebmeem neuroprotective. Raws li pom nyob rau hauv daim duab 4 thiab Table 3, qhov nruab nrab thiab qhov siab tshaj plaws ciaj sia taus tau nce ntau hauv daf-2 mutant worms kho nrog GLE.

2.4. Cov teebmeem ntawm GLE ntawm DAF-16 Localization

Nws tau raug pom tias DAF-16 kev ua kom raug tswj hwm los ntawm nws cov khoom siv nuclear [12]. Tom qab ntawd, peb tau tshawb xyuas seb GLE puas tuaj yeem ua rau muaj kev cuam tshuam nuclear ntawm DAF-16 nyob rau hauv ib hom transgenic TJ356 uas qhia txog DAF-16::GFP fusion protein. Cov txiaj ntsig tau pom tias tom qab 48 teev ntawm incubation nrog 100 µg / mL GLE, ntsuab fluorescence siv ntawm DAF-16 hauv cov nucleus tau nce ntau dua piv rau cov pab pawg uas tsis kho (Daim duab 5).

2.5. Phytochemical Characterization hauv GLE

LC-MS tau ua rau kev ua kom pom cov phytochemicals hauv GLE, thiab nws cov txiaj ntsig tau nthuav tawm hauv daim duab6. Cov chromatographic peaks tau txheeb xyuas los ntawm kev sib piv cov ntaub ntawv MS nrog databases raws li kev tshawb fawb ntawm m / z qhov tseem ceeb ntawm molecular ion peaks hauv zoo hom [M ntxiv rau H]ntxiv. Yog li ntawd, myricetin, coumestrin, chlorogenic acid, thiab hesperidin tau kuaj pom tias yog cov ntsiab lus tseem ceeb (Table4).

3. Kev sib tham

Nroj tsuag extracts yog ib tug nplua nuj qhov chaw ntawm natural bioactive compounds. Ntau cov kev tshawb fawb tau soj ntsuam cov nroj tsuag extracts siv nyob rau hauv cov teb chaws Es Xias Qab Teb Hnub Tuaj, suav nrog Thaib teb, qhov twg cov extracts yog cov khoom siv tshuaj pej xeem [13,14]. Nyob rau hauv txoj kev tshawb no, cov extracts ntawm 20 edible nroj tsuag nplooj los ntawm Thaib teb raug soj ntsuam, thiab G. littorale raug xaiv rau kev soj ntsuam ntxiv vim hais tias nws pom muaj phenol ntsiab lus, flavonoid cov ntsiab lus, thiab radical-scavenging kev ua si. Ntau qhov kev tshawb fawb tau tshawb xyuas ntau hom ntawm genus Glochidion [15–19]; Txawm li cas los xij, muaj qee qhov kev tshawb fawb txog kev ua haujlwm thiab cov khoom siv ntawm G. littorale. Peb cov ntaub ntawv tau qhia tias GLE tiv thaiv C. elegans tiv thaiv H2O2-induced oxidative stress los ntawm kev txo cov intracellular ROS tsub zuj zuj. Qhov no tej zaum yuav yog vim muaj cov ntsiab lus siab ntawm phenolic tebchaw xws li flavonoids, uas paub tias muaj zog antioxidant kev ua haujlwm [20]. Cov kev tshawb pom no zoo ib yam li cov tau txais los ntawm Duangjan li al. (2019), leej twg tau pom tias G. zeylanicum nplooj extracts tuaj yeem tiv thaiv C. elegans tiv thaiv oxidative kev nyuaj siab [21]. Txoj hauv kev zoo li insulin/insulin-like signaling (IIS) tswj txoj kev loj hlob, kev ntxhov siab, thiab kev ua neej ntev hauv C. elegans [22,23]. Peb pom tias daf-16 null mutant C. elegans kho nrog GLE yog qhov cuam tshuam rau oxidative kev nyuaj siab. Qhov txiaj ntsig no qhia tau hais tias cov nyhuv antioxidant ntawm GLE hauv kev txo qis oxidative kev nyuaj siab hauv nematodes tuaj yeem koom nrog tsis yog tsuas yog radical-scavenging kev ua si xwb tab sis kuj yog cov kev cai ntawm DAF-16 transcription factor.

Kev tiv thaiv los ntawm GLE tiv thaiv MPP ntxiv rau -induced toxicity hauv C. elegans raug kuaj. DA neurons nyob rau hauv nematodes coj MPP ntxiv rau feem ntau ntawm high-affinity DA transporters, uas zoo sib xws nyob rau hauv cov tsiaj. Kev sib sau ntawm MPP ntxiv rau hauv cov neurons inactivates lub mitochondrial complex I ntawm txoj hlab pa thiab induces cell tuag [24–27]. GLE kev kho mob tau pom tias txo qis qhov tuag taus cuam tshuam nrog MPP ntxiv rau kev kho cov kab tsiaj qus. Txoj kev IIS yog hloov kho los ntawm insulin-zoo li peptides los ntawm DAF-2 receptor hauv C. elegans [28]. Raws li ib txwm muaj, txoj hauv kev IIS inhibits phosphorylation ntawm DAF-16 thiab tiv thaiv nws txoj kev hloov pauv hauv nuclear. Hauv daf-2 null mutants, pawg GLE-kho tau muaj sia nyob ntev dua li pawg tswj hwm. Hauv qhov sib piv, tsis muaj qhov sib txawv ntawm kev ciaj sia tau pom ntawm pawg tswj hwm thiab pab pawg kho GLE uas muaj daf-16 null mutant worms. Nws yog paub tias downregulated DAF -2 signaling pab txhawb kev nkag ntawm DAF{14}} mus rau hauv lub nucleus, qhov uas nws muaj peev xwm upregulate cov kev qhia ntawm lub hom phiaj genes thiab tswj kev ntxhov siab thiab thiav [29]. Qhov no yuav piav qhia yog vim li cas daf-2 cov kab mob mutant kho nrog GLE pom tias muaj kev ciaj sia ntau dua. Tsis tas li ntawd, qhov nce ntxiv ntawm cov khoom siv hluav taws xob ntau ntawm DAF-16 hauv cov kab mob uas tau kho nrog GLE tau pom tias siv transgenic TJ356 DAF-16::GFPC. cov elegans. Ntxiv rau, cov txiaj ntsig no tau qhia tias GLE tuaj yeem nthuav tawm nws cov teebmeem neuroprotective los ntawm kev ua kom DAF-16.

4.3. Tag Nrho Phenolic ContentsThe Folin-Ciocalteu txoj kev tau siv los txiav txim siab tag nrho cov ntsiab lus phenolic. Luv luv, 11.4 µL ntawm cov extract (1 mg / mL) yog tov nrog 227.3 µL ntawm 2 feem pua ​​(w/v) Na2CO3 tov, thiab ces cov sib tov raug tso cai sawv ntawm chav tsev kub rau 2 min. Tom qab ntxiv 11.4 µL ntawm 10 feem pua ​​(v/v) Folin-Ciocalteu reagent. Lub incubation nyob rau hauv qhov tsaus ntuj yog ua rau 30 min. Tom qab ntawd, qhov nqus tau ntsuas ntawm 750 nm siv lub microplate nyeem ntawv (Nivo 3F Multimode Plate Reader, PerkinElmer, Waltham, MA, USA). Gallic acid tau siv los ua tus qauv rau lub calibration nkhaus. Tag nrho cov ntsiab lus phenolic tau qhia raws li qhov sib npaug ntawm gallic acid (mg gallic acid sib npaug / g ntawm cov nroj tsuag extract).

4.4. Tag nrho Flavonoid ContentsThe aluminium chloride colorimetric method tau siv los ntsuas tag nrho cov ntsiab lus flavonoid. Luv luv, 25 µL ntawm cov extract (2 mg / mL) yog tov nrog 7.5 µL ntawm 5 feem pua ​​(w/v) NaNO2solution thiab 152.5 µL ntawm distilled dej. Tom qab 6 min, 15 µL ntawm 10 feem pua ​​(w/v) AlCl3 tov tau ntxiv thiab tso cai rau sawv ntsug li 5 feeb. Tom qab ntawd, 50 µL ntawm 1 M NaOH tov tau ntxiv rau qhov sib tov. Tom qab ntawd, qhov sib tov tau muab tso rau hauv qhov tsaus ntuj rau 15 feeb, thiab qhov nqus tau ntsuas ntawm 510 nm siv tus nyeem ntawv microplate. Tag nrho cov ntsiab lus flavonoid raug xam los ntawm kev tsim cov calibration nkhaus siv quercetin raws li tus qauv thiab cov txiaj ntsig tau qhia tias quercetin sib npaug (mg quercetin sib npaug / g ntawm cov nroj tsuag extract).4.5. Free Radical-Scavenging Activity Lub peev xwm txhawm rau tshem tawm cov dawb radicals raug soj ntsuam siv DPPH kev soj ntsuam [32]. Luv luv, 100 µL ntawm cov extract (1 mg / mL) tau tov nrog 100 µL ntawm DPPH kua. Tom qab 30 feeb, qhov nqus tau ntsuas ntawm 517 nm siv tus nyeem ntawv microplate. Cov txiaj ntsig tau qhia raws li feem pua ​​​​ntawm inhibition ntawm DPPH radicals.

4.1 0. Nuclear Localization ntawm DAF-16Transgenic C. elegans TJ356, uas qhia txog DAF-16-GFP fusion protein, tau siv los tshuaj xyuas qhov kev faib tawm hauv lub cev ntawm DAF-16. L1 theem nematodes tau kho nrog GLE rau 48 teev ntawm 2{{30}} ◦C. Tom qab ntawd cov cab tau hloov mus rau 2 feem pua ​​agarose ncoo ntawm lub iav swb thiab tshuaj loog los ntawm kev ntxiv ib qho poob (kwv yees li 20 µL) ntawm 25 µM sodium azide rau agarose ncoo. Kev qhia ntawm GFP tau kuaj xyuas los ntawm fluorescence microscopy (EVOSflfl; Advanced Microscopy Group, Bothell, WA, USA). Qhov nruab nrab fluorescence siv ntawm DAF-16 nyob rau hauv lub nuclei raug tshuaj xyuas siv Image J software (National Institutes of Health, Bethesda, MD, USA). 4.11. Phytochemical Profiling Siv LC-MS Cov nplooj extract tau txheeb xyuas siv LCMS-8040 (Shimadzu). Mass spectra tau txais ntau dua m/z 50–1000 siv Q3 scan hom. Cov tshuaj tau txhaj rau ntawm Inertsil ODS-3 (250 × 2.1 mm, 5 µm, GL Sciences, Tokyo Nyiv) ntawm qhov kub thiab txias ntawm 40 ◦C siv gradient ntawm (A) 0.1 feem pua ​​formic acid thiab (B ) acetonitrile / dej (80/20) muaj 0.1 feem pua ​​formic acid. Cov nram qab no gradient nrog tus nqi ntws ntawm 0.2 mL / min tau siv: 0-100 feem pua ​​B (0-45 min), 100 feem pua ​​B (45-50 min), thiab 0 feem pua ​​B (50-60 min). Cov khoom sib xyaw tau raug txheeb xyuas los ntawm kev sib piv cov kev sim m/z qhov tseem ceeb rau lub tsev qiv ntawv ntawm theoretical xam m/z qhov tseem ceeb hauv cov ntaub ntawv, suav nrog Human Metabolome Database thiab METLIN database. 4.12. Cov ntaub ntawv txheeb xyuas kev txheeb xyuas tau qhia raws li qhov nruab nrab ± tus qauv sib txawv rau txhua pawg. Qhov sib txawv tseem ceeb ntawm ob pawg tau soj ntsuam siv t-test, qhov sib txawv ntawm peb thiab ntau pawg tau soj ntsuam siv ib-txoj kev ANOVA, ua raws li Tukey's post-hoc kev sib piv. Kev txheeb xyuas qhov tseem ceeb tau teeb tsa ntawm p < 0.001="" thiab="" p="">< 0.0001.rau="" qhov="" kev="" ntsuam="" xyuas="" lifespan,="" c.="" elegans="" ciaj="" sia="" taus="" tau="" npaj="" siv="" kaplan–meier="" ciaj="" sia="" taus="" nkhaus="" thiab="" txheeb="" xyuas="" los="" ntawm="" kev="" ntsuas="" ntsuas="" ntsuas="" siv="" graphpad="" prism="" software="" (version="" 9.01;="" graphpad="" software,="" san="" diego,="" ca,="">

Abdel Fawaz Bagoudou 1, Yifeng Zheng 2, Masahiro Nakabayashi 2, Saroat Rawdkuen 3, Hyun-Young Park 4, Dhiraj A. Vattem 4,5, Kenji Sato 6, Soichiro Nakamura 1 thiab Shigeru Katayama 1,2,*

1 Kawm Tiav Tsev Kawm Ntawv Kho Mob, Science thiab Technology, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Nyiv;

2Institute for Biomedical Sciences, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Nyiv;

3 School of Agro-Industry, Mae Fah Luang University, 333 Moo 1, Thasud, Muang, Chiang Rai 57100, Thailand;saroat@mfu.ac.th

4 Edison Biotechnology Institute, Konneker Research Laboratories, Ohio University, Athens, OH 45701, USA;

5 College of Health Sciences & Professions, Ohio University, Athens, OH 45701, USA

6 Kawm Tiav Tsev Kawm Ntawv ntawm Kev Ua Liaj Ua Teb, Kyoto University, Kyoto 606-8502, Nyiv;

Tus sau kev koom tes:

Sau Kev Koom Tes: Conceptualization, SR, DAV, thiab SK; kev tshawb nrhiav, AFB, YZ, MN, SR, H.-YP, DAV, thiab KS; sau ntawv-kev npaj ua ntej, AFB; sau- tshuaj xyuas thiab kho, SK; kev saib xyuas, SN Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.
Kev Kawm Txuj Ci: Qhov kev tshawb fawb no tsis tau txais nyiaj txiag sab nraud.
Institutional Review Board Statement: Tsis siv tau.
Cov Lus Qhia Txog Kev Pom Zoo: Tsis siv tau.
Cov Lus Qhia Txog Cov Ntaub Ntawv: Cov ntaub ntawv muaj los ntawm tus kws sau ntawv raws li qhov kev thov tsim nyog.
Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.
Sample Availability: Cov qauv ntawm cov tebchaw tsis muaj los ntawm cov kws sau ntawv

Cov ntaub ntawv

1 Pohl, F.; Lin, PKT Qhov Muaj Peev Xwm Siv Cov Khoom Siv Nroj Tsuag Ntuj thiab Cov Tsob Ntoo Extracts nrog Antioxidant Properties rau Kev Tiv Thaiv / Kev Kho Mob Neurodegenerative Diseases: Hauv Vitro, Hauv Vivo thiab Kev Kho Mob. Molecules 2018, 23, 3283. [CrossRef] [PubMed]

2. Kim, GH; Kim, JE; Rhie, SJ; Yoon, S. Lub luag hauj lwm ntawm Oxidative Stress nyob rau hauv Neurodegenerative Kab Mob. Exp. Neurobiol. 2015, 24, 325–340. [CrossRef] [PubMed]

3. Lu, X.-l.; Yao, X.-l.; Liu, Z.; Zhang, H. Li, W.; Li, Z.; Wang, G.-L.; Paj, J.; Lin, Y.; Xu, Z. Tiv thaiv cov teebmeem ntawm xyloketal B tiv thaiv MPP ntxiv rau -induced neurotoxicity hauv Caenorhabditis elegans thiab PC12 hlwb. Lub hlwb Res. 2010, 1332, 110–119. [CrossRef]

4. Trimmer, PA; Bennett, JP, Jr. Tus qauv cybrid ntawm tus kab mob Parkinson tus kab mob. Exp. Neurol. 2009, 218, 320–325. [CrossRef]

5. Cheon, S.-M.; Yaj, I.; Li, MH; Kim, DK; Yog, H.; Cha, DS Sorbus alnifolia tiv thaiv dopaminergic neurodegeneration hauv Caenorhabditis elegans. Pharm. Biol. 2016, 55, 481–486. [CrossRef]

6. Schmidt, N.; Ferger, B. Neurochemical tshawb pom hauv MPTP qauv ntawm Parkinson tus kab mob. J. Neeb Transm. 2001, 108, 1263–1282. [CrossRef] [PubMed]

7. Harrington, ib.; Yacoubian, TA; Slon, SR; Caldwell, K.; Caldwell, G. Functional Analysis of VPS41-Mediated Neuroprotection in Caenorhabditis elegans thiab Mammalian Models of Parkinson's Disease. J. Neeb. 2012, 32, 2142–2153. [CrossRef] [PubMed]

8. Fu, R.-H.; Han, H.-J.; Liu, S.-P.; Chen, C.-S.; Chang, W.-L.; Chen, Y.-M.; Huang, J.-E.; Li, R.-J.; Tsai, S.-Y.; Hung, H.-S.; ua al. n-Butylidenephthalide tiv thaiv Dopaminergic Neuron Degeneration thiab -Synuclein Accumululation nyob rau hauv Caenorhabditis elegans Qauv ntawm Parkinson's Disease. PLOS IB 2014, 9, e85305. [CrossRef]

9. Yadiya, P.; Khan, A.; Sammi, SR; Kev, S.; Mir, SS; Nazir, A. Anti-Parkinsonian teebmeem ntawm Bacopa monnieri: Kev nkag siab los ntawm kev hloov pauv thiab tshuaj tshuaj Caenorhabditis elegans qauv ntawm Parkinson tus kab mob. Biochem. Biophys. Res. Pawg. 2011, 413, 605–610. [CrossRef] 10. Andrade, JMDM; Fasolo, D. Polyphenol Antioxidants los ntawm Natural Sources thiab pab txhawb kev noj qab haus huv. Hauv Polyphenols hauv Tib Neeg Kev Noj Qab Haus Huv thiab Kab Mob; Elsevier BV: Amsterdam, Lub Netherlands, 2014; ib., 253–265.

11. Hsu, A.-L.; Murphy, CT; Kenyon, C. Txoj Cai Kev Laus thiab Hnub Nyoog Txog Kab Mob los ntawm DAF-16 thiab Heat-Shock Factor. Science 2003, 300, 1142–1145. [CrossRef]

12. Henderson, ST; Johnson, TE daf-16 integrates kev loj hlob thiab ib puag ncig inputs los kho kev laus nyob rau hauv lub nematode Caenorhabditis elegans. Curr. Biol. Xyoo 2001, 11, 1975–1980. [CrossRef]

13. Hutadilok-Towatana, N.; Chaiyamutti, P.; Panthong, K.; Mahabusarakam, W.; Rukachaisirikul, V. Antioxidative thiab Dawb Radical Scavenging Activities ntawm Qee Cov Nroj Tsuag Siv hauv Thaib Cov Tshuaj Kho Mob. Pharm. Biol. 2006, 44, 221–228. [CrossRef]

14. Stewart, P.; Boonsiri, P.; Puthong, S.; Rojpibulstit, P. Antioxidant kev ua haujlwm thiab kev hloov pauv hauv cov kab mob qog noj ntshav hauv plab tau tshwm sim los ntawm Northeastern Thai edible folk plant extracts. BMC Complement. Hloov. Med. 2013, 13, 60. [CrossRef]

15. Hui, W.; Li, W.; Ng, K.; Chan, C. Qhov tshwm sim ntawm triterpenoids thiab steroids hauv peb hom Glochidion. Phytochemistry 1970, 9, 1099–1102. [CrossRef]

16. Takeda, Y.; Mima, C.; Masuda, T.; Hirata, E.; Taus, A.; Otsuka, H. Glochidioboside, ib qho glucoside ntawm (7S,8R)-dihydrodeh ydrodiconiferyl cawv los ntawm nplooj ntawm glochidia obovatum. Phytochemistry 1998, 49, 2137–2139. [CrossRef]

17. Zhang, X.; Chen, J.; Gao, K. Chemical constituents los ntawm Glochidion wrightii Benth. Biochem. Syst. Ecol. 2012, 45, 7–11. [CrossRef]

18. Tian, ​​J.-M.; Fu, X.-Y.; Zhang, Q.; He, H.-P.; Gao, J.-M.; Hao, X.-J. Cov tshuaj lom neeg los ntawm Glochidion assamicum. Biochem. Syst. Ecol. Xyoo 2013, 48, 288–292. [CrossRef]

19. Kongkachuichai, R.; Charoensiri, R.; Yog, K.; Kringkasemsee, A.; Insung, P. Nutrients value and antioxidant content of indigenous zaub los ntawm Southern Thailand. Khoom noj khoom haus Chem. 2015, 173, 838–846. [CrossRef]

20. Pietta, P.-G. Flavonoids li Antioxidants. J. Nat. Prod. 2000, 63, 1035–1042. [CrossRef] [PubMed]

21. Duangjan, C.; Ransinth, P. Gu, X.; Zhang, S.; Kev, M.; Tencomnao, T. Glochidion zeylanicum nplooj extracts nthuav tawm lifespan-extending thiab oxidative stress resistance zog nyob rau hauv Caenorhabditis elegans ntawm DAF-16/FoxO thiab SKN-1/Nrf-2 txoj kev taw qhia. Phytomedicine 2019, 64, 153061. [CrossRef]

22. Jensen, VL; Gallo, M.; Riddle, DL Lub Hom Phiaj ntawm DAF-16 koom nrog hauv Caenorhabditis elegans cov neeg laus ua haujlwm ntev thiab tsim dauer. Exp. Gerontol. 2006, 41, 922–927. [CrossRef] [PubMed]

23. Daitoku, H.; Fukamizu, A. FOXO Transcription Factors in the Regulatory Networks of Longevity. J. Biochem. 2007, 141, 769–774. [CrossRef]

24. Lakso, M.; Vartiainen, S.; Moilanen, A.-M.; Sib, J.; Thomas, JH; Nas, R.; Blakely, RD; Wong, G. Dopaminergic neuronal poob thiab lub cev muaj zog tsis txaus hauv Caenorhabditis elegans overexpressing tib neeg -synuclein. J. Neeb. 2004, 86, 165–172. [CrossRef] [PubMed]

25. Nas, R.; Hall, DH; Miller, DM; Blakely, RD Neurotoxin-induced degeneration ntawm dopamine neurons hauv Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 2002, 99, 3264–3269. [CrossRef]

26. Wang, Y.-M.; Puv, P.; Le, W.-D. ATP depletion yog qhov tseem ceeb ntawm MPP ntxiv rau induced dopamine neuronal tuag thiab cab lethality nyob rau hauv -synuclein transgenic C. elegans. Neurosci. Bull. 2007, 23, 329–335. [CrossRef]

27. Braungart, E.; Gerlach, M. Riederer, P. Baumeister, R.; Hoener, M. Caenorhabditis elegans MPP plus Model of Parkinson's Disease for High-Throughput Drug Screenings. Neurodegener. Dis. 2004, 1, 175–183. [CrossRef]

28. Panowski, SH; Dillin, A. Cov cim qhia ntawm cov hluas: Endocrine tswj kev laus hauv Caenorhabditis elegans. Trends Endocrinol. Metab. 2009, 20, 259–264. [CrossRef]