Part 1: Genistein: Lub peev xwm ntawm Ntuj Lead Molecule Rau Kev Tsim Tshuaj Tshiab Thiab Kev Txhim Kho Rau Kev Kho Mob Tsis Txaus Siab
Mar 20, 2022
Yog xav paub ntxiv, hu rautina.xiang@wecistanche.com
Abstract: Genisteinyog ib yam tshwm sim tshwm sim polyphenolic molecule nyob rau hauv lubisoflavonespab pawg uas paub zoo rau nws cov neuroprotection. Hauv qhov kev tshuaj xyuas no, peb piav qhia qhov ua tau zoo ntawm genistein hauv kev txo qis cov teebmeem ntawmnco tsis taus(MI) hauv tsiaj. Scopus, PubMed, thiab Web of Science databases tau siv los nrhiav cov khoom muaj feem xyuam thiab sib tham txog qhov cuam tshuam ntawm genistein hauv lub hlwb, suav nrog nws cov tshuaj pharmacokinetics, bioavailability, kev coj cwj pwm, thiab qee lub peev xwm ntawm kev ua haujlwm ntawm kev nco hauv ntau tus tsiaj qauv. Cov txiaj ntsig ntawm cov kev tshawb fawb preclinical tau pom zoo tias genistein muaj txiaj ntsig zoo hauv kev txhim kho kev paub txog kev paub ntawm MI tsiaj qauv, tshwj xeeb hauv kev nco, suav nrog spatial, lees paub, tuav, thiab siv nco, los ntawm nws lub peev xwm los txo qis.oxidative kev nyuaj siabthiab attenuateneuroinflamation. Qhov kev tshuaj xyuas no tseem qhia txog cov teeb meem thiab cov hauv kev los txhim kho kev xa tshuaj ntawm genistein rau kev kho MI. Nrog rau qhov ntawd, cov qauv kev hloov kho thiab cov txiaj ntsig ntawm genistein los txhim kho nws cov physicochemical thiab tshuaj zoo li cov khoom kuj tau tham. Cov txiaj ntsig ntawm kev tshuaj xyuas tau ua pov thawj tias genistein tuaj yeem txhim kho kev txawj ntse thiab ua kom muaj txiaj ntsig MI hauv cov kev tshawb fawb sib txawv, yog li qhia tias nws muaj peev xwm ua tus thawj coj hauv ntuj tsim thiab tsim cov tshuaj tshiab neuroprotective.
Ntsiab lus: genistein; isoflavone; nco tsis taus; neuroprotection; phytom tshuaj
Nyem qhov no kom paub ntau ntxiv txog cov khoom
1. Taw qhia
Kev nco yog lub xeev ntawm kev tau txais, khaws cia, thiab khaws cov ntaub ntawv uas suav nrog txhua qhov kev paub tau txais thoob plaws hauv ib qho kev paub xws li qhov tseeb uas paub, qhov xwm txheej nco qab, thiab lub peev xwm txhawb nqa thoob plaws hauv lub neej. Ob yam tseem ceeb ntawm kev nco yog cov lus tshaj tawm thiab tsis tshaj tawm kev nco, nrog rau yav dhau los yog qhov kev nco niaj hnub thaum lub sijhawm kawg feem ntau suav nrog kev nco tau rov qab rov qab los [1. Cov teeb meem nco, feem ntau hu ua kev puas hlwb (MI), yog cov cim tseem ceeb rau kev kuaj xyuas qee yam aetiologies cuam tshuam nrog cov tsos mob. Qee qhov xwm txheej hauv cov ntsiab lus suav nrogAlzheimer tus kab mob, Parkinson tus kab mob, Huntington's, Korsakoff's, thiab Creutzfeldt-Jakob's kab mob (Daim duab 1)[2-5]. MI feem ntau cuam tshuam rau kev nco qab, ib yam li cov xwm txheej nrog amnesia thiab dementia, tab sis qhov no tsis yog ib txwm muaj rau tom kawg, vim tias dementia txhais tau tias yog qhov poob ntawm ob lossis ntau qhov chaw ntawm kev paub. Hauv lwm lo lus, dementia tsis txwv rau kev tshaj tawm kev nco tsis meej ib leeg vim nws kuj cuam tshuam rau lwm qhov ntawm lub cim xeeb [1].
Dementia tuaj yeem cuam tshuam kev nco hauv ob qho tib si thawj thiab theem nrab. Kev tsis taus ntawm lub cim xeeb tseem ceeb tuaj yeem suav nrog kev poob qis hauv kev nco qab uas Alzheimer's tus kab mob yog ib qho kev ua qauv zoo vim tias kev nco qab tshaj tawm yog ib qho ntawm cov kev txawj ntse uas raug kev txom nyem los ntawm kev poob. Ntawm qhov tod tes, qhov thib ob uas muaj peev xwm nco tau cuam tshuam yog thaum muaj kev paub tsis txaus ntseeg uas tuaj yeem cuam tshuam kev nco, xws li kev xav tsis meej dementia uas tuaj yeem cuam tshuam ntau yam ntawm kev nco [1].
Tam sim no, tsis muaj kev lees paub kev kho mob uas tuaj yeem txo qis kev txhim kho ntawm Ml. Txawm li cas los xij, kev kho kev nco txog kev txhim kho kev nco yog qhov tseem ceeb rau kev tswj tus neeg mob txoj kev paub txog kev ua haujlwm nrog lub hom phiaj ntawm kev sib ntaus sib tua MI kev pheej hmoo. Cov tshuaj estrogen, uas yog ib qho kev ua me nyuam cov tshuaj hormones, muaj kev ua haujlwm dav dav nrog nws lub luag haujlwm neuroprotective. Txawm li cas los xij, nws lub peev xwm ua tus neeg saib xyuas neuroprotective tuaj yeem ua kom zoo dua los ntawm kev loj hlob thiab cov teebmeem oncogenic ntawm qee lub hlwb, ua rau muaj kev xav tau rau kev tsim cov tshuaj estrogen receptor modulators (SERMs), suav nrog cov phytoestrogens tshwm sim [6] zoo li genistein.
Genisteinyog ib qho isoflavone (Daim duab 2) feem ntau pom hauv Glycine max (soybean) rho tawm ntawm ntau lwm qhov chaw, xws li legumes, txiv laum huab xeeb, thiab peas ntsuab. Genistein yog tsim los tom qab cov metabolism hauv cov roj ntsha muaj zog glycoside genistin [7]. Txij li ntau cov khoom noj Esxias ib txwm ua los ntawm cov taum pauv, xws li natto, taum paj, thiab sufu [8], Cov teb chaws Esxias tau sau cov genistein ntau heev (25-30 mg/hnub) noj thaum piv nrog cov teb chaws Western (2 mg. / hnub). Qhov tseeb, fermentation ntawm soybeans kuj yog ib txoj hauv kev zoo tshaj plaws los tso genistein uas tsis yog kev zom zaub mov [9].
Cov tshuaj pharmacological ntawm genistein tau qhia tias nws muaj peev xwm los ua cov tshuaj lead molecule hauv kev kho mob ntau yam kab mob, suav nrog cov tsos mob tom qab yug menyuam, mob qog noj ntshav, pob txha, hlwb, thiab teeb meem plawv [l0. Txij li thaum genistein ntseeg tau dhau los ntawm cov ntshav-hlwb teeb meem los ua nws cov txiaj ntsig neuroprotective, nws tau siv dav hauv kev tshawb nrhiav kev kho mob ntawm cov kab mob neurodegenerative, xws li Alzheimer's, Huntington's, thiab Sanfilippo kab mob (Daim duab 3) [11-13 ]. Kev tshawb nrhiav tsis ntev los no tau tsom mus rau nws cov txiaj ntsig ntawm MI qhov twg genistein tiv thaiv MI los ntawm (1) txo qis kev tsim cov ß-amyloid protein (A), (2) tiv thaiv neuro-inflammatory los ntawm inhibiting nuclear factor-activated B hlwb (NF-kB) , (3) inhibiting qhov kev ua ntawm acetylcholinesterase (AChE), (4) txo cov hyperphosphorylation ntawm tau protein los tiv thaiv neuronal fiber entanglement (NFT), (5) up-regulating cov kev ua ntawm Apolipoprotein E (ApoE) kom txo tau deposition ntawm A , thiab (6) exerting nws antioxidant zog thiab txo oxidative kev nyuaj siab los ntawm tshem tawm reactive oxygen hom (ROS) [14-19].
Ib qho kev piav qhia ntawm ntau yam kev tshawb fawb ntawm genistein tawm tsam MI tau muab rau hauv qhov kev tshuaj xyuas no kom nkag siab zoo dua cov haujlwm ntawm genistein hauv ameliorating MI. Txoj kev tshawb fawb tsim ntawm txhua qhov haujlwm tseem ceeb ntawm Ml, hais txog cov qauv tsiaj, cov qauv ntsuas kev nco, thiab nws cov koob tshuaj, kuj tau sau tseg. Tsis tas li ntawd, ib qho kev nthuav dav ntawm cov ntaub ntawv sau txog kev ua tau zoo ntawm genistein hauv kev kho mob ntawm MI tau nthuav tawm. Cov txheej txheem tiv thaiv muaj peev xwm muab los ntawm genistein kuj tseem ceeb kom kaw qhov sib txawv ntawm kev paub, hais txog nws txoj kev siv tshuaj ntxiv lossis ib qho ntxiv rau MI. Qhov kev tshuaj xyuas no tseem qhia txog qee qhov teeb meem rau thiab lub peev xwm los txhim kho cov tshuaj genistein rau kev kho MI. Tsis tas li ntawd, ntau yam kev hloov kho thiab derivatives ntawm genistein tau tham txog txhawm rau txhawm rau txhawm rau txhim kho nws txoj kev nyab xeeb, kev ua tau zoo, physicochemical, thiab tshuaj zoo li cov khoom.
2. Kev piav qhia ntawm Kev Kawm Tsim
2.1. Tsiaj
Cov nas thiab nas tau siv feem ntau ntawm kev tshawb nrhiav. Txhua qhov kev sim ua raws cai tau tso cai los ntawm cov koom haum cuam tshuam ntawm pawg tswj hwm kev noj qab haus huv tsiaj thiab ua raws li cov lus qhia rau kev siv thiab saib xyuas cov tsiaj txhu.
2.2. MI Models
Txhua qhov kev tshawb fawb tau tsom mus rau ntau hom MI qauv. Piv txwv li, Rum-manet al. [19] tsom mus rau hypoxia-induced Ml thaum Luet al. [20] soj ntsuam kev pw tsaug zog ntev ntev (CSD)-vim kev nco tsis txaus. Ob txoj kev tshawb fawb tau ua haujlwm rau tus qauv streptozotocin (STZ)-induced qauv ntawm MI, qhov twg Pierzynowska li al. [13] tshawb xyuas STZ-induced Alzheimer's kab mob (AD) qauv thaum Rajput et al. [21] tsom rau STZ-induced diabetes rau tus qauv MI. Ntawm qhov tod tes, lwm cov qauv MI suav nrog scopolamine-induced cognitive impairment, lipopolysaccharide (LPS), lead, kainic acid (KA), laus, thiab -amyloid [22-27].
2.3. Genistein UAS
During the course of the treatment, all of the selected investigations used purchased genistein (purity>98 feem pua). Feem ntau ntawm cov kev tshawb fawb tau siv genisteinat 0 5-150 mg/kg. Ob qhov koob tshuaj ntau tshaj plaws xaiv hauv MI hauv-vivo qauv yog 10 thiab 20 mg / kg. Hais txog txoj hauv kev ntawm kev tswj hwm, yim qhov kev tshawb nrhiav tau siv qhov ncauj (po) genistein, thaum nyob rau hauv ob txoj kev tshawb fawb nws tau muab intraperitoneally (ip). Ua ntej kev ntsuam xyuas tus cwj pwm, kev kho genistein tau ua rau tsawg kawg ntawm 4 hnub thiab siab kawg ntawm 90 hnub.
2.4. Toxicity Profile ntawm Genistein
Hauv kev tshawb nrhiav vivo, Ek et al. [28] tshawb xyuas qhov toxicity profile thiab pharmacokinetics ntawm genistein hauv nas. Poj niam BALB/c nas tau siv thaum lub sijhawm kev tshawb fawb, uas txhua tus nas tau txais kev txhaj tshuaj intraperitoneal nrog 0.2 mL(10%) dimethylsulphoxide/phosphate buffer solution (DMSO/PBS) uas muaj 0. , 2,20,200,400 thiab 800 ug ntawm genistein txhua hnub rau 10 hnub. Tom qab ntawd, cov nas raug saib xyuas rau 14 hnub, tom qab ntawd cov nas uas muaj sia nyob tau muab txi rau kev soj ntsuam histology. Cov kev tshawb pom tau qhia tias cov nas uas kho nrog genistein tsis pom cov tsos mob ntawm toxicity, thiab lawv tsis ua tsis taus, qaug zog, lossis poob ib qho hnyav, txawm tias tom qab kev kho mob nrog cov tshuaj genistein ntau tshaj (40 mg / kg). Tsis tas li ntawd, genistein tau txais txiaj ntsig zoo nyob rau hauv vivo subchronic thiab kev tshawb nrhiav kev nyab xeeb ntev ntawm cov koob tshuaj txog li 500 mg / kg / hnub muab tshuaj rau qhov ncauj ntev txog 52 lub lis piam raws li Nasri thiab Pohjanvirta [29].
2.5. Memory Test Procedure
Levin thiab Buccafusco [30] tau hais tias muaj peb lub ntsiab lus tseem ceeb hauv kev tshawb fawb tsiaj, xws li (1) cov qauv tshuaj, (2) cov qauv tshuaj lom neeg, thiab (3) cov qauv hloov kho caj ces. Neural hauv paus ntawm kev kawm, kev nco, thiab kev saib xyuas tau txiav txim siab los ntawm kev siv cov qauv tsiaj txhu tseem ceeb ntawm kev paub tsis meej. Pharmacological qauv yog cov siv dav tshaj plaws hauv kev paub txog kev puas siab puas ntsws vim lawv muab lub hauv paus rau kev nkag siab txog lub luag haujlwm ntawm neurotransmitter-receptor system koom nrog cov txheej txheem kev paub, xws li kev kawm, kev nco, thiab kev saib xyuas [30].
"Lub cholinergic system (muscarinic thiab nicotinic) thiab glutamate receptors, feem ntau cov N-methyl-D-aspartate (NMDA) receptors ua lub luag haujlwm tseem ceeb hauv lub hlwb hauv kev txawj ntse. Acetylcholine yog tsim los ntawm kev noj haus choline thiab acetyl coenzyme A ntawm enzyme choline. acetyltransferase (CAT) Cov metabolism hauv acetylcholine tshwm sim hauv neuronal synapse, txhawb nqa los ntawm cov enzyme acetylcholinesterase. Txog rau tam sim no, qee cov cholinesterase inhibitors tau tsim kho kom txo qis kev nco, xws li donepezil, rivastigmine, thiab galantamine [31].
Txhawm rau ua kom tsis nco qab hauv cholinergic system tsiaj cov qauv, cov tshuaj antimuscarinic, suav nrog scopolamine, atropine, pirenzepine, trihexyphenidyl, benztropine, biperiden, thiab dicyclomine [32], tau siv. Nicotinic receptor antagonists, xws li mecamylamine (ib qho tsis sib tw tsis muaj kev xaiv nicotinic receptor antagonist), chlorison diamine thiab d-tubocurarine (tsis tshwj xeeb nicotinic antagonists), dihydro- -erythroidine hydrobromide (Dh E; ib qho tshwj xeeb receptor }} antagonist), thiab methyl aconitine (MLA) (tshwj xeeb receptor 7 antagonist), txhua tus tau siv los txhawb kev paub tsis meej hauv cov qauv tsiaj [33]. Ib yam li ntawd, NMDA receptors tseem ua lub luag haujlwm tseem ceeb hauv kev paub txog kev ua haujlwm, txij li lawv qhov kev ua kom muaj feem cuam tshuam nrog kev muaj peev xwm mus sij hawm ntev (LTP) kom ntxiv dag zog rau cov teeb liab kis ntawm cov neurons. Yog li ntawd, txhawm rau txhawb kev paub tsis meej hauv cov qauv tsiaj los ntawm glutamate-receptor system, ntau tus kws tshawb fawb tau xaiv rau kev siv NMDA receptor antagonists, xws li MK-801, ketamine, thiab phencyclidine (PCP) [34].
Neurological toxicology tau ua tiav nyob rau hauv kev tshawb nrhiav ntawm kev paub tsis meej hauv cov qauv tsiaj. Neurotoxicity nyob rau hauv cov qauv tsiaj yog ua tiav los ntawm kev siv cov tshuaj neurotoxicants, xws li txhuas, mercury, thiab polychlorinated biphenyls (PCBs) txij li cov kev paub tsis zoo tau ua qauv zoo hauv cov qauv liab thiab nas [30]. Lead, tshwj xeeb, tau tshaj tawm nyob rau hauv ntau cov kev tshawb fawb los txhawb oxidative kev nyuaj siab. Nws induces oxidative kev nyuaj siab los ntawm kev ua kom tsis muaj zog ntawm reactive oxygen hom (ROS) thiab txo cov antioxidants xws li catalase (CAT) thiab superoxide dismutase (SOD). ROS feem ntau yog tsim los ntawm cov protein kinase C (PKC) thiab nuclear factor-activated B hlwb (NF-kB), uas tuaj yeem raug ntxias los ntawm kev raug lead. Cov hmoov txhuas kuj tuaj yeem ua rau cov cell apoptosis los ntawm kev ua cov calcium ions thiab khi rau qhov voltage-gated calcium ion channels, yog li cuam tshuam rau cov neurotransmitter tshuav nyiaj li cas hauv hippocampus uas tuaj yeem ua rau apoptosis thiab autophagy. Thaum kawg, txhuas tuaj yeem ua rau muaj kev cuam tshuam neuroinflammatory los ntawm kev ua kom NF-kB [24].
Streptozotocin (STZ) yog dav siv nyob rau hauv induction ntawm ntshav qab zib nyob rau hauv tsiaj qauv ntawm Alzheimer's kab mob (AD). Intracerebroventricular txhaj ntawm STZ induces hyperphosphorylation ntawm tau protein thiab tsub zuj zuj ntawm -amyloid uas yuav ua tau rau MI [13] .STZ kuj yog siv los induce ib tug mob ntshav qab zib lub xeev nyob rau hauv cov tsiaj qauv los txhawb MI los ntawm ua rau hyperglycemia thiab hypoinsulinemia. Cov ntshav qabzib siab tsis tu ncua ua rau muaj kev mob o thiab oxidative kev nyuaj siab, nrog rau kev ua kom muaj ntau yam hauv qab kinases uas ua kom tso tawm cov pro-inflammatory cytokines, xws li IL-6, IL-1 , thiab TNF- , ntxiv kev puas tsuaj rau cov neurons. (Daim duab 4). Txawm hais tias STZ tuaj yeem ua rau poob ceeb thawj hauv cov qauv tsiaj, ua raws li cov tsos mob tseem ceeb ntawm hyperglycemia, kev kho mob nrog cov tshuaj tiv thaiv hyperglycemics thiab insulin rhiab heev tuaj yeem txo qhov kev xav tsis zoo [35].
Cov tsiaj hloov pauv hloov pauv tau nce ntxiv hauv kev tshawb fawb txog kev paub tsis meej vim lawv tuaj yeem ua raws li qee yam tsis xws luag, suav nrog Alzheimer's disease (AD), -amyloid deposition, amyloid precursor protein (APP), thiab cholinergic-receptor knockout, yuav tsum tau ua hauj lwm rau kev txhim kho tshuaj tshiab [ 30]. Ntawm qhov tod tes, nco tau siv cov txheej txheem kev sim sib txawv, suav nrog (1) Morris dej maze (MWM), (2) passive avoidance test (PAT), (3) Novel object recognition (NOR), (4) object location recognition. (OLR), (5) tshiab khoom kev ntxub ntxaug (NOD), (6) elevated plus maze (EPM), (7) ncua sij hawm spatial alternation (DSA), (8) qhov sib txawv ntawm qhov sib txawv ntawm cov lus teb tsawg (DRL), (9) ) Radial arm maze (RAM) ua hauj lwm, thiab (10) Y-maze. Ntawm cov kev tshawb fawb no, MWM, NOR, thiab OLR yog peb txoj kev siv ntau tshaj plaws rau kev sim nco.
2.5.1.Morris Water Maze (MWM)
Lub Morris dej maze (MWM) yog lub pas dej ua ke, uas muaj steel nrog qhov sib txawv thiab qhov siab, xws li 100-160 cm inch thiab 38-80 cm nyob rau hauv qhov siab. Lub pas dej tau muab faib ua plaub qhov zoo sib xws (cim raws li NE, SE, NW, thiab SW) thiab lub platform yuav muab tso rau hauv qab dej hauv nruab nrab ntawm ib qho ntawm cov quadrants [19,22]. Lub platform tau khaws cia rau tib qhov chaw thoob plaws hauv kev sim.
Cov tsiaj raug cob qhia ob peb hnub los txiav txim qhov chaw ntawm lub platform Thaum lub sij hawm kev cob qhia, lawv raug tso tawm los ntawm cov quadrants sib txawv thaum ntsib cov quadrants yuav thiab yuav ua luam dej ntawm lub submerged platform rau 60,90, los yog 120 s. Yog tias cov tsiaj tsis pom lub platform thaum lub sijhawm faib, lawv yuav muab tso rau hauv lub platform rau lwm 10 lossis 30 s kom lawv paub. Cov theem kev cob qhia yuav txuas ntxiv rau ob peb hnub ua ntej qhov kev sim tiag tiag uas tsis muaj teeb meem opaque number case yuav muab tso rau hauv lub pas dej kom nkaum qhov chaw ntawm lub platform [22]. Cov tsiaj yuav tau muab lub sijhawm los txiav txim qhov chaw ntawm lub submerged zais platform. Lub sijhawm siv yuav raug kaw los ntsuas qhov kev nco mus ntev. Lwm qhov kev ntsuam xyuas kuj tseem tuaj yeem ua tau los ntsuas kev nco qab, uas thaum lub sijhawm sim, lub platform yuav raug tshem tawm thiab tus naj npawb ntawm cov tsiaj hla ntawm lub hom phiaj platform qhov chaw qub yuav raug kaw siv lub koob yees duab video [24].
2.5.2.Passive Avoidance Task (PAT)
Txoj haujlwm tiv thaiv tsis pub dhau (PAT) suav nrog kev siv lub cuab yeej uas tau muab faib ua qhov pom thiab tsaus nti uas txuas nrog lub rooj vag me me. Thaum lub sij hawm acclimatization, cov tsiaj tau muab tso rau hauv lub cuab yeej rau 15 feeb kom paub lawv tus kheej nrog rau qhov chaw tshiab. Thaum lub sijhawm kev cob qhia, cov tsiaj yuav muab tso rau hauv qhov tsaus ntuj nti, thiab hluav taws xob me me (39 V rau 3s lossis 1 mA rau 1 s) yuav raug tso tawm rau lawv ko taw. Tom qab 24 teev ntawm kev cob qhia mus sib hais, qhov kev sim tiag tiag yuav ua rau lub sijhawm uas txhua tus tsiaj yuav raug muab tso rau hauv qhov chaw teeb pom kev zoo. Lub sijhawm latency ua ntej nws nkag mus rau hauv qhov tsaus ntuj yuav raug kaw txog qhov siab tshaj plaws ntawm 300 s txhawm rau txheeb xyuas cov tsiaj khaws cia nco txog hluav taws xob poob siab kom tsis txhob muaj qhov tsaus ntuj thaum lawv tau txais qhov poob siab [19,27].
2.5.3. Novel Object Recognition (NOR)
Cov khoom tshiab paub qhov tseeb (NOR) yog ua los ntsuas tus tsiaj lub cim xeeb. Kev ntsuam xyuas yog ua nyob rau hauv ib lub thawv duab plaub (40 cm × 50 cm × 50 cm) uas yog pleev xim rau hauv cov xim dub nrog lub koob yees duab video teeb tsa saum lub chamber los sau tus tsiaj tus cwj pwm. Nyob rau theem nyob, cov tsiaj tau muab tso rau hauv lub chamber yam tsis muaj cov khoom siv tsawg kawg yog 10 min rau peb hnub sib law liag. Thaum lub sijhawm sim, cov tsiaj yuav raug tso cai rau hauv lub thawv uas muaj ob yam khoom zoo tib yam (feem ntau cov khoom yas) rau 5 min. Tom qab 30 feeb, qhov kev sim sim yuav ua qhov twg ib qho ntawm cov khoom yuav raug hloov nrog lwm yam khoom ntawm cov xim sib txawv. Kev soj ntsuam tus cwj pwm ntawm cov tsiaj yuav raug soj ntsuam raws li kev hnov mob lossis kov ntawm qhov khoom, Lub sijhawm ntawm kev sib cuag nrog txhua yam ntawm cov khoom yuav raug kaw los ntsuas lub cim xeeb [19,20].
2.5.4.Object Location Recognition (OLR)
Qhov khoom siv qhov chaw paub qhov chaw kuaj yog siv los ntsuas qhov kev paub nco, uas zoo ib yam li NOR xeem. Cov cuab yeej yog lub thawv duab plaub (40 × 50 × 50 cm) nrog cov xim tsaus nti sab hauv thiab lub koob yees duab yees duab mounted rau sab saum toj ntawm lub chamber los soj ntsuam cov tsiaj 'kev soj ntsuam tus cwj pwm. Cov khoom siv yog ob lub raj mis yas me me, zoo ib yam ntawm qhov loj thiab cov duab tab sis txawv xim. Txoj kev tau muab faib ua peb theem: kev nyob, kev paub, thiab kev xeem theem [20].
Habituation theem: Cov tsiaj raug tso cai taug kev ywj pheej hauv lub chamber yam tsis muaj khoom rau 10 min rau peb hnub sib law liag.
Kev paub txog theem: Hnub plaub, cov tsiaj raug muab tso rau hauv lub chamber uas muaj ob yam khoom zoo tib yam rau 5 feeb.
Kev sim theem: 30 feeb tom qab qhov kev paub dhau los lawm, cov tsiaj yuav muab tso rau hauv lub chamber dua, tab sis ib qho ntawm cov khoom qub yuav raug hloov nrog ib qho khoom sib txawv thaum cov khoom qub tseem nyob hauv chav.
Txhawm rau kom tsis txhob muaj cov ntxhiab tsw ntxhiab, cov khoom thiab hauv pem teb ntawm lub chamber raug ntxuav siv 70 feem pua ethanol thaum kawg ntawm txhua qhov kev sib tham. Cov tsiaj 'kev soj ntsuam tus cwj pwm thaum lub sij hawm xeem yog soj ntsuam raws li sniffing los yog kov tej yam khoom siv cov tsiaj lub qhov ntswg [22].
2.5.5. Novel Object Discrimination (NOD)
Qhov kev ntsuam xyuas kev ntxub ntxaug tshiab tso cai rau cov tsiaj tshawb nrhiav ob yam khoom rau 5min thaum lub sijhawm paub txog. Tom qab 4 teev, ib qho ntawm cov khoom yuav raug hloov nrog ib qho tshiab. Tom qab ntawd, kev tshawb nrhiav tus cwj pwm ntawm cov tsiaj, xws li zom, licking, sniffing, lossis kov cov khoom nrog lawv lub qhov ntswg [23], yuav raug kaw.
2.5.6. Elevated Plus Maze (EPM)
Qhov siab ntxiv-kev tshawb fawb suav nrog kev siv lub tshuab ua kom siab ntxiv uas muaj plaub txoj hlua elongated (caj npab), ob qho uas yog qhib caj npab thiab ob sab caj npab. Ob txhais caj npab qhib yog nyob thoob plaws ib leeg, nyob rau ntawm sab caj npab nrog lub platform hauv nruab nrab [36]. Thaum lub sij hawm kev cob qhia, cov tsiaj raug muab tso rau ntawm qhov kawg ntawm qhib caj npab, tig mus deb ntawm lub hauv paus platform rau peb hnub. Lub sij hawm hloov latency (TLT) tau sau tseg raws li lub sij hawm coj los ntawm cov tsiaj kom nkag mus rau hauv lub caj npab los ntawm qhov pib ntawm qhov qhib caj npab hauv 90s. Hnub plaub, thaum lub sijhawm sim, TLT tau kaw 24 teev tom qab lub ntiaj teb cerebral ischemia-reperfusion (IR) lub hlwb puas, uas yog qhov ntsuas rau kev nco [21].
2.5.7.Delayed Spatial Alternation (DSA)/Differential Reinforcement of Low Rate of Responding (DRL)
Qhov ncua sij hawm spatial alternation (DSA) thiab qhov sib txawv ntawm qhov sib txawv ntawm cov lus teb tsawg (DRL) koom nrog kev siv cov cuab yeej zoo sib xws, lub thawv Skinner, uas muaj ob lub zog retractable ntawm pellet dispensers nrog ib khub ntawm cue teeb ncaj qha saum txhua qib. Thaum lub sij hawm kev cob qhia, cov tsiaj raug cob qhia kom nias lub zog raws li lub teeb ci rau cov khoom noj pellets ua ib qho kev txhawb zog, raws li qhov kev pab cuam autoshaping. Txhawm rau tiv thaiv cov tsiaj los ntawm kev txhim kho ib sab kev tsis ncaj ncees rau ntawm lub zog, lub zog sib txuas nrog qhov kev txhawb nqa yog cuam tshuam nrog txhua tsib lub zog txhawb nqa. Txoj haujlwm DSA cuam tshuam qhov ncua sij hawm ntawm lub zog nias rau 0, 3,6,9 lossis 18s. Cov txheej txheem teb qeeb tau muab faib ua rau qhov kev cob qhia tseem ceeb, thawj ob ntu uas suav nrog cov sijhawm teem sijhawm 1 rau 200 qhov kev sim lossis 90 feeb. Qhov thib peb thiab plaub ntu yog tsim los ntawm DRL-5 lub sijhawm, thaum kev txhawb nqa yog nyob ntawm 5s ncua ntawm cov lus teb. Ib yam yog siv rau ob qhov kev sib tham tseem ceeb kawg nrog DRL-10 lub sijhawm uas yuav tsum muaj 10s ncua ntawm cov lus teb. Cov tsiaj raug sim ntawm DRL-15s teem sijhawm tsawg kawg 30 ntu [26].
2.5.8.RAM Task
Txoj haujlwm radial caj npab maze (RAM) ua haujlwm yog ua haujlwm los ntsuas qhov chaw nco thiab suav nrog kev siv lub siab yim-armed radial maze nrog txhua caj npab txuas los ntawm octagonal central platform. Thaum kawg ntawm txhua sab caj npab, ib lub thawv zaub mov muaj rau tus kws sim tso zaub mov rau kev txhawb nqa. Txawm li cas los xij, thaum lub sijhawm sim, tsuas yog qee qhov ntawm caj npab yuav muaj cov khoom noj pellets hauv lub thawv khoom noj.
Thaum lub sij hawm kev cob qhia, cov tsiaj yuav raug muab tso rau ntawm lub hauv paus platform thiab yuav raug tso cai mus tshawb nrhiav dawb do kom tau cov zaub mov pellets. Thaum lub sij hawm tus txheej txheem, cov tsiaj yuav kawm tsis tau rov qab mus rau hauv lub caj npab uas lawv tau mus xyuas nyob rau hauv tib lub sim thaum tsis muaj zaub mov. Hauv kev sim sim, 10min yuav muab rau cov tsiaj txhawm rau tshawb nrhiav qhov tshawb nrhiav thiab siv tag nrho cov pellets tso rau hauv qee yam ntawm caj npab. Cov kev xaiv raug thiab tsis raug yog siv los ntsuas txhua tus tsiaj ua yeeb yam. Yog tias cov tsiaj rov nkag mus rau hauv caj npab yam tsis muaj zaub mov uas lawv tau mus xyuas, nws yuav raug suav tias yog qhov yuam kev [27].
2.5.9.Y-Maze
Kev xeem Y-maze yog siv los ntawm Bagheri li al.[27] thiab Shahmohammadi et al.[23] los soj ntsuam lub spatial recognition nco ntawm cov tsiaj. Cov cuab yeej siv yog lub pob zeb peb-armed, qhov twg txhua caj npab yog 120 degree los ntawm lwm tus thiab zoo ib yam li lub peev "Y". Txhua lub caj npab yog txuas nrog ib qho kev sib tshuam. Cov txheej txheem tau ua los ntsuas qhov kev kawm spatial siv qhov kev hloov pauv hloov pauv uas cov tsiaj tsis paub zoo rau qhov xwm txheej ntawm qhov tshawb. Cov tsiaj raug muab tso rau ntawm qhov kawg ntawm ib sab caj npab thiab yuav raug tso cai txav mus los ntawm 8 feeb. Kev hloov pauv tau pom raws li kev nkag mus rau txhua yam ntawm peb caj npab ntawm kev sib tshooj triplet, txhua tus nrog caj npab tsis rov ua dua. Qhov feem pua alternations yog tom qab xam raws li qhov sib piv ntawm qhov tseeb rau qhov ua tau hloov pauv × 100.
3. Kev ua tau zoo ntawm Genistein
3.1.HypOoxia
Hauv kev tshawb fawb los ntawm Rumman et al. [19] cuam tshuam ntawm genistein ntawm hypoxia-induced MI tau tshawb xyuas siv cov txiv neej Swiss albino nas. Cov nas txuas ntxiv kho nrog 10,20 lossis 30 mg / kg / hnub ntawm genistein po rau 28 hnub. Tus qauv nas rau amnesia tau tsim los ntawm hypoxia, los ntawm kev nthuav tawm cov nas mus rau qis qis (10 feem pua) txhua hnub rau lub sijhawm zoo ib yam li ntawd rau kev kho mob genistein. Morris water maze (MWM), passive avoidance test (PAT), thiab tshiab object recognition (NOR) tau siv los soj ntsuam cov teebmeem ntawm genistein hauv ameliorating nco defects nyob rau hauv amnesiac nas.
Cov txiaj ntsig raws li MWM tau pom tias cov nas tau kho nrog genistein koob tshuaj ntawm 20 thiab 30 mg / kg tau nthuav tawm qis latency thiab nce tus lej hla ntawm lub platform quadrant. Raws li rau PAT, muaj qhov nce hauv latency hauv 20 thiab 30 mg / kg genistein pawg. Thaum kawg, hauv NOR, ob pawg nas uas tau txais 20 thiab 30 mg / kg genistein pom qhov nce hauv kev tshawb nrhiav tus cwj pwm ntawm cov khoom tshiab piv nrog rau cov khoom paub. Zuag qhia tag nrho, qhov kev tshawb pom pom tias kev kho mob nrog genistein tuaj yeem pab txo qis kev nco hauv hypoxia-induced MI.
3.2.Chronic Sleep Depreciation (CSD)
Hauv lwm txoj kev tshawb fawb los ntawm Lu li al. [20] cov teebmeem ntawm genistein ntawm kev pw tsaug zog ntev (CSD)-vim MI tau tshawb xyuas hauv txiv neej lub koom haum ntawm Kev Tshawb Fawb Cancer (ICR) nas. Cov nas raug kho nrog genistein (10,20, lossis 40 mg / kg / hnub) podaily rau 23 hnub. Induction ntawm CSD tau ua los ntawm kev siv lub tshuab hluav taws xob tsis siv neeg pw tsaug zog cuam tshuam (SIA) uas muaj cov hlau tsis muaj hlau rotator uas tig rau 1 min tom qab 2 min nres rau 24h / hnub rau tag nrho 14 hnub. Morris water maze (MWM), object location recognition (OLR), and novel object recognition (NOR) tau siv los ntsuam xyuas lub spatial thiab recognition memory ntawm CSD-induced nas.
Rau MWM, genistein-kho pab pawg tshwj xeeb tshaj yog 40 mg / kg pawg tau txo qis latency hauv kev nrhiav lub submerged platform. Tsis tas li ntawd, nyob rau hauv kev sojntsuam sojntsuam qhov twg lub platform raug tshem tawm, muaj kev nce ntau ntawm cov lej hla hauv lub hom phiaj quadrant ntawm genistein 20 thiab 40 mg / kg. Cov pab pawg kho mob genistein (20 thiab 40 mg / kg) tau pom tias muaj kev ntxub ntxaug ntau ntxiv (DI piv nrog CSD pawg hauv OLR. Hauv NOR txoj haujlwm, muaj qhov nce siab hauv DI, tshwj xeeb tshaj yog cov genistein 20 thiab Zuag qhia tag nrho, genistein kev kho mob (tshwj xeeb tshaj yog 20 thiab 40mg / kg) muaj txiaj ntsig zoo hauv kev txo cov kev nco tsis raug cuam tshuam los ntawm CSD.
3.3.Streptozotocin (STZ)
Txhawm rau tshawb xyuas cov txiaj ntsig neuroprotective ntawm genistein tiv thaiv streptozotocin (STZ)-vim kev paub tsis meej, txiv neej Wistar nas tau muab tshuaj nrog streptozotocin (STZ) los ntawm kev txhaj tshuaj intracerebroventricular (icv) rau kev sib sau 3 mg / kg tshaj li ob qhov kev txhaj tshuaj nrog 43 h. ]. Cov nas raug kho nrog genistein 150 mg / kg / hnub po rau 90 hnub. Cov pab pawg kho mob genistein tau qhia qis qis dua los ua luam dej ntawm lub platform thaum lub sijhawm Morris dej maze (MWM) sim. Txawm li cas los xij, hauv kev soj ntsuam kuaj, lub sijhawm siv los ntawm genistein-kho nas nyob rau hauv lub hom phiaj quadrant tau ntev dua li lwm pab pawg, qhia tias kev kho genistein pom tau tias muaj txiaj ntsig zoo hauv ameliorating STZ-induced MI.
3.4.Scopolamine
Lu et al[22] tshawb xyuas cov teebmeem ntawm genistein ntawm scopolamine-induced MI hauv txiv neej lub koom haum ntawm Cancer Research nas. Cov nas tsuag tau muab tso rau hauv lub cev (ip) nrog scopolamine 0.75 mg/kg/hnub rau xya hnub sib law liag. Genistein (10, 20, lossis 40 mg / kg / hnub, po) tau muab txhua hnub rau cov nas rau 24 hnub. Cov kev ntsuam xyuas tus cwj pwm koom nrog tau tawm tsam qhov chaw lees paub (OLR) thiab Morris dej maze (MWM) rau kev ntsuam xyuas ntawm qhov chaw nco. Hauv txoj haujlwm OLR, pawg genistein-kho (40 mg / kg) tau pom qhov nce ntxiv hauv qhov kev ntxub ntxaug (DI). Hauv ob qho tib si kev sim thiab kev sojntsuam ntawm MWM, pawg genistein-kho tau pom qhov qis dua khiav tawm latency los nrhiav lub submerged platform thiab pom cov lej hla ntau dua hauv lub hom phiaj quadrant, qhia tias kev kho genistein tuaj yeem txhim kho kev txawj ntse.
3.5. Lipopolysaccharides (LPS)
Shahmohammadi et al. [23] tau tshawb fawb txog cov txiaj ntsig ntawm kev kho genistein ntawm lipopolysaccharide (LPS)-induced neuro-inflammation ntawm txiv neej albino Wistar nas. Neuro-inflammation tau tshwm sim los ntawm kev qhia txog 500 ug / kg / hnub LPS(ip). Kev kho genistein tom qab tau ua rau xya hnub ntawm 10,50 lossis 100 mg / kg / hnub. Spatial thiab kev nco nco tau raug soj ntsuam los ntawm kev siv Y-maze, kev ntxub ntxaug lwm yam khoom tshiab (NOD), thiab kev ua haujlwm tsis zoo (PAT). Hauv tag nrho peb qhov kev ntsuam xyuas, genistein (50 thiab 100 mg / kg) tau txais kev txhim kho tseem ceeb hauv cov kev cuam tshuam uas cuam tshuam ntxiv. tias kev kho genistein tuaj yeem txo qhov kev paub tsis meej.
3.6. Streptozotocin (STZ)-Induced Diabetes
Kev tshawb fawb hauv vivo tau ua los ntawm Rajput li al. [21] txhawm rau tshawb xyuas lub luag haujlwm neuroprotective ntawm genistein ntawm SIZ-induced ntshav qab zib hauv txiv neej albino Swiss nas. Mob ntshav qab zib hauv cov nas tau tshwm sim los ntawm kev qhia 200 mg / kg ntawm STZ los ntawm iproute. Mob ntshav qab zib tau raug ntxias kom ua rau hyperglycemia hauv cov nas, uas tuaj yeem ua rau ischemia-reperfusion (IR)-induced neuronal puas. Tom qab ntawd, kev kho genistein tau muab los ntawm ip rau cov nas mob ntshav qab zib (2.5,5, lossis 10 mg / kg / hnub) rau 14 hnub. Cov kev nco thiab khaws cia tau raug soj ntsuam los ntawm kev siv qhov nce ntxiv ntxiv (EPM) uas ua rau muaj kev poob qis hauv lub sijhawm hloov latency rau genistein (5 thiab 10 mg / kg) pab pawg kho mob hauv cov nas mob ntshav qab zib nrog IR. Zuag qhia tag nrho, qhov kev tshawb pom pom tau hais tias kev paub tsis meej tuaj yeem txo nrog kev kho genistein.
3.7. Cov
Su et al. [24] soj ntsuam cov nyhuv tiv thaiv ntawm genistein kev kho mob ntawm cov hlau lead qib raws li ib tug toxicant. Txiv neej Sprague-Dawley nas tau hais lus (po) nrog ob qho tib si txhuas thiab genistein ntawm 1 mg / kg / hnub rau 56 hnub. Morris dej maze (MWM) tau siv los ntsuas qhov kev paub txog kev ua haujlwm ntawm cov nas thiab ua rau muaj zog. Genistein kev kho mob tau txo qis qhov latency rau lub platform thiab ua rau cov lej hla ntau dua hauv lub hom phiaj quadrant hauv ob qho tib si kev sim thiab kev sojntsuam, yog li qhia tias kev kho genistein tuaj yeem txo cov nyhuv ntawm MI.
3.8. Kainic Acid (KA)-Induced Seizure
Hauv kev tshawb fawb los ntawm Khodamoradi et al. [25], genistein kev kho mob tau tshawb xyuas rau nws qhov ua tau zoo ntawm kainic acid (KA) vim qaug dab peg ntawm poj niam Wistar nas. KA-induced qaug dab peg ua rau MI thiab neuronal raug mob. KA tau muab tshuaj rau cov nas ntawm txoj kev intracerebroventricular (icv) (0.5 ug/μL). Tom qab ntawd, kev taw qhia ntawm KA rau cov nas tau ua plaub hnub tom qab kev kho genistein ntawm 0.5 thiab 5 mg / kg / hnub los ntawm ip A Morris dej maze (MWM) tau siv los ntsuas qhov chaw nco. Zuag qhia tag nrho, cov txiaj ntsig tau qhia tias muaj txiaj ntsig zoo ntawm genistein rau KA-induced seizure nas.
3.9. Kev laus
Neeb et al. [26] tshawb xyuas cov kev paub txog kev laus uas muaj feem cuam tshuam thiab kawm txog qhov muaj peev xwm tiv thaiv ntawm genistein hauv kev txo qis qhov tsis txaus. Lawv tau siv 14-hli poj niam Long-Evans nas los simulate cov teebmeem kev laus ntawm kev txawj ntse. Ob lub zog nias thiab Skinner lub thawv ncua sij hawm spatial alternation (DSA) thiab qhov sib txawv ntawm qhov sib txawv ntawm cov lus teb qis (DRL) tau siv los ntsuas qhov ua haujlwm nco. Txawm li cas los xij, cov txiaj ntsig tau qhia tias genistein tsis muaj txiaj ntsig hauv kev ua kom muaj kev paub tsis txaus ntseeg hauv tus qauv nas laus MI.
3.10.— . Amyloid
Bagheri et al. [27] soj ntsuam cov nyhuv neuroprotective ntawm kev kho genistein ntawm -amyloid induced MI. -amyloid 1-40 tau txhaj icv (4 μL) rau cov txiv neej Wistar nas, ua raws li qhov ncauj qhia ntawm genistein (10 mg / kg / hnub). Y-maze, passive zam kev xeem (PAT), thiab radial caj npab maze (RAM) kev ntsuam xyuas tau siv los ntsuas qhov kev paub txog kev ua haujlwm uas cov nas kho nrog genistein pom qhov tseem ceeb ntawm qhov nce ntxiv hauv Y-maze thiab PATwhile hauv RAM, tsis muaj tseem ceeb nce nyob rau hauv qhov kev xaiv ntawm caj npab los yog txo qis ntawm kev xaiv caj npab tsis raug. Zuag qhia tag nrho, qhov kev tshawb pom pom tias kev kho mob nrog genistein tuaj yeem tiv thaiv -amyloid induced MI.
Yog xav paub ntxiv, nyem qhov link:https://www.xjcistanche.com/news/part2-genistein-a-potential-natural-lead-mol-55084044.html
