Phenylethanoid Glycosides: Txoj Kev Sib Cais Tag Nrho Glycosides Ntawm Phenethyl Cawv Thiab Nws Inhibitory Effect Ntawm Monoamine Oxidase-A

Hu rau:joanna.jia@wecistanche.com

Kev rho tawm thiab kev txheeb xyuas ntawm Phenylethanoid Glycosides Los ntawm Aloysia Polystachya Thiab Nws Cov Kev Ua Haujlwm Raws li Inhibitors Ntawm Monoamine Oxidase-A

Cov kws sau ntawv

Ana Maria S. Pereira1, Camila C. Guimarães1, Sarazete IV Pereira1, Eduardo J. Crevelin2, Gustavo HT Pinto1, Lucas JF Morel1, Bianca W. Bertoni1, Suzelei C. França1, Silvia H. Taleb-Contini1

Kev koom tes

1 Departamento de Biotecnologia em Plantas Medicinais, Universidade de Ribeirão Preto (UNAERP), Ribeirão Preto, SP, Brazil

2 Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de

São Paulo (USP), Monte Alegre, Ribeirão Preto, SP, Brazil

Lo lus tseem ceeb:aloysia polystachya, verbenaceae, antidepressant kev ua si, phenylethanoids, monoamine oxidase inhibitors, Acteoside

Abstract

Aloysia polystachya yog siv los ua sedative thiab antidepressant los ntawm cov neeg hauv paus txawm ntawm Argentina thiab Paraguay, tab sis cov tebchaw cuam tshuam nrog cov dej num no tsis tau txiav txim siab. Peb tau sib cais thiab txheeb xyuas cov ntsiab lus tseem ceeb ntawm hydroethanolic extract ntawm A. polystachya los ntawm ultra-performance kua chromatography-mass spectrometry thiab tau lees paub tias muaj cov acteoside, isoacteoside, 6'-acetylacteoside, thiab 4',4'',5, 5''-tetrahydroxy-6,6'',3'''-trimethoxy-[C7– O–C7'']-biflavone los ntawm NMR spectroscopy. Inhibitory kev ua ub no ntawm hydroethanolic extract thiab purifiedphenylethanoid glycosidestiv thaiv monoamine oxidase-A raug soj ntsuam siv tus qauv fluorometric assay. Cov hydroethanolic extract inhibited monoamine oxidase-A kev ua haujlwm nyob rau hauv koob tshuaj nrog IC50 ntawm 9.2 µg/mL, thaum xaiv monoamine oxidase inhibitor clorgyline nthuav tawm IC50 ntawm 0.06 µg / mL ( 0.22 µM).Acteosideyog qhov muaj zog tshaj inhibitor ntawm monoamine oxidase-A (IC50 tus nqi ntawm 5 µM), thaum isoacteoside thiab 6'-acetylacteoside pom IC50 qhov tseem ceeb ntawm thaj tsam 10 µM. Cov txiaj ntsig tau pom tias phenylethanoids los ntawm hydroethanolic extract ntawm A. polystachya tau pom tias muaj cov haujlwm inhibitory tiv thaiv monoamine oxidase-A. Nws yuav zoo li tias hom kev ua ntawm cov acteosides yog ntau lub hom phiaj, nrog rau kev txo qis ntawm cov kab mob inflammatory thiab neutralization ntawm cov tshuaj tiv thaiv oxidation nrog rau inhibition ntawm monoamine oxidase-A.

Taw qhia

Raws li tsab ntawv ceeb toom tsis ntev los no los ntawm Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Ntiaj Teb [1], ntau dua 320 lab tus tib neeg (4.4 feem pua ​​​​ntawm cov neeg hauv ntiaj teb) raug kev nyuaj siab thiab kev ntxhov siab, nrog ib ncig ntawm 800,000 tus neeg tua tus kheej hauv ib xyoos tau ua txhaum los ntawm cov teeb meem kev puas siab puas ntsws. . Txawm hais tias kho nrog hluavtaws antidepressants

muaj, ntau tus neeg mob raug kev txom nyem los ntawm qhov ncauj qhuav, cem quav, kiv taub hau, qhov muag tsis pom kev, nce qab los noj mov, hnyav nce, insomnia, thiab teeb meem raum [2]. Vim li no, txoj hauv kev siv cov tshuaj ntxiv thiab lwm yam tshuaj, suav nrog phytotherapy, tau siv los kho ntau hom kev puas hlwb [3].

Cistanche deserticola muaj ntau yam teebmeem, nyem qhov no kom paub ntau ntxiv

Ntau yam kev tshawb fawb txog kev kho mob thiab kev kho mob tau muab pov thawj los txhawb cov txiaj ntsig ntawm cov tshuaj cog qoob loo hauv kev kho mob ntawm kev ntxhov siab thiab kev ntxhov siab tshwj xeeb [4, 5]. Ntawm qhov kev txaus siab tshwj xeeb yog kev tshawb nrhiav rau cov khoom anxiolytic ntawm Aloysia polystachya (Griseb.) Moldenke (Verbenaceae), ib hom tshuaj tsw qab uas pom muaj nyob hauv Argentina thiab Paraguay. Raws li kev tshawb fawb ethnopharmacological, cov pej xeem hauv zos siv cov nroj tsuag, uas feem ntau hu ua burrito, ua lub plab zom mov, sedative, thiab antidepressant tonic [6, 7]. Txawm hais tias anxiolytic thiab antidepressant prop- tog ntawm hydroethanolic rho tawm los ntawm A. polystachya tau lees paub los ntawm kev tshawb fawb preclinical [8–10], tsis muaj kev tshawb nrhiav phytochemical tau ua nrog lub hom phiaj ntawm kev txheeb xyuas cov tebchaw cuam tshuam nrog cov dej num no.

Nws tau dhau los ua pov thawj tias cov tshuaj tiv thaiv kev ntxhov siab ntawm qee cov nroj tsuag tshuaj, piv txwv li, Hypericum perforatum L. (Hypericaceae) thiab Peganum harmala L. (Nitrariaceae), yog txuam nrog inhibition ntawm monoamine oxidase-A (MAO-A) [11. —13]. MAO tsev neeg tau muab faib thoob plaws hauv nruab nrab thiab cov hlab ntsha peripheral thiab overexpression ntawm cov enzymes txhawb oxidative deamination ntawm monoamines nrog kev txo qis hauv cov theem ntawm cov neurotransmitters serotonin, norepinephrine, thiab dopamine, uas ua rau qhov pib ntawm kev puas siab puas ntsws. Cov txheej txheem deamination kuj tsim cov khoom xws li hydrogen peroxide, oxygen-dawb radicals, thiab aldehydes uas yog lub luag haujlwm rau oxidative kev nyuaj siab ntawm hlwb. MAOs muaj nyob rau hauv ob lub isoforms loj uas txawv ntawm kev faib khoom, substrate specificity, thiab rhiab heev rau inhibitors. MAO-A isoform plays lub luag haujlwm tseem ceeb hauv kev nyuaj siab thiab kev ntxhov siab, thaum MAO-B koom nrog cov kab mob neurodegenerative [13-17].

Nyob rau hauv lub teeb ntawm cov saum toj no, peb xav tias anxiolytic thiab antidepressant zog ntawm A. polystachya derived, tsawg kawg yog ib feem, los ntawm lub xub ntiag ntawm inhibitors ntawm MAO-A. Txhawm rau ntsuas qhov kev xav no, peb tau txheeb xyuas cov ntsiab lus tseem ceeb tam sim no hauv hydro-ethanolic extract los ntawm nplooj ntawm A. polystachya thiab soj ntsuam cov txiaj ntsig ntawm cov extract crude thiab cov ntsiab lus tseem ceeb cais tawm ntawm MAO-A kev ua.

Cov txiaj ntsig thiab kev sib tham

Cov hydroethanolic extract los ntawm nplooj ntawm A. polystachya tau xa mus rau ultra-kev ua tau zoo kua chromatography-mass spectrometry (UPLC-MS), thiab cov chromatogram thiaj li tau yog pre- scented nyob rau hauv ▶ Daim duab. 1 ib a. Lub ntsiab Cheebtsam ntawm cov extract tau purified los ntawm kem chromatography thiab reversed-theem high-performance kua chromatography (RP-HPLC), thiab txheeb xyuas raws liacteoside(syn verbascoside), isoacteoside, 6'-acetylacteoside, thiab 4',4'',5,5'-tetrahydroxy-6,6',3''-trimethoxy-[C7–O– C7'']-biflavone los ntawm kev sib piv ntawm lawv cov 1H- thiab 13C-NMR, HSQC, HMBC (▶Table 1S, 2S, Cov Ntaub Ntawv Txhawb Nqa), thiab MS cov ntaub ntawv (▶Daim duab 1b-e) nrog cov txiaj ntsig tau tshaj tawm hauv cov ntaub ntawv [18 -20]. Qhov concentration ntawmacteosideHauv hydroethanolic extract, raws li kev txiav txim los ntawm HPLC, yog 108.65 ± 1.3 µg / mg ntawm qhuav extract. Qhov no sawv cev rau thawj cov ntaub ntawv ntawm cov khoom sib xyaw ntawm cov nplooj ntawm A. polystachya, txawm hais tias cov roj tseem ceeb ntawm cov nroj tsuag tau txheeb xyuas yav dhau los thiab pom tias muaj cov monoterpenes carvone thiab limonene ua cov khoom tseem ceeb [21].

Lub crude hydroethanolic extract los ntawm nplooj ntawm A. polystachya inhibited MAO-A kev ua si nyob rau hauv ib tug npaum li cas ntawm koob tshuaj (▶Fig. 2a) nrog ib tug IC50 ntawm 9.2 µg/mL, thaum lub xaiv MAO inhibitor clorgyline nthuav tawm IC5. 0 ntawm 0.06 µg/mL (0.22 µM). Lub purifiedtshuaj acteosideskuj tau nthuav tawm cov haujlwm inhibitory tiv thaiv MAO-A (▶Fig. 2b), nrog acteoside nthuav qhia tus nqi qis tshaj IC50 ntawm 5 µM (3.1 µg / mL) tom qab los ntawm isoacteoside nrog IC50 ntawm 10.1 µM (6.3 µg / mL) thiab 6'- acetylacteoside nrog IC50 ntawm 9.5 µM (6.3 µg / mL). Inhibition ntawm MAO-A ua rau rov tsim kho cov qib ntawm serotonin, norepinephrine, dopamine, thiab tyramine, uas yog cov neurotransmitters tseem ceeb hauv kev tswj hwm kev ntxhov siab thiab kev nyuaj siab [16]. Yog li, muaj ntau haiv neeg MAO-A inhibitors nyob rau hauv nplooj ntawm A. polystachya piav qhia, yam tsawg kawg ntawm ib feem, cov yav tas los qhia txog antidepressant thiab anxiolytic kev ua si ntawm hom [8-10].

Kev siv cov nroj tsuag sib xyaw ua ke tuaj yeem ua tau zoo hauv kev kho mob ntawm cov kab mob nyuaj xws li kev ntxhov siab, kev nyuaj siab, thiab lwm yam mob paj hlwb. Tam sim no, kev siv phytomedicines hauv kev kho mob ntawm cov kab mob uas cuam tshuam rau lub paj hlwb yog ua raws li lub hauv paus ntsiab lus ntawm ntau lub hom phiaj ntawm ligands,

piv txwv li, cov tshuaj uas muaj ntau lub hom phiaj ua haujlwm los ntawm kev muaj cov tshuaj xws li polyphenolics nrog cov tshuaj tiv thaiv kab mob, antioxidant, thiab MAO inhibitory zog uas muaj peev xwm sib tham txog kev tiv thaiv neuroprotection [20, 22–25].

Nws yog ib qho tsim nyog sau cia, txawm li cas los xij, tias lub cim ncov qaum teb ntawm cov tshuaj polyphenolic tuaj yeem cuam tshuam kev cuam tshuam nrog lawv lub hom phiaj molecular. Txawm li cas los xij, cov kev tshawb fawb soj ntsuam tau pom tias kev sib cuag ntawm polyphenolics thiab nonpolar theem nrab metabolites tam sim no nyob rau hauv cov extracts yuav hloov cov permeability ntawm cell daim nyias nyias thiab pab txhawb lub uptake ntawm polar compounds [23]. Yog li, cov nroj tsuag nyuaj uas muaj ntau lub hom phiaj uas cuam tshuam nrog lawv cov receptors nyob rau hauv lub pleiotropic zam tsim ib tug pharmacological synergism uas cuam tshuam rau ntau cov txheej txheem, nrog rau kev txav ntawm polar metabolites thoob plaws cell membranes. Hauv cov ntsiab lus no, Li et al. [26] siv tus qauv zebrafish los ua kom pom qhov ntawdacteosidetuaj yeem nkag mus rau hauv cov ntshav-hlwb teeb meem, thiab tau npaj siab tias phenylethanoid glycoside yuav muaj peev xwm kho tau tus kab mob Parkinson.

Monoaminergic neurotransmitters yog lub hom phiaj tseem ceeb ntawm cov tshuaj tiv thaiv kev nyuaj siab niaj hnub no vim tias lawv qhov tsis txaus yog lub luag haujlwm rau cov tsos mob ntawm kev nyuaj siab. Kev tshawb fawb tsis ntev los no hauv vivo tau pom tias cov ethanolic thiab aqueous rho tawm ntawm Lippia citriodora (Verbenaceae) thiab lawv cov khoom tseem ceeb.acteosidenthuav tawm anxiolytic, hypnotic, thiab cov leeg nqaij so thiab cov khoom no tau raug ntaus nqi, ib feem, rau kev cuam tshuam nrog hom A gamma-aminobutyric acid (GABAA) receptor [27].

Cov kev tshawb fawb soj ntsuam tau qhia tias cov tshuaj uas muaj peev xwm los thaiv cov kab mob cytokines, xws li TNF-, lossis lwm yam khoom siv ntawm txoj kev inflammatory signaling, piv txwv li, cyclooxygenase-2 (COX-2), zoo txo Cov tsos mob ntawm kev nyuaj siab hauv cov neeg mob rheumatoid mob caj dab, psoriasis, thiab mob qog noj ntshav, nrog rau cov neeg muaj kev puas siab puas ntsws loj [28]. Hauv cov ntsiab lus no, nws tau raug tshaj tawm tiasacteosidetuaj yeem txo qis kev tsim khoom thiab tso tawm cov kab mob inflammatory, xws li nitric oxide (NO), TNF- , thiab interleukin 12 (IL-12) hauv lipopolysaccharide/interferon-gamma (LPS/IFN- )-stimulated macrophages [29] , nrog rau histamine thiab arachidonic acid hauv RBL-2H3 mast cells [30]. Ntxiv rau,acteosidemuaj peev xwm txo tau cov theem ntawm TNF-, IL-1 , IL-8, IL-6, thiab TSIS TAU, thiab kom qhib tau caspase-1, nuclear factor-kappa-B

(NF-κB), TSIS MUAJ synthase thiab activator protein-1 [31] induced los ntawm IL-32 thiab/los yog LPS hauv TH-1 hlwb thiab macrophages [32].

Qee cov neeg kho mob inflammatory no, xws li IFNs, IL-6, IL-8, thiab IL-1 , tau pom nyob rau ntawm cov theem txawv txav hauv ob qho tib si peripheral thiab post-mortem cov qauv ntawm cov neeg muaj kev nyuaj siab. , thiab tau hais txog cov tsos mob ntawm kev nyuaj siab [33]. Kev ua kom cov molecules los ntawm kev ntxhov siab txog kev puas siab puas ntsws tuaj yeem txhawb kev hloov pauv tseem ceeb hauv lub hlwb, ua rau muaj kev loj hlob ntawm kev nyuaj siab thiab lwm yam kev puas siab puas ntsws. IFNs, IL-1 , thiab TNF- , piv txwv li, yuav ua rau kom cov lus qhia thiab kev ua haujlwm ntawm serotonin, noradrenaline, thiab dopamine receptor twj tso kua mis, yog li txo qhov muaj ntawm cov neurotransmitters hauv synaptic cleft [28]. Tsis tas li ntawd, IFN- , IL-6, TNF- , thiab oxidative kev nyuaj siab tuaj yeem ua rau indoleamine 2,3 dioxygenase (IDO), ib qho enzyme ua lub luag haujlwm rau kev degradation ntawm tryptophan thiab, yog li, txo qhov concentration ntawm thawj precursor ntawm serotonin synthesis [34].

Acteoside, isoacteoside, thiab 6'-acetylacteoside muaj hydroxy-phenylethyl thiab caffeoyl moieties uas paub tias muaj kev cuam tshuam nrog antioxidant zog [35, 36], thiab acteoside nws tus kheej nthuav tawm cov haujlwm antioxidant ntau [37]. Cov kev tshawb fawb tau qhia tiasacteosideinhibits kev sib sau ntawm -amyloid peptide (A) nyob rau hauv ib koob tshuaj, ua haujlwm raws li tus neeg saib xyuas neuroprotective, thiab txhim kho kev nco, thiab cov khoom no tau raug ntaus nqi los ntawm kev ua haujlwm antioxidant ntawm tus neeg sawv cev [38, 39]. Xav txog tias ntau hom phenolic-nplua nuj nrog cov khoom siv antioxidant yog siv los kho cov kab mob neurological [15], nws tau pom tias cov tshuaj tiv thaiv kev ntxhov siab thiab kev ntxhov siab ntawm cov tshuaj tiv thaiv.phenylethanoid glycosidescais tawm los ntawm A. polystachya kuj tuaj yeem tshwm sim los ntawm lawv cov dej num tiv thaiv oxidant. Qhov kev xav no tau txhawb nqa los ntawm Xu et al. [40], uas tau nthuav tawm cov pov thawj hais txog kev sib raug zoo ntawm oxidative kev nyuaj siab thiab kev nyuaj siab / ntxhov siab.

Raws li cov saum toj no, peb txiav txim siab hais tias cov antidepressant zog ntawm hydroethanolic extract los ntawm nplooj ntawm A. polystachya, thiab ntawm cov purified phenylethanoids cais tawm, tuaj yeem piav qhia los ntawm ntau hom phiaj ntawm kev nqis tes ua cuam tshuam nrog inhibition ntawm MAO-A, downregulation ntawm inflammatory molecules, thiab neutralization ntawm cov tshuaj tiv thaiv oxidation. Li no, cov txiaj ntsig tau nthuav tawm ntawm no txhawb nqa peb qhov kev xav thawj zaug tias cov kev ua ub ua no anxiolytic thiab antidepressant ntawm hydroethanolic extract ntawm A. polystachya tshwm sim, tsawg kawg hauv ib feem, los ntawm inhibition ntawm MAO-A. Txawm li cas los xij, tus qauv-kev sib raug zoo ntawm covphenylethanoid glycosidestxheeb xyuas nyob rau hauv txoj kev tshawb no xav tau kev saib xyuas ntxiv kom cov molecules tshiab tuaj yeem tsim los rau kev kho mob ntawm cov kab mob neurological tshwj xeeb.

Cov ntaub ntawv thiab cov txheej txheem

Cov khoom cog

Cov nplooj ntawm A. polystachya tau sau nyob rau ntawm Farmácia da Na-tureza da Terra de Ismael (Jardinópolis, SP, Brazil) thaum Lub Ib Hlis 2016. Cov khoom cog tau txheeb xyuas los ntawm Dr. Lúcia Rossi (Instituto Botânico, São Paulo, SP, Brazil), thiab daim ntawv pov thawj tau muab tso rau hauv Herbarium of Medicinal Plants ntawm UNAERP nrog tus lej voucher

HPM-1213.

HPM-1213. Kev tso cai los soj ntsuam bioactivities ntawm cov extracts los ntawm Brazilian nroj tsuag tau tso cai los ntawm Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis ​​(no. 02001.005074/ 2011-19).

Kev npaj ntawm hydroethanolic extract ntawm Aloysia polystachya

Nplooj (1000 g) tau qhuav rau 72 teev nyob rau hauv lub qhov cub cua ntawm 45 degree, pulverized, thiab dhau los ntawm 40-mesh sieve. Cov hmoov nplej tau muab tso rau hauv dej: ethanol (20:80; v / v) rau 7 hnub thiab tom qab lim los ntawm Whatman No. 41 lim ntawv. Cov filtrate raug txo kom qhuav ntawm lub evaporator teb thiab lyophilized kom tawm los

130.2 g ntawm qhuav crude extract, uas ua rau ib tug tshuaj extract piv ntawm 7.6: 1.

Kev sib cais thiab kev txheeb xyuas cov ntsiab lus los ntawm ultra-kev ua haujlwm ua kua chromatography-mass spectrometry

Kev soj ntsuam chromatographic tau ua tiav siv Waters Acquity UPLC H-Class system nruab nrog lub diode array detector (DAD) thiab Waters Xevo TQ-S tandem quadrupole mass spectrometer nrog Z-txhaj qhov chaw ua haujlwm hauv hom tsis zoo ion. Cov kev daws teeb meem uas muaj 1.0 mg/mL ntawm extract los yog cov qauvacteoside, isoacteoside, 6'-acetylacteoside, thiab 4',4'',5,5'-tetrahydroxy-6,6',3''- trimethoxy-[C7-O-C7'] -flavone nyob rau hauv LC-qib methanol tau pre-pared nyias, nrog sonication rau 30 min txhua thaum tsim nyog, thiab lim los ntawm 0.45 μm Millipore filters (Merck Millipore). cov tshuaj tau diluted rau 10 µg/mL nrog methanol, thiab aliquots (5 μL) tau txhaj rau ntawm Sigma-Aldrich Ascentis Express C18 kem (100} × 4.6 mm id; 2.7 µm particle loj). Cov theem ntawm lub xov tooj ntawm tes muaj cov dej uas muaj 0.1 feem pua ​​​​ formic acid (cov kuab tshuaj A) thiab methanol uas muaj 0.1 feem pua ​​​​ formic acid (cov kuab tshuaj B) nkag ntawm tus nqi ntws ntawm 0.5 mL / min raws li qhov elution profile: isocratic nrog 3 feem pua ​​B ntawm 0 thiab 4 min, ua raws li cov kab gradients ntawm 3 mus rau 60 feem pua ​​B ntawm 4 thiab 19 feeb thiab los ntawm 60 mus rau 90 feem pua ​​B ntawm 19 thiab 23 feeb, thiab thaum kawg rov mus rau 3 feem pua ​​B ntawm 23 thiab 28 feeb. Cov dej ntws tau raug saib xyuas los ntawm DAD nyob rau hauv thaj tsam ntawm 210 txog 720 nm thiab los ntawm MS nrog rau qhov zoo tshaj plaws thiab kev ua haujlwm tsis zoo raws li hauv qab no: capillary volt-

muaj hnub nyoog 2.50 kV, Z-spray qhov kub ntawm 150 degree, desolvation kub (N2) 350 degree, desolvation gas txaus 600 L / h, thiab huab hwm coj ntau ntawm m / z 150 txog 600 nyob rau hauv tag nrho scan hom.

Purification ntawm cov khoom uas tau txheeb xyuas

Lub crude hydroethanolic extract (10 g) yog yaj nyob rau hauv dej: ethanol (50:50; v / v) thiab partitioned consecutively tiv thaiv hexane, ethyl acetate, thiab n-butanol. Lub butanol feem yog concentrated nyob rau hauv rotary evaporator thiab ib tug 3g qauv ntawm cov fractionated extract tau siv rau ib khob kem (10 × 3 cm od) puv nrog C-18 RP silica gel (230-400 mesh; Sigma -Aldrich) thiab eluted nrog dej, ua raws li kev sib xyaw ua ke ntawm dej: methanol (90: 10, 50: 50, thiab 10: 90; v / v). Cov subfraction tau los ntawm elution nrog dej: methanol (90:10; v/v) tau ntxiv purified los ntawm RP-HPLC siv ib tug Shimadzu LC{19}}AP System ua ke rau ib tug SPD-20A UV/Vis detector thiab nruab nrog Phenomenex Luna® C-18 kem (250 × 10 mm id; 5 μm particle loj). Lub sijhawm txawb yog dej: methanol pib ntawm 90: 10 (v / v) thiab hloov mus rau 30: 70 (v / v) hauv 100 min kom tawm los ntawm plaub qhov sib txuas.acteoside(750 mg), isoacteoside (430 mg), 6'-acetylacteoside (42 mg), thiab 4',4'',5,5'-tetradroxy-6,6',3'' -trimethoxy-[C7–O–C7'']-flavone (13 mg). Tus nqi ntws ntawm lub xov tooj ntawm tes yog 1 mL / min, qhov ntim ntim yog 500 μL, chromatogram tau kaw ntawm 340 nm, thiab UV spectra tau txais nyob rau hauv thaj tsam ntawm 240 txog 400 nm. Cov cim ntawm cov khoom siv purified tau lees paub los ntawm lawv cov 1H- (500 MHz) thiab 13C-NMR (125 MHz) spectra kaw rau ntawm Bruker qauv DPX 500 spectrometer, thiab kev sib piv ntawm cov ntaub ntawv nrog cov muaj nyob rau hauv cov ntaub ntawv [18, 19, 41] ib. Purities ntawm cov khoom sib cais tau lees paub los ntawm UPLC-DAD-MS (▶Daim duab 1b–d) thiab NMR (▶Daim duab S1–S12, Cov Ntaub Ntawv Txhawb Nqa).

Kev ntsuas ntawm acteoside los ntawm HPLC-diode arrayntes

Qhov kev daws teeb meem no tau txheeb xyuas ntawm Shimadzu LC{{{{10}}}}}APvp system txuas rau SPD-M10Avp DAD thiab fitted nrog Phenomenex Luna C18 kem (250 × 4.6 mm id, 5 µm) tiv thaiv los ntawm Phenomenex C18 precolumn (4.0 × 3.0 mm id, 5 µm). Kev sib cais tau ua nyob rau hauv chav tsev kub (22 ± 1 degree) siv lub xov tooj ntawm tes uas muaj acetic acid 0.1 feem pua ​​​​hauv dej (hloov A) thiab methanol (hloov B;

JT Baker HPLC qib) muab los ntawm tus nqi tsis tu ncua ntawm 1.0 mL / min raws li qhov kev pab cuam: linear gradient los ntawm 10 mus rau 70 feem pua ​​B ntawm 0 thiab 32 min, los ntawm 70 mus rau 10 feem pua ​​B ntawm 32 thiab 35 min, thiab qhov kawg isocratic elution nrog 10 feem pua ​​B ntawm 35 thiab 40 min. Kev kuaj pom wavelength tau teem rau ntawm 330 nm.

Cov ntsiab lus ntawm acteoside hauv cov extract tau kwv yees sivacteoside(Sigma-Aldrich; CAS no. 61276-17-3) raws li tus qauv sab nraud. Cov kev daws teeb meem uas muaj 500, 250, 125, 62.5, 31.2, thiab 15.6 ug/mL ntawm tus qauv siv tau raug npaj, thiab calibration curves tau tsim los ntawm kev muab txhua qhov kev daws rau HPLC tsom xam hauv triplicate [42 ]. Qhov piv ntawm thaj chaw ncov ntawm tus qauv acteoside rau qhov sib thooj ntawm cov tshuaj ntsuam xyuas tau tsim los ntawm cov kab rov tav ntawm cov qauv nkhaus (▶ Daim duab S13, Cov Ntaub Ntawv Txhawb Nqa). Cov ntaub ntawv txheeb xyuas tau raug lees paub nrog rau kev sib luag, kev raug, thiab raug raws li cov lus qhia los ntawm Agência Nacional de Vigilância Sanitária [42]. Kev txwv ntawm kev kuaj pom (LoD) thiab ntau npaum li cas (LoQ) ntawm acteoside yog 0.30 thiab 0.92 µg / mL, feem.

Monoamine oxidase-A inhibition kev soj ntsuam

Recombinant human MAO-A, tyramine, clorgyline, vanillic acid, 4-amino antipyrine, thiab horseradish peroxidase tau muas los ntawm Sigma-Aldrich. MAO-A inhibition kev soj ntsuam tau ua tiav siv 96- cov phiaj zoo tom qab hloov kho ntawm txoj kev piav qhia los ntawm López li al. [43]. Txhua lub qhov dej tau ntim nrog 50 μL ntawm cov tshuaj chromogenic (0.8 mM vanillic acid, 2.5 mM 4-amino antipyrine, thiab 4 U / mL horseradish peroxidase hauv phosphate tsis nyob ntawm pH 7.6), 100 μL ntawm 3 mM tyramine, thiab ib 50-μL aliquot ntawm crude hydroethanolic extract los yog ib qho ntawm cov purified phenylethanoids yaj hauv methanol. Thaum kawg, 50 μL aliquots ntawm 8 U / mL MAO-A tau ntxiv rau txhua lub qhov dej thiab lub phaj tau incubated ntawm 37 degree rau 30 min, thaum lub sij hawm absorbances tau sau txhua txhua 5 min siv lub microplate nyeem ntawv. Clorgyline (Ntau dua lossis sib npaug rau 97 feem pua ​​​​GC; Sigma-Aldrich) thiab methanol tau suav nrog kev tswj xyuas qhov zoo thiab tsis zoo, raws li, ntawm txhua daim ntawv tshuaj ntsuam.

Kev txheeb cais

Peb qhov kev ntsuam xyuas ywj pheej ntawm MAO-A inhibitory kev ua ub no tau ua thiab cov ntaub ntawv tau txais tau raug tshuaj xyuas siv Graph-Pad Prism software. Lub IC50 qhov tseem ceeb ntawm hydroethanolic extract, purified phenylethanoids, thiab kev tswj zoo tau suav los ntawm nonlinear regression, simulating cov phiaj xwm ntawm cov cav (inhibitor concentration) piv rau cov feem pua ​​​​txheej txheem inhibition.

Txhawb cov ntaub ntawv

H- thiab 13C-NMR spectra ntawmacteoside, isoacteoside, 6'-acetylacteoside, thiab 4',4'',5,5'-tetrahydroxy-6,6',3''-trimethoxy-[C7–O–C7’] -flavone thiab HSQC / HMBC kev txheeb xyuas kev sib raug zoo rau peb lub phenylethanoids yog muaj raws li Cov Ntaub Ntawv Txhawb.

tau txais 04.06.2018

hloov kho 19.10.2018

txais 24.10.2018

Cov ntawv sau cia

DOI https://doi.org/10.1055/a-0787-1665

Planta Med Int Qhib 2019; 6: e1e6

© Georg Thieme Verlag KG Stuttgart · New York ISSN 2509-9264

Kev sau ntawv

Ana Maria S. Pereira

Departamento de Biotecnologia em Plantas Medicinais

Universidade de Ribeirão Preto Av. Costábile Romano 2201 14096-900 Ribeirânia

Ribeirão Preto, SP

Brazil

Cov ntaub ntawv

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