Abstract:Kev cuam tshuam ntawm tib neeg daim tawv nqaij rau 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) paub tias ua rau tshuaj lom neeg / ua haujlwm leukoderma. RK yog carbonyl derivative ntawm 4-(4-hydroxyphenyl)-2-butanol (rhododendron), cov tawv nqaij-dawb tus neeg sawv cev uas tau pom ua rau leukoderma hauv daim tawv nqaij ntawm ntau tus neeg siv khoom. Ob lub phenolic tebchaw no yog oxidized los ntawm tyrosinase thiab cov khoom tshwm sim zoo li ua rau cytotoxicity rau melanocytes los ntawm kev tsim cov pa oxygen reactive thiab depleting cellular thiols los ntawm o-quinone oxidation khoom. Yog li ntawd, nws yog ib qho tseem ceeb kom nkag siab txog biochemical mechanism ntawm oxidative transformation ntawm cov tebchaw. Cov kev tshawb fawb yav dhau los qhia tias RK yog pib oxidized rau RK quinone los ntawm tyrosinase thiab tom qab ntawd hloov mus rau ib sab saw desaturated catechol hu ua 3,4- dihydroxybenzalacetone (DBL catechol). Hauv txoj kev tshawb fawb tam sim no, peb qhia txog oxidation chemistry ntawm DBL catechol. Siv UV-pom spectroscopic kev tshawb fawb thiab kua chromatography-mass spectrometry, peb tau soj ntsuam cov tshuaj tiv thaiv ntawm DBL catechol nrog tyrosinase thiab sodium periodate. Peb cov txiaj ntsig tau qhia tias DBL quinone tsim nyob rau hauv cov tshuaj tiv thaiv yog qhov tsis tshua muaj tshwm sim thiab ua kom yooj yim dimerization thiab trimerization cov tshuaj tiv thaiv los tsim ntau yam khoom isomeric los ntawm cov tshiab ionic Diels-Alder hom condensation tshua. Kev tsim cov khoom lag luam ntau yam quinonoid los ntawm cov tshuaj tiv thaiv zoo li no yuav ua rau muaj kev phom sij ntau dua rau cov hlwb los ntawm kev ua rau tsis yog oxidative kev nyuaj siab tab sis kuj yog myelotoxicity los ntawm kev nthuav tawm cov tshuaj tiv thaiv cellular macromolecules thiab thiols.

Raws li cov kev tshawb fawb cuam tshuam, cistanche yog ib hom tshuaj ntsuab uas hu ua "cov tshuaj ntsuab muaj txuj ci uas ua rau lub neej ntev". Nws lub ntsiab tivthaiv yog cistanoside, uas muaj ntau yam teebmeem xws li antioxidant, tiv thaiv kev mob, thiab kev tiv thaiv kev ua haujlwm. Cov txheej txheem ntawm cistanche thiab tawv nqaij dawb yog nyob rau hauv cov nyhuv antioxidant ntawm cistanche glycosides. Melanin nyob rau hauv tib neeg daim tawv nqaij yog tsim los ntawm oxidation ntawm tyrosine catalyzed los ntawm tyrosinase, thiab cov tshuaj tiv thaiv oxidation yuav tsum muaj kev koom tes ntawm oxygen, yog li cov pa-dawb radicals nyob rau hauv lub cev ua ib qho tseem ceeb cuam tshuam rau melanin ntau lawm. Cistanche muaj cistanoside, uas yog ib qho antioxidant thiab tuaj yeem txo qhov tsim ntawm cov dawb radicals hauv lub cev, yog li inhibiting melanin ntau lawm.

Nyem rau ntawm Rou Cong Rong Cov txiaj ntsig rau Kev Kho Kom Zoo Nkauj

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david.deng@wecistanche.com WhatApp:86 13632399501

Ntsiab lus:rhododendron toxicity; raspberry ketone; 3, 4-dihydroxybenzalacetone; DBL catechol; ionic Diels-Alder ntxiv; myelotoxicity; leukoderma; daim tawv nqaij lightening compounds

1. Taw qhia

Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone, RK), yog ib qho phenolic compound dav siv los ua tshuaj pleev ib ce, naj hoom, thiab zaub mov flavoring agent [1]. Qee tus neeg ua haujlwm koom nrog cov txheej txheem tsim khoom ntawm qhov sib xyaw no hauv Nyij Pooj tau tsim ua haujlwm leukoderma [2]. Hauv cov ntsiab lus no, nws yog ib qho tseem ceeb uas yuav tsum tau ua tib zoo mloog rau rhododendron, 4-(4-hydroxyphenyl)-2-butanol, derivative ntawm RK nrog nws pawg carbonyl txo qis rau cov cawv thib ob. Rhododendron kuj tau siv dav hauv kev lag luam tshuaj pleev ib ce raws li cov khoom siv tawv nqaij dawb. Rov ua daim ntawv thov ntawm rhododendron raws li daim tawv nqaij xim-lightening tus neeg sawv cev ua rau kev loj hlob ntawm leukoderma ntawm lub ntsej muag, caj dab, thiab tes [3]. Ob lub tebchaw no tuaj yeem hloov pauv hauv lub cell los ntawm oxidation-txo cov tshuaj tiv thaiv. Yog li ntawd, lawv toxicity tej zaum yuav tshwm sim los ntawm tib yam tshuaj tiv thaiv.

Tyrosinase-catalyzed oxidation ntawm RK ua rau nws sib raug zoo quinone uas nthuav tawm sai isomerization ntawm nws quinone methide rau (E)-4-(3,4-dihydroxyphenyl)-3-buten-2-ib, feem ntau hu ua 3,4-dihydroxybenzalacetone (DBL catechol) [11]. Xws li kev qhia nonenzymatic ntawm ob daim ntawv cog lus nyob rau hauv cov saw hlau los ntawm kev tsim nruab nrab ntawm quinone thiab quinone methide yog cov ntaub ntawv pov thawj zoo rau ob peb catecholamine derivatives [12–15]. Cov kev tshawb fawb ua ntej tau qhia tias qhov tshwm sim ntawm DBL catechol yog qhov muaj zog heev thiab cov khoom lag luam quinonoid tsim los ntawm cov khoom sib xyaw no tuaj yeem hnov ​​​​mob sai nrog cov cellular thiol compounds [11]. Tsis tas li ntawd, muaj peev xwm oligomerization ntawm cov khoom quinonoid tau txiav txim siab tab sis tsis tau tshuaj xyuas vim qhov kev ua haujlwm siab ntawm cov nruab nrab. Nyob rau hauv xyoo tas los no, ib qho ntawm peb lub chaw soj nstuam tau ua tiav siv cov kev tshawb fawb loj los tshawb xyuas cov ntsiab lus sib txawv ntawm oxidative transformations ntawm ob peb dehydrodopa thiab dehydrodopamine derivatives [12-20]. Peb cov kev tshawb fawb tau muab cov ntaub ntawv tseem ceeb ntawm kev hloov pauv oxidative ntawm ntau cov catecholamine derivatives. Yog li ntawd, peb txiav txim siab los soj ntsuam cov tshuaj tiv thaiv kab mob siv los ntawm DBL catechol kuj siv cov txheej txheem no, thiab tshaj tawm hauv daim ntawv no cov tshiab oxidative transformations nthuav tawm los ntawm DBL quinone.

2. Cov txiaj ntsig thiab kev sib tham

Daim duab 2A qhia txog UV-pom pom kev hloov pauv nrog cov oxidation ntawm DBL catechol los ntawm nceb tyrosinase. Sai li sai tau tyrosinase ntxiv, cov kev hloov pauv sai sai tshwm sim hauv qhov absorbance spectra. UV ncov vim DBL catechol nyob ib ncig ntawm 320 nm nce zuj zus thiab absorbance hauv thaj av pom ntawm txog 420 nm nce tsis tu ncua. Cov kev hloov pauv spectral nrog rau qhov kev hloov pauv no tau nthuav tawm ob lub ntsiab lus isosbestic ntawm txog 285 nm thiab 385 nm, qhia txog kev hloov pauv ncaj qha ntawm DBL catechol mus rau qhov sib xyaw ua kom pom qhov nqus ntawm li 420 nm. Cov khoom sib xyaw no, uas muaj xim daj, yuav tsum yog cov quinone sib xws li tyrosinase paub zoo kom nthuav tawm dav substrate tshwj xeeb thiab oxidize ntau o-diphenolic tebchaw rau lawv cov o-quinones sib xws [15]. Thaum cov tshuaj tiv thaiv tau ua rau me ntsis alkaline tej yam kev mob (ntawm pH 8), cov xim ntawm cov tshuaj tiv thaiv sib xyaw ua kom sib zog thaum cov tshuaj tiv thaiv tau nce (Daim duab 2B). Thaum kawg, qhov sib xyaw ua ke nthuav tawm dav dav ntawm ib puag ncig 330 nm tau tsim. Ib tug kuj tuaj yeem pom qhov hloov pauv me ntsis hauv cov spectral scans ntawm lub substrate thiab cov khoom kawg, qhia tias ib feem ntawm cov conjugation nyob rau hauv lub substrate yog poob rau hauv cov khoom. Cov txiaj ntsig no tau qhia tias tyrosinase-tsim DBL quinone tab tom hloov pauv ntxiv.

Txhawm rau pom txoj hmoo ntawm DBL quinone, peb tsim cov quinone no los ntawm quantitatively oxidizing DBL catechol nrog sodium periodate thiab saib xyuas UV thiab pom kev hloov pauv spectral. Cov kev tshawb fawb pib ntawm pH 6 lossis 7 tau qhia tias oxidation ceev heev thiab ua rau tsim cov khoom kawg uas nthuav tawm qhov absorbance siab tshaj plaws nyob ib ncig ntawm 265 nm nrog qhov dav absorbance ntawm thaj tsam pom ntawm 380 thiab 440 nm (Daim duab 3A)

Txij li thaum cov tshuaj tiv thaiv tau tshwm sim sai heev, saib xyuas cov kev hloov spectral ua nyuaj heev. Li no, peb txiav txim siab kom qeeb cov tshuaj tiv thaiv los ntawm kev ua nws ntawm acidic pH qhov tseem ceeb. Txhawm rau qeeb cov tshuaj tiv thaiv thiab saib xyuas cov quinone tsim, peb tau ua cov kev tshawb fawb hauv 0.2 M acetic acid. Daim duab 3B qhia txog kev tsim sai ntawm DBL quinone los ntawm DBL catechol los ntawm oxidation ntawm sodium periodate hauv acetic acid. Cov oxidation tau ua tiav hauv tsawg dua ib feeb thiab cov quinone tsim tuaj yeem pom los ntawm nws qhov nqus ntawm thaj tsam pom. Txawm li cas los xij, quinone tau dhau los ua qhov tsis ruaj khov thiab nthuav tawm kev hloov pauv sai rau cov khoom lag luam uas nthuav tawm ultraviolet absorbance ntawm 280-480 nm raws li pom hauv daim duab 4.

Ob yam khoom - ib qho eluting ntawm 18 min thiab lwm qhov eluting ntawm 21 min - pom qhov loj ntawm m / z 355.1171 (Daim duab 5B), uas yog nyob rau hauv 3 ppm ntawm cov theoretical loj rau cov khoom ntxiv ntawm DBL quinone rau DBL catechol (C20H18O6) . CID spectrum ntawm lub dimer eluting ntawm 18 min (Daim duab 6) txawv heev ntawm qhov eluting ntawm 21 min (Daim duab 7). Lub dimer eluting ntawm 18 min nthuav tawm cov khoom loj ions ntawm m / z qhov tseem ceeb ntawm 337 (tsis dej), 313 (poob ntawm acetyl pawg), thiab 295 (poob dej thiab acetyl pawg). Kev poob ntawm ob pawg dej thiab acetyl tsuas yog ua tau rau cov benzodioxan-hom dimer uas pom nyob rau hauv inset. Nco ntsoov qhov no m / z 295 ion ncov tsis yog lub ncov tseem ceeb hauv CID spectrum ntawm 21 min ncov. Qhov kev soj ntsuam no ua ke nrog kev tsim tawm ntawm 189 (poob ntawm pawg ntseeg thiab CH2=CO-CH3 pawg) qhia tias 21 min ncov yog vim muaj qhov sib txawv dimer uas nws cov qauv npaj tau pom nyob rau hauv inset ntawm daim duab 7 .

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