Kev txheeb xyuas ntawm cov kab mob siab ua haujlwm ntawm Lub Ntiaj Teb Bioactive Compound Echinacoside, Purified Los ntawm Cistanche

3.1. Quantification ntawm echinacoside A nyob rau hauv nas thiab tib neeg daim siab S9 tsom xam

echinacoside cov tshuajA tau tshuaj xyuas siv nas thiab tib neeg lub siab S9 feem thiab ntsuas los ntawmHPLC-QQQ/MS ntawm lub sijhawm sib txawv. Cov nqe vaj lug kub ntxiv rau lub sij hawm profile ntawm echinacosideA, nyob rau hauv nas thiab tib neeg daim siab S9 feem kev kho mob, yog qhia nyob rau hauv daim duab1. Siv cov 'zoo- stirredqauv' thiab cov qauv kev suav [27], tus nqi kwv yees tau qhia hauv Table1. Ratdaim siab S9 metabolized ~ 75.4 feem pua ​​​​ntawm echinacoside A hauv 60 min. Tib neeg lub siab S9 metabolized~ 49.8 feem pua ​​​​ntawm echinacoside A hauv 120 min. Nyob rau hauv lub xub ntiag ntawm NADPH, echinacoside A yogmetabolized qeeb dua, nrog at1/2 = 114.92 min hauv tib neeg. EH yog ib feem ntawm cov tshuajraug lim los ntawm daim siab nyob rau hauv ib tug pass, nyob rau hauv uas cov tshuaj yog irreversibly tshem tawm (extracted).Peb pom tias EH ntawm nas yog siab dua li ntawm tib neeg. Qhov tshwm sim no yog tsim nyog,kev txiav txim los ntawmt1/2 qhov tseem ceeb, vim nas daim siab tau tshaj tawm tias metabolize sai duatib neeg lub siab [28]. Piv nrog rau lwm cov ntaub ntawv sib xyaw siv nas daim siab S9, GKB202 ntawmtusAntrodia cinnamomeamycelium (t1/2 = 3.68 min) tau metabolized sai dua echinacoside cov tshuaj A [29]. 

Daim duab 1.EchinacosideQhov seem piv rau lub sijhawm profile hauv nas thiab tib neeg lub siab S9. Cov ntaub ntawv tau nthuav tawm hauvtxhais tau tias qhov tseem ceeb ntawm kev ntsuas triplicate.

Daim ntawv tshaj tawm yav dhau los tau qhia tias tsis muaj-saib-kev cuam tshuam-kev cuam tshuam ntawm 3 g / kglub cev hnyav/hnub echinacoside A-enriched HE hauv 28-hnub noj qhov ncauj hauv Sprague-Dawley nas.Txoj kev tshawb fawb tam sim no ntau npaum li cas cov lus qhia rau daim siab cell metabolism muab kev sib raug zoo,nrog yav dhau loshauv vivoKev tshawb fawb, ntawm echinacoside A compound pharmacokinetics (PK) [30,31]. Hauv ib qho tsis ntev los nohauv vivoreport, the Tsai et al. pab pawg kuaj pom echinacoside A hauv nas ntshav tom qabKev tswj qhov ncauj ntawm HE mycelia (50 mg / kg) ntawm 60 min [32]. Qhov no tuaj yeem cuam tshuam nrog covtam sim nohauv vitrokev tshawb pom, uas peb tau pom, theoretically, tias tseem muaj ~ 24.6 feem puatshuav ntawm cov compound tom qab nas lub siab S9 metabolism. Tsis tas li ntawd, kwv yees li ib nrabntawm unmetabolized echinacoside A tau pom nyob rau hauv seem tib neeg lub siab S9, ua qauv qhiauas ua tiav cov qauv sib xyaw tuaj yeem nkag mus rau hauv cov hlab ntsha, uas ua rau nwsmuaj txiaj ntsig zoo hauv kev tiv thaiv neuroprotection. Seb puas los yog tsis yog cov metabolites ntau muab, lubKev ua haujlwm lom neeg tseem nyob hauv kev tshawb nrhiav thiab yuav raug tshaj tawm hauv kev tshawb fawb cais

Nyem qhov no Kom Paub Cistanche Echinacoside Function

3.2. Hauv Vitro Metabolite Kev txheeb xyuas hauv nas thiab tib neeg

Ultra-performance kua chromatography/quadrupole lub sij hawm-ntawm-flight huab hwm coj spectrometry (UPLC-QTOF/MS) tau siv los txheeb xyuas cov metabolites nyob rau hauv lub zoo thiab tsis zoo hom. Ib qho kev sib piv ntawm echinacoside A metabolites, hauv txoj kev tshawb no, nrog nas thiab tib neeg lub siab S9 metabolites tau qhia hauv Table2. Nees nkaum-plaub metabolites tau pom tom qab echinacoside A incubation thiab raug muab ua M1-M24 (Table S1). Tsib yam metabolites tau kuaj pom tom qab incubation nrog nas thiab tib neeg lub siab S9. Qhov yuam kev loj yog tag nrhoTsawg dua los yog sib npaug5ppm ua. Qhov saum toj kawg nkaus peb cov metabolites ntau, raws li thaj chaw ncov, yog Gluthation conjugation ntxiv rau Demethylation (M6), Demethylation (M2), thiab Demethylation ntxiv rau Hydrogenation (M3). Dej Cawv Dej (M1), Demethylation (M2), Demethylation ntxiv rau Hydrogenation (M3), 2× Hydroxylation (M4), Demethylation, thiab ob Hydroxylations (M5) metabolites ob leeg tau txheeb xyuas hauv nas thiab tib neeg lub siab S9. Txoj kev npaj metabolic thiab ua tau metabolites ntawm echinacoside A tau qhia hauv daim duab2. 

Rooj 2.Cov kab mob siab metabolites ntawm echinacoside A, tau kuaj pom hauv nas thiab tib neeg lub siab S9,UPLC-QTOF/MS.

Cov niam txiv compound ntawm echinacoside A formula yog C25H36O6. MS spectrum ntawmechinacoside cov tshuajA tau pom ntawm [M plus H]ntxiv= 433.2573 thiab [M plus Na]ntxiv= 455.2405 (Daim duab3A). CovMS / MS spectrum los ntawm kev sib tsoo lub zog ntawm 10 V yog pom hauv daim duab3B uas sib raug raukev sib cais ntawm CO ether daim ntawv cog lus ([C20H29O2] ntxiv= 301.2162 thiab [C20H27O]ntxiv= 283.2052) (Daim duab3C) [15,32]. Cov mis Alcohols Dehydration metabolites (M1) yog C25H34O5, nrog echinacoside A poob ib H2O [33,34]. MS spectrum ntawm M1 tau pom ntawm [M ntxiv rau H]ntxiv= 415.2472 thiab [M plus Na]ntxiv= 437.2255. Ntawm kev sib tsoo zog ntawm 10V, cov khoom tseem ceeb ionstaum/z 283.2036, 215.1701, 181.1249, 135.0817, 119.0856, 105.0709, thiab 69.0327 (Daim duab4A). Ob yam khoomions tau zoo sib xws rau cov echinacoside A ions (m/z 283.2036 ibm/z 119.0856), thiab ntau lawmm/z 301.2162 ploj lawm. Lub cev qhuav dej M1 tuaj yeem yogsiv los qhia txog kev poob dej hauv cov khoom pentose [35]. Demethylation metabolites (M2)formula yog C24H34O6, nrog echinacoside A poob methylene (-CH2) [36]. Ntawm kev sib tsooLub zog ntawm 40 V, MS spectrum ntawm M2 tau pom ntawm [M ntxiv rau H]ntxiv= 419.2407. Cov khoom tseem ceebua ionsm/z 312.0488, 269.9469, 231.0432, 123.0552, thiab 179.0486 (Daim duab4B). Kev tsim khoomntawmm/z 269.9469, 179.0486 sib raug rau cleavage ntawm methylene (-CH3) thiab plusHntxiv. Cov mis demethylation plus Hydrogenation metabolites (M3) yog C24H36O6 nrogM2 txo qis hauv alkene (ntxiv rau H2) [37–39]. MS spectrum ntawm M3 tau pom ntawm [M ntxiv rau H]ntxiv= 421.2569 thiab [M plus Na]ntxiv= 443.2355. Ntawm kev sib tsoo zog ntawm 40 V, cov khoom tseem ceebua ionsm/z 353.2141, 277.2183, 147.1172, thiab 77.0054 (Daim duab4C). Production ntawmm/z 353.2141, 277.2183 tau coj mus rau Hydrogenation. Qhov 2× HydroxylationCov mis metabolites (M4) yog C25H36O8 Nrog echinacoside Ib Hydroxylation ntawm isopropylsab saw thiab cyclopentene [40–42]. MS spectrum ntawm M4 tau pom ntawm [M ntxiv rau H]ntxiv= 465.2461 and [M plus Na]ntxiv= 487.2315. Ntawm kev sib tsoo zog ntawm 20V, cov khoom tseem ceeb ions yogm/z 297.1842, 255.1389, 177.1115, 133.0860, thiab 89.0597 (Daim duab4D). Production ntawmm/z 297.1842, thiab 89.0598 tau coj mus rau Hydroxylation. Demethylation thiabOb hom Hydroxylation metabolites (M5) yog C24H34O8 nrog M11 poob ib methylene(-CH2). MS spectrum ntawm M5 tau pom ntawm [M ntxiv rau H]ntxiv= 451.2413 and [M plus Na]ntxiv= 473.2158 ib. Ntawm kev sib tsoo zog ntawm 40 V, cov khoom tseem ceeb ions yogm/z 321.1516, 178.1225, 101.0705, thiab 59.0601 (Daim duab4E). Production ntawmm/z 321.1516 sib raug rau M4cleavage ntawm methylene (-CH3) thiab ntxiv rau Hntxiv.

Muaj 70 qhov sib txawv ntawm cov metabolites cais los ntawm HE sporophorelos yog mycelium. Cov metabolites no tau txheeb xyuas tiaspolysaccharidespolyketides,phenols, terpenoids, thiabbioactive molecules [43–45]. Peb kwv yees tias cov metabolites no,uas peb soj ntsuam, kuj yuav yog cov precursors los yog nruab nrab cov khoom ntawm myceliumSecondary metabolites hais ua ntej. Txawm li cas los xij, nws tau raug tshaj tawm tias M1, M2,M3, M4, thiab M5 tuaj yeem sawv cev tseem ceeb nruab nrab ntawm echinacoside A thiab theem nrabmetabolites rau nas thiab tib neeg kev tshawb fawb. Vim muaj kev siv ntau ntxiv ntawm HE mycelium li ahaumxeeb ntxiv, txheeb xyuas cov metabolites tseem yuav nthuav tawm cov txiaj ntsig biomarkers.Noj cov cholesterol ua piv txwv, cov precursors lossis cov khoom nruab nrab ntawm ntau yamCov tshuaj, tsim los ntawm lub siab enzymes txheej txheem, tau metabolized rau oxysterol, uas yogTam sim no nkag siab tias yog lub zog metabolite hauv sterol metabolism thiabkev cai synthesis [46]. 

Daim duab 3.(AMS spectrum ntawm echinacoside A nrog kev ua haujlwm siab ua kua chromatography-tandemquadrupole time-of-flight mass spectrometry. (B) MS/MS spectrum ntawm echinacoside A nrog ibultra-siab ua kua chromatography-tandem quadrupole lub sij hawm-ntawm-flight huab hwm coj spectrometry.(C) Cov qauv tsim ntawm cov khoom ions, tsim los ntawm echinacoside A, ntawm kev sib tsoo zog ntawm 10 V.(a) [C20H29O2]ntxiv= 301.2162, (b) [C20H27O]ntxiv= 283.2052.  : Niam Txiv ion.

Daim duab 4.MS thiab MSMS spectrum ntawm (A) Alcohols Dehydration (M1), (B) Demethylation metabolites(M2), (CDemethylation ntxiv rau Hydrogenation metabolites (M3), (D) 2 × Hydroxylation metabolites (M4),(E) Demethylation thiab ob Hydroxylations (M5) metabolite siv cov kua ua haujlwm siab heevchromatography-tandem quadrupole lub sij hawm-ntawm-flight huab hwm coj spectrometry. : Niam Txiv ion.

M2 thiab M3 tau kuaj pom ntawm 60 min rau nas daim siab S9, thaum tib neegcev s9, M2 thiab M3 raug kuaj pom ntawm 10, 30, 60, thiab 120 min. Peb kwv yees tias M3 yuav raug tsim tawmlos ntawm ob txoj hauv kev metabolic; ib qho los ntawm echinacoside A rau M3, thiab lwm qhov tau muab loslos ntawm M1. Hauv qhov sib piv, M4 thiab M5 tau kuaj pom ntawm 10, 30, thiab 60 min nas.cev s9. Hauv tib neegdaim siab S9, M4 tau kuaj pom ntawm 10, 30, 60, thiab 120 min. M5 tau kuaj pom ntawm120 feeb. Lub sijhawmCov tsos mob tuaj yeem piav qhia tias M5 metabolic txoj hauv kev tuaj yeem muab tau los ntawm M4.

Txoj kev tshawb no muab cov ntaub ntawv ntxiv rau HE mycelium kev tshawb fawb soj ntsuamcov ntaub ntawv uas ploj lawm, uas yog qhov kev txiav txim ntawm metabolic los ntawm bioactive compound. Hauv ibTsis ntev los no randomized, ob-dig muag placebo-tswj txoj kev tshawb no, peb 350 mg / g HE mycelia(muaj 5 mg / g echinacoside A) kev cuam tshuam cov tshuaj ntsiav, rau 49 lub lis piam, pom tau tias ntau duaCognitive Abilities Screening Instrument, Mini-Mental State Examination, thiabInstrumentalCov qhab nia ntawm Kev Ua Si Txhua Hnubthiab ua tiav qhov zoo sib xws rhiab heev, hauv cov neeg mob nroghnub nyoog> 50 xyoo thiab kuaj mobTej zaum Alzheimer's Disease, thaum piv rau covpab pawg placebo [19]. Los ntawm kev nkag siab echinacoside A metabolites profile, peb tuaj yeem txhaisuasechinacoside Ib enriched HE mycelia txhim kho neurocognitive teeb meem, uas tej zaum yuav yogpab txhawb feem ntau los ntawm unmetabolized compound. Raws li rau echinacoside A,metabolites yogzoo-tolerated thiab tej zaum yuav yog ib qho tseem ceeb hauv kev ua tiav cov txiaj ntsig neuro-kev noj haus, uas yuavraug tshawb nrhiav hauv kev tshawb fawb yav tom ntej. 

Qhov no yog thawj txoj kev tshawb fawb los tsim kom muaj kev tsom xam loj spectrometry ntawm metabolic stabilitythiab txheeb xyuas kaum tsib cov metabolites ntawm echinacoside A pom hauv nas thiab tib neeg lub siab S9ib feem. Cov txiaj ntsig los ntawm txoj kev tshawb no yuav pab kom nkag siab cov yam ntxwv, kev nyab xeeb, thiabefficiency ntawm no cim bioactive compound. Peb cov qhabnias qhia tau tiasechinacoside A's kho mobCov txiaj ntsig tuaj yeem tshwm sim los ntawm kev sib xyaw thiab nws cov metabolites. Yav tom ntej, peb yuav tshuaj xyuasmetabolites los ntawm cov ntshav, kabmob, thiab cov ntaub so ntswg los tsim kom tiav cov ntaub ntawv metabolism.Cov hauj lwm zoo li no yuav tsum tau pab kev tshawb fawb cov zaub mov, nutraceutical ntxiv, thiabtshuaj precision.

Cov khoom siv ntxiv:Cov hauv qab no muaj nyob online ntawm1, Table S1: Cov cim ntawm echinacoside A metabolites hauv nas thiab tib neeg lub siab S9nrog UPLC-QTOF/MS.

Tus sau kev koom tes:Kev txhais cov ntaub ntawv, Y.-HK, T.-WL, J.-YL, Y.-WC thiab T.-JL; txheej txheem;Y.-HK, T.-WL and T.-JL; kev tshawb nrhiav los ntawm T.-JL thiab C.-CC; raw khoom muab los ntawm:Y.-HK, T.-WL, J.-YL, Y.-WC, T.-JL thiab C.-CC; kev pom: Y.-HK; thawj daim ntawv npajtau ua los ntawm Y.-HK, T.-WL, T.-JL thiab C.-CC; sau-saib thiab kho, Y.-HK, T.-JL thiabC.-CC Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.

Nyiaj txiag:Qhov kev tshawb fawb no tsis tau txais nyiaj txiag sab nraud.

Cov ntaub ntawv muaj nyob:Cov ntaub ntawv raw thiab cov khoom sib txuas tau nthuav tawm hauv txoj kev tshawb fawb no muajlos ntawm tus sau sau raws li kev thov.

Kev tsis sib haum xeeb ntawm kev txaus siab:Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab.

Qauv Muaj:Cov qauv ntawm cov tebchaw yog muaj los ntawm cov kws sau ntawv.

Cov ntaub ntawv

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