Abstract

Kev txaus siab ntawm cov neeg siv khoom hauv kev lag luam tshuaj pleev ib ce nrog cov teebmeem ntawm cov tawv nqaij-lightening tau nce qhov kev thov rau kev npaj uas txo melanogenesis. Ntau cov tshuaj tiv thaiv melanogenic paub txog lawv cov kev mob tshwm sim, xws li kev sib cuag dermatitis thiab toxicity siab, thiab cov tawv nqaij tsis zoo. Cov kev tshawb fawb tsis ntev los no tau tsom mus rau cov khoom lag luam los ntawm cov nroj tsuag los ua lwm txoj hauv kev rau cov tshuaj chemotherapeutic nrog tsawg dua qhov tshwm sim.

Hauv txoj kev tshawb fawb tam sim no, peb tau tshuaj xyuas cov tshuaj tiv thaiv melanogenic ntawm cov hlab ntsha extracellular (EVs) muab rho tawm los ntawm nplooj thiab stems ntawm Dendropanax pathogenic. Ua haujlwm nrog spectrophotometric thiab biochemical txoj kev, peb pom tias nplooj-derived extracellular vesicles (LEVs) thiab stem-derived extracellular vesicles (SEVs) txo melanin cov ntsiab lus thiab tyrosinase (TYR) kev ua nyob rau hauv ib tug concentration-dependent yam nyob rau hauv B16BL6 nas melanoma cell kab. Electron microscopic tsom xam ntxiv qhia tau hais tias LEVs thiab SEVs induced concentration-dependant txo qis hauv melanin cov ntsiab lus hauv melanoma hlwb. Muab piv rau arbutin raws li kev tswj hwm zoo, LEVs thiab SEVs tau pom tias muaj zog ua kom dawb huv ntawm cov hlwb melanoma, thiab cov nyhuv whitening ntawm LEVs muaj zog dua. Qhov tseem ceeb, tsis yog LEVs lossis SEVs ua rau muaj kev cuam tshuam cytotoxicity. Peb kuj tau tshuaj xyuas cov teebmeem ntawm EVs cog qoob loo ntawm kev qhia ntawm tyrosinase-related proteins (TRPs) hauv melanoma hlwb. LEVs inhibited qhov kev qhia ntawm melanogenesis ntsig txog cov noob thiab cov proteins, suav nrog microphthalmia-associated transcription factor (MITF), TYR, TRP-1, thiab TRP-2. Hauv tib neeg tus qauv epidermal, LEVs inhibited melanogenesis ntau dua li arbutin. Ua ke, peb cov ntaub ntawv qhia tias lev los ntawm D. cov kab mob tuaj yeem yog cov neeg sib tw tshiab cov khoom siv los ua cov tshuaj tiv thaiv melanogenic hauv kev npaj tshuaj.

lo lus tseem ceeb:EVs cog-derived; LEV andSEV; anti-melanogenic; TYRkev ua si; melanin cov ntsiab lus thiabCistanche extract cov txiaj ntsig

Nyem qhov no kom tau txaisCov txiaj ntsig ntawm Cistanche rau cov tawv nqaij dawbthiabCov teebmeem ntawm Cistanche extract

Taw qhia

Melanin, ib feem tseem ceeb ntawm tib neeg cov plaub hau, qhov muag, thiab daim tawv nqaij pigmentation system, yog tsim los ntawm melanocytes los ntawm tus txheej txheem hu ua melanogenesis. Aberrant melanin tsub zuj zuj tuaj yeem ua rau cov tawv nqaij mob xws li freckles, sun freckles, thiab melasma, thiab tuaj yeem ua rau mob qog noj ntshav thiab vitiligo. Regulating melanogenesis yog li ntawd lub tswv yim tseem ceeb hauv kev kho cov kab mob hyperpigmented. Piv txwv li, hydroquinone, hydroxyphenyl compound uas cuam tshuam nrog TYR kev ua, yog siv los ua cov tshuaj pleev xim rau hauv kev lag luam tshuaj pleev ib ce. Txawm li cas los xij, hydroquinone tuaj yeem ua rau muaj kev phiv xws li kev sib cuag dermatitis thiab kab mob exogenous browning. Va-acid yog lwm cov khoom siv hluavtaws uas inhibits TYR kev ua, tab sis nws siv yog txuam nrog ntau zaus ntawm edema los yog khaus khaus.

Muaj kev txaus siab ntxiv rau kev txheeb xyuas lwm yam tshuaj los ntawm cov khoom siv ntuj tsim tawm tsam melanogenesis, muab cov kev txwv ntawm cov tshuaj lom neeg uas twb muaj lawm, uas qhia txog qhov tseeb tias cov khoom siv tshuaj pleev ib ce ua los ntawm cov nroj tsuag thiab tshuaj ntsuab zoo li mos, ntau biodegradable, thiab ua kom pom muaj toxicity tsawg dua li hluavtaws. tshuaj sib xyaw. Dendrobium kab mob nplooj rho tawm tau pom tias inhibit melanin ntau lawm los ntawm kev cuam tshuam ncaj qha nrog intracellular TYR ua kom thiab kev qhia ntawm cov enzymes koom nrog hauv melanin biosynthesis. Ib yam li ntawd, Croton officinalis nplooj extract suppressed melanin cov ntsiab lus thiab cellular TYR kev ua los ntawm inhibiting melanogenesis ntsig txog kev hloov pauv (MITF) thiab melanogenic enzymes. Tsis tas li ntawd, mulberry nplooj muaj cov nyhuv inhibitory ntawm TYR kev ua thiab tsim melanin hauv melan-A hlwb. P-coumaric acid los ntawm ginseng nplooj tau txheeb xyuas tias yog TYR inhibitor loj.

Herba Cistanche

Txawm hais tias muaj ntau yam ntawm botanical compounds tau siv nyob rau hauv cov tshuaj kho kom zoo nkauj formulations, lawv cov solubility tsis tshua muaj, tsis tshua muaj hom phiaj affinity, thiab nruab nrab ntawm daim tawv nqaij-lightening txiav txim tau hindered kev nce qib hauv kev txhim kho cov teebmeem ntawm botanical tshuaj pleev ib ce. Qhov no tau txhawb txoj kev tshawb nrhiav tshiab thiab cov tswv yim zoo los txhim kho cov txiaj ntsig ntawm cov tshuaj thiab cov tshuaj bioactive thiab txhim kho lawv cov txiaj ntsig ntawm kev xa mus rau daim tawv nqaij. Piv txwv li, ib tug xov tooj ntawm nano-xa technologies tau ntse tsim, nrog rau nano-zoo nkauj rau kev tu tawv nqaij zoo, nano-quercetin rau ncua cell puas los ntawm ultraviolet (UV) hluav taws xob, nano-fullerenes rau collagen regeneration thiab tiv thaiv ntawm daim tawv nqaij laus. , nano-luteolin rau tswj kev ua haujlwm antioxidant thiab nano-resveratrol tiv thaiv daim tawv nqaij los ntawm UV hluav taws xob.

Hauv txoj kev tshawb fawb tam sim no, peb tsom mus rau lub luag haujlwm ntawm cov nroj tsuag-derived extracellular vesicles (EVs). Cov kev tshawb fawb tsis ntev los no tau pom tias cov nroj tsuag tau txais los ntawm EVs muaj cov qauv zoo ib yam li cov tsiaj txhu cais tawm exosomes thiab ua raws li cov tub txib extracellular mediating intercellular kev sib txuas lus. Tsis tas li ntawd, cov hlab ntsha no muaj peev xwm hloov pauv mRNA, micro-RNA (miRNA), bioactive lipids, thiab cov proteins rau hauv cov tsiaj hlwb.

Nyob rau lub sijhawm no, peb tau kawm txog cov nyhuv inhibitory ntawm EVs tau los ntawm nplooj thiab stems ntawm cov kab mob legumes ntawm melanogenesis. Peb qhia txog qhov loj thiab cov khoom ntawm nplooj ntoos-derived extracellular vesicles (LEVs) thiab stem-derived extracellular vesicles (SEVs) muab rho tawm los ntawm nplooj thiab stems ntawm cov kab mob legumes thiab pom tau tias cov EVs tau nkag los ntawm melanoma hlwb thiab tsis yog cytotoxic. Txhawm rau ua kom pom cov tshuaj tiv thaiv melanogenic ntawm LEVs thiab SUVs, peb tau tshuaj xyuas cov ntsiab lus melanin thiab TYR kev ua haujlwm hauv cov hlwb melanoma. Peb tau soj ntsuam ntxiv cov txiaj ntsig ntawm EVs ntawm cov txheej txheem nyuaj ntawm melanin synthesis los ntawm kev saib xyuas cov kev hloov pauv ntawm ntau qib ntawm cov protein thiab enzymes.

Alpha-melanocyte stabilizing hormone (-MSH) khi rau melanocortin 1 receptor (MC1R) ntawm lub xovtooj ntawm tes thiab ua kom adenylate cyclase, ua rau kom nce qib hauv cov cell ntawm cyclic adenosine monophosphate (cAMP). cAMP yog kho los ntawm cAMP-dependent protein kinase A, ua rau phosphorylation ntawm cAMP teb cov ntsiab lus khi cov protein (CREB). Activated CREB induces MITF, uas tau nthuav tawm hauv melanocytes thiab ua lub luag haujlwm tseem ceeb hauv kev sib txawv melanocyte thiab kev loj hlob. -TRP1 yog qhov tseem ceeb rau kev hloov pauv ntawm TYR rau melanin synthesis thiab TRP2 ua lub luag haujlwm tseem ceeb hauv kev ua haujlwm catalytic ntawm TRP nyob rau theem pib ntawm melanin synthesis. Peb qhov no cuam tshuam hauv cov hlwb melanoma (Ntxiv daim duab 1).

Peb pom qhov txo qis ntawm MITF hauv LEVs kho melanoma hlwb, ua raws li kev txo qis ntawm TYR, TRP-1, thiab TRP-2, thiab tau lees paub los ntawm electron microscopy tias melanin synthesis raug txo nyob rau hauv cov hlwb ntawm lub qib ultrastructural. Peb tau lees paub ntxiv txog cov nyhuv anti-melanogenic ntawm LEVs siv cov qauv tsim kho tib neeg epidermal. Txhawm rau kom muaj nuj nqis ntsuas qhov inhibitory nyhuv ntawm LEVs ntawm cellular melanin synthesis, peb npaj cov qauv kev daws teeb meem los ntawm cov ntaub so ntswg thiab ntsuas cov ntsiab lus melanin siv lub colorimeter. melanin melanin raug txo nyob rau hauv Fontana-Masson stained cov ntaub so ntswg. cov LEVs inhibited melanin ntau lawm zoo dua li TYR inhibitor arbutin, uas yog siv los tswj qhov zoo.

Hauv cov ntsiab lus, cov kev tshawb pom no qhia tau hais tias kev siv cov khoom siv ntuj tsim los ntawm EVs rau kev tswj hwm hyperpigmentation yog qhov ua tau rau yav tom ntej rau kev lag luam kws tshuaj. Tsis tas li ntawd, nrog rau qhov zoo ntawm qhov me me, tsis muaj toxicity, siab uptake, thiab ib puag ncig kev nyab xeeb, cov nroj tsuag tau txais los ntawm EVs yuav tsum yog tiam tom ntej ntawm kev kho mob xa mus rau kev kho mob ntawm lwm yam kab mob. Qhov tseem ceeb, EVs cog qoob loo muaj txiaj ntsig zoo los tiv thaiv melanogenic ntawm tib neeg cov tawv nqaij rov tsim dua tshiab (zoo ib yam li tib neeg epidermis), teeb tsa theem rau kev sim tshuaj tom ntej.

Cistanche ntxiv

Cov ntaub ntawv thiab cov txheej txheem

1. Kev rho tawm ntawm D. morbifera LEVs thiab SUVs

Cov nplooj tshiab thiab stems tau sau los ntawm Poge Island, Guandao-phom, thiab Jeollanam-do. EVs raug cais tawm ntawm 50 g ntawm nplooj thiab qia, raws li, los ntawm kev sib tsoo siv lub extractor thiab hla cov kua txiv hmab txiv ntoo los ntawm cov ntawv lim, thiab centrifuging ntawm 10,000 × g rau 10 min. Cov khib nyiab loj tau raug tshem tawm los ntawm kev lim cov supernatant los ntawm 0.22 μm membrane, ua raws li centrifugation siv Amicon Ultra -4 PL 100 K centrifuge lim (Merck Millipore. Darmstadt, Lub teb chaws Yelemees) kom mloog zoo rau EVs los ntawm centrifuging cov qauv ntawm 5000 × g rau 10 feeb ntawm 4 degree. Tom qab centrifugation, cov protein concentration ntawm EVs tau txiav txim siab siv bis quinolinic acid (BCA) protein assay kit (Thermo Fisher Scientific, Waltham, MA, USA).

2. Qhov loj tus yam ntxwv ntawm kev cais EVs

Lub hydrodynamic loj ntawm EVs cais tau ntsuas los ntawm dynamic light scattering (DLS), cov txheej txheem siv los txiav txim qhov loj me ntawm cov khoom me me hauv kev ncua, siv Zetasizer Nano ZS90 system (Malvern Instruments, Malvern, UK). Cov EVs khaws cia tau muab tso rau hauv qhov kub thiab txias ntawm 20 degrees. Lub particle loj tis thiab z-nruab nrab siv los txiav txim siab hydrodynamic particle loj tis tau txiav txim los ntawm kev ntsuas qhov tawg siv autocorrelation muaj nuj nqi. Cov EVs cais tawm tau diluted los ntawm vesicle-dawb npuas dej thiab tom qab ntawd raug rau nanoparticle tracking analysis (NTA) (Nanosight; siv lub laser 488 nm ntawm 25 degree).

3. Kev sib kis ntawm electron microscopy tsom xam ntawm EVs

5 μL ntawm cov qauv kev daws teeb meem tau thauj mus rau hauv daim phiaj tooj liab-coated carbon zaj duab xis rau kev sib kis electron microscopy (TEM) tsom xam. Tom qab cov qauv adsorption rau 1 min, cov kab sib txuas tau ntxuav nrog ib qho dej ntshiab thiab tom qab ntawd ua rau tsis zoo nrog 1 feem pua ​​​​uranyl acetate rau 1 min. Ntau cov stain raug tshem tawm nrog cov ntawv lim thiab cov kab sib txuas tau cua qhuav. Cov qauv tau muab tso rau hauv kev ua kom pom tseeb ntawm 0.8 - 1.5 μm siv JEM- 1400 Ntxiv kev xa hluav taws xob hluav taws xob microscope (JEOL Ltd., Tokyo, Nyiv) nruab nrog rab phom Lab6 khiav ntawm 120 kV . Cov duab raug kaw siv lub koob yees duab UltraScan OneView CMOS (Gatan, Pleasanton, CA, USA).

Cistanche tubulosa

4. Kev npaj ntawm liposomes

Cov liposome blends tau npaj siv 95:5 (mol/mol) piv ntawm DMPC (1,2-stearoyl-sn-glycerol-3-}phosphocholine) (Avanti Polar Lipids, Alabaster, AL, USA) nrog DSPE-mPEG (1,2-stearoyl-sn-glycerol-3-phosphoethanolamine-[methoxy(polyethylene glycol)- 2000}] (Avanti polar lipids) los npaj cov liposome blends li lipid membranes. hydrophobic fluorescent dye 1,1-dioctadecyl-3,3,3ʹ,3ʹ-tetramethylindocarbocyanine perchlorate (DiI, Invitrogen, Waltham, MA, USA) yog tov nrog EVs, 725.49 ug DMPC4PE-1ug15 Thiab 15 ug DiI. Tom qab evaporation ntawm cov organic hnyav, cov membrane uas muaj cov lipids thiab DiI sib tov yog hydrated nrog 1 mL ntawm phosphate-buffered saline (PBS). Lipids).

5. Cell kab lis kev cai thiab kev soj ntsuam kev muaj sia nyob

B16BL6 melanoma hlwb tau coj mus rau hauv alpha-tseem ceeb nruab nrab (alpha-MEM) muaj 10 feem pua ​​​​fetal bovine serum (Rocky Mountain Biologicals, Missoula, MT, USA) thiab 1 feem pua ​​penicillin / streptomycin (Lonza, Basel, Switzerland) (Gibco, Thermo) Fisher Scientific) hauv kab lis kev cai. Cells raug incubated ntawm 37 degree nyob rau hauv ib tug humidified 5 feem pua ​​CO2 cua. 100 μL ntawm B16BL6 melanoma hlwb raug inoculated nyob rau hauv 96-zoo daim hlau (5 × 104 hlwb/zoo) rau kev soj ntsuam ntawm cell viability. Tom qab incubation rau 24 teev, cov hlwb raug kho nrog LEVs thiab SEVs ntawm qhov siab ntawm 1, 5, thiab 10 µg / mL, raws li, rau 24 teev. Qhov siab ntawm liposomes thiab arbutin yog 10 µ g / mL thiab 70 µ g / mL, raws li, rau txhua qhov kev sim. 10 µL ntawm EZ-Cytox reagent (Daeil Lab Service, Seoul, Kaus Lim Kauslim) tau ntxiv rau txhua lub qhov dej Cov phaj tau incubated rau 1 h. Cov phiajcim tau maj mam shaken thiab qhov nqus tau tom qab ntsuas ntawm 450 nm siv tus cim enzyme (BioTek, Winooski, VT, USA).

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