Whitening Effect Of Novel Peptide Mixture By Regulating Melanosome Biogenesis, Transfer And Degradation Part 2

Peptide sib xyaw inhibits qhov kev qhia ntawm melanosome biogenesis / kev thauj mus los cuam tshuam

Txhawm rau tshawb xyuas cov txheej txheem ntawm depigmenting kev txiav txim uas pom los ntawm peptide sib tov, qhia qib ntawm melanogenesis ntsig txog yam thiab melanosome cuam tshuam txog kev thauj mus los.

Ntxiv rau,cistanchekuj muaj cov haujlwm ntawm kev txhawb nqa collagen ntau lawm, uas tuaj yeem ua rau kom elasticity thiab luster ntawm daim tawv nqaij thiab pab kho cov tawv nqaij puas.CistanchePhenylethanol Glycosides muaj qhov cuam tshuam tseem ceeb ntawm kev ua haujlwm ntawm tyrosinase, thiab cov nyhuv ntawm tyrosinase tau pom tias muaj kev sib tw thiab thim rov qab inhibition, uas tuaj yeem muab lub hauv paus kev tshawb fawb los tsim thiab siv cov khoom xyaw whitening hauv Cistanche. Yog li ntawd,cistanchemuaj lub luag haujlwm tseem ceeb hauv daim tawv nqaij dawb. Nws tuaj yeem cuam tshuam melanin ntau lawm kom txo cov xim thiab dullness; thiab txhawb kev tsim collagen rautxhim kho daim tawv nqaij elasticity thiab radiance. Vim qhov kev lees paub dav dav ntawm cov teebmeem ntawm cistanche, ntaucov khoom siv tawv nqaij dawbtau pib infuse cov khoom xyaw tshuaj ntsuab xws li Cistanche kom tau raws li cov neeg siv khoom xav tau, yog li nce kev lag luam tus nqi ntawm Cistanche hauvtawv nqaij dawbcov khoom. Hauv cov ntsiab lus, lub luag haujlwm ntawm cistanche hauvtawv nqaij dawbyog qhov tseem ceeb. Nws cov nyhuv antioxidant thiab collagen-tsim cov nyhuv tuaj yeem txo cov xim thiab dullness, txhim kho daim tawv nqaij elasticity thiab luster, thiab yog li ua tiav cov nyhuv whitening. Tsis tas li ntawd, daim ntawv thov dav ntawm Cistanche hauvtawv nqaij dawbcov khoom qhia tau hais tias nws lub luag hauj lwm nyob rau hauv kev lag luam tus nqi yuav tsis underestimated.

Nyem rau qhov twg Kuv Yuav Yuav Cistanche ntawm Whitening

Nug ntxiv:

david.deng@wecistanche.com WhatApp:86 13632399501

Raws li pom nyob rau hauv daim duab 2A, transcription theem ntawm MITF thiab nws downstream noob, TYR, TYPR1, thiab TYRP2, tau poob los ntawm peptide sib tov nyob rau hauv B16F10 hlwb. Tsis tas li ntawd, -MSH-induced protein ntau ntawm MITF thiab Tyrosinase tau txo qis los ntawm peptide sib xyaw hauv B16F10 hlwb (Fig. 2B).

Cov txiaj ntsig no qhia tau hais tias melanogenesis inhibition nyhuv ntawm peptide sib tov tshwm sim los ntawm inhibiting kev qhia ntawm melanogenesis ntsig txog yam.

Nws tau raug luam tawm tias MITF kuj ua raws li qhov kev hloov pauv uas ua rau lub cev muaj zog uas muaj lub luag haujlwm hauv kev thauj mus los melanosome [28,29]. Txhawm rau txheeb xyuas seb cov peptide sib xyaw, uas muaj qhov cuam tshuam rau MITF qhia, txo qis kev qhia ntawm lub cev muaj zog, peb tau soj ntsuam mRNA thiab qib protein. Raws li pom nyob rau hauv daim duab 2C, transcription theem ntawm RAB27A, MLPH, thiab MYO5A noob tau txo qis los ntawm peptide sib xyaw hauv B16F10 hlwb. Tsis tas li ntawd, -MSH-induced protein ntau ntawm Rab27a thiab Melanophilin tau txo qis los ntawm peptide sib xyaw hauv B16F10 hlwb (Fig. 2D).

Cov txiaj ntsig no qhia tias inhibition ntawm MITF qhia los ntawm peptide sib tov tuaj yeem ua rau inhibition ntawm kev thauj mus los ntawm melanosome.

Peptide sib xyaw inhibits MITF kev ua haujlwm los ntawm kev tswj hwm ntawm CREB thiab ERK phosphorylation

Txhawm rau tshawb xyuas cov txheej txheem ntawm kev ua haujlwm ntawm peptide sib xyaw ntawm MITF qhia, peb tau txheeb xyuas qib phosphorylation ntawm kev hloov pauv thiab tom qab kev txhais lus tswj hwm ntawm MITF.

Raws li pom nyob rau hauv daim duab 3A, phosphorylated CREB, ib tug transcription yam activating MITF qhia, yog npaum li cas-dependently txo los ntawm peptide sib tov. Yav dhau los, nws tau raug txheeb xyuas tias cov haujlwm ntawm MITF nyob ntawm nws qhov kev hloov pauv tom qab kev hloov pauv thiab proteasome-mediated MITF protein degradation tuaj yeem raug ntxias los ntawm phosphorylated ERK1/2 [30]. Peptide sib xyaw ua kom nce qib p-ERK1/2 hauv qab -MSH-stimulated mob hauv B16F10 hlwb (Fig. 3B).

Cov txiaj ntsig no qhia tias qhov kev qhia thiab kev ua ntawm MITF yuav raug txo qis los ntawm kev tswj hwm ntawm CREB thiab ERK1/2 phosphorylations los ntawm peptide sib tov.

Peptide sib tov suppresses melanosome uptake ntawm HaCaT keratinocytes

Melanosomes paub tias tau hloov los ntawm cov lus qhia dendrite ntawm melanocytes rau keratinocytes los ntawm phagocytosis ntawm keratinocytes. Txhawm rau txheeb xyuas seb cov peptide sib xyaw puas tuaj yeem cuam tshuam cov melanosome hloov mus rau keratinocytes, HaCaT keratinocytes tau kho nrog cov peptide sib xyaw ntawm qhov ntau ntawm 10, 50, 100, thiab 200 M thiab kho ntxiv nrog melanosomes cais los ntawm B16F10 hlwb. Tus naj npawb ntawm melanosomes pauv mus rau lub hlwb yog koob tshuaj-raws li txo qis los ntawm peptide sib tov (Fig. 4A). Cov duab tsom xam los ntawm Fontana-Masson staining pom tau tias kev faib cov xim av-stained melanosomes txo qis hauv cov tshuaj peptide sib tov-kho pab pawg raws li koob tshuaj (Daim duab 4B).

Tsis tas li ntawd, qhov kev qhia ntawm F2RL1 (PAR-2) gene, ib qho receptor uas tswj cov phagocytosis ntawm keratinocytes, tau txo qis los ntawm peptide sib tov nyob rau hauv cov mob trypsin-stimulated (Fig. 4C).

Cov txiaj ntsig no qhia tau tias cov peptide sib tov tuaj yeem txo phagocytosis los ntawm inhibition ntawm PAR-2 qhia hauv keratinocytes los ntawm peptide sib tov.

Peptide sib xyaw ua rau melanosome degradation hauv HaCaT keratinocytes

Melanosomes pauv mus rau hauv keratinocytes paub tias yuav maj mam tshem tawm los ntawm cov pob kws ntawm keratinocytes los yog degraded los ntawm cov kab mob autophagy intracellular. Txhawm rau txheeb xyuas seb qhov sib xyaw peptide puas tuaj yeem txhawb nqa melanosome degradation, peb tau kho cov peptide sib tov rau melanosome uas muaj HaCaT keratinocytes. Thaum cov nqi ntawm melanosomes seem tau saib xyuas, qhov koob tshuaj-dependant txo tau pom los ntawm cov cell lysate kho nrog peptide sib tov (Fig. 5A). Kev txheeb xyuas duab los ntawm Fontana-Masson staining pom tias kev faib cov xim av-stained melanosomes txo qis hauv cov tshuaj peptide sib tov-kho pab pawg raws li koob tshuaj (Daim duab 5B).

Tsis tas li ntawd, thaum cov kev ua autophagic muaj feem cuam tshuam-cov protein ntau hauv keratinocytes raug saib xyuas, cov qib protein ntawm Beclin-1 thiab LC3-II txog kev tsim autophagosome tau nce los ntawm kev kho peptide sib tov, thaum cov protein ntau ntawm p62 degraded. los ntawm autophagolysosomes tau txo los ntawm kev kho peptide sib tov (Fig. 5C).

Cov txiaj ntsig no qhia tias cov peptide sib xyaw ua rau muaj kev ua haujlwm autophagic los txhawb kev degradation ntawm melanosomes hauv keratinocytes.

Cov peptide sib tov tau pom tias muaj kev tiv thaiv pigmentation hauv cov qauv sib npaug ntawm daim tawv nqaij

Ib qho kev sim siv MelanoDerm tau ua los txheeb xyuas seb cov peptide sib tov puas tuaj yeem ua rau muaj kev tiv thaiv pigmentation ntawm daim tawv nqaij. Tom qab kev kho mob ntawm liposome uas muaj 2, 000 ppm ntawm peptide sib tov tau ua nyob rau hauv koob tshuaj 50 thiab 100 g rau 2 lub lis piam, lub teeb microscopy tau ua. Kev tsim ntawm melanosomes tsaus nti tau raug ntxias tag nrho hauv lub cev melanocyte thiab cov lus qhia dendrite ntawm cov ntaub so ntswg tswj, thaum lub cev tag nrho ntawm lub cev tau ci nrog cov dendrites tsawg dua vim tias melanin ntau lawm yog inhibited hauv cov ntaub so ntswg kho nrog peptide sib tov (Fig. 6A. ). Tsis tas li ntawd, cov ntsiab lus melanin tau koob tshuaj txo qis los ntawm peptide sib xyaw, txhawb kev pom kev pom (Daim duab 6B).

Tsis tas li ntawd, histology tau ua los soj ntsuam cov melanin faib thoob plaws hauv lub epidermis. Raws li qhov tshwm sim, cov ntaub so ntswg tswj tau pom qhov nce ntawm melanogenesis nyob rau hauv melanocytes ntawm lub basal txheej, thiab xim av-stained melanin tau pom nyob rau hauv keratinocytes vim qhov kev hloov mus rau keratinocytes nyob ze. Ib qho kev txiav txim siab ntawm melanin kuj tau pom nyob rau hauv cov khaubncaws sab nraud povtseg. Ntawm qhov tod tes, cov ntsiab lus melanin ntawm melanocytes tsawg nyob rau hauv cov ntaub so ntswg kho nrog peptide sib tov, thiab qhov txo qis ntawm melanin ntsiab lus tau pom thoob plaws keratinocytes thiab cornified txheej hauv kev sib piv rau pawg tswj hwm (Fig. 6C).

Cov txiaj ntsig no tau lees paub qhov tseem ceeb los tiv thaiv pigmentation ntawm peptide sib xyaw ntawm daim tawv nqaij sib npaug.

Kev sib tham

Txoj kev loj hlob ntawm cov ntaub ntawv ntxuav hniav dawb tau tsom mus rau inhibit melanogenesis hauv melanocytes los ntawm kev tswj hwm ntawm melanogenesis ntsig txog yam [31-35]. Tsis ntev los no, lwm lub hom phiaj ntawm depigmentation, suav nrog melanosome tsiv teb tsaws, hloov pauv, thiab degradation, tau kawm thiab ntau tus neeg sawv cev tau txheeb pom [36-42]. Vim tias pigmentation yog ib qho kev txiav txim nrog ntau lub tswv yim, nws yuav ua tau zoo los siv kev sib xyaw ua ke ntawm cov tshuaj kho mob uas muaj kev tswj xyuas cov txiaj ntsig rau txhua lub hom phiaj.

Txoj kev tshawb no tau tshawb xyuas qhov kev ua kom dawb huv ntawm peptide sib xyaw uas muaj plaub qhov sib txawv peptides nrog tib tus molar piv. Lub tswv yim kev ua haujlwm ntawm peptide sib tov tawm tsam melanosome biogenesis, hloov mus, thiab degradation yog qhia hauv daim duab 7. Hauv melanocytes, cov peptide sib tov inhibits CREB phosphorylation uas ua rau txo qis MITF qhia thiab induces phosphorylation ntawm ERK1/2 tshwm sim hauv MITF phosphorylation thiab degradation. . Raws li qhov tshwm sim, kev qhia ntawm melanosome biogenesis thiab thauj cov proteins uas cuam tshuam nrog, suav nrog Tyrosinase, TYRP1, TYRP2, Rab27A, Melanophilin, thiab MYO5A, txo qis. Hauv keratinocytes, peptide sib tov txo qhov kev qhia ntawm PAR-2 uas kho cov keratinocyte phagocytic muaj peev xwm cuam tshuam nrog actin filament reorganization. Tsis tas li ntawd, cov tshuaj peptide sib xyaw ua kom autophagic flux, thiab pauv melanosomes yog degraded hauv autophagolysosome.

Peptides tau raug tshuaj xyuas raws li cov khoom xyaw nquag rau cov tshuaj pleev ib ce vim tias lawv cov biocompatibility siab thiab protein-mimicking kev ua si [43]. Tab sis lawv kuj muaj qee qhov tsis zoo nyob rau hauv uas lawv tuaj yeem yooj yim degraded los ntawm proteases tam sim no nyob rau hauv daim tawv nqaij thiab tsis yooj yim rau nkag mus rau lub epidermis uas muaj lipids vim lawv hydrophilicity [44]. Cov kev tshawb fawb txog kev nce peptide stability tau qhia txog cov txheej txheem ntawm kev hloov cov amino acids ntawm qhov kwv yees cleavage sites, acetylation ntawm N davhlau ya nyob twg, thiab amidation ntawm C davhlau ya nyob twg [45]. Tsis tas li ntawd, muaj ntau yam kev tshawb fawb los txhim kho transdermal penetration ntawm peptides: txoj kev uas siv cov nkag inducers xws li cawv, azones, hexanoates, thiab unsaturated fatty acids; txoj kev uas siv cov peptide ib ntus uas pab txhawb permeation; txoj kev sib xyaw lipophilic derivatives; thiab cov txheej txheem encapsulating peptides xws li liposomes, transfersomes, niosomes, thiab ethosomes [46-48]. Hauv qhov no, peb tau npaj liposome encapsulating cov peptide sib tov los kuaj nws cov nyhuv whitening hauv daim tawv nqaij sib npaug qauv los ntawm kev kho mob tshuaj pleev ib ce, thiab qhov txo qis ntawm melanin cov ntsiab lus thoob plaws hauv cov txheej txheem epidermal tau pom nyob rau hauv cov kev sim liposome kho pab pawg (Fig. 6C).

Hauv kev xaus, cov peptide sib xyaw ntawm txoj kev tshawb no tau nthuav tawm cov nyhuv whitening los ntawm ntau yam kev ua, nrog rau inhibition ntawm melanin synthesis thiab tsiv teb tsaws, nrog rau inhibition ntawm melanosome uptake rau keratinocytes thiab txhawb nqa melanosome degradation. Cov peptide sib xyaw ntawm txoj kev tshawb no tuaj yeem siv los ua cov khoom siv dawb huv tshiab thiab liposome uas pab txhawb kev ruaj ntseg thiab kev nkag mus ntawm daim tawv nqaij ntawm peptides tuaj yeem siv los tsim cov khoom siv dawb.

TXOJ CAI

Txoj kev tshawb no tau ua los ntawm kev txhawb nqa ntawm Ntiaj Teb Chav Kawm 300 R & D Project los ntawm Ministry of Trade, Industry, thiab Energy (Project number: S2641452).

Kev tsis sib haum xeeb ntawm kev txaus siab

Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab.

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