Melanocyte Activation Mechanisms Thiab Rational Therapeutic Treatments Of Solar Lentigos

Abstract:Txhawm rau ua tus yam ntxwv ntawm pathobiology ntawm hnub ci lentigos (SLs), kev tshuaj xyuas los ntawm semiquantitative RT-PCR, Western blotting, thiab immunohistochemistry tau nthuav tawm cov lus qhia ntawm endothelin (EDN) -1 / endothelin B receptors (EDNBRs), stem cell factor (SCF) )/c-KIT, thiab qog necrosis factor (TNF) nyob rau hauv lesional epidermis, uas contrasted nrog downregulated qhia ntawm interleukin (IL) 1 . Cov kev tshawb pom no txhawb nqa qhov kev xav tias yav dhau los rov ua dua UVB ua rau keratinocytes txuas ntxiv tsim TNF . TNF tom qab ntawd txhawb kev tso tawm ntawm EDNs thiab kev tsim tawm ntawm SCF hauv autocrine zam, ua rau kev ua kom melanogenic txuas ntxiv ntawm cov neeg nyob sib ze melanocytes, uas ua rau SLs. Kev tshawb fawb soj ntsuam ntawm 36 cov neeg mob nrog SLs rau rau lub hlis kho nrog M. Chamomilla extract nrog lub peev xwm los tshem tawm EDN1-induced nce hauv DNA synthesis thiab melanization ntawm tib neeg melanocytes hauv kab lis kev cai qhia txog kev txhim kho cov qhab nia xim. thiab xim sib txawv qhia raws li L tus nqi. Lwm qhov kev tshawb fawb soj ntsuam siv atyrosinaseinhibitor L-ascorbate-2-phosphate 3 Na (ASP) pom tau tias L qhov tseem ceeb ntawm cov tshuaj pleev ib ce (6 feem pua ​​​​APS)-kho cov tawv nqaij tau nce ntau hauv SLs thiab hauv cov tawv nqaij uas tsis yog lesional nrog tus nqi siab dua ∆L hauv SLs thaum piv nrog cov tawv nqaij tsis-lesional. Cov txiaj ntsig ntawm cov kev tshawb pom no qhia tau hais tias ua ke nrog kev kho mob nrog EDN signaling blockers thiabtyrosinaseinhibitors yog qhov kev xaiv kho mob zoo rau SLs.

Lo lus tseem ceeb: hnub ci lentigo; endothelin; qia cell factor; keratinocyte kev loj hlob zoo; interleukin -1; qog necrosis factor; intracellular signaling; calcium mob; signaling blocker; M. chamomilla; ascorbate-phosphate Na; tus neeg ua kom dawb; tyrosinase inhibitor

Cistanche yog tyrosinase inhibitor.

Nyem rau cistanche teebmeem rau inhibiting tyrosinase

1. Taw qhia

Feem ntau tshwm sim epidermal hyperpigmentary teeb meem nyob rau hauv Esxias daim tawv nqaij yog solar lentigos (SLs), uas feem ntau tshwm sim ntawm lub ntsej muag thiab ntawm lub dorsum ntawm ob txhais tes. Nyob rau hauv sib piv rau UVB-induced hyperpigmentation (UVB melanosis), uas, nyob ntawm seb lub hnub nyoog ntawm cov kev kawm, ploj nyob rau hauv ob lub lis piam mus rau ob peb lub hlis tom qab discontinuation ntawm lub UVB raug, SLs tsim nyob rau hauv lub hnub-tso tawv nqaij, tshwj xeeb tshaj yog lub ntsej muag, thiab yeej tsis ploj mus vim muaj DNA puas nyob rau hauv keratinocytes elicited los ntawm rov UVB irradiation ntawm lesional epidermis. Feem ntau, cov kab mob hyperpigmentary feem ntau yog tsom los ntawm cov tshuaj tiv thaiv pigmenting thiab suav nrog UVB-melanosis, SLs, thiab melasma. Raws li qhov zaus ntawm qhov kev kuaj mob zaum kawg rau cov neeg mob uas muaj ntau yam kab mob pigmentary hauv Nyij Pooj, SLs muaj qhov tshwm sim siab tshaj plaws, tshwm sim hauv kwv yees li 60 feem pua ​​​​ntawm tag nrho cov neeg mob uas muaj kab mob hyperpigmentary, thaum melasma thiab post-inflammatory hyperpigmentation (xws li UVB-melanosis) tshwm sim hauv tsawg li 5.2 feem pua ​​thiab 3.3 feem pua ​​ntawm cov neeg mob, feem [1]. Qhov no qhia tias SLs yog lub hom phiaj tseem ceeb ntawm cov tshuaj tiv thaiv pigmenting rau cov tawv nqaij Asian. Txawm li cas los xij, muaj ob peb cov ntaub ntawv luam tawm ntawm kev kho mob los ntawm cov tshuaj tiv thaiv pigmenting ntawm SLs vim tias muaj ntau cov tshuaj tiv thaiv pigmenting ua haujlwm.tyrosinaseinhibitors thiab nws tsis tau xav tiastyrosinaseinhibition yuav txaus rau ameliorate lub hyperpigmentation ntawm SLs. Tsis tas li ntawd, nws zoo li nyuaj rau kev tsim kho cov tshuaj pleev ib ce zoo rau SLs vim tias melanocyte activation mechanisms nyob rau hauv cov lesional epidermis. Hauv tsab xov xwm no, peb qhia txog cov kab mob pathobiology ntawm SLs raws li kev kho mob rau SLs vim tias melanocyte activation mechanisms nyob rau hauv cov kab mob lesional epidermis. Hauv tsab xov xwm tshuaj xyuas no, peb qhia txog cov kab mob ntawm SLs raws li lub npe hu ua melanogenic paracrine cytokine networks, thiab raws li kev tshawb pom melanocyte activation mechanisms nyob rau hauv lesional epidermis ntawm SLs, peb qhia rational soj ntsuam mus kom ze rau cov tshuaj pleev ib ce rau SLs ameliorate lub hyperpigmentation. qib.

2. Cov yam ntxwv kho mob

SLs kho mob raws li lub tiaj tus, zoo-circumscribed thaj ua rau thaj ntawm daim tawv nqaij nrog txawv xim thiab ntau thiab tsawg, nquag tshwm sim ntawm lub ntsej muag thiab ntawm dorsum ntawm ob txhais tes (Daim duab 1a) [2]. Lub histochemistry ntawm SL lesions stained nrog Hemoxylin & Eosin qhia me ntsis acanthosis thiab pigmentation raws cov basal cell txheej (Daim duab 1b) [2]. Muaj ob tus qauv hais txog cov yam ntxwv histopathological ntawm SLs ntawm lub ntsej muag: ib qho qauv qhia tau hais tias ib tug flattened epidermis nrog basal melanosis, thiab lwm yam qauv pom epidermal hyperplasia nrog elongated rete ridges muaj li ntawm sib sib zog nqus pigmented basaloid hlwb [3].

3. Mechanisms of Melanocyte Activation in Solar Lentigo Raws li Melanogenic Paracrine Cytokine Network

3.1. Melanocyte Number thiab Tyrosinase Qhia

Txawm hais tias muaj qee qhov kev sib cav txog qhov nce ntawm melanocytes hauv SLs, immunohistochemical tsom xam siv cov cim tshwj xeeb ntawm melanocytes MART-1 tau nthuav tawm ntau cov melanocytes hauv hnub ci lentigo [5–7]. Txawm li cas los xij, qhov tseeb qhov ceev ntawm melanocytes nyob rau ntawm ciam teb ntawm dermis thiab epidermis hauv SLs zoo ib yam li hauv perilesional tswj ntawm daim tawv nqaij vim kev loj hlob ntawm keratinocytes [7]. Immunohistochemistry siv cov tshuaj tiv thaivtyrosinaseqhia tiastyrosinase-zoo melanocytes tau nce ntau ntxiv los ntawm 2-fold hauv lesional epidermis ntawm SLs [4]. Gene tsom xam los ntawm semiquantitative RT-PCR qhia tau hais tias tyrosinase mRNA qhia theem tau nce siab los ntawm 2.3-fold hauv lesional epidermis [4]. Cov kev tshawb pom saum toj no txhawb nqa qhov ua tau tias muaj kev txhawb nqa ntawm ob qho tib si proliferation thiab melanization hauv SL lesional melanocytes. Yog li ntawd, peb xav tias me ntsis proliferating keratinocytes nyob rau hauv SLs ua rau lub activation ntawm cov nyob sib ze melanocytes los ntawm secreting melanocyte-stimulating cytokines.

3.2. Melanogenic Paracrine Cytokine Networks

Peb, thiab lwm pab pawg, tau qhia meej tias muaj ntau qhov tseem ceeb melanogenic paracrine cytokine tes hauj lwm ntawm cov tawv nqaij (Daim duab 2). Feem ntau, cov no suav nrog endothelin (EDN)-1 [8–15], membrane-bound stem cell factor (mSCF) [16], proopiomelanocortin (POMC) [17–20], prostaglandin E2 [21], granulocyte macrophage colony stimulation factor (GM-CSF) [22], basic fibroblast growth factor [23], growth-related oncogene [24] and keratinocyte growth factor (KGF) [25,26] koom nrog keratinocyte/melanocyte interactions thiab soluble SCF [27] ], hepatocytegrowth factor (HGF) [8,10,27–29] thiab KGF [30] koom nrog hauv kev sib cuam tshuam ntawm fibroblast / melanocyte. Raws li cov elucidated melanogenic paracrinecytokine tes hauj lwm nrog rau lawv cov receptors sib raug, nws yog ib qho tseem ceeb los txiav txim siab uas melanogenic paracrine cytokine networks koom nrog thiab tshwj xeeb hauv vivo hauv cov txheej txheem hyperpigmentation hauv lesional epidermis ntawm SLs.

3.3. Loj Paracrine Cytokines thiab Receptors Lub luag haujlwm rau Melanocyte Activation hauv SLs

Ntawm cov saum toj no melanogenic cytokines thiab lawv cov receptors sib raug zoo, peb thawj zaug txiav txim siab lub luag haujlwm ntawm kev loj hlob ntawm fibroblast (bFGF) thiab kev loj hlob ntawm oncogene (GRO) nyob rau hauv lub epidermis ntawm SLs. Basic FGF tau pom tias muaj overexpressed nyob rau hauv UVB-exposed tib neeg keratinocytes, nws homogenates muaj qhov txawv lub peev xwm los txhawb melanogenesis thiab proliferation ntawm tib neeg melanocytes nyob rau hauv kab lis kev cai, tab sis cofactors nrog lub peev xwm los nce cyclic AMP theem yog qhov tseem ceeb yuav tsum tau rau melanogenic stimulation [23 ]. GRO tau txheeb xyuas los ntawm peb pab pawg tshawb fawb raws li melanogenic cytokine uas ua lub luag haujlwm tseem ceeb hauv phenylazo-naphtol-induced hyperpigmentation tom qab nws tsis haum rau hauv cov tawv nqaij daj daj daj [24,31]. Semiquantitative RT-PCR qhia tau hais tias tsis muaj kev hloov pauv hauv cov noob qhia theem ntawm bFGF thiab GRO hauv SL lesional epidermis thaum piv nrog cov tsis muaj lesional epidermis [2]. Raws li mRNA qhia theem ntawm bFGF thiab GRO, immunohistochemistry tau qhia tias tsis muaj qhov sib txawv ntawm kev tiv thaiv kev siv tshuaj tiv thaiv bFGF (Daim duab 1c, d) thiab anti-GRO (Daim duab 1e, f) ntawm SL lesional thiab non-lesional. epidermis [2]. Cov kev tshawb pom no tau qhia tias tsis muaj kev koom tes ntawm bFGF lossis GRO raws li intrinsic melanogenic cytokines rau melanocyte activation mechanism hauv SLs.

Hauv cov txheej txheem lom neeg ntawm UVB-induced hyperpigmentation, kev qhia ntawm EDN1, vasoconstrictor peptide Ameslikas cais tawm ntawm porcine endothelial hlwb [32], thiab mSCF [16] yog upregulated nyob rau hauv ib tug autocrine zam los ntawm qhov kev txiav txim ntawm UVB-stimulated tso tawm ntawm interleukin ( IL)-1 los ntawm kev tsim cov pa oxygen reactive (ROS) [15]. Cov cytokines ua rau cov neeg nyob sib ze melanocytes kom lawv nthuav tawm qhov tseem ceeb ntawm melanin synthesizing enzymes tyrosinase [14,33], EDNBR [34], thiab melanosome matrix protein PMEL17 [34] nrog rau cov enzymes proliferation xws li cyclic dependent kinase (CD) [34], uas ua rau hyperpigmentation hauv UVB-tshuaj tawv nqaij. Raws li qhov loj melanogenic cytokines tseem ceeb koom nrog UVB-melanosis, peb tom ntej txiav txim siab lub luag haujlwm ntawm EDN1 hauv cov txheej txheem melanocyteactivation hauv epidermis ntawm SLs. Tus cwj pwm ntawm mRNA qhia theem ntawm EDN1 nyob rau hauv lub epidermis los ntawm semiquantitative RT-PCR tsom xam pom tau hais tias muaj ib tug cim nce nyob rau hauv kev qhia los ntawm qhov nruab nrab ntawm 3. [4]. Raws li qhov nce qib ntawm cov noob qhia ntawm EDN1, muaj kev tiv thaiv kab mob ntau ntxiv nrog kev tiv thaiv EDN1 thoob plaws hauv SL lesional epidermis (Daim duab 1g, h) [4].

Ntxiv rau EDN1, peb tom ntej txiav txim siab lub luag haujlwm ntawm EDN receptors hauv melanocyte activation mechanism hauv qab SLs. Kev khi ntawm EDN rau nws cov receptor yog thawj kauj ruam hauv cov kab mob paracrine loj ntawm keratinocytes thiab melanocytes uas txhawb nqa cov tawv nqaij pigmentation [11,14,35,36]. EDN receptors yog xya-transmembrane G-protein coupled receptors nrog ob isoforms (A thiab B) uas cuam tshuam tshwj xeeb nrog EDN1 thiab nrog txhua hom EDNs (EDN1, EDN2, thiab EDN3), feem [37]. Hais txog cov teebmeem inhibitory ntawm EDN receptor antagonists ntawm EDN-stimulated proliferation ntawm tib neeg melanocytes nyob rau hauv kab lis kev cai, ib tug tseem ceeb inhibitory nyhuv tshwm sim nyob rau hauv lub xub ntiag ntawm BQ 788, anendothelin B receptor (EDNBR) antagonist, tab sis tsis yog BQ123 los yog BQ610, ib tug endothelin. Ib tug receptor (EDNAR) antagonist [9], uas qhia tias EDN1 / EDN receptor signaling yog kho los ntawm EDNBR. Semiquantitative RT-PCR tsom xam ntawm kev qhia ntawm EDNBR mRNA qhia tau hais tias ntawm ntau hom ntawm daim tawv nqaij hlwb, melanocytes yog tib yam loj ntawm tes qhia EDNBR. Txij li thaum peb twb tau pom tias EDN1 secreted los ntawm keratinocytes ua rau kev ua kom cov intracellular protein kinase C (PKC) ntawm EDNBR [35], peb txiav txim seb qhov qhia theem ntawm EDNBR kuj accentuated nyob rau hauv melanocytes nyob rau hauv lub lesional SL epidermis. Semiquantitative RT-PCR tsom xam ntawm EDNBRmRNA nyob rau hauv lub epidermis ntawm SLs pom tau hais tias ib tug markedly nthuav qhia los ntawm qhov nruab nrab 6.8-fold nyob rau hauv lub lesional SL epidermis [4]. Raws li kev nthuav qhia ntawm EDNBR mRNA, muaj kev tiv thaiv ntau ntxiv nrog kev tiv thaiv EDNBR hauv zos hauv melanocytes hauv lesional SL epidermis (Daim duab 1i,j) [4]. Cov txiaj ntsig ntawm cov kev tshawb pom no qhia tau hais tias kev sib koom ua ke nce hauv kev qhia ntawm EDN1 thiab nws qhov kev sib txuas ntawm cov neeg txais kev sib txuas hauv lesional epidermis ntawm SLs.

Raws li qhov loj melanogenic cytokines koom nrog hauv UVB-melanosis, peb tom ntej txiav txim siab lub luag haujlwm ntawm SCF hauv melanocyte activation mechanism hauv lesional SL epidermis. Peb twb tau tshaj tawm tias UVB raug ntawm kab lis kev cai ntawm tib neeg keratinocytes nrog rau tib neeg cov kab mob epidermis txhawb kev nthuav qhia ntawm SCF ntawm ob theem noob thiab cov protein [15,16]. Semiquantitative RT-PCR tsom xam ntawm SCF mRNA nyob rau hauv lub epidermis ntawm SLs qhia tau hais tias muaj ntau zog qhia los ntawm qhov nruab nrab ntawm 3.9-fold nyob rau hauv lub lesional SL epidermis piv nrog non-lesional epidermis [2]. Western blotting rau SCF nyob rau hauv daim tawv nqaij ntawm rau tus neeg mob nrog SLs pom tau hais tias muaj qhov tseem ceeb nce los ntawm qhov nruab nrab ntawm 1.6-fold hauv SCF protein nyob rau hauv lesional SL epidermis piv nrog non-lesional epidermis [2].

Raws li qhov nce qib ntawm cov noob thiab cov protein qhia ntawm SCF, muaj kev tiv thaiv kab mob ntau ntxiv nrog kev tiv thaiv SCF thoob plaws hauv lesional SL epidermis (Daim duab 1k,l) [2]. Muaj kev sib cav txog seb SCF tau tswj hwm ntawm qib protein hauv lesionalepidermis yog hom soluble lossis hom membrane-bound. Yog hais tias hauv qab daus daim nyias nyias-permeable-soluble SCF yog upregulated nyob rau hauv lub epidermis, mast hlwb nyob rau hauv lub dermis yuav tsum tau qhib kom proliferate thiab nce nyob rau hauv ntau. Txij li thaum toluidine xiav staining nyob rau hauv SLs tsis pom muaj ntau ntxiv nyob rau hauv tus naj npawb ntawm mast hlwb nyob rau hauv lub lesional SL dermis [2], nws yog zoo li hais tias hom SCF upregulated nyob rau hauv SLs yog hom membrane-bound.

Ntxiv rau SCF, peb tom ntej txiav txim siab lub luag haujlwm ntawm SCF receptor c-KIT hauv melanocyte activation mechanism hauv qab SLs. Peb twb tau tshaj tawm tias UVB raug pom ntawm kab lis kev cai ntawm tib neeg melanocytes nrog rau tib neeg epidermis txhawb kev nthuav qhia ntawm c-KIT ntawm ob theem noob thiab protein [15,38]. Tsis tas li ntawd, nyob rau hauv UVB-stimulated pigmentation ntawm brownish daj guinea npua daim tawv nqaij, ib qho kev thaiv cov tshuaj tiv thaiv rau c-KIT ho abrogated tus naj npawb ntawm dopa-zoo melanocytes thiab hyperpigmentation nyob rau hauv ib tug thaum ntxov theem ntawm UVB-induced pigmenting txheej txheem [16] , uas qhia tau hais tias kev khi ntawm SCF rau c-KIT plays lub luag haujlwm tseem ceeb hauv UVB-inducedactivation ntawm melanocytes, ua rau hyperpigmentation. Concomitant nrog kev nthuav qhia ntawm SCF ntawm cov noob thiab cov protein ntau, cov qib qhia cov noob ntawm nws cov c-KIT receptor kuj tau nce los ntawm qhov nruab nrab ntawm 2.{13}}fold hauv lesional SL epidermis [2]. Raws li kev nthuav qhia ntawm c-KIT mRNA, muaj kev tiv thaiv ntau ntxiv nrog rau c-KIT antibody localized hauv melanocytes hauv lesional SL epidermis (Daim duab 1m,n) [2]. Qhov no qhia tau hais tias muaj kev sib koom ua ke nce hauv kev qhia ntawm SCF thiab nws cov receptor c-KIT hauv lesional SL epidermis.

Ntawm qhov tod tes, lwm pab pawg tau xav tias keratinocyte kev loj hlob zoo (KGF) / KGF receptor (KGFR) ua lub luag haujlwm tseem ceeb hauv kev pib ntawm SL tsim thiab nce pigmentation tsuas yog nyob rau hauv cov epidermis ntawm cov theem ua ntej SLs [25]. Hauv lesional epidermis [30] thiab/los yog dermis [25] ntawm SLs, KGF qhia tau kho tsuas yog nyob rau hauv lub cev tiv thaiv kab mob txawm hais tias ntxiv kev tshawb fawb ntawm nws cov noob thiab cov protein qhia yuav tsum tau rau ib qho kev txiav txim zaum kawg ntawm nws raws li ib tug intrinsic cytokine ua rau. SLs. Thaum IL-1 paub tias yuav ua rau keratinocytes los txhawb kev tsim KGF, nws tseem tsis tau paub meej tias yuav ua li cas KGF qhia tau raug kho nyob rau hauv cov kab mob lesional epidermis qhov twg IL-1 kev qhia yog qhov tsis txaus ntseeg [2]. Tau kawg, nws yuav tsum tau txiav txim siab seb TNF (uas yog upregulated nyob rau hauv lesional epidermis) muaj peev xwm los txhawb KGF ntau lawm. Txij li thaum KGF qhia nyob rau hauv daim tawv nqaij yog feem ntau nyob rau hauv dermal fibroblasts, nws yog plausible hais tias qhov kev nthuav qhia ntawm KGF los ntawm dermal fibroblasts nyob rau hauv lub lesional dermis ntawm SLs [25] yog txuam nrog ob qho tib si nce proliferation ntawm keratinocytes thiab lub stimulated melanogenesis. Yog li, nws zoo li tias dermal fibroblasts tau ua haujlwm tsis tu ncua los ntawm UV raug tso tawm KGF, uas ua ncaj qha lossis tsis ncaj qha rau cov keratinocytes los hloov cov kev qhia ntawm SCF, pab txhawb rau hyperpigmentation ntawm SL [25].

Peb tom ntej no txiav txim siab txog cov txheej txheem lom neeg uas EDN1 secretion yog upregulated nyob rau hauv lesional epidermis ntawm SLs. Nws yog qhov paub zoo tias cov tshuaj lom neeg muaj feem cuam tshuam nrog kev txhawb nqa ntawm EDN secretion los ntawm tib neeg keratinocytes suav nrog IL-1, qog necrosis factor (TNF), thiab endothelin converting enzyme (ECE)-1 . Peb qhov kev tshawb pom ntawm autocrine cytokine stimulation txuam nrog UVB melanosis pom tau hais tias qhov upregulation ntawm IL-1 yog lub luag hauj lwm rau stimulating zus tau tej cov EDN1 thiab SCF nyob rau hauv UVB-exposed human keratinocytes [12,16]. Yog li, IL-1 thiab tau pom tias yog cov potentstimulators ntawm EDN secretion nrog lub ncov qeeb hauv tib neeg keratinocytes hauv kab lis kev cai uas zoo li tus qauv ntawm UVB-induced secretion ntawm EDN [11]. Nws kuj tseem paub zoo tias UVB irradiation ua rau muaj txiaj ntsig zoo rau kev tso tawm IL-1 tab sis tsis yog IL-1 hauv kab lis kev cai tib neeg keratinocytes thiab qhov thaiv cov tshuaj tiv thaiv rau IL-1 ua rau muaj kev cuam tshuam ntau ntxiv ntawm EDN1. [11], uas qhia tau hais tias UVB-induced hyperpigmentation yog kho los ntawm kev ua kom cov epidermal melanocytes uas tshwm sim los ntawm ib qho ntxiv secretion ntawm EDN1 los ntawm UVB-exposed keratinocytes. Tsis tas li ntawd, qhov kev qhia ntawm mSCF protein tau pom tias muaj kev txhawb nqa los ntawm kev kho mob nrog IL-1 hauv tib neeg keratinocytes hauv kab lis kev cai [16]. Yog li ntawd, tom ntej no peb txiav txim siab seb IL-1 kuj tseem raug tswj hwm los txhawb qhov kev qhia ntawm EDN1 thiab/lossis SCF hauv cov kab mob lesional ntawm SLs. Interestingly, semiquantitative RT-PCR tsom xam tau qhia tias qhov kev qhia ntawm IL-1 mRNA yog qhov tsis zoo-tswj nyob rau hauv lesional epidermis [16]. Raws li qhov kev tshuaj ntsuam RT-PCR, immunohistochemistry nrog IL-1 cov tshuaj tiv thaiv tau pom tias muaj kev tiv thaiv kab mob tsis muaj zog hauv cov kab mob lesional epidermis tshaj li ntawm cov kab mob uas tsis yog lesional epidermis (Daim duab 1o, p) [2], uas qhia tias IL{ {33}} tsis yog lub luag haujlwm rau kev nthuav qhia ntau ntxiv ntawm EDN1 thiab SCF hauv cov kab mob lesional epidermis ntawm SLs.

Hais txog cov txheej txheem hauv qab qhov kev nthuav qhia ntawm EDN1 hauv SLs, ntxiv rau IL-1 , TNF ntawm 10 ng / mL tau tshaj tawm los ntawm Tsuboiet al. los ua ib tug muaj zog stimulator (los ntawm 10- quav) ntawm EDN secretion los ntawm cultured human keratinocytes [39]. Raws li rau lub hauv paus ntsiab lus ntawm kev nthuav qhia ntawm SCF hauv SLs, peb txuas ntxiv mus tshuaj xyuas cov teebmeem ntawm TNF ntawm SCF kev qhia hauv kab lis kev cai tib neeg keratinocytes. Western blotting siv ananti-SCF cov tshuaj tiv thaiv kab mob pom tau tias TNF txhawb nqa ntau lawm ntawm mSCF [15]. Yog li ntawd, tom ntej no peb txiav txim siab seb puas los yog tsis TNF yog upregulated los txhawb txoj kev qhia ntawm EDN1 thiab / los yog SCF nyob rau hauv lub lesional epidermis ntawm SLs. Interestingly, semiquantitative RT-PCRanalysis qhia tau hais tias qhov kev qhia ntawm TNF mRNA yog heev upregulated nyob rau hauv lub lesional SL epidermis [2]. Raws li kev soj ntsuam RT-PCR, immunohistochemistry nrog anti-TNF cov tshuaj tiv thaiv tau pom muaj zog tiv thaiv kab mob hauv cov kab mob SL epidermis dua li ntawm cov kab mob uas tsis yog lesional epidermis (Daim duab 1q, r) [2]. Yog li, nws tau pom tias qhov kev qhia tawm ntawm TNF feem ntau yog lub luag haujlwm rau kev nthuav qhia ntawm EDN1 thiab SCF hauv cov kab mob lesional ntawm SLs.

Raws li rau cov txheej txheem koom nrog hauv kev nthuav qhia ntawm EDN1, peb tom ntej txiav txim siab seb ECE-1 puas raug kho nyob rau hauv lesional SL epidermis. Raws li tsis muaj kev tshawb fawb tau piav qhia txog ECE -1 hauv tib neeg keratinocytes nyob rau lub sijhawm no, peb qhia ECE -1 hauv kab lis kev cai tib neeg keratinocytes piv nrog cov kab mob endothelial. Kev tshuaj xyuas ECE-1 kev ua haujlwm hauv ntau hom tawv nqaij tau pom tias tib neeg keratinocytes thiab tsis yog tib neeg melanocytes muaj ECE-1 kev ua haujlwm, uas tshwm sim tsawg dua hauv cov hlwb endothelial [40]. Western blotting, siv cov tshuaj tiv thaiv peb npaj rau ECE-1 , pom tau tias ECE-1 protein muaj nyob rau hauv tib neeg endothelial hlwb, tib neeg fibroblasts, thiab tib neeg keratinocytes, tab sis tsis nyob rau hauv tib neeg melanocytes [40]. Kev soj ntsuam ntawm ECE-1 kev ua haujlwm hauv supernatants tom qab immunoprecipitation nrog ECE-1 cov tshuaj tiv thaiv tau pom tias cov cell endothelial thiab tib neeg keratinocytes muaj cov dej num ntawm ECE-1 ntawm pH 6.8, uas cuam tshuam zoo nrog ECE{ {15}} immunoprecipitated nrog peb cov tshuaj tiv thaiv rau ECE-1 [40]. Semiquantitative RT-PCR tsom xam ntawm ECE{19}} mRNA theem qhia tias IL-1 , tab sis tsis yog TNF , muaj kev cuam tshuam me ntsis ntawm ECE -1 noob qhia hauv kab lis kev cai tib neeg keratinocytes [40]. Raws li kev txheeb xyuas RT-PCR, Western blotting qhia tias IL-1 , tab sis tsis yog TNF , txhawb nqa ECE -1 cov protein qhia hauv kab lis kev cai tib neeg keratinocytes [40]. Thaum kawg, peb tau txiav txim siab seb ECE-1 puas tseem raug tswj hwm los txhawb EDN1 kev qhia hauv cov kab mob lesional ntawm SLs. Raws li qhov tsis muaj qhov cuam tshuam ntawm TNF, uas tau hloov kho hauv SLs, tsis muaj qhov sib txawv ntawm mRNA qhia theem ntawm ECE-1 ntawm qhov lesional thiab tsis-lesional epidermis ntawm SLs [2], uas qhia tias ECE-1 tsis yog lub luag haujlwm rau kev tso tawm ntau ntxiv ntawm EDN1 hauv SLs.

Daim duab 3 qhia txog cov ntsiab lus ntawm autocrine stimulation hauv tib neeg keratinocytes hauv kab lis kev cai. Raws li rau cov txheej txheem lom neeg ua rau kev ua kom EDN thiab SCF signaling cascades [9], peb cov kev tshawb fawb hauv vitro qhia txog qhov sib txawv uas nthuav tias thaum lub zog ntawm IL-1 yog lub luag haujlwm tseem ceeb rau kev txhawb nqa EDN1 thiab SCF ntau lawm hauv UVB- melanosis, kev txhim kho ntawm TNF feem ntau cuam tshuam nrog kev tsim tawm ntawm tib ob cytokines hauv SLs.

3.4. Synergistic Stimulatory Effects ntawm kev sib xyaw ntawm EDN1 thiab SCF

Peb twb tau tshaj tawm tias muaj kev sib koom ua ke hauv kev txhawb nqa DNA synthesis hauv kab lis kev cai tib neeg melanocytes raws li ntsuas los ntawm 14C-thymidine kev koom ua ke hauv kev sib koom ua ke ntawm SCF thiab EDN1 [41]. Kuj tseem muaj kev sib koom ua ke zoo sib xws hauv kev txhawb nqa ntawm melanin synthesis ntsuas los ntawm 14C-thiouracil kev koom ua ke hauv kab lis kev cai tib neeg melanocytes hauv kev sib koom ntawm SCF thiab EDN1 [41]. Hauv qhov sib piv, tsis muaj qhov sib koom ua ke ntawm EDN1 thiab granulocyte macrophage colony stimulatory factor (GM-CSF) lossis HGF [13,42]. Raws li rau cov kev taw qhia cov txheej txheem koom nrog cov kev sib koom ua ke, peb pom tias kev sib tham ntawm SCF thiab EDN1 kev taw qhia tau pib los ntawm tyrosinephosphorylation ntawm c-KIT uas tau txhawb nqa tsis ncaj los ntawm kev qhib PKC, uas txhim kho kev tsim ntawm Shc-Grb{ {18}}SOS complex uas ua rau tig mus rau kev sib koom ua ke ntawm Ras/Raf-1/MEK/MAP kinase voj [41].

3.5. Kev sib nrig sib cuam tshuam ntawm EDN/EDNBR thiab SCF/c-KIT

Peb tom ntej txiav txim siab yog tias qhov kev tsim tawm ntau ntxiv ntawm SCF ua rau EDNBR qhia lossis nws txoj kev sib raug zoo rau EDN ligand hauv tib neeg melanocytes ntxiv rau nws cov txiaj ntsig zoo rau lawv cov kev loj hlob. Western blotting tsom xam pom tias SCF tuaj yeem txhawb kev nthuav qhia ntawm EDNBR protein nyob rau hauv kab lis kev cai tib neeg melanocytes [43]. Thaum qhov kev sib raug zoo ntawm EDNBR rau nws cov ligand raug soj ntsuam nyob rau hauv kab lis kev cai tib neeg melanocytesusing ib tug ligand binding assay, lub binding ntawm 125I-lableled EDN1 rau EDNBR tau pom tias yuav tsum tau nce ob hnub tom qab incubation nrog SCF [43]. Ua ke, cov kev tshawb pom no qhia tau hais tias SCF tau qhia nyob rau theem pib tuaj yeem txhim kho qhov kev qhia ntawm EDNBR, uas ua rau melanocytes ua rau muaj kev nkag siab ntau dua rau tom qab tso tawm ntawm EDN1. Ntawm qhov tod tes, thaum kab lis kev cai tib neeg melanocytes raug kho rau 48 h nrog EDN1 ntawm 10 nM, ligand binding assay siv 125I-SCF qhia tias EDN1 txawv qhov kev sib txuas ntawm SCF rau c-KITreceptor [43].

4. Cov ntsiab lus ntawm Pathobiology ntawm SLs

Table 1 qhia cov ntsiab lus ntawm paracrine cytokine tes hauj lwm uas tshwm sim nyob rau hauv ntau yam epidermal hyperpigmentary disorders. Nrog rau cov tes hauj lwm, SLs zoo ib yam li UVB-melanosis tshwj tsis yog rau cov cytokines xws li TNF rau kev tsim cov EDN1 thiab SCF.

Raws li rau cov txheej txheem lom neeg uas ua rau muaj kev nce ntxiv ntawm EDN thiab SCF signaling cascades, peb cov kev tshawb fawb hauv vitro tau qhia tias thaum lub sij hawm upregulation ntawm IL-1 yog lub luag hauj lwm rau stimulating EDN1 thiab SCF ntau lawm nyob rau hauv UVB-melanosis, lub upregulation. ntawm TNF yog txuam nrog kev tsim tawm ntawm tib ob cytokines hauv SLs. Daim duab 4 qhia txog cov ntsiab lus ntawm cov kev sib raug zoo ntawm SCF thiab EDN1 kev sib txuas hauv cov epidermis ntawm SLs. Qhov ntawd suav nrog kev sib koom ua ke ntawm SCF thiab EDN1 nrog rau kev ua kom EDNBR thiab c-KIT los ntawm SCF thiab los ntawm EDN1, feem. Kev tso tawm ntawm TNF los ntawm keratinocytes simulates cov khoom ntawm SCF thiab EDN nyob rau hauv ib tug autocrine zam, ob qho tib si uas muaj ib tug synergistic nyhuv ntawm melanocyte activation raws li zoo raws li ib tug stimulatory nyhuv ntawm kev qhia ntawm lawv coj receptors, c-KIT thiab EDNBR. Cov kev sib koom ua ke thiab kev sib cuam tshuam ntawm tes pab txhawb kev ua kom melanocyte mus rau qhov loj dua hauv cov kab mob epidermisof SLs dua li ntawm UVB-exposed epidermis, ua rau muaj kev mob hnyav heev ntawm SLs.

Sib sau ua ke, peb cov txiaj ntsig tau qhia tias ob lub teeb liab cascades, EDN1 / EDNBR thiab mSCF / c-KIT, ua si lub luag haujlwm tseem ceeb thiab kev sib koom ua ke inaccentuating mitogenesis thiab melanogenesis ntawm melanocytes hauv hyperpigmented epidermis ntawm SLs. Daim duab 5 qhia txog cov kab mob lom neeg rau hyperpigmentation mechanisms koom nrog hauv SLs, qhov uas tsis paub txog cov qog nqaij hlav vim kev puas tsuaj DNA ntau nyob rau yav dhau los ua raukeratinocytes los tsim thiab zais TNF. Yog li, TNF ua rau keratinocytes dhau los tsim melanogenic cytokines xws li SCF thiab EDN1 hauv ib qho autocrine zam, ua rau melanocytes uas nyob ib sab los txhawb melanin synthesis, ua rau epidermal hyperpigmentation.

5. Txoj Kev Kho Mob Tshuaj Kho Mob

Raws li kev sib koom ua ke ntawm melanogenic paracrine network thiab ua kom pom cov teeb liab ua rau melanocyte activation nyob rau hauv lesionalSL epidermis, thaiv qhov tseem ceeb melanogenic intracellular signaling yog ib qho kev xav tau kev kho mob kom ua tiav cov teebmeem ntawm cov pigmenting onSLs. Xws li ib txoj hauv kev tuaj yeem ua rau hypopigmentation, tab sis yuav tsum tsis txhob ua haujlwm zoo hauv cov tawv nqaij uas tsis yog lesional qhov twg cov teeb liab cascades tsis qhib rau hauv melanocytes. Ntawm qhov tod tes, inhibiting tyrosinase kev ua ub no yog lwm txoj hauv kev los txhim kho cov hyperpigmentation hauv SLs, txawm hais tias nws yuav ua rau hypopigmentation thiab kuj tseem yuav ua rau cov tawv nqaij tsis zoo.

5.1. Thaiv qhov tseem ceeb Melanogenic Intracellular Signaling

Txij li yuav luag tag nrho cov kev hloov pauv uas ua rau cov kab mob qog nqaij hlav hypopigmentary tshwm sim hauv EDN1 / EDNBR thiab SCF / c-KIT axis [44] thiab vim li no yog ib qho kev sib koom ua ke ntawm EDN1 / SCF ntawm cell proliferation thiab melanization nyob rau hauv cultured human melanocytes, nws yog conceivablethat thaiv. EDN1 / EDNBR lossis SCF / c-KIT signaling tuaj yeem tiv thaiv hyperpigmentation vim qhov kev sib koom ua ke nce ntxiv ntawm EDN1 thiab SCF vim tias muaj kev sib koom ua ke stimulatory tsis tshwm sim. Yog li ntawd, peb tau sim ua kom tiav los tiv thaiv pigmenting los ntawm SLs los ntawm kev thaiv cov EDN / EDNBR signaling kab.

EDN-activated intracellular signaling pathway muaj kev khi rau EDNBR, ua kom PKC, MAP kinase cascade, thiab cAMP/PKA cascade [34,35,41]. Yog li, cov kev ua ntawm tes no yog pib los ntawm kev khi ntawm EDN1 rau G-protein-coupled EDNBR, ua raws li cov txheej txheem sib txuas lus uas muaj feem ntau ntawm PKC thiab MAPK. Tom qab khi rau nws cov receptor, EDN1 ua rau lub hydrolysis ntawm polyphosphoinositide los ntawm activating phospholipase C, uas generates inositol-trisphosphates (IP3) thiab diacylglycerol, mobilizing intracellular Ca ntxiv thiab ua kom PKC, raws li. Kev ua kom PKC tau txais los ntawm nws qhov kev hloov pauv ntawm cytosol mus rau plasma membrane thiab ua rau Raf-1 los ntawm phosphorylation. Yog li, Raf-1 zoo li yog qhov sib koom ua ke ntawm PKC thiab MAPK txoj hauv kev. Raf-1 kev ua kom ua rau ua rau muaj kev ua kom muaj ntau yam ntawm MAPK txoj kev nruab nrab uas muaj MEK, ERK, thiab RSK.Phosphorylated Raf-1 qhib MEK los ntawm phosphorylation thiab qhib MEK phosphorylates ERK. Lub tshuab txais ERK tom qab ntawd phosphorylates microphthalmia-associated transcription factor (MITF) ntawm serine 75, ua rau kev nrhiav neeg ua haujlwm rau kev tswj cov noob qhia txog ntau yam melanogenic [41]. Ib txhij, qhib MAPK tshwm sim hauv kev ua kom RSK, uas phosphorylates CREB, ua rau cov ntawv sau ntawm MITF. Ntawm qhov tod tes, qhib PKC muaj kev sib tham nrog adenyl cyclase cascade los tsim cAMP[8], ua rau kev ua haujlwm ntawm PKA, uas kuj ua rau CREB los ntawm phosphorylation, ua rau muaj kev nthuav qhia ntawm MITF. Kev nce qib ntawm MITF protein txhawb kev nthuav qhia ntawm melanocyte-specific noob suav nrog tyrosinase, PMEL17, EDNBR, c-KIT, thiab CDK2.

Txij li ob peb txoj hauv kev taw qhia intracellular ua rau muaj kev txhawb nqa melanogenesis hauv melanocytes, thiab EDN signaling cascade tshwj xeeb nrog PKC txoj hauv kev, uas suav nrog calcium mobilization los ntawm endoplasmic reticulum [13], peb siv calciummobilization assay los tshuaj xyuas EDNBR antagonists los ntawm ntau yam. ntawm herbal extracts. Calcium mobilization los ntawm endoplasmic reticulum tshwm sim tom qab tiam IP3 thiab diacylglycerol vim hydrolysis ntawm polyphosphoinositide los ntawm activated phospholipase C. Thaum humanmelanocytes raug kho nyob rau hauv kab lis kev cai nrog EDN1, kev sib koom ua ke ntawm calcium nrhiav tau los ntawm fura-2AM reagent tsim fluorescence tom qab khi rau tso tawm calcium, raws li pom los ntawm cov tsos ntawm cov xim daj uas tuaj yeem ntsuas lub sijhawm tiag tiag los ntawm digital imaging microscopy. Los ntawm kev tshuaj ntsuam ntau yam tshuaj ntsuab, peb pom tias ua ntej incubation nrog Matricaria chamomilla extract cuam tshuam cov calciummobilization induced los ntawm EDN1 [1], uas qhia tias nws muaj peev xwm ua tau zoo antagonist tiv thaiv EDNBR. M. chamomilla, feem ntau hu ua chamomile, yog ib tsob nroj txhua xyoo ntawm tsev neeg Asteraceae. M. chamomilla yog qhov nrov tshaj plaws ntawm cov khoom siv tshuaj ntsuab chamomile, txawm tias lwm hom kuj siv los ua chamomile.

Raws li cov nyhuv inhibitory ntawm cov qauv fractionated los ntawm M. chamomilla extract ntawm EDN{{{0}}}induced calcium mobilization nyob rau hauv culturedhuman melanocytes, peb tau txheeb xyuas spiroether li nws active compound nrog ib tug muaj peev xwm mus cuam tshuam calcium mobilization (Daim duab 6 ) [1]. Muaj ob lub isomers ntawm spiroether (E thiab Z), thiab spiroether E-isomer tuaj yeem tshem tawm cov calcium ntau ntawm ntau tshaj 1 µM. Kev kho mob nrog spiroether E-isomer ntawm 0.2 thiab 1.0 feem pua ​​​​cov concentrations txo qis UVB-induced pigmentation nyob rau hauv brownish daj guinea npua daim tawv nqaij raws li kev soj ntsuam los ntawm ∆L tus nqi, uas qhia tias thaiv EDN-mediated signaling cascade. muaj txiaj ntsig zoo los tiv thaiv UVB-induced hyperpigmentation. Qhov no yog qhov tseem ceeb hauv vivo pov thawj uas qhia tau hais tias qhov kev koom tes ntawm EDN cascade hauv UVB-melanosis. Ntawm qhov tod tes, raws li xav tau, thaum ua ntej los yog co-incubated hauv melanocyte kab lis kev cai, M. chamomilla extract muaj peev xwm tshem tawm. EDN1-induced nce hauv DNA synthesis (raws li ntsuas los ntawm 14C-thymidine incorporation) nrog rau cov melanin synthesis (raws li ntsuas los ntawm 14C-thiouracil incorporation) los ntawm cultured human melanocytes. Nyob rau hauv ib qho kev tshawb fawb sib txuas uas siv cov kab ke tib neeg keratinocytes, peb tau txheeb xyuas tias M.chamomilla extract tsis muaj kev cuam tshuam rau IL-1 -induced secretion ntawm EDN1 [1]. Tsis tas li ntawd, siv tyrosinases muab tau los ntawm humanmelanocytes, peb tau lees paub tias M. chamomilla extract tsis muaj kev cuam tshuam rau kev ua haujlwm tyrosinase hauv vitro hauv qhov sib piv rau qhov sib txawv inhibitory los ntawm cov neeg paub zoo nkauj, kojic acid thiab arbutin [1]. Thaum M. chamomilla extract tau pleev xim rau txhua hnub tobrownish daj guinea pigskin rau ob lub lis piam tam sim ntawd tom qab UVB irradiation, qhov kev siv ntawm UVB-induced pigmentation tau txo qis thaum piv nrog kev kho mob nrog 10 feem pua ​​​​arbutin lossis tsheb nkaus xwb [1].

Hauv kev tshawb nrhiav tib neeg, kev siv tshuaj pleev ib ce ntawm M. chamomilla extracts rau UVB-tshwj xeeb tib neeg forearm ntawm daim tawv nqaij rau rau lub lis piam tam sim tom qab irradiation tau pom tias muaj txiaj ntsig zoo tiv thaiv UVB-induced hyperpigmentation raws li ntsuas los ntawm qhov sib txawv xim thiab qhia raws li ∆ L tus nqi.

Siv ib qho M. chamomilla extract-muaj stick type wax, peb tshuaj xyuas cov teebmeem ntawm pigmentation inSLs. Hauv qhov kev tshawb fawb soj ntsuam no, txhua qhov chaw pigmented tau tshuaj xyuas cov xim hloov thiab qib ntawm kev kho mob thiab kev siv tau raug soj ntsuam. Kev soj ntsuam kev soj ntsuam tau ua nyob rau hauv Tokyo Women's Medical University tau qhia tias kev kho mob rau ob lub hlis nrog M.chamomilla extract tau ua rau 48 feem pua ​​​​ntawm cov ntsiab lus uas qhia txog kev txhim kho thiab 40 feem pua ​​nrog kev txhim kho me ntsis [1]. Hauv cov kev hloov pauv ntawm cov xim pigmentation ntsuas los ntawm ∆L qhov tseem ceeb, tag nrho cov neeg mob uas muaj SLs muaj qhov sib txawv nce ntau dua ob ntawm lawv cov nqi ∆L, ib qib pom tau zoo, tom qab kev kho mob rau 2 ~ 3 lub hlis. Muaj qhov txo qis hauv cov xim pigmentation raws li ntsuas los ntawm ∆L qhov tseem ceeb ntawm 0, 1, thiab 2 hlis tom qab kev kho mob (Daim duab 7). Zuag qhia tag nrho, kev soj ntsuam kev soj ntsuam rau peb lub hlis tau qhia tias kev kho mob nrog M. chamomilla extract tau ua rau 42 feem pua ​​​​ntawm cov ntsiab lus uas qhia txog kev txhim kho, 12 feem pua ​​​​ntawm kev txhim kho me ntsis, thiab 25 feem pua ​​​​ntawm kev txhim kho me ntsis. Lwm qhov kev sim tshuaj tau ua nyob rau hauv ob lub tsev kho mob dermatological hauv Tokyo tau qhia tias kev kho mob nrog M. chamomilla extract maj mam txo cov pigmentation thiab tom qab rau lub hlis, ua rau kwv yees li 70 feem pua ​​​​ntawm cov ntsiab lus uas qhia ntau tshaj qhov kev txhim kho me ntsis suav nrog 10 feem pua ​​​​tsis pom thiab 15 feem pua ​​nrog kev txhim kho. . Muaj ob qhov xwm txheej uas cov SLs ploj lawm tom qab kwv yees li rau lub hlis ntawm kev kho mob, nrog ∆L qhov tseem ceeb nce mus txog 8.4 thiab 6.9 tom qab rau lub hlis ntawm kev kho mob (Daim duab 8) [1].

Hauv kev xaus, hais txog cov txheej txheem kho mob rau SLs los ntawm kev thaiv qhov tseem ceeb melanogenic intracellular signaling, cov kev tshawb fawb soj ntsuam saum toj no qhia tias thaiv EDN1 / EDNBR-kev cuam tshuam cov teeb liab yog ib qho kev kho mob zoo rau SLs yam tsis muaj cov teebmeem hypopigmenting.

5.2. Inhibiting Tyrosinase Kev Ua Haujlwm

Inhibiting tyrosinase kev ua ub no yog lwm txoj hauv kev rau ameliorating cov hyperpigmentation hauv SLs uas muaj peev xwm ua rau muaj qhov tsis zoo ntawm cov kab mob hypopigmentation, tab sis cov txiaj ntsig zoo ntawm kuj tseem muaj txiaj ntsig zoo hauv cov tawv nqaij tsis muaj lesional. Raws li cov tshuaj ntxuav hniav dawb feem ntau tsim los kho UVB-melanosis, tsis tau muaj kev tshawb fawb ob qhov muag tsis pom kev rau qhov muaj peev xwm los tiv thaiv cov xim ntawm cov tshuaj pleev xim rau ntawm SLs. Peb tau ua ob qhov muag tsis pom kev ib nrab ntawm lub ntsej muag ntawm 27 tus poj niam Nyij Pooj tuaj yeem pab dawb nrog SLs. Hauv qhov kev tshawb fawb soj ntsuam, cov tshuaj pleev xim nrog lossis tsis muaj 6 feem pua ​​​​L-ascorbate-2-phosphate 3 Na (APS) (cov tshuaj pleev tshuaj / cov tshuaj placebo, raws li) tau pleev xim ob zaug ib hnub rau ntawm lub ntsej muag rau 24 lub lis piam [45]. Cov duab sawv cev ntawm cov ntsej muag ntawm cov ntsiab lus No. 012 thiab No. 016 ua ntej thiab tom qab kev kho mob pom tau tias cov xim pigmentation ntawm cov tshuaj pleev tshuaj kho SLs tshwm sim me ntsis hauv kev hais kwv txhiaj nrog me ntsis txo qis hauv cov tshuaj pleev xim-kho cov tawv nqaij uas tsis muaj lesional [ 45] ib. Hauv qhov sib piv, qib pigmentation ntawm cov placebo lotion-kho SLs thiab cov tawv nqaij tsis-lesional tshwm sim tsis hloov. Whereas L qhov tseem ceeb hauv cov tshuaj pleev tshuaj kho SLs tau nce ntau ntxiv tom qab 24 lub lis piam ntawm kev kho mob, L qhov tseem ceeb hauv cov tshuaj placebo-kho SLs tseem tsis tau hloov pauv (Daim duab 9) [45].Kev sib piv ntawm oL qhov tseem ceeb ua ntej thiab tom qab kev kho mob tau qhia ntau dua. oL tus nqi hauv cov tshuaj pleev tshuaj kho SLs dua li ntawm cov placebo lotion-treated SLs (Daim duab 9). Cov kev tshawb pom no qhia tias APS-muaj cov tshuaj pleev ib ce muaj zog tiv thaiv pigmenting nyhuv ntawm SLs dua li cov tshuaj placebo. Whereas L qhov tseem ceeb hauv kev kuaj tshuaj pleev xim-kho tsis-lesional ntawm daim tawv nqaij tau nce ntxiv tom qab kev kho mob rau 24 lub lis piam, L qhov tseem ceeb hauv cov tshuaj pleev xim-kho tsis-lesional ntawm daim tawv nqaij tseem tsis hloov pauv. Kev sib piv ntawm oL qhov tseem ceeb ua ntej thiab tom qab kev kho mob tau nthuav tawm ntau dua oL tus nqi hauv kev kuaj tshuaj pleev xim-kho cov tawv nqaij uas tsis yog lesional dua li cov placebo lotion-kho tsis-lesional daim tawv nqaij [45]. Cov kev tshawb pom no qhia tias qhov kev kuaj tshuaj pleev ib ce muaj zog ua kom tawv nqaij zoo dua rau ntawm daim tawv nqaij tsis zoo dua li cov tshuaj placebo. Kev sib piv ntawm cov tshuaj tiv thaiv pigmenting ntawm SLs thiab cov tawv nqaij uas tsis yog-lesional qhia tau hais tias thaum muaj ntau dua oL qhov tseem ceeb ntawm qhov ua ntej thiab tom qab kho nrog cov tshuaj pleev ib ce hauv SLs dua li ntawm cov tawv nqaij uas tsis yog lesional, oL qhov tseem ceeb tshwm sim ntawm qib zoo sib xws. nyob rau hauv SLs thiab tsis-lesional daim tawv nqaij tsis muaj qhov sib txawv tseem ceeb ntawm lawv [45].

Cistanche inhibits tyrosinase kev ua haujlwm.

Kev sib raug zoo ntawm L qhov tseem ceeb thiab melanin indices rau tag nrho cov kev ntsuas thaum lub sij hawm kev tshawb fawb soj ntsuam no qhia ib tug tseem ceeb correlation ntawm lawv ob leeg. Cov txiaj ntsig no tau qhia tias ib qho 2.0 ∆L tus nqi yog kwv yees li ntawm 20 ∆ melanin Performance index nrog rau 10-fold siab rhiab heev nyob rau hauv melanin Performance index dua li L tus nqi. Kev sib piv ntawm L qhov tseem ceeb thiab melanin indices rau txhua qhov kev ntsuas ntawm lub lis piam 0 thiab 24 ntawm SLs qhia txog kev sib raug zoo. Cov kev sib piv ntawm L qhov tseem ceeb thiab melanin indices qhia tau hais tias muaj ib tug cim tis hloov mus rau ib tug sib zog xim xws li ib tug ntau dua L tus nqi thiab ib tug melanin Performance index nyob rau hauv cov tshuaj pleev ib ce-kho SLs whereas muaj nosuch txawv tis pauv hloov nyob rau hauv cov tshuaj pleev ib ce. - kho SLs [45].

Hauv kev xaus, hais txog kev kho mob rau SLs siv cov tshuaj tyrosinase inhibitor, cov txiaj ntsig ntawm cov kev tshawb pom saum toj no qhia tau hais tias APS muaj qhov tsis muaj zog tab sis tseem ceeb los tiv thaiv pigmenting nyhuv ntawm SLs thiab cov nyhuv whitening tseem ceeb txawm ntawm cov xim zoo nkauj ntawm daim tawv nqaij, tsis muaj cov nyhuv hypopigmenting.

6. Cov lus xaus

Hauv kev xaus, hais txog melanocyte activation mechanisms thiab kho cov tshuaj pleev ib ce ntawm SLs, raws li cov kev tshawb pom saum toj no ntawm melanocyte activation mechanism hauv SLs nrog rau cov kev kho mob tau txais kev siv EDN signaling blocker thiab tyrosinaseinhibitor, nws tau pom zoo tias kev kho mob ua ke. Ib qho EDN signaling blocker thiab tyrosinase inhibitor yog qhov kev kho mob uas xav tau rau SLs.

cistanche ntsiav tshuaj

Yog xav paub ntxiv, thov nias daim duab.