Flavonoids nyob rau hauv daim tawv nqaij Senescence Tiv thaiv thiab kho
Aug 22, 2022
Thov hu rauoscar.xiao@wecistanche.comyog xav paub ntxiv
Abstract:Kev laus ntawm daim tawv nqaij yog txuam nrog kev txuam nrog cov hlwb senescent thiab muaj feem cuam tshuam rau ntau yam kev hloov pauv pathological, suav nrog txo kev tiv thaiv cov kab mob, ua rau muaj kev cuam tshuam rau kev ua xua, ncua lub qhov txhab kho, thiab ua kom mob qog noj ntshav. Senescent hlwb secrete cov txheej txheem tshwj xeeb ntawm cov neeg kho mob uas muaj kev sib haum xeeb, xa mus rau qhov kev sib koom ua ke ntawm kev zais zais zais zais (SASP), uas tuaj yeem ua rau muaj kev hloov pauv loj hauv cov ntaub so ntswg thiab kev ua haujlwm. Yog li, cov tshuaj uas xaiv tshem tawm cov senescent hlwb (senolytics) los yog neutralize SASP (senostatics) sawv cev rau kev kho kom zoo nkauj rau cov hnub nyoog uas muaj feem cuam tshuam ntawm daim tawv nqaij. Muaj cov pov thawj loj hlob uas cov nroj tsuag muab los ntawm cov tshuaj (flavonoids) tuaj yeem ua rau qeeb (txog lossis txawm tias tiv thaiv kev laus ntawm cov tawv nqaij thiab kev ua haujlwm los ntawm kev tsom mus rau cellular txoj hauv kev tseem ceeb rau kev tswj cov cellular senescence thiab SASP. tiv thaiv daim tawv nqaij laus.
Ntsiab lus:senescent hlwb; Senescence-associated secretory phenotype (SASP); flavonoids; Senolyt-ics; Senostatics A.; 100
Thov nias ntawm no kom paub ntxiv
1. Taw qhia
Dhau li ntawm qhov teeb meem nyiaj txiag thiab kev sib raug zoo, kev laus feem ntau yog teeb meem kho mob. Yog li, muaj kev xav tau ntau ntxiv kom nkag siab txog cov txheej txheem hauv qab no cov txheej txheem nyuaj heev [1], uas ua rau lub cev tsis zoo hauv lub cev thiab kev ua haujlwm, muaj kev pheej hmoo ntawm cov kab mob nyuaj, thiab thaum kawg, kev tuag.
Cellular senescence pab txhawb rau cov hnub nyoog txog cov ntaub so ntswg thiab lub cev tsis ua hauj lwm thiab dis-eases los ntawm cov txheej txheem uas cuam tshuam stemcell niches, induce aberrant cell txawv, cuam tshuam lub extracellular matrix, txhawb cov nqaij mos o, thiab induce senesce nyob rau hauv cov hlwb nyob sib ze [2-4]. Senescent hlwb secrete ib txheej ntawm pro-inflammatory cytokines, chemokines, loj hlob yam, lipids, thiab proteases, ib tug tshwm sim hu ua lub senescence-associated secretory phenotype (SASP) [5]. Nws ntseeg tau hais tias kev sib sau ntawm cov hlwb senescent hauv cov ntaub so ntswg ua rau muaj kev cuam tshuam ntawm lawv cov homeostasis thiab ua rau muaj kev pheej hmoo ntawm ntau yam kab mob uas muaj hnub nyoog [6]. SASP, nyob rau hauv lem, tuaj yeem ua rau mob ntev (piv txwv li, hauv zos lossis dav dav) thiab kev hloov pauv ntawm cov ntaub so ntswg thiab kev ua haujlwm [7].cistanche cov txiaj ntsigYog li ntawd, tshem tawm senescent hlwb los yog neutralizing SASP Cheebtsam yuav muab cov txiaj ntsig tsis tau tsuas yog rau cov ntaub so ntswg cuam tshuam, tab sis kuj rau tag nrho cov kab mob. Cov tshuaj uas xaiv tshem tawm cov senescent hlwb (senolytics) los yog neutralize SASP (senostatics) sawv cev rau kev kho kom zoo nkauj rau kev ncua kev laus thiab cov kab mob uas muaj hnub nyoog [8].
Kev laus ntawm daim tawv nqaij yog txuam nrog ntau cov hlwb senescent thiab muaj feem xyuam rau ntau yam kev hloov pauv pathological, suav nrog kev tiv thaiv qis dua cov kab mob, ua rau muaj kev cuam tshuam rau kev ua xua, ncua lub qhov txhab kho, thiab nce kev mob qog noj ntshav [9]. Yog li ntawd, cov kev kho mob uas txo cov xov tooj ntawm tes los yog thaiv SASP tej zaum yuav yog ib qho kev kho mob zoo rau kev laus ntawm daim tawv nqaij deterioration [10]. Cov kev ua haujlwm senolytic thiab hemostatic ntawm ntau cov tshuaj (xws li metformin thiab rapamycin) twb tau pom nyob rau hauv kev sim ua ntej [11,12]. Txawm li cas los xij, hauv vitro thiab hauv vivo cov ntaub ntawv qhia tias cov flavonoids sib txawv muaj cov khoom zoo sib xws; yog li ntawd, lawv tuaj yeem suav hais tias yog ib qho kev xaiv kho mob rau cov tawv nqaij laus tiv thaiv thiab kho.
Cistanche tuaj yeem tiv thaiv kev laus
2. Cov tawv nqaij laus thiab Senescence
Cov tawv nqaij muaj txheej txheej txheej txheej epidermal (epidermis), uas ua rau muaj kev cuam tshuam rau ib puag ncig, thiab txheej txheej sab hauv (dermis) txuas nrog hauv qab daus daim nyias nyias. Lub epidermis muaj ntau txheej txheej epithelium uas feem ntau yog keratinocytes proliferate los ntawm qia hlwb nyob rau hauv lub basal txheej txuas mus rau hauv qab daus daim nyias nyias Tom qab, lawv detach, nres proliferating, thiab undergo ib tug terminal sib txawv qhov kev pab cuam uas xaus nyob rau hauv ib tug tshwj xeeb daim ntawv ntawm programmed cell tuag. , hu ua cornification. Lub epidermis tseem muaj melanocytes uas tiv thaiv ultraviolet (UV) hluav taws xob vim lawv cov ntsiab lus xim. Langerhans hlwb yog ib hom cell thib peb nyob rau hauv cov epidermis uas belongs rau cov antigen-presenting dendritic hlwb. Epidermal homeostasis tso siab rau kev ua haujlwm zoo thiab kev sib cuam tshuam ntawm tag nrho cov Cellular Cheebtsam [13]. Lub dermis muaj cov papillary txheej hauv qab ntawm lub epidermal hauv qab daim nyias nyias thiab qis reticular txheej. Lub papillary txheej muaj fibroblasts, ib tug me me ntawm cov roj hlwb (adipocytes), cov hlab ntsha, thiab phagocytes, thaum lub reticular txheej muaj tsawg fibroblasts tab sis thicker collagen fibers nyob rau hauv lub dermal matrix. Lub dermis tseem muaj cov hlab ntsha, cov hlab ntsha, pericytes, thiab cov hlwb ntawm lub cev tiv thaiv kab mob, nrog rau cov hlwb mast thiab macrophages [14].
Kev laus ntawm daim tawv nqaij tuaj yeem txhais tau tias yog intrinsic lossis extrinsic. Intrinsic daim tawv nqaij laus yog raws sij hawm thiab nyob ntawm endogenous yam, xws li noob caj noob ces thiab metabolic thiab hormonal xwm txheej. Extrinsic tawv nqaij laus yog tshwm sim los ntawm ib puag ncig yam. Ob leeg intrinsic thiab extrinsic aging ntawm daim tawv nqaij yog tshwm sim los ntawm kev cuam tshuam ntawm noob qhia,Cistanche Extract Anti RadiationKev poob qis hauv kev rov ua dua tshiab ntawm cov mitochondria tsis zoo, thiab cov khoom sib txuam ntawm cov khoom siv cellular uas ua rau txo qis cellular bioenergy[15,16]. Thaum lub sij hawm aging, senescent hlwb accumulates nyob rau hauv lub dermis thiab epidermis. Qhov kev txuam no tuaj yeem raug ntxias thiab nrawm los ntawm ntau yam kev cuam tshuam ntawm tes, suav nrog DNA puas thiab mitochondrial tsis ua haujlwm [17]. Ntau yam sab nraud, xws li DNA ua rau cov neeg ua haujlwm puas tsuaj (piv txwv li, X-rays, UV, thiab cov pa luam yeeb), tuaj yeem ua rau muaj qhov tsis zoo hauv daim tawv nqaij thiab daim tawv nqaij. UV hluav taws xob ua lub luag haujlwm tseem ceeb hauv daim tawv nqaij senescence thiab kev loj hlob ntawm daim tawv nqaij. UV hluav taws xob yog tsim los ntawm peb yam tseem ceeb raws li photon wavelength: UVA muaj qhov ntev tshaj plaws wavelengths (315-400 nm), UVB yog nruab nrab (290-320} nm), thiab UVC yog qhov luv tshaj wavelengths ({{ 8}}nm). Txhua hom UV tuaj yeem ua raws li ib puag ncig mutagens ua rau ncaj qha thiab tsis ncaj (los ntawm kev tsim cov oxidative dawb radicals ntau ntxiv) DNA puas, thiab txhua tus tuaj yeem ua rau mutagenesis hauv daim tawv nqaij hlwb UVA hluav taws xob yog cov feem ntau ntawm hnub ci UV hluav taws xob. Nws nkag mus tob dua li UVB (uas muaj qhov tseem ceeb ntawm cov epidermis) rau hauv daim tawv nqaij thiab ua rau muaj kev hloov pauv ntawm cov ntaub so ntswg dermal connective [18,19]. Cov kev tshawb fawb hauv vitro kuj qhia tau tias UVC muaj qhov cuam tshuam tsis zoo rau genome stability, ua rau kev laus ntawm fibroblasts thiab keratinocytes [20,21]. Txawm li cas los xij, txiav txim siab tias feem ntau ntawm cov hluav taws xob no yog absorbed los ntawm ib txheej ozone, nws qhov kev soj ntsuam tseem ceeb tsawg dua. Txhawm rau muab cov duab tiav, nws tseem ceeb heev uas yuav tau hais txog qhov cuam tshuam ntawm infrared tawg (IR) ntawm daim tawv nqaij laus. Cov kev tshawb fawb tsis ntev los no qhia tias IR thiab cua sov tuaj yeem ua rau cov tawv nqaij laus ntxov ntxov los ntawm kev txhawb nqa ntawm matrix metalloproteinases (MP) kev qhia thiab kev hloov pauv ntawm elastin thiab fibrillin synthesis. Tsis tas li ntawd, nyob rau hauv tib neeg cov tawv nqaij, cua sov txhawb kev tsim cov hlab ntsha tshiab, kev nrhiav neeg ua haujlwm ntawm cov hlwb, thiab ua rau oxidative DNA puas tsuaj [22].
Cov hlwb senescent hauv daim tawv nqaij tuaj yeem txheeb xyuas tau los ntawm kev qhia siab ntawm cov cell-cycle inhibitors p21 thiab p16 thiab cov proteins koom nrog hauv DNA kho, nce lysosomal enzyme -galactosidase kev ua haujlwm, poob ntawm nuclear siab zog pab pawg lub thawv 1 (HMGB1), txo lamin B1. kev qhia, thiab kev hloov kho chromatin [16,18].
Senescence kuj tshwm sim los ntawm kev hloov pauv hauv cell secretory profile, xws li kev tso tawm ntau ntxiv ntawm interleukin (IL)-10,IL-1,IL-6,IL-8,MMP -1, thiab -3 uas degrade lub dermal matrix, thiab ntau yam kev loj hlob thiab transcription yam [23]. Cov tawv nqaij irradiation plays lub luag haujlwm tseem ceeb hauv kev hloov kho ntawm SASP, ib yam nkaus. Thaum feem ntau ntawm UVC raug thaiv los ntawm ozone txheej, UVA thiab UVB ua rau cov tawv nqaij tsis zoo thiab mob los ntawm kev ua kom SASP noob xws li IL-1, IL-6, thiab MMPs[24]. Nyob rau hauv lem, ob qho tib si UVA thiab UVB tuaj yeem txo cov qog kev loj hlob (TGF)-, ua rau txo qis collagen hom I synthesis, ua rau dermal thinning thiab wrinkle tsim [25].
Cov cim ntawm senescence no siv rau ntau hom cell hauv daim tawv nqaij; Txawm li cas los xij, cov hlwb nyob ntev dua hauv cov ntaub so ntswg raug cuam tshuam ntau dua los ntawm kev poob ntawm cov cellular txij nkawm thiab kho cov txheej txheem ntau dua li cov uas muaj kev loj hlob thiab hloov ntau zaus[26] Qhov tshwm sim ntawm senescence cuam tshuam rau txhua yam ntawm daim tawv nqaij.
2.1.Keratinocytes
Thaum sib txawv, keratinocytes tawm ntawm basal txheej ntawm epidermis. Thaum lub sijhawm ntawd, lawv tsis tuaj yeem nthuav dav thiab nthuav tawm qee qhov kev hloov pauv hauv cellular metabolism thiab chromatin rearrangements ib yam ntawm cov hlwb senescent. Txawm li cas los xij, qhov kev pom zoo tam sim no ntawm International Cell Senescence Association (ICSA) hais tias qhov sib txawv ntawm cov hlwb tsis tsim nyog rau lawv li cov hlwb tsis zoo vim tias cov txheej txheem ntawm kev sib txawv tsis yog los ntawm kev ntxhov siab lossis kev puas tsuaj [27]. Cov hlwb no tsis muaj qee yam ntawm cov hlwb tsis zoo, xws li kev puas tsuaj macromolecular, protein oxidation, telomere shortening, thiab SASP.
Cov txheej txheem ntawm keratinocyte senescence yog complex thiab tseem tab tom tshawb nrhiav. Cov kev tshawb fawb hauv vitro qhia tias keratinocytes tsim cov senescent phenotype thaum tsis muaj cov cim sib txawv ntawm qhov sib txawv [28]. Lub cellular muaj ntawm nicotinamide adenine dinucleotide (NAD) zoo li yog qhov tseem ceeb hauv kev tswj cov txheej txheem no.cistanche tshuaj ntsuabCov qib siab ntawm NAM (nicotinamide), lub ntsiab precursor ntawm NAD, inhibit qhov sib txawv ntawm cov txheej txheej sab saud thiab tswj kev loj hlob hauv cov txheej txheem basal. Tiv thaiv kev hloov pauv ntawm NAM rau NAD ua rau muaj kev sib txawv ntxov ntawm tib neeg thawj keratinocytes thiab senescence [29].
Lwm qhov tshwj xeeb ntawm senescent keratinocytes yog ib qho kev txuam ntawm redox kev nyuaj siab-vim ib leeg-strand DNA so uas tseem tsis tau kho vim qhov txo qis hauv poly-ADP-ribosyltran erase (PARP1) kev ua haujlwm thiab txhawb nqa lub voj voog ntawm tes [30]. Senescent keratinocytes kuj yog tus cwj pwm los ntawm qhov qis dua qhov kev loj hlob ntawm cov tshuaj insulin receptor (IGF-1R) ntau ntau, ua rau cov lus teb tsis zoo DNA puas tsuaj [31]. Collagen 17A1 (Col17al) zoo nkaus li ua lub luag haujlwm tseem ceeb hauv kev laus ntawm cov qia hlwb hauv vivo. Nws depletion txhawb lub davhlau ya nyob twg sib txawv ntawm cov laus keratinocytes, ua rau corneocyte tsim [32]. Tsis tas li ntawd, kev poob ntawm Col17al nyob rau hauv lub epidermal basal keratinocytes cuam tshuam cov epidermal-dermal hlws ris [29].
Cov kev hloov keratinocyte no tuaj yeem ua kom nrawm dua los ntawm UVA thiab UVB hluav taws xob; Yog li ntawd, UV raug zoo li yog qhov kev txhawb nqa ntawm keratinocyte senescence [33]Vim tias keratinocyte proliferation yog thawj lub tswv yim ua rau kev rov ua dua tshiab ntawm cov epidermis, tsub zuj zuj ntawm nonproliferating senescent epidermal hlwb thiab ntev raug rau senescent cell-txog SASP ua rau muaj kev cuam tshuam nyob rau hauv. kev tsim kho ntawm cov epidermis ntawm cov neeg laus thiab pab txhawb kev txhim kho ntawm neoplasia thiab kho qhov txhab tsis zoo [34].
2.2.Fibroblasts
Fibroblasts yog cov hlwb ntau tshaj plaws ntawm cov dermis, thiab lawv cov kev ua haujlwm tsis zoo ua rau cov tawv nqaij laus. Lub ntsiab nta ntawm fibroblast senescence muaj xws li tsub zuj zuj ntawm ob-strand DNA so, oxidative DNA puas, chromosomal thiab epigenetic aberrations, shortening los yog oxidation ntawm telomeres, thiab kev puas tsuaj ntawm DNA kho mechanisms. Lwm feature ntawm fibroblast senescence yog poob ntawm cellular proteome homeostasis uas manifests as aberrant synthesis; kev hloov kho tom qab kev txhais lus; degradation ntawm cov protein; thiab kev hloov pauv hauv kev sib txuas thiab tso tawm ntawm lipids, nucleic acids, thiab lwm yam metabolites. Nyob rau hauv tib neeg daim tawv nqaij laus, senescent fibroblasts feem ntau sau nyob rau hauv lub dermis. Piv rau cov hlwb uas tsis yog senescent, senescent fibroblasts yog tus cwj pwm los ntawm kev txo qis ntawm cov cellular matrix thiab nce MMP ntau lawm. Interestingly, senescent daim tawv nqaij fibroblasts tuaj yeem hloov cov hlwv extracellular (EV) uas muaj bioactive microRNAs thiab SASP Cheebtsam rau cov hlwb hauv qhov sib thooj (xws li, keratinocytes) kom nthuav tawm lawv cov yam ntxwv senescent [35]. Nyob rau hauv sib piv rau keratinocytes, UVA hluav taws xob vim nws qhov tob tob yog qhov tseem ceeb stimulus inducing fibroblast senescence nyob rau hauv vivo [18,19], thaum tag nrho cov hom ntawm UV hluav taws xob thiab X-rays tau pom tias yuav txhawb fibroblasts senescence nyob rau hauv vitro [36,37] ]
2.3.Melanocytes
Txawm hais tias melanocytes yog 5-10 feem pua ntawm cov hlwb hauv cov txheej txheem basal ntawm epidermis, lawv cuam tshuam rau cov tawv nqaij laus.
Melanocytes muaj tshwj xeeb lysosome-lineage organelles hu ua melanosomes nplooj siab rau synthesis thiab cia melanin, ib tug photoprotective pigment uas tiv thaiv tawv nqaij los ntawm UVB, UVA, thiab pom xiav teeb. Melanin-muaj melanosomes tuaj yeem hloov los ntawm melanocytes mus rau ib puag ncig keratinocytes uas ua ke ua ib chav tsev melano-epidermal. Melanin ua raws li redox UV-absorbing tus neeg saib xyuas thiab, nyob rau hauv txoj kev no ncaj qha tiv thaiv DNA ntawm epidermal hlwb los ntawm photodamage. Txawm li cas los xij, melanin pab txhawb rau DNA tiv thaiv tsis ncaj los ntawm kev tshem tawm cov pa oxygen reactive (ROS) tsim thaum lub sij hawm UV-inducing oxidative kev nyuaj siab hauv daim tawv nqaij [38]. Kev laus yog cuam tshuam nrog ntau qhov kev hloov pauv ntawm daim tawv nqaij pigmentary system uas tuaj yeem ua kom nrawm dua los ntawm kev nthuav tawm rau UV hluav taws xob, ua rau muaj kev hloov pauv hauv melanocytes thiab lawv cov hyperactivity.cistanche noov loj hlobEctopic up-regulation ntawm melanocytes txhawb kev tsim ntawm senile lentigines / lentigo thiab lwm yam muaj hnub nyoog-hais txog hyperpigmentation teeb meem thiab tej zaum yuav ua rau kev loj hlob ntawm melanoma - feem ntau tuag ntawm txhua hom qog nqaij hlav ntawm daim tawv nqaij - nyob rau hauv uas tshwm sim loj hlob nrog lub hnub nyoog [39] .
Tsis tas li ntawd, nws tau pom tias qhov nruab nrab los ntawm senescent melanocytes ua rau txo qis hauv fibroblast proliferation thaum ntxiv rau fibroblast cell kab lis kev cai, qhia tias SASP Cheebtsam secreted los ntawm cov melanocytes kho qhov teeb meem tsis zoo paracrine [40] Tsis tas li ntawd, keratinocytes nyob rau hauv lub xub ntiag ntawm senescent melanocytes muaj. nce kev qhia ntawm cov cim kev laus thiab txo kev loj hlob. Interestingly, tshem tawm cov laus melanocytes nrog cov tshuaj senolytic ABT737 ua rau inhibition ntawm kev laus thiab thickening ntawm epidermis. Cov txiaj ntsig zoo sib xws tau txais nrog MitoQ antioxidant, tsom mitochondria, qhia lub luag haujlwm tseem ceeb ntawm oxidative kev nyuaj siab hauv daim tawv nqaij senescence. Senescent melanocytes kuj ua rau muaj hnub nyoog ntsig txog epidermal atrophy, inducing telomere puas thiab laus nyob ib puag ncig keratinocytes thiab fibroblasts [4].
2.4.Langerhans Cells
Kev laus qhia txog ntau yam kev hloov pauv ntawm daim tawv nqaij tiv thaiv kab mob, suav nrog txo qis ntawm Langerhans hlwb, txo cov tshuaj tiv thaiv kab mob tshwj xeeb, thiab nce cov neeg tswj hwm (piv txwv li, tswj T hlwb). Cov kev hloov pauv no ua rau txo qis kev tiv thaiv kab mob hauv cov neeg laus, ua rau muaj kev pheej hmoo siab mob qog noj ntshav thiab kis kab mob. Tsis tas li ntawd, Langerhans hlwb los ntawm cov laus pub dawb muaj peev xwm txo tau mus rau cov qog nqaij hlav [42] thiab qhia tsawg dua tib neeg b-defensin-3, tshuaj tua kab mob peptide [43].
3. Qhov cuam tshuam ntawm Senescent Cells thiab SASP ntawm Kev Ua Haujlwm ntawm Daim tawv nqaij
Lub sijhawm ntev ntawm cov hlwb senescent hauv cov ntaub so ntswg thiab lawv cov secretome ua rau kev laus ntawm cov ntaub so ntswg poob thiab cancerogenesis. Txawm li cas los xij, senescence thiab SASP ua ib qho kev tiv thaiv kev tiv thaiv kev hloov pauv ntawm cov hlwb puas rau hauv cov qog hlwb thiab ua lub luag haujlwm tseem ceeb hauv lub cev hauv kev kho qhov txhab. 3.1.Cellular Senescence thiab qhov txhab kho
Senescent hlwb ua lub luag haujlwm nyuaj thaum lub qhov txhab zoo thiab nyob rau hauv cov qhov txhab mob ntev. Kev tshawb fawb ua los ntawm Demaria et al. qhia tau tias cov hlwb senescent sau thaum lub qhov txhab kho thiab zais cov platelet-derived kev loj hlob yam tseem ceeb AA (PDGF-AA) los ua kom muaj kev sib txawv ntawm myofibroblast thiab maturation xav tau rau lub qhov txhab kaw [44]. Kev tshem tawm ntawm cov hlwb senescent txo cov myofibroblasts, ncua lub qhov txhab kho thiab ua kom cov fibrosis nce ntxiv [45].Tshwj xeeb, cov hlwb senescent hauv cov laus tawv nqaij tiv thaiv qhov txhab kaw, ua rau cov qhov txhab mob ntev. Ntxiv mus, nyob rau hauv daim tawv nqaij raug hluav taws xob, lub tsub zuj zuj ntawm senescent hlwb txhawb kev tsim ntawm hluav taws xob ulcers, thiab lawv tshem tawm (xws li, nrog dasatinib thiab quercetin kev kho mob) accelerates tus kho [46].
Qhov tshwm sim no tuaj yeem piav qhia qee qhov los ntawm kev muaj nyob ntawm ob hom senescent hlwb. "L luv-lived" hlwb ua haujlwm zoo ntawm kev kho qhov txhab vim tias lawv txhawb kev tsim cov ntaub so ntswg granulation, thiab kho cov ntaub so ntswg, thiab tiv thaiv hyperproliferation ntawm tej zaum premalignant lossis malignant hlwb. Conversely, "ntev-nyob" los yog cov ntaub so ntswg senescent hlwb cuam tshuam rau cov txheej txheem kho los ntawm kev tsim cov ntaub so ntswg ib puag ncig nrog cov mob ntev uas txhawb nqa collagen degradation [26,48].
3.2.Skin Senescence thiab Cancerogenesis
Cell senescence tiv thaiv cov cell proliferation uncontrolled, inhibiting qog tsim. Kev tsim tawm SASP yog qhov tseem ceeb rau kev nrhiav cov kab mob tiv thaiv kab mob nrog kev tiv thaiv qog nqaij hlav. Txawm li cas los xij, senescent hlwb thiab SASP kuj tuaj yeem ua rau mob qog noj ntshav [49]. Kev raug mob rau SASP tuaj yeem tsim cov qog nqaij hlav-favoring microenvironment uas txhawb nqa malignant phenotypes hauv vitro thiab hauv vivo [34]. Piv txwv li, txawm hais tias ntau yam ntawm SASP tsim los ntawm fibroblasts yog qhov tseem ceeb rau kev kho thiab kho daim tawv nqaij, qee qhov (e., IL-6, IL-8, thiab qee yam microRNAs) tuaj yeem ua rau mob qog noj ntshav, thiab kev loj hlob, ntxeem tau,cistanche salsa cov txiaj ntsigangiogenesis, thiab thaum kawg metastasis[50-52]. Interestingly, non-senescent mob qog noj ntshav-mob qog nqaij hlav fibroblasts muaj ib tug secretory qauv zoo li SASP, qhia hais tias lub hom phiaj SASP tuaj yeem ua rau muaj txiaj ntsig ntawm kev kho mob qog noj ntshav [53].
4. Cov tswv yim kho mob Targeting Skin Senescence
Vim muaj kev phom sij ntawm senescent hlwb thiab SASP Cheebtsam ntawm ntau yam teeb meem, cov tswv yim tsom rau kev xaiv induction ntawm senescent cell tuag los yog inhibiting SASP yam tsis cuam tshuam rau kev xaiv induction ntawm kev tuag ntawm cov hlwb nyob ib puag ncig tam sim no raug tshawb xyuas [54]. Kev tshem tawm ntawm cov hlwb senescent los ntawm cov ntaub so ntswg laus yog suav tias yog kev cog lus los tiv thaiv kev laus. Txawm li cas los xij, nyob rau qee qhov xwm txheej, cov hlwb ntawm daim tawv nqaij no tuaj yeem ua lub luag haujlwm zoo [55]. Yog li ntawd, SASP hloov kho thiab tswj cov txiaj ntsig zoo ntawm cell senescence zoo li yog ib txoj hauv kev kho kom zoo dua li kev tshem tawm ntawm tes.
Complex signaling pathways tswj SASP ntau lawm. Nuclear factor k-light-chain enhancer of activated B cells (NF-kB) yog qhov tseem ceeb tshaj plaws rau SASP induction. Txawm li cas los xij, DNA kev puas tsuaj teb (DDR), p38 mitogen-activated protein kinase (MAPK), CCAAT/enhancer-binding protein b (C/EBPb), lub hom phiaj ntawm rapamycin (mTOR), phosphoinositide-3-kinase(PI3K ), Janus kinase / signal transducer thiab activator of transcription (JAK/STAT), protein kinase LD1, thiab ob peb lwm yam tseem koom nrog hauv kev tswj hwm SASP ntau lawm los ntawm cov hlwb senescent [56].
Cov tshuaj sib txawv tshwj xeeb thaiv cov teeb liab cuam tshuam nrog senescent cell secretion. Piv txwv li, glucocorticosteroids tuaj yeem txo qis SASP secretion thiab mob tshwm sim los ntawm cov hlwb senescent thiab SASP vim lawv muaj peev xwm txo qis kev ua haujlwm ntawm NF-kB[2]. Txawm li cas los xij, ntau qhov kev phiv tsis zoo ntawm kev kho glucocorticoid (xws li, tawv nqaij thinning thiab kho qhov txhab tsis zoo) txwv lawv daim ntawv thov raws li daim tawv nqaij senolytics [57]. Lwm cov kev pom zoo SASP regulators yog cov tshuaj tiv thaiv kab mob ntshav qab zib metformin (1,1-dimethyl biguanide) thiab cov tshuaj tua kab mob thiab tshuaj tiv thaiv kab mob, rapamycin, uas ob qho tib si cuam tshuam nrog NF-KB thiab mTOR txoj hauv kev thiab ua rau cov txheej txheem laus [23]. Muaj cov pov thawj loj hlob uas flavonoids tuaj yeem tiv thaiv cov tawv nqaij los ntawm kev laus los ntawm kev tsom mus rau txoj hauv kev ntawm tes tseem ceeb rau kev tswj hwm cellular senescence thiab SASP ntau lawm.
5. Flavonoids raws li Senostatic thiab Senolytic Strategy
Flavonoids yog cov khoom ntuj tsim nrog cov qauv phenolic sib txawv uas muaj 15 carbon atoms. Lawv muaj ob lub nplhaib benzene txuas nrog luv luv peb-carbon saw. Ib qho ntawm cov pa roj carbon monoxide nyob rau hauv cov saw hlau no txuas nrog cov pa roj carbon monoxide hauv ib lub nplhaib benzene, los ntawm tus choj oxygen lossis ncaj qha yielding lub nplhaib nruab nrab thib peb [58], Daim duab 1. Txog rau hnub tim, ntau tshaj 8000 flavonoids sib txawv tau raug txheeb xyuas [59] .
Flavonoids tau muab faib ua ntau yam subtypes: flavones, flavonols, isoflavones, flavanones, anthoxanthins, anthocyanins, thiab chalcones. Lawv muaj nyob rau hauv txiv hmab txiv ntoo, zaub, nplej, paj, tshuaj yej, thiab caw, thiab paub zoo txog lawv cov txiaj ntsig zoo rau kev noj qab haus huv. Flavonoids yog ib qho tseem ceeb ntawm cov khoom siv tshuaj, kev kho mob, thiab tshuaj pleev ib ce vim lawv cov tshuaj tiv thaiv kab mob, tiv thaiv kab mob, tiv thaiv mutagenic, thiab cov tshuaj tiv thaiv kab mob ua ke nrog lawv lub peev xwm los hloov kho cov enzyme tseem ceeb. Tag nrho cov yam ntxwv no ua rau cov flavonoids zoo tshaj plaws rau kev tiv thaiv kev laus.
Kev txhim kho kev khi ntawm NF-kB rau nuclear DNA yog ib qho ntawm cov cim ntawm kev laus thiab tau pom nyob rau hauv ntau cov ntaub so ntswg. NF-kB yog ib qho tseem ceeb ntawm kev hloov pauv hauv kev tsim cov SASP thiab cov kab mob ntawm ntau lub hnub nyoog cuam tshuam, nrog rau cov kab mob inflammatory thiab metabolic [60]. Ob peb flavonoids tuaj yeem cuam tshuam kev ua haujlwm ntawm NF-KB thiab lwm txoj hauv kev, suav nrog kinase 1 kev taw qhia txoj hauv kev cuam tshuam nrog IL-1 receptor(IRAK1)/IkB thiab IkBL, uas thaiv SASP hauv vitro [61]. Kev txheeb xyuas cov qauv siv hluavtaws flavones qhia tias hydroxyl hloov pauv ntawm C-2, 3,4,5', thiab 7 yog qhov tseem ceeb hauv inhibiting SASP ntau lawm [62]. Tsis tas li ntawd, flavonoids muaj kev tiv thaiv hauv tsiaj cov qauv ntawm cov hnub nyoog cuam tshuam los ntawm kev tiv thaiv kev tsim tawm ntawm IL-1 thiab qog necrosis factor (TNF)- [63].
Hauv kev tshuaj xyuas no, peb tau tsom mus rau cov neeg sawv cev ntawm flavones, flavonols, isoflavones, thiab flavanones, uas nws muaj peev xwm tiv thaiv kab mob hauv cov ntsiab lus ntawm cov tawv nqaij cell senesce tau pom hauv vitro lossis hauv vivo (Daim duab 1). Txawm li cas los xij, nws yuav tsum tau hais tias ob peb lwm cov tshuaj los ntawm pab pawg ntawm flavonoids (xws li, curcumin) raug kuaj rau lawv cov khoom senolytic thiab hemostatic hauv cov ntsiab lus ntawm cov tawv nqaij mob [64].
5.1.Flavones
Flavones tshwm sim nyob rau hauv ntau yam txiv hmab txiv ntoo, zaub, thiab cereal nplej nyob rau hauv daim ntawv ntawm glycosides. Raws li nrog rau lwm cov flavonoid glycosides hauv cov khoom noj, flavones yuav tsum tau hydrolyzed rau aglycones kom nqus tau. Tom qab ntawd lawv tau metabolized rau glucuronidated los yog sulfated cov ntaub ntawv ua ntej mus txog qhov systemic ncig. Lub ntsiab flavones hauv kev noj haus yog apigenin thiab luteolin; Txawm li cas los xij, qee qhov sib xyaw ua ke (piv txwv li, baicalin thiab wogonin) kuj tsim nyog hais txog [65].
5.1.1.Apigenin
Apigenin, flavone muaj nyob hauv cov txiv hmab txiv ntoo, zaub, thiab tshuaj ntsuab, tuaj yeem ua rau apoptosis thiab inhibit proliferation thiab angiogenesis hauv ntau kab mob qog noj ntshav [66]. Kev tiv thaiv kab mob qog noj ntshav ntawm apigenin tshwm sim los ntawm nws lub peev xwm los cuam tshuam nrog PI3K / protein kinase B (ERK) / mTOR, JAK / STAT, NF-KB, MAPK, thiab Wnt / -catenin txoj kev [67]. Kev cuam tshuam nrog mTOR signaling yog ib qho tseem ceeb mechanism uas apigenin inhibits kev loj hlob ntawm daim tawv nqaij thiab kev loj hlob [68]. Ntxiv mus, apigenin muaj cov tshuaj tua kab mob antioxidant thiab tiv thaiv kab mob thiab tuaj yeem rov ua haujlwm zoo ntawm daim tawv nqaij (xws li, kho DNA thiab kev muaj peev xwm ntawm tib neeg keratinocytes thiab dermal fibroblasts) tom qab kev puas tsuaj los ntawm kev raug UVA thiab UVB hluav taws xob [69-71] . Cov txheej txheem molecular hauv qab cov xwm txheej no koom nrog lub peev xwm ntawm apigenin los tiv thaiv kev qhia ntawm cyclooxygenase-2 (COX-2) thiab NF-KB txoj hauv kev, uas tswj cov kab mob tshwm sim los ntawm UVA thiab UVB hluav taws xob [66] . Kev sib cuam tshuam ntawm apigenin thiab NF-kB txoj hauv kev kuj zoo li yog lub luag haujlwm tseem ceeb rau kev txo qis ntawm ntau yam SASP (piv txwv li, IL-6 thiab IL-8) hauv tib neeg fibroblasts induced mus rau senescence los ntawm Bloomycin [62]. Ntxiv mus, cov tshuaj pleev ib ce ntawm apigenin rau cov nas uas raug UVB hluav taws xob txo qhov mob ntawm daim tawv nqaij los ntawm inducing thrombospondin 1(TSP{18}}) qhia thiab repressing IL-6 thiab IL{20}} qib thiab inflammatory infiltrates [72] .
Kev laus muaj feem cuam tshuam nrog kev nce qib interferon-y-inducible protein 10 (IP10) uas tuaj yeem cuam tshuam kev tiv thaiv kab mob tsis zoo hauv cov neeg laus [73]. Interestingly, apigenin inhibits zus tau tej cov IP10, ib feem ntawm SASP secreted los ntawm senescent fibroblasts. IP10 thiab lwm yam chemokines (CXCL9 thiab CXCL11) txhawb nqa Th1 cov lus teb rau kev puas tsuaj ntawm tes. Apigenin tiv thaiv daim tawv nqaij tiv thaiv UVA thiab UVB hluav taws xob cuam tshuam kev puas tsuaj ntawm collagen matrix, uas ua rau poob ntawm elasticity thiab tawv nqaij qhuav, los ntawm kev txo qis ntawm MMP-1. Nws kuj induces collagen hom I thiab III de novo synthesis nyob rau hauv dermal fibroblasts nyob rau hauv vitro thiab nce dermal thickness thiab collagen deposition nyob rau hauv lub dermis nyob rau hauv vivo nyob rau hauv nas [74,75]. Cov teebmeem tiv thaiv kev laus ntawm apigenin tau lees paub hauv kev sim tshuaj; nws cov tshuaj pleev ib ce txhim kho cov cim ntawm daim tawv nqaij laus, xws li firmness, elasticity, thiab nplua wrinkling, thiab tswj hydration [70,76].
5.1.2.Baicalin ua
Baicalin yog flavone cais los ntawm cov hauv paus hniav ntawm Scutellaria lateriflora Georgi (Huang Qin Hauv Suav Teb) uas ua lub luag haujlwm hauv kev tiv thaiv tawv nqaij tiv thaiv UVB-induced photodamage [7]. Qhov kev ua haujlwm no muaj feem xyuam rau nws cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob los ntawm kev hloov pauv NF-KB, COX-1, thiab inducible nitric oxide synthase (iNOS) kev ua haujlwm [78]. Los ntawm inhibiting UV-induced tiam ntawm ROSin fibroblasts, baicalin tiv thaiv kev ua haujlwm ntawm cov khoom siv hloov pauv (xws li, activator protein 1, AP-1) lub luag haujlwm rau kev hloov pauv ntawm MMP-encoding noob thiab tom qab collagen degradation. Cov khoom analytic ntawm baicalin tsis txwv rau nws cov teebmeem ntawm SASP. Cov flavone no tuaj yeem txo qis feem pua ntawm -galactosidase-zoo hlwb thiab p16, p21, thiab p53 qhia hauv UVB-kho fibroblast kab lis kev cai[79]. Ntxiv mus, kho cov tawv nqaij fibroblasts nrog baicalin txo tus naj npawb ntawm DNA ob-strand so vim los ntawm UVB[79]. Anti-mutagenic zog ntawm baicalin kuj tau pom nyob rau hauv keratinocytes, qhov no flavone tiv thaiv kev tsim ntawm oxidative adducts induced los ntawm UVC [21]. Txawm li cas los xij, nws yuav tsum tau hais tias baicalin tsis cuam tshuam cov hlwb uas tsis tau raug UV irradiation.
5.1.3.Luteolin
Lub flavone luteolin yog glycoside pom nyob rau hauv paj, tshuaj ntsuab, zaub, thiab txuj lom. Tom qab noj, nws yog metabolized rau lub active aglycone, uas muaj antioxidative zog vim lub cim luteolin tshuaj qauv. C2-C3 ob daim ntawv cog lus pub ib hydrogen/electron thiab stabilizes cov radical hom thiab oxo pab pawg neeg ntawm C4 uas khi cov hloov pauv hlau ions (xws li, hlau thiab tooj liab) los tiv thaiv oxidative puas tsuaj. Los ntawm kev txo qis ROS ntau lawm, luteolin hloov pauv ntau txoj hauv kev ntawm tes, suav nrog MAPK thiab NF-KB, thiab ntau cov noob caj ces (xws li COX-2, IL-6, IL-1, TNF-a) , ua kom muaj zog tiv thaiv kab mob [80]. Cov khoom no tseem ceeb tshwj xeeb hauv cov ntsiab lus ntawm daim tawv nqaij photoaging. Luteolin txo UV-induced ROS ntau lawm thiab tom qab tso tawm ntawm pro-inflammatory cytokines (piv txwv li, IL-6 thiab IL-20) los ntawm keratinocytes thiab MMP-1 los ntawm fibroblasts [81,82]. Los ntawm kev txo qis ROS ntau lawm, luteolin tiv thaiv kom tsis muaj zog ntawm hyaluronic acid, uas, ua ke nrog collagen, yog qhov tseem ceeb tsis-fibrous tivthaiv ntawm dermis thiab epidermis extracellular matrix [83]. Ntxiv mus, luteolin ib leeg lossis ua ke nrog apigenin tuaj yeem cuam tshuam ncaj qha UVB-induced MMP-1 ntau lawm hauv fibroblasts los ntawm inhibiting Ca2t influx uas tiv thaiv phosphorylation ntawm Ca2t / calmodulin-dependent MAPKs thiab khi ntawm AP-1 Kev hloov pauv mus rau tus txhawb nqa ntawm MMP-1 noob [84,85].
5.1.4.Wogonin
Wogonin yog flavone muab rho tawm los ntawm Scutellaria baicalensis nrog cov pov thawj ua tau zoo raws li SASP regulator hauv mob qog noj ntshav [86]. Los ntawm inactivating lub MAPK/AP-1 thiab NF-kB/IKBa signaling txoj kev, wogonin downregulates COX-2 thiab iNOS qhia nyob rau hauv daim tawv nqaij fibroblasts thiab MMP-1 thiab IL-6 nyob rau hauv UVB -induced keratinocytes [87,8]. Tsis tas li ntawd, kev kho mob nrog wogonin zoo rov qab kho cov qib procollagen hom I thiab nce qhov kev qhia ntawm cytoprotective antioxidants (xws li, heme oxygenase-1 [HO-1] thiab NAD(P)H dehydrogenase[quinone] 1 [NQ- O1]) hauv keratinocytes los ntawm kev ua kom cov qog loj hlob (TGF- )/Smad txoj kev [88]. Wogonin kuj tseem txo cov dermis prostaglandin E2 (PGE2), TNF-x, intercellular adhesion molecule-1 (ICAM1), thiab IL-1 qib hauv cov tsiaj qauv ntawm daim tawv nqaij mob thaum siv tshuaj pleev ib ce [87,89,90 ].
5.2.Flavonol
Flavonols yog cov flavonoids uas muaj nyob rau hauv cov khoom noj, suav nrog txiv hmab txiv ntoo, zaub, cawv liab, thiab tshuaj yej, thiab sawv cev los ntawm quercetin, kaempferol, thiab fisetin. Ib yam li lwm cov flavonoids, flavonols sau hauv cov ntaub so ntswg hauv cov ntaub ntawv glycosylated txuas rau mono-, di-, thiab tri-saccharides. Vim lawv cov tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob, tiv thaiv kab mob cancer, thiab vasodilating zog, flavonols muaj ntau yam txiaj ntsig rau tib neeg kev noj qab haus huv, suav nrog lawv cov teebmeem ntawm kev laus [91]. 5.2.1. Quercetin
Quercetin muaj nyob rau hauv cawv liab, txiv hmab txiv ntoo, thiab zaub. Nws tuaj yeem cuam tshuam nrog cov protein kinase C (PKC) S thiab Janus kinase 2 (JAK2) los thaiv UV-induced qhia ntawm COX-2 thiab MMP-1 thiab collagen degradation hauv tib neeg cov tawv nqaij thiab tawv nqaij fibroblasts [92] .JAK2 ki-nase yog ib qho kev tswj hwm ntawm STAT3. Txoj hauv kev STAT3 yog koom nrog hauv stimulating inflammatory teb. Nyob rau hauv lem, PKCS yog ib tug regulator ntawm MAPK thiab Akt signaling pathways thiab modulates cov kev qhia ntawm collagen noob nyob rau hauv daim tawv nqaij hlwb [93]. Cov kev tshawb pom zoo sib xws los ntawm kev kawm nrog quercetin nto-functionalized FegOa nanoparticles (MNPQ). MNPQ-stimulated 5'AMP-activated protein kinase (AMPK) kev ua haujlwm hauv daim tawv nqaij fibroblasts yog nrog los ntawm kev txo qis ntawm cov hlwb uas muaj kev ntxhov siab thiab kev tawm tsam ntawm senescence-sociated secretion ntawm inflammatory mediators IL-8 thiab interferon - [9]. Hauv keratinocytes, quercetin txo UV-induced activation ntawm NF-kB, ua rau sup-pressed qhia ntawm IL-1, IL-6, IL-8, thiab TNF- . Nws tsis cuam tshuam rau UV-mediated activation ntawm ERK, JNK, lossis p38. Ntxiv mus, qhov induction ntawm AP -1 lub hom phiaj noob (piv txwv li, MMP-1 thiab MMP-3) tsis raug txwv los ntawm quercetin [95]. Sib nrug los ntawm hemostatic, quercetin kuj muaj cov khoom senolytic. Kev sib xyaw ua ke ntawm dasatinib thiab quercetin zoo tshem tawm cov senescent fibroblasts hauv vitro thiab txo qhov kev loj hlob ntawm thawj nas embryonic fibroblasts (MEFs) hauv vivo hauv cov hnub nyoog hnub nyoog lossis cov nas uas raug hluav taws xob thiab kuj yog cov nas ua qauv [8].
5.2.2.Kaempferol Cov
Cov flavonol kaempferol muaj nyob rau hauv ntau cov nroj tsuag noj tau los yog tshuaj ntsuab thiab muaj cov tshuaj tua kab mob antioxidant thiab tiv thaiv kab mob los ntawm inhibiting iNOS, COX-2, thiab NF-kB txoj kev [96]. Kev tswj hwm ntawm kaempferol rau cov hnub nyoog (24-lub lim tiam) cov nas txo qis cov khoom lag luam glycation endproducts (AGE) hauv cov kab mob sib txawv thiab txo qhov kev qhia ntawm AGE receptor (RAGE) thiab AGE-induced reactive hom (RS). Vim tias RS yog cov muaj zog activators ntawm NF-KB, ob qho tib si kaempferol-kho fibroblasts thiab tsiaj muaj qis dua qhia ntawm MMP-9, adhesion molecules (xws li., ICAM-1), thiab ntau yam pro-inflammatory genes. Raws li, nyob rau hauv bleomycin-induced senescent fibroblasts thiab cov laus nas, kaempferol inhibits qhov induction ntawm ib tug subset ntawm SASP mRNA thiab ua kom lub NF-KB txoj kev [62].
5.2.3.Fisetin ua
Fisetin yog flavonol nrog cov qauv tshuaj zoo ib yam li quercetin. Nws muaj nyob rau hauv ntau cov txiv hmab txiv ntoo thiab zaub (piv txwv li, txiv apples, persimmon, txiv hmab txiv ntoo, dos, thiab dib) ntawm qhov tsis tshua muaj siab thiab siab siab hauv cov txiv pos nphuab. Fisetin tau pom muaj zog senolytic thiab hemostatic zog hauv vitro thiab hauv vivo. Kev tswj hwm ntawm fisetin rau progeroid thiab cov nas qub qub txo cov cim senescence (iep16 thiab p21), hloov kho SASP muaj pes tsawg leeg hauv ntau cov ntaub so ntswg, thiab kho cov ntaub so ntswg homeostasis los ntawm inhibiting PI3K / AKT / mTOR thiab NF-KB txoj hauv kev thiab cov tshuaj tiv thaiv kab mob [97 ].
Hauv cov ntsiab lus ntawm kev laus ntawm daim tawv nqaij, fisetin tuaj yeem cuam tshuam TNF- -induced o thiab hydrogen peroxide-induced oxidative puas tsuaj hauv tib neeg keratinocytes [9]. Nws tuaj yeem txo UVB-vim kev puas tsuaj los ntawm inhibiting ROS tiam thiab MAPK/AP-1/MP teeb liab txoj kev thiab txo collagen degradation thiab inflammatory teb nyob rau hauv tib neeg daim tawv nqaij fibroblasts [99]. Thaum siv tshuaj pleev rau cov nas tsis muaj plaub hau, fisetin inhibits iNOS, MMP-1, MMP-2, thiab COX-2 thiab ua kom cov tawv nqaij nthuav tawm ntawm filaggrin thiab aquaporins, tiv thaiv cov tsiaj los ntawm cov duab-mob thiab tawv nqaij qhuav [10]. Kev sim tshuaj kho mob tam sim no tab tom ntsuas los ntsuas cov txiaj ntsig ntawm kev kho fisetin ntawm ntau yam ntawm kev laus [101]. 5.3. Isoflavones
Isoflavones yog non-active hydrophilic glycosides (piv txwv li, daidzin thiab genistein nyob rau hauv soy-taum) los yog methylated lipophilic derivatives (piv txwv li, formononetin thiab biochanin A nyob rau hauv liab clover) nyob rau hauv cov nroj tsuag los ntawm Leguminosae tsev neeg uas yog hydrolyzed los ntawm -glucosidases nyob rau hauv lub digestive system. . Cov bioactive aglycones (piv txwv li, daidzein thiab genistein tsim los ntawm daidzin thiab genistin, feem) yog absorbed hla lub plab hnyuv epithelium thiab metabolized rau -glucuronides thiab sulfate esters nyob rau hauv cov hnyuv mucosa hlwb. Cov metabolites tom qab ntawd tawm mus rau hauv cov ntshav thiab cov kua tsib [102].
Cov teebmeem pleiotropic ntawm isoflavones nyob ntawm lawv lub peev xwm los cuam tshuam nrog ntau lub cev muaj zog, suav nrog cov tshuaj estrogen receptors (ER); peroxisome proliferator-activated receptors (PPARs) a, S thiab y; retinoid acid receptor (RAR); thiab aryl hydrocarbon receptor (AhR). Txawm li cas los xij, cov isoflavones kuj ua los ntawm cov txheej txheem ntawm cov receptor-kev ywj pheej, suav nrog inhibition ntawm cov protein tyrosine kinases (xws li, ERK1/2, tseem ceeb rau kev tswj cov cell proliferation thiab sib txawv), txo qis ROS theem, induction ntawm antioxidant enzymes, thiab inhibition ntawm COX{ {4}} thiab NF-kB kev ua haujlwm thiab thromboxane A2(TXA2) synthesis. Tag nrho cov haujlwm no ua rau muaj kev tiv thaiv kab mob ntawm isoflavones [60]. Daidzein thiab Genistein
Daidzein ib leeg lossis ua ke nrog genistein inhibits UV-induced MMP-1 thiab MMP-2 qhia thiab collagen degradation hauv tib neeg cov tawv nqaij fibroblasts hauv vitro thiab hauv cov nas tsis muaj plaub hau hauv vivo [103]. UV hluav taws xob tuaj yeem cuam tshuam cov tawv nqaij collagen matrix los ntawm inhibiting TGF- txoj kev [94]. Daidzein nce TGF-kev qhia thiab ua kom nws cov receptors (cim transducer thiab activator ntawm transcription 2/3-Smad2/3) nyob rau hauv daim tawv nqaij fibroblasts. Qhov tseem ceeb, daidzein tsis cuam tshuam rau ntawm daim tawv nqaij ntawm tes [104]. Ntxiv mus, los ntawm nws cov kev cuam tshuam nrog RAR nyob rau hauv tib neeg keratinocytes, daidzein tuaj yeem cuam tshuam qhov kev qhia ntawm MMP-9, metalloproteinase koom nrog kev txhim kho cov kab mob ntev hauv cov neeg mob ntshav qab zib [105,106].
Genistein tiv thaiv UV-dependent COX-2 kev qhia hauv tib neeg keratinocytes hauv vitro thiab kev tso tawm cov neeg kho mob pro-inflammatory[107]. Ntxiv mus, tshuaj pleev genistein los yog nws cov metabolite equol tiv thaiv UVB-induced oxidative DNA puas (DNA pyrimidine dimer tsim) thiab ROS ntau lawm nyob rau hauv daim tawv nqaij ntawm cov nas tsis muaj plaub hau [108]. Zoo li daidzein, genistein nce qhov tuab ntawm daim tawv nqaij collagen fibers los ntawm inducing TGF- qhia thiab nce cov nqaij mos inhibitor ntawm metalloproteinase (TIMP) protein ntau ntau [109]. Ob leeg genistein thiab daidzein muaj qhov cuam tshuam loj rau kev tiv thaiv kab mob thiab txhawb kev kho genomic thiab mitochondrial DNA kho hauv tib neeg cov tawv nqaij fibroblasts raug UVB hluav taws xob (REF). Lawv kuj ua haujlwm sib koom ua ke los tsim cov nyhuv photoprotective [110,11]. Ntxiv mus, daidzein thiab genistein txhawb kev tsim cov hyaluronic acid hauv kev hloov pauv tib neeg keratinocyte kab lis kev cai thiab cov tawv nqaij tsis muaj plaub hau [112].
Muaj cov kev tshawb fawb qhia tias kev tswj hwm ntawm isoflavones tuaj yeem thim rov qab cov tsos mob ntawm daim tawv nqaij laus hauv tib neeg. Piv txwv li, 12-kev kho mob lub lim tiam nrog 40 mg ntawm soy isoflavone aglycones txhim kho cov wrinkles zoo thiab elasticity ntawm daim tawv nqaij nruab nrab. cov poj niam hnub nyoog Japanese [113]. Txawm li cas los xij, 24-lub lim tiam ntawm cov tshuaj genistein kev tswj hwm tsis muaj qhov zoo dua li estradiol thiab tsis muaj txiaj ntsig zoo dua li cov tshuaj no hauv kev txhim kho epidermal tuab, tus naj npawb ntawm cov dermal papillae, fibroblasts, thiab cov hlab ntsha hauv cov poj niam tom qab yug me nyuam [114].
5.4.Flavanones
Flavanones muaj nyob hauv cov txiv hmab txiv ntoo citrus; flavanone tshaj plaws yog naringenin tam sim no nyob rau hauv txiv kab ntxwv, txiv qaub, tangerines, thiab txiv kab ntxwv. Naringenin muaj ntau yam khoom siv tshuaj, suav nrog tshuaj tiv thaiv atherogenic, tiv thaiv qog noj ntshav, antioxidant, thiab tshuaj tiv thaiv kab mob. Hauv cov ntsiab lus ntawm kev laus ntawm daim tawv nqaij, naringenin tuaj yeem tiv thaiv tib neeg keratinocytes tiv thaiv UVB-induced carcinogenesis thiab kev laus hauv vitro thiab UVB-tsim oxidative kev nyuaj siab thiab mob hauv vivo [115,116]. Cov tshuaj naringenin tiv thaiv cov nas tsis muaj plaub hau los ntawm UVB-induced tawv nqaij puas tsuaj los ntawm inhibiting zus tau tej cov SASP Cheebtsam (TNF-a, IL-1, IL-6, thiab IL-10) thiab lipid hydroperoxides, thaum. tswj cov kev qhia ntawm cov noob caj noob ces, suav nrog glutathione peroxidase 1, glutathione reductase, thiab cov khoom siv hluav taws xob nuclear erythroid 2-txog yam 2(Nrf2) transcription factor [117]. Cov teebmeem no yog ib feem vim muaj peev xwm ntawm naringenin txo NF-kB, MMP-1, thiab MMP-3 qib [118].
Cov txheej txheem ntawm hemostatic thiab senolytic kev ua ntawm cov flavonoid subtypes sib txawv nyob rau hauv cov ntsiab lus ntawm daim tawv nqaij laus yog cov ntsiab lus nyob rau hauv Table 1.
6. Cov ntsiab lus thiab cov lus xaus
Targeting senescent hlwb tau dhau los ua lwm txoj kev kho mob rau kev kho ntau yam mob hnub nyoog thiab kab mob. Lub hom phiaj no tuaj yeem ua tiav ntawm ob theem: kev tshem tawm cov hlwb senescent thiab inhibition ntawm lawv cov secretory phenotype. Vim hais tias senescent hlwb ua lub luag haujlwm tseem ceeb hauv daim tawv nqaij physiology thiab pathophysiology, lawv tshem tawm tej zaum yuav muaj kev cuam tshuam tsis zoo. Yog li, kev hloov pauv ntawm SASP tuaj yeem yog lub tswv yim muaj kev nyab xeeb dua los tiv thaiv qhov tsis zoo ntawm daim tawv nqaij. Hauv vitro thiab hauv vivo cov kev tshawb fawb qhia tias kev tswj hwm ntawm flavonoids ob qho tib si hauv lub cev thiab lub cev muaj ntau yam txiaj ntsig hauv qhov no. Txawm li cas los xij, vim muaj qhov sib txawv ntawm cov txheej txheem kev kawm, cov kev tshawb pom ua ntej no tsis tuaj yeem muab txhais ncaj qha rau hauv kev kho mob. Yog li ntawd, peb tseem tsis tau ntseeg cov kev tshawb fawb soj ntsuam kom paub meej tias qhov ua tau zoo thiab kev nyab xeeb ntawm flavonoids hauv kev kho hnub nyoog ntawm daim tawv nqaij hloov pauv thiab qhov txhab. Kev tshawb fawb ntxiv yog xav tau los txhim kho cov kev kho mob uas tsim nyog thiab ntsuam xyuas qhov muaj feem cuam tshuam ntawm kev siv flavonoid. Kev sim tshuaj kho mob yuav tsum tau txais kev txhawb nqa los ntawm cov txiaj ntsig ua ntej kho mob tau txais hauv cov qauv tsim nyog ntawm tes thiab tsiaj. Nws kuj tseem tsim nyog los tsim cov txheej txheem kho mob thiab cov cim ntawm tes tsim nyog los ntsuas qhov ua tau zoo ntawm txoj kev kho. Tsis tas li ntawd, cov txheej txheem tshawb fawb yuav tsum tau sib sau ua ke kom cov txiaj ntsig tau txais nrog cov qauv kev tshawb fawb sib txawv sib piv thiab txhais tau rau kev kho mob.
Noj mus rau hauv tus account lub peev xwm muaj txiaj ntsig zoo ntawm flavonoids rau ntawm daim tawv nqaij laus, kev noj zaub mov nplua nuj nyob rau hauv zaub, txiv hmab txiv ntoo, thiab cereals, uas yog ib qho ntawm cov khoom xyaw ntuj, yuav tsum tau pom zoo hauv kev tswj xyuas kev laus. Qhov tseem ceeb, cov khoom ntuj tsim muaj kev sib xyaw ntawm ntau yam flavonoids uas tuaj yeem ua tiav thiab sib koom ua ke thiab, yog li ntawd, muaj txiaj ntsig zoo dua li cov tshuaj ntsuam xyuas hauv qhov chaw sim. Tsis tas li ntawd, txij li flavonoids nyob rau hauv cov khoom ntuj muaj nyob rau hauv me me / nruab nrab concentrations, lawv muaj peev xwm yuav xyuam xim tswj tsis muaj kev pheej hmoo ntawm overdosage. Tsis tas li ntawd, kev sim tshuaj ua ntej pom tau tias muaj ntau yam kev nyab xeeb kho mob ntawm flavonoids. Yog li ntawd, nutraceuticals thiab cov khoom noj khoom haus uas muaj ob qho tib si ntuj flavonoids nrog rau cov khoom siv hluav taws xob thiab cov khoom siv hluavtaws nrog ntau yam hloov pauv thiab cov haujlwm pov thawj tuaj yeem suav hais tias yog ib txoj hauv kev tiv thaiv kev laus ntawm daim tawv nqaij.
kab lus no yog muab rho tawm los ntawm Int. J. Mol. Sci. 2021, 22, 6814. https://doi.org/10.3390/ijms22136814 https://www.mdpi.com/journal/ijms
