Ntu 2: Polyphenols Raws li Kev Noj Qab Haus Huv Kev Noj Qab Haus Huv Rau Kev Kho Mob Endometriosis-Tam sim no Kev xav thiab Kev Pom Zoo rau yav tom ntej

Yog xav paub ntxiv, hu rautina.xiang@wecistanche.com

Nyem qhov link rau Part 1:https://www.xjcistanche.com/news/polyphenols-as-a-diet-therapy-concept-for-endo-55045838.html

5. Muaj peev xwm ntawm Polyphenol Compounds hauv Kev Tswj Xyuas Endometriosis

Muaj kev tshawb nrhiav ntxiv txog cov txiaj ntsig zoo ntawm cov tshuaj bioactive hauv kev tiv thaiv cov kab mob tsis sib xws, suav nrog cov kab mob plawv thiab mob qog noj ntshav. Ntau qhov kev tshawb fawb tau soj ntsuam kev sib raug zoo ntawmpolyphenols' kev tswj hwm, xws li flavonoids thiab phytoestrogens, thiab poj niam muaj mob qog noj ntshav. Grosso et al. (2016) tau pom tias kev noj zaub mov tsis tu ncua uas muaj flavonoids cuam tshuam nrog kev pheej hmoo mob qog noj ntshav ntawm lub mis thiab zes qe menyuam [80]. Hauv kev soj ntsuam meta, Micek li al.(2020) tau pom tias kev noj zaub mov ntau dua ntawm phytoestrogens (ie, isoflavones) cuam tshuam nrog kev pheej hmoo ntawm kev mob qog noj ntshav mis thiab rov tshwm sim [81].Endometriosisthiab mob qog noj ntshav mis yog cov mob estrogen-dependant thiab sib koom cov txheej txheem ntawm tes zoo xws li kev loj hlob, kev ntxeem tau, neo-angiogenesis, metastases, thiab cov kev pheej hmoo ntawm kev yug me nyuam. Qhov tseem ceeb zoo sib xws ntawm endometriosis thiab mob qog noj ntshav txhawb kev tshawb nrhiav kev tiv thaiv ntawm ntuj bioactive molecules tawm tsam tus kab mob no [82].

Tsis tas li ntawd, endometriosis tau txuas nrog kev mob ntevmob, oxidative kev nyuaj siab, thiab atherogenic lipid profile, ua rau pib thiab tswj cov kab mob plawv [83]. Qhov kev ntsuam xyuas meta tau pom tias muaj kev sib raug zoo ntawm kev noj zaub mov kom tsawg ntawm tag nrho cov flavonoids thiab txo qis kev pheej hmoo ntawm cov kab mob plawv [84]. Cov qauv kev noj zaub mov zoo sib xws uas nplua nuj nyob hauv cov khoom noj bioactive tuaj yeem ua rau muaj txiaj ntsig zoo rau endometriosis.

Cov nroj tsuag tshwj xeeb muab los ntawm bioactive compounds, nthuav tawm los tiv thaiv kev loj hlob, tiv thaiv oxidant, tiv thaiv inflammatory, anti-angiogenic, pro-apoptotic, immunomodulating, thiab estrogen modulating kev ua ub no, tuaj yeem cuam tshuam ntau txoj hauv kev koom nrog endometriosis's etiopathogenesis thiab muab cov tswv yim tshiab rau kev kho lossis regressing endometriosis [85, 86]. Ntau qhov kev tshawb fawb preclinical thiab kev sim tshuaj nyob rau hauv cov kev tshawb fawb endometriosis tau ntaus nqi rau phytochemicals ntau yam ntawm cov kev ua ub no muaj txiaj ntsig zoo thiab piav qhia txog cov txheej txheem molecular thiab txoj hauv kev uas lawv tuaj yeem cuam tshuam cov kab mob kev loj hlob [68,87]. Cov kev tshawb fawb txog kev kho mob phytochemicals feem ntau tsom rau cov tshuaj polyphenolic.

Nyem qhov no kom paub meej ntxiv

Polyphenols suav nrog ib pawg loj ntawm bioactive tebchaw tsim los ntawm cov nroj tsuag uas yog ib feem tseem ceeb ntawm tib neeg kev noj haus, dav lees paub rau lawv cov txiaj ntsig kev noj qab haus huv ntau yam, feem ntau yog los tiv thaiv oxidant thiab anti-inflammatory zog, nrog rau qhov tseem ceeb hauvendometriosis[88]. Phenol-Explorer, thawj cov ntaub ntawv nthuav dav ntawm cov ntsiab lus polyphenol hauv cov khoom noj (http://phenol-explorereu/)( nkag mus rau 12 Lub Plaub Hlis 2021), faib cov polyphenols rau hauv 6 pawg thawj: flavonoids, lignans, non-phenolic metabolites, lwm yam polyphenols, phenolic acids thiab stilbenes. Flavonoids uas yog pawg loj tshaj plaws ntawm kev noj haus polyphenols tau muab faib ua cuaj pawg, suav nrog anthocyanins, chalcones, dihydrochalcones, dihydro.flavonol, flavonols, flavanones, flavones, flavonols, thiab isoflavonoids (http://phenol-explorer.eu/) ( nkag mus rau 12 Plaub Hlis 2021). Cov kev faib tawm saum toj no tau siv los npaj cov txheej txheem sib txawv polyphenol sib txuas ua cov neeg sib tw tau zoo rau kev tsim cov tswv yim tshiab hauv kev kho mob endometriosis. Kab lus no piav qhia txog polyphenols 'molecular action profiles, uas lub hom phiaj tseem ceeb ntawm cov kab mob ua rau cov kab mob pathophysiology nyuaj. Table 1 piav qhia txog polyphenols cov txheej txheem ntawm kev ua thiab cov hom phiaj molecular hauv kev tswj hwm endometriosis.

5.1. Flaconoids

5.1.1.Flavonols Quercetin

Quercetin yog flavonol tshwm sim nyob rau hauv ntau yam txiv hmab txiv ntoo thiab zaub xws li dos, zaub qhwv, txiv apples, berries, thiab kua txob [89]. Quercetin siv cov tshuaj tiv thaiv kab mob los ntawm kev txo cov qog nqaij hlav qog noj ntshav thiab txhim kho apoptosis thiab autophagy los ntawm kev hloov kho ntawm Akt, mammalian lub hom phiaj ntawm rapamycin (mTOR), thiab HIF-1 qhia txoj hauv kev [130]. Ib qho kev tshawb fawb hauv vitro tau pom tias quercetin inhibits cell proliferation thiab induces cell voj voog ntes thiab apoptosis nyob rau hauv endocervical cell kab VK2 / E6E7 thiab End1 / E6E7. Cell apoptosis cov tsos mob suav nrog DNA fragmentation, poob ntawm mitochondrial membrane peev xwm, thiab downregulation ntawm extracellular teeb liab tswj kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK), thiab AKT signaling molecules [89].

Antiproliferative thiab anti-inflammatory teebmeem ntawm intraperitoneally txhaj quercetin tau pom nyob rau hauv ib tug pib-implanted nas qauv ntawm endometriosis. Kev txo qis hauv cyclin D1 qhia hauv luminal thiab glandular epithelium tau pom nyob rau hauv cov lus teb rau quercetin txhaj [89]. Hauv cov nas nrog induced endometriosis, quercetin kev tswj hwm txo qis endometrial implants loj thiab serum E2 thiab TNF- qib piv rau pawg tswj hwm. Cov txiaj ntsig tau qhia tias kev kho mob quercetin ua rau muaj zog antioxidant NAD(P)H enzyme quinone oxidoreductase 1 (NOO1) kev ua haujlwm thiab nws qhov tseem ceeb ntawm cov khoom siv hluav taws xob nuclear erythroid 2-txog yam 2(Nrf2) qhia. Txoj kev tshawb no tau piav qhia tias quercetin, tsis zoo li cov kev kho mob endometriosis, tsis cuam tshuam rau cov tshuaj estrogen thiab progesterone ntau lawm, hais txog qhov zoo ntawm cov tshuaj no tshaj cov tshuaj siv tam sim no. Tsis tas li ntawd, regression ntawm cov kab mob endometrial tau pom tias yog ib qho txiaj ntsig ntawm kev txhim kho autophagy los ntawm mTOR inhibition thiab overexpression autophagy-txog cov cim, suav nrog Beclin-1 thiab Atg5, tom qab kev kho mob ua ke nrog quercetin thiab metformin [90].

Cov txiaj ntsig zoo ntawm cov khoom xyaw ntuj uas cuam tshuam rau lub ntsiab pathophysiological txoj hauv kev ntawm endometriosis pom nyob rau hauv cov qauv preclinical xav tau cov pov thawj hauv kev sim tshuaj. Signorile et al. (2018) tau tshawb xyuas 30 tus neeg mob uas txhais tau tias yog theem IV ntawm endometriosis kho tau peb lub hlis nrog kev noj zaub mov ntxiv uas muaj, piv txwv li, 200 mg quercetin. Clini cians tau soj ntsuam qhov txo qis hauv cov lus teb inflammatory thiab endometriosis cov tsos mob thiab nws cov teeb meem cuam tshuam rau cov kab mob hauv cov neeg mob endometriosis. Kev sim cov ntaub ntawv tau txais pov thawj muaj txiaj ntsig zoo hauv kev txo qhov mob thiab lwm yam kab mob tsis zoo hauv cov neeg mob kho nrog kev noj zaub mov ntxiv. Kev txo qis hauv cov ntshav PGE2 ntau ntau tau pom tom qab kev kho mob qhia tias muaj peev xwm tiv thaiv kab mob ntxiv. Ntxiv mus, hauv cov neeg mob kho, qhov loj me ntawm endometriosis foci raug txo vim qhov txo qis hauv cov ntshav CA-125 concentration, raws li cov kws sau ntawv ntseeg. Cov kws sau ntawv qhia tias kev tshawb fawb ntxiv ntawm kev noj zaub mov ua ke nrog cov qauv kev kho mob yog tsim nyog los tsim kom muaj peev xwm siv tau cov tswv yim kho mob endometriosis tshiab [91].

5.1.2.Flavones Apigenin

Cov kws tshawb fawb pom zoo tias apigenin (4',5,6-trihydroxy flavone), muaj nyob rau hauv ntau yam txiv hmab txiv ntoo (apples, grapes, txiv kab ntxwv) thiab zaub (dos, parsley, celery), yog haum rau kev tiv thaiv thiab kev kho mob. ntawm ntau yam kab mob xws li ntshav qab zib, kab mob metabolic, kab mob plawv thiab neuronal, thiab mob qog noj ntshav [131]. Apigenin tiv thaiv los yog inhibits kab mob kev loj hlob los ntawm kev koom tes hauv cell voj voog ntes, apoptosis induction, anti-inflammatory, thiab dawb radical scavenging mechanisms; Yog li, nws kuj tau npaj los ua tus neeg sawv cev kho mob hauv cov kab mob kev sib deev [92]. Hauv cov ntsiab lus no, apigenin txo qis kev loj hlob ntawm ob tus tib neeg cov kab mob endometriotic cell nyob rau hauv koob tshuaj thiab induced apoptosis los ntawm inhibition ntawm phosphorylation ntawm ERK1/2 thiab c-Jun N-terminal kinase (JNK) proteins thiab nce pro-apoptotic proteins, suav nrog BAX thiab cytochrome c. Tsis tas li ntawd, apigenin-kho cov hlwb tau sau ntau dhau ROS tau ntsib lipid peroxidation thiab endoplasmic reticulum kev nyuaj siab, thiab poob mitochondrial membrane muaj peev xwm nrog kev nce hauv calcium ions hauv cytosol [92]. Hauv lwm txoj kev tshawb fawb, apigenin txo qis kev ua haujlwm mitogenic, inflammatory teb, thiab attenuated TNF- -induced cell proliferation thiab COX{15}}/PGE2 synthesis ntawm inactivation ntawm NF-kB txoj hauv kev endometriotic stromal hlwb [93]. Lub peev xwm lom neeg ntawm apigenin derivatives-nplua nuj extracts tau los ntawm A. austriaca paj tau pom nyob rau hauv tus qauv nas endometriosis. Cov feem ntau nquag apigenin-nplua nuj zoo kawg li txo qis adhesion thiab endometriotic implant ntim thiab TNF-, VEGF, thiab I-6 qib [94]. Raws li cov txiaj ntsig ntawm apigenin cov txiaj ntsig lom neeg, cov flavone no tau pom zoo tias yog tus neeg sawv cev kho mob tshiab los daws cov kev txwv tam sim no hauv kev tiv thaiv lossis kho endometriosis. Txawm li cas los xij, ntxiv kev tshawb fawb hauv tsev kho mob thiab kev sim tshuaj, tshwj xeeb, yog xav tau.

Baicalein

Baicalein (5,6,{2}}trihydroxy flavone) yog ib qho flavonoid muab los ntawm Scutellaria baicalensis Georgi lub hauv paus, ib txwm tshuaj ntsuab hauv Suav tshuaj ntsuab [132]. Baicalein's pharmaco-logical zog, xws li tshuaj tiv thaiv qog, tiv thaiv kab mob, tiv thaiv kab mob, tiv thaiv kev ua xua, tiv thaiv oxidant, thiab cytoprotective teebmeem, tau raug tshuaj xyuas tsis ntev los no [95]. Los tiv thaiv mob qog noj ntshav, lub hom phiaj mechanisms, thiab cov kev taw qhia ntawm baicalein yog qhov txaus siab los ntawm cov kws tshawb fawb. Baicalein tau kawm nyob rau hauv ntau hom malignancy, nrog rau lub zais zis, melanoma, prostate, thiab cancer ntawm lub mis, nrog rau cov qog gynecological xws li mob qog noj ntshav thiab zes qe menyuam [133]. Baicalein tiv thaiv kev loj hlob ntawm mob qog noj ntshav mis MCF{13}} hlwb thiab induced apoptosis los ntawm suppressing 17 -estradiol-induced transactivation [134]Lwm yam hauv vivo kev tshawb fawb qhia qhov inhibitory nyhuv ntawm baicalein tiv thaiv qog noj ntshav [135]. Cov txheej txheem molecular tau piav qhia txog tam sim no suav nrog kev tswj hwm ntawm lub voj voog ntawm tes los ntawm inhibition ob peb cyclins lossis cyclin-dependent kinases (CDK), cell proliferation ntes los ntawm Wnt / -catenin signaling pathway, suppression of PD-L1 qhia los txhawb kev tiv thaiv qog noj ntshav, thiab. Raws li induction ntawm apoptosis thiab autophagy ntawm ERK/phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)/Akt pathway thiab caspase activation [{27}}]. Vim cov ntaub ntawv qhia txog cov qog nqaij hlav, Jin li al. (2017) and Ke et al. (2021) soj ntsuam baicalein anti-endometriotic muaj peev xwm siv tib neeg endometrial stromal hlwb hauv vitro. Cov txiaj ntsig tau qhia tias baicalein txo qis ectopic endometrial stromal cell viability thiab induces apoptosis los ntawm NF-kB signaling pathway. Tom qab kev kho mob baicalein, qib ntawm anti-apoptotic protein BCL-2 poob qis heev. Tus naj npawb ntawm cov hlwb hauv G1 theem tau nce nrog ib txhij poob ntawm cov cell hauv theem S thiab G2 / M piv nrog cov hlwb tsis kho [95]. Cov kev tshawb pom tsis ntev los no qhia tau tias baicalein txo qis ectopic endometrial stromal cell invasiveness, raws li tau pom los ntawm kev soj ntsuam ntawm kev cuam tshuam txog cov proteins, suav nrog MMP-9, MMP-2, thiab membrane hom 1-matrix metalloproteinase (MT 1-MMP)[96]. Hauv nas qauv ntawm endometriosis, intraperitoneal kev tswj hwm ntawm baicalein inhibited ectopic lesions loj hlob, txo MT1-MMP, proprotein convertase ntawm MMPs (FURIN), thiab TGFB1 qhia. Yog li, baicalein nrog lub zog pro-apoptotic thiab tiv thaiv kev ua haujlwm tuaj yeem muab cov tswv yim kho tshiab rau endometriosis, raws li cov kws sau ntawv pom zoo [96]. Kev cog lus kev tshawb fawb txog kev tshawb fawb pom tau hais tias ua kev tshawb fawb soj ntsuam ntawm kev kho mob endometriosis nrog baicalein tau lees paub thiab pom zoo kom tau txais cov pov thawj muaj zog rau kev kho mob baicalein muaj peev xwm.

Wogonin

Wogonin (O-methylated flavone), lwm qhov chaw flavonoid pom nyob rau hauv Scutellaria baicalensis Georgi cag extract, tau raug tshaj tawm nyob rau hauv cov kev tshawb fawb preclinical raws li ib tug anti-tumor agent [97]. Ib qho kev tiv thaiv kev loj hlob ntawm wogonin tau raug tshuaj xyuas hauv tib neeg endometrial stromal T-HESC cell kab thiab thawj stromal cell kab lis kev cai tsim los ntawm endometrial biopsies los ntawm cov poj niam uas muaj endometriosis. Hauv cov qauv hauv vitro, wogonin cuam tshuam qhov tseem ceeb thiab T-HESC cell proliferation ua rau lub voj voog ntawm tes raug ntes ntawm G2 / M theem thiab txo qis ERa qhia. Nyob rau hauv ib tug murine qauv ntawm endometriosis, wogonin txo qhov mob loj thiab txo cov cell nyob rau hauv lub proliferation lub xeev, ib txhij nce tus naj npawb ntawm apoptotic hlwb [97].

5.1.3. Isoflavonoids Daidzein thiab Genistein

Isoflavones, ib pawg ntawm cov flavonoids pom nyob rau hauv cov taum pauv, qhia cov qauv zoo sib xws nrog estradiol tab sis tshaj tawm qhia cov tshuaj tiv thaiv estrogen [22]. Cov qauv zoo sib xws vim lawv cov qauv heterocyclic phenolic pab txhawb isoflavones khi rau cov tshuaj estrogen receptors ER thiab ER thiab ua raws li kev ua estrogenic [139]. Soy isoflavones feem ntau yog glycosides nrog daidzein thiab genistein yog tus sawv cev tseem ceeb ntawm isoflavone aglycones ntau nyob rau hauv cov taum, uas yog hloov los ntawm -glycosidase tau los ntawm cov kab mob uas colonize cov hnyuv me thiab loj [140,141].

Qee qhov kev tshawb fawb hauv vitro thiab hauv vivo tau tshawb xyuas cov txiaj ntsig ntawm isoflavones ntawm endometriosis. Daidzein-nplua nuj isoflavone aglycones (DRIA) inhibited cell proliferation ntawm endometriotic stromal hlwb ntawm kev kho mob cov concentrations. DRIAs tau ua rau txo qis kev qhia ntawm I-6, IL-8, COX-2, thiab txwv kev ua haujlwm aromatase, nrog rau kev txo qis ntawm glucocorticoid-regulated kinase thiab PGE, hauv cov ntshav. DRIAs kuj txo tus naj npawb, qhov hnyav, thiab Ki-67 kev ua haujlwm loj ntawm cov kab mob endometriosis zoo li hauv murine endometriotic qauv [142]. Lwm txoj kev tshawb fawb pom tau tias genistein ua rau regression ntawm endometriotic implant nyob rau hauv tus qauv nas. Nyob rau hauv lub xub ntiag ntawm estrogen, genistein tau qhia antagonistic estrogen kev ua ntawm endometriotic implants [98]. Cov txiaj ntsig los ntawm kev tshawb fawb tsiaj qhia DRIAs ua tus neeg sawv cev kho mob zoo rau kev txhim kho cov tswv yim kho mob hauv endometriosis.

Kev tshawb fawb soj ntsuam tau pom tias txo qis kev pheej hmoo ntawm kev txhim kho endometriosis tom qab soy isoflavones 'kev noj. Kev sib raug zoo ntawm cov zis isoflavone ntau dua (genistein thiab daidzein) thiab txo qis kev pheej hmoo ntawm endometriosis (theem I thiab IV), tab sis tsis tshwm sim thaum ntxov endometriosis (theem I thiab II) tshwm sim, tau pom nyob rau hauv cov ntaub ntawv tswj kev kawm nrog rau cov poj niam Japanese [ 99] ib. Cov kev tshawb fawb soj ntsuam yav tom ntej thiab kev ntsuam xyuas meta tsom rau cov txiaj ntsig ntawm phytoestrogen-nplua nuj cov khoom noj los ntawm cov neeg mob endometriosis yog xav tau.

Puerarin

Puerarin yog thawj cov khoom xyaw bioactive cais tawm ntawm lub hauv paus ntawm Pueraria lobata. Nws tau ua pov thawj muaj peev xwm hauv kev tswj cov kab mob plawv, kab mob hauv lub hlwb, mob qog noj ntshav, Parkinson's disease, Alzheimer's disease, ntshav qab zib, thiab mob ntshav qab zib muaj teeb meem [143]. Puerarin tau siv cov tshuaj vasodilatory los ntawm kev ua kom muaj qhov hluav taws xob loj thiab cov calcium-activated potassium raws hauv cov qauv nas. Puerarin tuaj yeem cuam tshuam cov ntshav qab zib vascular teeb meem los ntawm kev txo qis P-selectin, qis lipoproteins tsawg, thiab cov roj cholesterol hauv cov ntshav thiab txo qis mRNA qhia ntawm aorta vascular cell adhesion molecules hauv cov nas ntshav qab zib. Kev tiv thaiv ntawm puerarin tiv thaiv oxidative kev ntxhov siab vim neurodegeneration tau raug ntaus nqi los thaiv ROS overproduction thiab lipid peroxidation, inducing nuclear Nrf2 protein qhia, thiab activating catalase thiab GSH peroxidase thiab transcription thiab txhais qib ntawm heme oxygenase 1 [143].

Puerarin feem ntau suav hais tias yog phytoestrogen vim tias nws khi rau cov tshuaj estrogen receptors thiab sib tw nrog estradiol kom nthuav tawm cov nyhuv anti-estrogenic [144]. Nws lub luag haujlwm hauv kev kho cov kab mob endometriosis, ib qho kev cuam tshuam ntawm estrogen-dependent, tau piav qhia zoo hauv ntau qhov kev tshawb fawb. Puerarin suppressed ntxeem tau thiab vascularization ntawm endometriosis cov ntaub so ntswg qhib los ntawm E2 los ntawm kev txo cov tsub zuj zuj ntawm MMP-9, ICAM-1, thiab VEGF thiab nce qib ntawm cov ntaub so ntswg inhibitor ntawm metalloproteinase 1(TIMP-1) nyob rau hauv thawj endometriotic stromal hlwb thiab hauv qaib chorioallantoic membrane hauv vivo qauv [100]. Puerarin tuaj yeem cuam tshuam cov tshuaj estrogen-stimulated proliferation ntawm endometriotic stromal hlwb thiab downregulate cov transcription thiab protein theem ntawm cyclin D1 thiab cdc25A los ntawm kev txhawb ER corepressors recruitment thiab txwv kev recruitment ntawm coactivators. Kev tshawb nrhiav pom tau hais tias kev sib cuam tshuam ntawm puerarin-dependent ntawm ER thiab corepressor complexes yuav yog qhov tseem ceeb rau puerarin cov tshuaj tiv thaiv estrogenic, qhia tias cov isoflavone no tuaj yeem yog qhov muaj peev xwm kho tau rau kev kho mob endometriosis [101]. Hauv vivo kev tshawb nrhiav pom tias puerarin inhibits aromatase thiab COX-2 hauv ectopic endometrium, yog li txo E2 thiab PGE2 thiab yog li tiv thaiv kev loj hlob ntawm ectopic endometriotic hlwb [102]. Kev tshawb fawb soj ntsuam txog lub peev xwm ntawm puerarin hauv kev kho mob endometriosis tsis tau ua rau hnub no.

5.1.4 ib. Flavanones Naringenin

Naringenin, feem ntau pom nyob rau hauv cov txiv hmab txiv ntoo citrus, paub tias muaj antioxidant, tiv thaiv proliferative, anti-inflammatory, thiab anti-angiogenic zog nyob rau hauv cov kab mob ntev thiab metabolic [145,146]. Hauv cov qog nqaij hlav, raws li kev tshawb fawb preclinical qhia, naringenin induced ROS-mediated cell tuag thiab inhibited cell migration thiab ntxeem tau [146,147]. Naringenin yog phytoestrogen, cuam tshuam ERo signaling los ntawm kev cuam tshuam nrog MAPK, PI3K, thiab ERK1/2 signaling pathways [148]. Xav txog qhov muaj peev xwm lom neeg, cov kws tshawb fawb tau tshawb xyuas los ntsuas lub luag haujlwm ntawm naringenin hauv endometriosis.

Cov kev tshawb fawb hauv vitro tau pom tias naringenin suppresses proliferation thiab induces apoptosis hauv endometriosis hlwb los ntawm kev txo qis mitochondrial membrane peev xwm thiab ROS tiam. Cov nyhuv apoptotic ntawm naringenin koom nrog kev ua kom PI3K thiab MAPK cell signaling txoj hauv kev [103]. Ib txoj kev tshawb nrhiav tsiaj tau qhia txog qhov muaj peev xwm ntawm naringenin tiv thaiv endometriosis los ntawm kev txo cov kev qhia ntawm ntau yam endometriosis prognostic markers (TAK1, PAK1, VEGF, PCNA, MMP2, thiab MMP-9) hauv cov kab mob endometriotic tsim hauv nas. Naringenin tiv thaiv endometriosis propagation ntawm anti-inflammatory mechanisms los ntawm modulating cov ntshav TNF-, NOlevel, thiab proapoptotic teebmeem raws li ROS overproduction thiab poob ntawm mitochondrial membrane peev xwm. Tsis tas li ntawd, naringenin provoked depletion ntawm Nrf2, ib tug transcriptional yam tseem ceeb tswj transcription ntawm endogenous antioxidant enzymes, uas tiv thaiv cov hlwb tiv thaiv oxidative puas thiab thiaj li down-regulation ntawm cytoprotective noob, yog li inhibiting endometriotic cell proliferation [104]. Cov kev taw qhia tseem ceeb rau yav tom ntej kev tshawb fawb qhia los ntawm cov kws tshawb fawb txhawj xeeb txog kev tshawb fawb txuas ntxiv ntawm naringenin muaj peev xwm hauv kev kho mob endometriosis los ntawm kev siv cov qauv endometrium los ntawm cov pej xeem loj ntawm cov neeg mob endometriotic [104].

5.1.5. Chalcones Xanthohumol

Xanthohumol, prenylated flavonoid, originates los ntawm naringenin chalcone thiab muaj nyob rau hauv hop tus poj niam inflorescences (Humulus lupulus L.) [149]. Ntau cov kev tshawb fawb tau pom nws cov pleiotropic chemopreventive kev ua rau mob qog noj ntshav vim nws cov tshuaj tiv thaiv kab mob, tiv thaiv kab mob, thiab tshuaj tiv thaiv angiogenic [149]. Xanthohumol zoo inhibited endometriotic lesions txoj kev loj hlob thiab txo cov theem ntawm PI3K protein nyob rau hauv ib tug BALB / c nas qauv ntawm endometriosis. Tsis tas li ntawd, xanthohumol txo qis microvessels ntom thiab tsis cuam tshuam rau cov kab mob hauv plab hnyuv, qhia nws lub peev xwm rau kev xaiv kev kho mob endometriosis [105].

5.1.6. Flavanols Epigallocatechin Gallate

Epigallocatechin gallate (EGCG) yog lub ntsiab flavanol pom hauv cov tshuaj yej dub thiab dawb, tshwj xeeb tshaj yog hauv cov tshuaj yej ntsuab [150]. Cov tshuaj no tau txais kev kho mob loj heev vim nws cov txiaj ntsig zoo rau kev noj qab haus huv rau kev kho mob qog noj ntshav sib txawv, raws li nws cov tshuaj tiv thaiv antioxidant, anti-angiogenic, thiab cov khoom tiv thaiv proliferative [151,152]. Ex vivo cov kev tshawb fawb pom tias EGCG suppressed cell proliferation thiab induced cell tuag nyob rau hauv endometrial epithelial hlwb los ntawm tib neeg biopsies [119]. Interestingly, EGCG ua tau zoo inhibited cell proliferation ntawm endometriotic stromal hlwb tshaj li lawv cov counterparts ib txwm, xws li endometrial stromal hlwb [152]. Cov kev tshawb fawb ua los ntawm Matsuzaki thiab Darcha (2014) qhia tias kev kho mob nrog EGCG cuam tshuam loj heev,

tsiv teb tsaws, thiab ntxeem tau ntawm endometrial thiab endometriotic stromal hlwb ntawm inhibition ntawm MAPK thiab Smad signaling pathways. EGCG kuj txo qis cell-mediated collagen gel contraction raws li ob qho tib si endometriotic thiab endometrial hlwb. EGCG kev kho mob tau txo qis qhov kev qhia ntawm cov cim SMA, collagen-I, fibronectin (FN), thiab cov ntaub so ntswg loj hlob (CTGF) paub tias muaj kev koom tes hauv fibrogenesis hauv endometriotic stromal hlwb [106]. Lwm txoj kev tshawb fawb pom tau hais tias kev kho mob nrog EGCG rau ob lub lis piam txo cov kab mob endometriotic los ntawm downregulating angiogenic VEGFA mRNA qhia thiab upregulating NF-kB thiab MAPK1 mRNA qhia [153]. Cov kev sim tom ntej no tau pom tias EGCG tau ua rau muaj kev cuam tshuam rau kev cuam tshuam ntawm endometriosis-associated angiogenesis los ntawm kev txo tus naj npawb thiab qhov loj ntawm microvessels thiab VEGF-C/VEGF receptor 2(VEGFR-2) qhia thiab teeb liab [107]. Ib qho tshuaj tiv thaiv ntawm EGCG (pro-EGCG. EGCG tawm acetate) nrog txhim kho kev ruaj ntseg thiab bioavailability nthuav tawm ntau dua antioxidant, antiangiogenic, thiab inhibitory kev ua ub no dua li EGCG hauv cov qauv nas. Kev kho mob nrog cov pro-EGCG ua rau cov kab mob tsis zoo neovascularization thiab txo cov ntshav plasma VEGF concentration [108]. EGCG, uas ua rau muaj zog tiv thaiv kab mob, tuaj yeem sawv cev rau tus neeg sawv cev tiv thaiv angiogenic rau endometriosis.

Tam sim no, Tuam Tshoj University of Hong Kong tau pib qhov kev sim tshuaj ntsuam xyuas cov tshuaj yej ntsuab qhov ua tau zoo thiab kev nyab xeeb hauv endometriosis. Hauv txoj kev tshawb no, 185 tus neeg mob uas muaj endometrioma yuav randomize rau hauv ib pawg kev sim, uas yuav tau txais EGCG siab-purity EGCG (400 mg ntawm SUNPHENON EGCG) ob zaug ib hnub twg, lossis ib pawg placebo. Kev tswj xyuas ntxiv yuav siv sijhawm peb lub hlis ua ntej qhov kev npaj phais. Kev hloov pauv hauv qhov loj me ntawm cov kab mob endometriotic yuav yog qhov kev ntsuas thawj zaug ntawm txoj kev tshawb no. Tsis tas li ntawd, kev soj ntsuam qhov mob, kev ua neej zoo, cov kab mob endometriotic sau ua biopsies, tus naj npawb thiab qhov ceev ntawm neovasculature, thiab cov xwm txheej tsis zoo thiab cov kev mob tshwm sim tau teem tseg raws li cov txiaj ntsig thib ob (Clinical Trials.gov ID: NCT02832271).

5.2. Lwm yam Polyphenols Curcumin

Curcumin yog ib qho polyphenolic monomer muab rho tawm los ntawm turmeric ntawm Curcuma longa L. Kev tshawb fawb pom tau tias curcumin sawv cev rau qee qhov kev kho mob muaj peev xwm raws li kev tiv thaiv kab mob, tiv thaiv qog noj ntshav, thiab tiv thaiv kev laus [154]. Ntau qhov kev tshawb fawb hauv vitro thiab hauv vivo tau ua pov thawj nws cov haujlwm pharmacological hauv kev tswj hwm endometriosis.

Hauv tib neeg endometriotic stromal hlwb, curcumin attenuated TNF- - txhawb kev qhia ntawm ICAM-1, VCAM-1, thiab tso tawm ntawm IL-6, IL-8, thiab MCP -1 los ntawm inhibiting activation ntawm transcription factor NF-kB [109]. Tsis tas li ntawd, curcumin txo qis endometrial cell proliferation los ntawm kev txo cov tshuaj estrogen [110]. Ntxiv mus, kev kho mob nrog curcumin hloov pauv tib neeg endometriotic thiab endometrial stromal cell morphology, thiab cuam tshuam nrog cell proliferation thiab cell division. Curcumin tau ntes lub voj voog ntawm tes hauv G1 theem thiab ua rau apoptosis los ntawm kev txo qis ntawm VEGF qhia hauv tib neeg endometriotic thiab endometrial stromal hlwb [111]. Ib txoj kev tshawb fawb tsis ntev los no tau pom tias curcumin yog ib qho muaj zog inhibitor ntawm kev tso tawm ntawm pro-inflammatory thiab pro-angiogenic chemokines thiab cytokines los ntawm stromal hlwb muab tau los ntawm eutopic endometrium nyob rau hauv endometriosis thiab los ntawm ib txwm endometrial stromal hlwb [112].

Hauv cov qauv murine, kev tswj hwm curcumin tau cuam tshuam nrog kev txo qis hauv endometriosis kev loj hlob thiab kev ua kom apoptosis. Curcumin ua rau muaj kev rov qab los ntawm endometriosis feem ntau ntawm cytochrome c-mediated mitochondrial txoj hauv kev ntawm apoptosis, thiab cov lus teb apoptotic suav nrog ob qho tib si p53- txoj hauv kev nyob thiab ywj pheej. Curcumin ua raws li tus inhibitor ntawm NF-kB translocation thiab downregulated MMP-3, yog li kho endometriosis regression [113]. Tsis tas li ntawd, kev kho curcumin hauv cov nas endometriosis tau pom lub luag haujlwm tiv thaiv lipid peroxidation thiab protein oxidation [114]. Hauv kev sim cov qauv nas, curcumin txo qhov hnyav thiab ntim ntawm cov ntaub so ntswg endometriotic nyob rau hauv ib koob tshuaj ntawm kev txo qis VEGF qhia [115]. Curcumin inhibited endometriotic foci txoj kev loj hlob los ntawm kev cuam tshuam nrog microvessel ntom, qhia muaj zog antiangiogenic kev ua haujlwm [116]. Hauv cov ntsiab lus, curcumin tsom ntau yam molecular

thiab cellular mechanisms nyob rau hauv pathogenesis ntawm endometriosis, xws li o, txuas, thiab angiogenesis, uas yuav ua tau zoo heev thiab txo cov kev tswj endometriosis.

Interestingly, Lub Tsev Kawm Ntawv Kho Mob ntawm Vienna tau nrhiav cov neeg mob endometriosis rau qhov kev sim tshuaj ntsuam xyuas kev sim ntawm curcumin noj tshuaj ntxiv hu ua Flexofytol, muab tshuaj rau hauv ob lub tshuaj uas muaj 42 mg ntawm curcumin ob zaug hauv ib hnub rau plaub lub hlis. Cov kws kho mob xav tias qhov mob nruab nrab ntawm qhov pib mus rau plaub lub hlis tom qab pib kho mob yuav yog thawj qhov txiaj ntsig ntsuas. Raws li cov txiaj ntsig thib ob, lawv tau txheeb xyuas qhov txo qis ntawm cov hnub nrog qhov mob, txo qis ntawm dyspareunia, dysuria, dyschezia, thiab kev hloov pauv ntawm lub neej zoo thiab kev ua haujlwm ntawm kev sib deev (Clinical Trials.gov ID: NCT04150406).

5.3. Phenolic Acids Rosmarinic Acid

Rosmarinic acid, pom nyob rau hauv ntau yam nroj tsuag xws li Rosmarinus Officinalis, Salvia officinalis, thiab Thymus sp., yog ib tug phenolic compound nrog ntau yam kev noj qab haus huv-txhim kho thiab kho cov khoom [155,156]. Nws cov tshuaj tiv thaiv kab mob antioxidant, tiv thaiv kab mob, tiv thaiv qog, thiab tiv thaiv angiogenic zog tuaj yeem cuam tshuam rau kev kho mob endometriosis. Farella's team (2018) tau soj ntsuam cov tshuaj tiv thaiv endometriosis muaj peev xwm ntawm rosmarinic acid thiab carnosic acid (phenolic diterpene), uas tshwm sim ua ke hauv rosemary (Rosmarinus officinalis) thiab sage (Salvia officinalis). Lawv siv tib neeg endometrial stromal cell kab lis kev cai thiab BALB / c qauv nrog induced endometriotic-zoo li qhov txhab. Hauv txoj kev tshawb no, ob lub tebchaw suppressed cell proliferation thiab txo qhov loj ntawm endometriotic lesions nyob rau hauv nas. Tsis tas li ntawd, rosmarinic acid txhawb apoptosis nyob rau hauv cov ntaub so ntswg endometriotic thiab txo intracellular ROS txuam nrog tib neeg endometrial stromal hlwb [97].

5.4.Stilbenes Resv eratrol

Resveratrol yog phytoalexin polyphenol, uas muaj ntau yam nroj tsuag ib txwm tsim nyob rau hauv teb rau ultraviolet hluav taws xob thiab fungal kab mob [157l. Resveratrol ib txwm tshwm sim hauv ntau hom nroj tsuag, suav nrog txiv laum huab xeeb, berries, legumes, thiab nyom; Txawm li cas los xij, resveratrol qhov chaw nplua nuj tshaj plaws yog txiv hmab txiv ntoo thiab cawv liab. Thawj cov ntawv tshaj tawm txog kev tshawb fawb txog qhov tshwm sim resveratrol tau nthuav tawm hauv xyoo 1992 tau qhia tias resveratrol yog tus neeg sawv cev cardioprotective hais rau Fabkis txoj kev tsis sib haum xeeb thiab pib tshawb fawb ntau yam ntawm cov khoom siv no [158]. Dhau li ntawm nws cov teebmeem cardioprotective, resveratrol tau dhau los ua neeg paub zoo vim nws cov peev xwm tiv thaiv kabmob kheesxaws, thawj zaug pom ob peb xyoos tom qab, raws li tau tshwm sim los ntawm nws lub peev xwm los tawm tsam txhua theem carcinogenesis [159]. Txij thaum ntawd los, ntau cov kev tshawb fawb qhia tias resveratrol muaj ntau yam kev noj qab haus huv cov khoom, nrog rau kev tiv thaiv mob qog noj ntshav, tiv thaiv kab mob, tiv thaiv oxidant, tiv thaiv kab mob, thiab tiv thaiv angiogenic zog [160]. Nws tseem tuaj yeem tiv thaiv ntau yam kab mob uas muaj hnub nyoog, xws li kab mob plawv, ntshav qab zib, mob caj dab, thiab mob neurodegenerative [161].

Ob peb lub hom phiaj molecular rau kev tiv thaiv los ntawm resveratrol tau raug npaj. COX-2, tus tswj hwm tseem ceeb ntawm kev loj hlob ntawm cov qog nqaij hlav thiab cov hlab ntshav homeostasis, tau raug inhibited los ntawm resveratrol nyob rau hauv vitro thiab hauv vivo qauv ntawm cov qog nqaij hlav. Cov txiaj ntsig ntawm cov hlab plawv ntawm resveratrol xa mus rau nws cov cuab yeej los pab txhawb endothelial NOpro-duction, tiv thaiv cov txheej txheem thrombogenic thiab atherogenic los ntawm kev so vascular du leeg hlwb thiab txhawb cov ntshav khiav [161]. Resveratrol lub peev xwm los txuas ntxiv kev ua neej nyob rau hauv kev ua kom lub suab ntsiag to hom ntaub ntawv tswj hwm homolog 1 (SIRT1), chav kawm IⅢI histone deacetylase lub luag haujlwm rau kev tswj cov noob qhia, kho DNA, metabolism, teb rau oxidative kev nyuaj siab, mitochondrial muaj nuj nqi, thiab biogenesis. SIRT1 tiv thaiv cov hlwb los ntawm kev hloov pauv ntawm oncogenic thiab ua rau cov hom phiaj tshwj xeeb hauv cov txheej txheem qhia xov tooj ntawm tes hauv cov qog. Resveratrol tau raug tshaj tawm tias muaj cov tshuaj tiv thaiv neuroprotective, anti-tumorogenic zog ntawm SIRT1 ua kom [162].

Resveratrol yog dav suav hais tias yog tus neeg sawv cev tshiab tshiab hauv lwm txoj hauv kev thiab kev kho mob ntxiv ntawm cov mob hnyav los ntawm kev cuam tshuam ntau txoj hauv kev cuam tshuam nrog kev sib kis kab mob. Resveratrol anti-inflammatory muaj peev xwm, suav nrog prostaglandin synthesis inhibition, tau qhia tias tej zaum yuav pab tiv thaiv thiab kho endometriosis [163]. Cov nyhuv kho ntawm resveratrol ntawm endometriosis yog thawj zaug soj ntsuam los ntawm Bruner-Tran li al.(2011). Lawv tau tshaj tawm tias resveratrol tuaj yeem txo tus lej thiab qhov loj ntawm cov kab mob endometriotic hauv tus qauv nas liab qab. Cov nyhuv resveratrol cuam tshuam nrog txo qis endometrial cell proliferation thiab nce apoptotic cell tuag hauv qhov txhab. Hauv kev tshawb fawb hauv vitro, resveratrol induced concentration-dependent txo nyob rau hauv endometrial stromal cell invasiveness [117]. Txij li daim ntawv tshaj tawm ntawd, kev txaus siab ntawm resveratrol tau nce zuj zus, suav nrog resveratrol cov txheej txheem tiv thaiv hauv endometriosis.

Hauv kev tshawb fawb tom ntej, resveratrol txo qis tib neeg endometrial epithelial cell proliferation thiab nce apoptosis hauv thawj kab lis kev cai|119]. Piv nrog rau cov tshuaj estrogen, resveratrol ua raws li ib tug agonist ntawm tsawg concentrations, whereas nws ua si lub luag hauj lwm antagonistic ntawm siab concentrations. Nyob rau hauv immunocompromised nas qauv ntawm endometriosis, txo cell proliferation nyob rau hauv qhov txhab tau pom nrog concomitantly txo epithelial Era theem [118]. Ntxiv mus, ib txoj kev tshawb fawb tsis ntev los no tau qhia tias kev kho resveratrol txo qis kev qhia ntawm IGF-1 thiab HGF, pivotal molecules hauv endometriotic lesion kev loj hlob thiab angiogenesis, hauv eutopic thiab ectopic endometrial stromal hlwb tau los ntawm cov neeg mob endometriosis [120]. Lwm qhov kev tshawb fawb tsis ntev los no tau saib cov txiaj ntsig ntawm resveratrol ntawm ntau qhov sib txawv ntawm cov ntaub so ntswg loj hlob, angiogenesis thiab NO secretion, thiab qhia txog cov noob caj noob ces ntawm apoptosis hauv tib neeg endometriotic thiab endometrial cov ntaub so ntswg hauv 3D kab lis kev cai. Qhov nruab nrab ntawm kev loj hlob ntawm endometriotic thiab endometrial cov ntaub so ntswg pom tau hais tias tseem ceeb koob tshuaj-dependent inhibition thaum kho nrog resveratrol. Tsis tas li ntawd, cov koob tshuaj resveratrol- thiab lub sij hawm-dependently txo tsis muaj concentration hauv endometriotic thiab endometrial cov ntaub so ntswg. Cov ntaub ntawv sim kuj tau pom tias qhov kev qhia ntawm cov noob proapoptotic P53, BAX, CASP3, thiab SIRT1 tau nce ntau hauv cov ntaub so ntswg endometriotic thiab endometrial tom qab kho nrog ntau yam tshuaj resveratrol [121]. Kev tshawb fawb hauv vitro tau pom tias cov tshuaj tiv thaiv kab mob ntawm resveratrol tau tshwm sim hauv kev tawm tsam ntawm MCP-1, I-6, I{16}}, thiab RANTES hauv ectopic endometrial stromal hlwb ntawm cov poj niam endometriotic [122] .

Ntau qhov kev cog lus zoo ib yam hauv vivo cov kev tshawb fawb qhia txog cov txiaj ntsig zoo ntawm resveratrol ntawm cov kab mob endometriotic hauv cov qauv tsiaj. Namely, resveratrol attenuated inflammatory teb nyob rau hauv lub peritoneal ib puag ncig thiab txo endometriosis txoj kev loj hlob los ntawm nws anti-angiogenic thiab anti-inflammatory zog. Resveratrol's inhibitory nyhuv raug soj ntsuam los ntawm kev sim ua rau cov kab mob endometriosis nas qauv. Cov txiaj ntsig tau pom qhov txo qis hauv qhov cog cog loj, qhov txo qis hauv VEGF thiab MCP-1 hauv cov kua dej hauv lub cev thiab VEGF hauv cov ntshav, thiab ua rau muaj kev cuam tshuam ntau ntawm VEGF qhia hauv cov ntaub so ntswg endometriotic tsis pub dhau kev hloov pauv histological hauv endometriotic foci tom qab { {3}}kev kho ib hnub nrog resveratrol ntawm ib koob ntawm 10 mg / kg [123]. Hauv cov qauv nas zoo sib xws nrog induced endometriosis, resveratrol qhov kev ua tau zoo tau raug soj ntsuam raws li nws lub peev xwm los inhibit angiogenesis thiab o. Tom qab 21-hnub kev tswj hwm, resveratrol hauv ib koob tshuaj 60 mg / kg txo qhov chaw cog thiab txo VEGF thiab MCP-1 qib. Interestingly, resveratrol lub peev xwm kho tau zoo piv nrog leuprolide acetate, siv los ua tshuaj hauv kev kho mob endometriosis |124]. Hauv lwm txoj kev tshawb fawb hauv cov qauv nas endometriosis, resveratrol tau pom tias muaj txiaj ntsig zoo rau kev cog qoob loo endometriotic vim nws cov khoom muaj zog antioxidant. Tom qab kev kho mob, cov kws tshawb fawb tau pom qhov txo qis ntawm cov tshuaj endometriotic implants thiab nce SOD thiab GPX cov dej num hauv nas 'sera thiab cov ntaub so ntswg [125]. Hauv kev tshawb fawb tsis ntev los no, Kong et al. (2020) nthuav qhia lub luag haujlwm ntawm kev hloov pauv ntawm epithelial-mesenchymal hauv endometriosis's pathogenesis thiab resveratrol suppressive peev xwm nyob rau hauv metastasis-txog txoj hauv kev hauv endometriosis. Resveratrol inhibited kev loj hlob, kev tsiv teb tsaws, thiab ntxeem tau ntawm endometrial stromal hlwb nyob rau hauv vitro kab lis kev cai, thiab suppressed ectopic endometrium loj hlob nyob rau hauv tus nas endometrio-sis qauv. Pab pawg neeg Kong tau pom tias resveratrol inhibited cov txheej txheem hloov pauv ntawm epithelial-mesenchymal hauv endometriosis nas thiab endometrial hlwb. Hauv cov qauv kev sim no, resveratrol downregulated qhov kev qhia ntawm metastasis-txuas nrog protein 1 (MTAl) thiab cov ntaub ntawv hloov pauv zinc ntiv tes E-box-binding homeobox 2 (ZEB2), cov khoom tseem ceeb uas ua rau metastasis los ntawm kev txhawb kev hloov pauv ntawm cov hlwb epithelial rau hauv mesenchymal hlwb. [126].

Cov kws kho mob kuj tau tshawb xyuas cov peev xwm kho tau ntawm resveratrol hauv endometriosis hauv ntau qhov kev sim tshuaj. Feem ntau cov kev tshawb fawb soj ntsuam feem ntau presupposed resveratrol lub peev xwm los potentiate cov kev ua ntawm lub qhov ncauj contraceptives nyob rau hauv kev kho mob ntawm endometriosis los ntawm nws hypo-estrogenic kev txiav txim [164]. Maia et al. (2012) tau soj ntsuam qhov zoo ntawm kev koom tes ntawm resveratrol nrog cov tshuaj tiv thaiv qhov ncauj rau kev tswj cov mob endometriosis. Lawv tau saib xyuas cov nyhuv resveratrol hauv 12 tus neeg mob uas tsis tau txais qhov mob nyem tom qab kho nrog cov tshuaj tiv thaiv qhov ncauj uas muaj drospirenone nrog ethinylestradiol. Tom qab ob lub hlis ntawm kev siv 30 mg ntawm resveratrol rau tus qauv kev kho tshuaj hormone, 82 feem pua ​​​​ntawm cov neeg mob tau tshaj tawm txog kev daws teeb meem ntawm dysmenorrhea thiab txo qhov mob tshwm sim. Hauv ib qho kev sim cais, tib cov kws sau ntawv tau tshawb xyuas resveratrol lub peev xwm los tswj COX-2 thiab aromatase qhia, vim tias txo cov enzymes no tseem ceeb hauv kev kov yeej qhov mob pelvic. Cov kws kho mob tau tshuaj xyuas cov aromatase thiab COX-2 qhia hauv cov ntaub so ntswg endometrial ntawm 42 tus neeg mob, ntawm 26 tus neeg mob tau muab kev sib xyaw ntawm resveratrol nrog tshuaj tiv thaiv qhov ncauj. Cov txiaj ntsig tau pom tias kev kho ua ke ua tiav tau zoo txo ​​qhov aromatase thiab COX{11}} qhia piv nrog kev kho tshuaj hormone ib leeg [127].

Lwm qhov kev sim tshuaj ntsuam xyuas kev siv cov tshuaj resveratrol ua ib qho kev kho mob ntawm qhov mob tau pom tias muaj kev sib tw, ob qhov muag tsis pom, tswj kev sib piv ntawm resveratrol piv rau cov placebo los kho cov mob endometriosis. Txoj kev tshawb no koom nrog 44 tus poj niam tsim nyog nrog kev kuaj mob laparoscopic ntawm endometriosis. Nws tau tshawb xyuas seb 40 mg / hnub ntawm resveratrol nrog cov tshuaj tiv thaiv kab mob monophasic tuaj yeem txo cov qhab nia mob tom qab 42 hnub ntawm kev tswj hwm. Cov txiaj ntsig tau nthuav tawm tsis muaj qhov sib txawv ntawm kev kho mob thaum sib piv cov qhab nia mob ntawm pab pawg tom qab kev kho mob nrog resveratrol ntxiv rau cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob nrog cov placebo. Cov txiaj ntsig thib ob ntawm qhov kev tshawb fawb no ntsuas CA-125 thiab qib prolactin. Cov ntaub ntawv tau txais tau sau tseg qhov txo qis hauv CA-125 plasma qib hauv ob pawg placebo thiab resveratrol tab sis tsis pom kev hloov pauv hauv qib prolactin [165].

Tsis ntev los no, cov kws tshawb fawb ntawm Tehran University of Medical Sciences tau ua qhov kev tshawb fawb soj ntsuam, uas suav nrog 34 tus neeg mob endometriosis cuam tshuam txog kev xeeb tub. Cov neeg koom nrog txoj kev tshawb no, sib npaug thiab sib npaug sib faib ua pawg tswj hwm thiab kho mob, tau noj 400 mg resveratrol ob zaug ib hnub rau 12-14 lub lis piam nrog rau cov tshuaj tiv thaiv qhov ncauj hauv peb lub lis piam dhau los. Kev sim tshuaj xyuas tau pom tias resveratrol tuaj yeem hloov kho cov txheej txheem o hauv cov poj niam endometrium. Cov txiaj ntsig tau txais tau qhia txog kev txo qis ntawm mRNA thiab cov protein qhia ntawm MMP-2 thiab MMP-9 hauv cov ntaub so ntswg endometrium, endometrium kua, thiab cov ntshav qabzib tom qab kev kho resveratrol. Hauv kev xaus, cov kws sau ntawv tau hais txog qhov yuav tsum tau muaj kev tshawb fawb ntxiv txog cov txiaj ntsig ntawm resveratrol ntawm MMP-2 thiab MMP-9 qhia hauv cov poj niam uas muaj endometriosis [128].

Tib pawg ntawm cov kws tshawb fawb tau tshuaj xyuas cov txiaj ntsig ntawm resveratrol ntawm VEGF thiab TNF- qhia hauv eutopic endometrium ntawm cov neeg mob infertile nrog endometriosis nyob rau hauv lub qhov rais implantation nyob rau hauv ib tug randomized exploratory sim. Raws li yav dhau los, txoj kev tshawb fawb tau koom nrog 34 tus neeg mob, muab faib ua pab pawg tswj hwm cov placebo thiab pab pawg kho mob ntawm 17 tus neeg mob tau txais 400 mg ntawm resveratrol rau 12 txog 14 lub lis piam. Cov txiaj ntsig tau pom tau hais tias resveratrol txo VEGF thiab TNF- qhia ua cov cim ntawm angiogenesis thiab mob. Raws li cov kws sau ntawv, kev sim tshuaj ntxiv yog tsim nyog los nthuav qhia resveratrol kev koom tes hauv ntau txoj hauv kev xws li angiogenesis, o, thiab oxidative kev nyuaj siab kom paub meej tias resveratrol muaj peev xwm raws li kev kho mob hauv kev kho mob endometriosis [129].

6. Cov lus xaus thiab cov kev xav yav tom ntej

Cov txheej txheem pathophysiologic koom nrog hauv kev tsim cov kab mob heterogeneous, zoo li endometriosis, tseem tsis tau paub meej, thiab muaj kev kho mob tam sim no txwv. Kev tshawb pom ntawm cov tshuaj kho tshiab thiab kev txhim kho hauv cov tswv yim kho mob uas twb muaj lawm zoo li tsim nyog. Ntuj polyphenols nthuav tawm pleiotropic kev ua haujlwm profile thiab tuaj yeem tiv thaiv cov kab mob endometriotic los ntawm kev sib cuam tshuam nrog ntau lub hom phiaj molecular cuam tshuam nrog endometriosis, xws li cell proliferation, apoptosis, o, oxidative stress, angiogenesis, thiab invasiveness. Ntxiv mus, qee qhov ntawm cov phytochemicals no tuaj yeem ua rau muaj zog phytoestrogen nyhuv modulating estrogen tes hauj lwm yam tsis muaj kev cuam tshuam loj heev cuam tshuam rau cov tshuaj tiv thaiv estrogenic tiv thaiv endometriosis. Cov txiaj ntsig muaj nyob ntawm qee qhov kev tshawb fawb qhia tias cov khoom siv bioactive ntuj tsis cuam tshuam rau fertility, kev ua me nyuam hauv plab, thiab kev loj hlob ntawm cov xeeb ntxwv [105,108]. Tsis tas li ntawd, lwm txoj kev kho mob endometriosis nrog kev kho mob zoo ib yam li kev tswj hwm ib puag ncig yog pheej yig thiab tsim nyog rau cov neeg mob endometriosis mus sij hawm ntev thiab nyab xeeb kev kho mob.

Txawm li cas los xij, cov pov thawj uas twb muaj lawm qhia txog qhov ntxim nyiam ntawm cov khoom muaj txiaj ntsig zoo rau kev kho mob endometriosis tau muab los ntawm kev tshawb fawb ua ntej hauv vitro thiab kev tshawb fawb tsiaj. Txawm hais tias muaj ntau qhov kev sim tshuaj tau ua tiav, tseem muaj pov thawj tsis txaus los pom zoo siv cov tswv yim kho mob hauv kev siv tshuaj kho mob txhua hnub. Ib sab, cov ncauj lus kom ntxaws pharmacokinetic thiab pharmacodynamic cov ntaub ntawv ntawm kev tswj hwm ntawm ntau cov polyphenols tseem tsis tau muaj; Yog li, kev tshawb fawb soj ntsuam ntxiv yog tsim nyog los lees paub qhov ua tau zoo ntawm cov tshuaj no hauv kev kho mob endometriosis. Lwm qhov kev txwv tseem ceeb yog qhov tsis muaj qhov cuam tshuam ntawm lub cev ntawm cov tshuaj polyphenol siab tsis tuaj yeem ua tiav ntawm kev noj zaub mov niaj hnub, feem ntau siv rau hauv kev sim endometriosis hauv vitro qauv. Tsis tas li ntawd, feem ntau ntawm cov kev tshawb fawb hauv vitro tau pom tias muaj peev xwm kho tau ntawm polyphenols tshwm sim yam tsis tau xav txog lawv txoj kev zom zaub mov thiab cov metabolism hauv plab hnyuv microorganisms. Cov metabolism hauv plab hnyuv loj ntawm polyphenol com-pounds cuam tshuam rau lawv cov bioavailability thiab plab hnyuv nqus thiab, yog li ntawd, lawv cov kev kho mob zoo hauv cov ntaub so ntswg thiab kabmob. Tsis tas li ntawd, nyob rau hauv kev sib txuas cov neeg ua hauj lwm ntuj nrog cov pa pharmacotherapy, cov kev tshawb fawb ntawm bioactive compound-drug interactions yog yuav tsum tau. Kev paub txog cov txheej txheem meej ntawm kev ua ntawm cov khoom sib txuas hauv lub cev endometriosis lub network ntawm ntau lub xov tooj ntawm tes taw qhia txoj hauv kev yog xav tau, thiab xav tau kev tshawb fawb ntxiv ntawm cov ncauj lus no.

Nws yog ib qho tsim nyog hais tias polyphenols 'kev siv ntau dhau, tshwj xeeb tshaj yog cov tshuaj muaj zog heev uas cais tawm ntawm cov zaub mov matrix, yuav ua rau muaj kev phom sij rau kev noj qab haus huv [166]. Txo cov thiamin thiab folic acid thauj tau raug tshaj tawm vim polyphenols 'ua ntej-absorptive kev sib cuam tshuam thaum digestive hauv plab hnyuv. Ib yam li ntawd, kev hloov pauv tseem ceeb hauv qee cov tshuaj 'kev muaj peev xwm ntawm bioavailability tuaj yeem pom vim yog polyphenols kev cuam tshuam nrog cov tshuaj thauj khoom lossis cov enzymes digestive [167]. Tsis tas li ntawd, polyphenols tuaj yeem ua rau cov hlau-chelating nyhuv thiab txo cov hlau nqus, uas ua rau cov hlau tsis zoo. Cov kev tshawb fawb luam tawm yav dhau los tau pom tias cov kua txiv hmab txiv ntoo los ntawm isoflavones cuam tshuam rau cov neeg mob endometriosis thiab estrogen-sensitive mis thiab endometrial cancer vim estrogen-zoo li biologic kev ua ub no thiab cov tshuaj hormone-interfering zog [168,169]. Txawm li cas los xij, kev sim tshuaj ntsuam xyuas tsis ntev los no tsis tau lees paub qhov tsis zoo ntawm isoflavones thiab lwm yam phytoestrogens rau cov poj niam uas muaj kev pheej hmoo thiab mob qog nqaij hlav estrogen-dependent [170,171]. Raws li cov ntaub ntawv tshiab tshaj plaws, cov khoom noj uas muaj isoflavone thiab cov tshuaj ntxiv yog cov khoom noj muaj txiaj ntsig zoo rau cov poj niam tom qab yug menyuam thiab cov neeg mob endometriosis [99,172].

Hauv peb lub tswv yim, kev kho mob endometriosis ntuj tsis zoo li yuav ua haujlwm tshwj xeeb rau kev kho mob thiab ua kom muaj txiaj ntsig zoo, tab sis lawv tuaj yeem kov yeej cov tsos mob ntsig txog endometriosis. Ua ke nrog cov txheej txheem kev kho mob zoo ib tus zuj zus los kho cov neeg mob cov kev xav tau, cov khoom siv ntuj tsim tuaj yeem ua ib feem tseem ceeb thiab lub hauv paus kev taw qhia ntawm kev txhim kho cov tswv yim kho mob endometriosis yav tom ntej.

Cov Nyiaj Txiag: Cov ntawv tshaj tawm no tau koom nrog nyiaj txiag nyob rau hauv lub moj khaum ntawm Polish Ministry of Science thiab Kev Kawm Qib Siab txoj haujlwm: "Regional Initiative Excellence" hauv xyoo 2019-2022(No. 005/RID/2018/19)", nyiaj txiag 12 000 000 PLN. Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.