Mechanism ntawm Qizhi Tongqiao Tshuaj Ntsiav Tshuaj Benign Hyperplasia thiab erectile kawg raws li cov network thiab molecular docking ⅱ

Daim duab 2 "Tshuaj Yeeb Tshuaj-Tshuaj-Hom Tshuaj-Kab Mob" Network Diagram

2.4 PPI network siv thiab cov hom phiaj kev tsom xam

Raws li cov qauv, PPI network daim duab tau tsim, raws li muaj nyob hauv daim duab 3. Sab saum toj 10 cov hom phiaj tseem ceeb tau tshuaj xyuas raws li daim duab 4a; Ib qho ntxiv, 10 lub chaw teeb tsa tau muaj dua los ntawm Cytohubba Plug-in MCC, raws li muaj nyob hauv Daim Duab 4B. Cov tub ntxhais tseem ceeb cov hom phiaj tau txais tom qab kev sib tshuam yog: AKT1, IL6, ESR1, Stat3, Tnf, Jun, casp3.

3 Qtc kho cov kab mob sib txawv nrog tib lub hom phiaj kev kho mob rau BPH thiab ED PPI network

2.5 Mus ua haujlwm thiab Keyghaway kev txheeb xyuas kev ua haujlwm

Mus rau kev txheeb xyuas tag nrho cov2,103Cov txheej txheem txheeb xyuas kev (BP), suav nrogteb rau cov tshuaj hormones, kev cai zoo ntawm cell tsiv teb tsaws, thiab kev cai zoo ntawm phosphorherlation cov txheej txheemCov. Tag nrho ntawm106Kev tivthaiv Cellular (CC) tau txheeb xyuas, suav nrogreceptor complex, membrane rafts, thiab focal adhesionsCov. Tsis tas li ntawd,174molecular muaj nuj nqi (MF) cov ntsiab lus tau txheeb xyuas, suav nrogProtein Kinase kev ua si, cov khoom sib txuas ua ke khi, thiab cov protein homodimerization kev ua siCov. Sab saum toj20cov ntsiab lus los ntawm txhua pawg tau nthuav tawm ua piv txwv hauvDaim Duab 5.

KeGG EnricSment tshuaj xyuas pom193Kev piav qhia txoj hauv kev, nrog rauCov kev mob cancer-cuam tshuam, prostate cancer-prostate bathways, NF-KAPTA BOrcomaling txoj kev, nrog sab saum toj20Txoj kev qhia ua piv txwv hauvDaim Duab 6.

2.6 molecular docking cov txiaj ntsig

Hauv txoj kev tshawb no,tus yaj, ib qho kev ua haujlwm nquag uas pom muaj nyob hauv ntau cov tshuaj suav hauv qtc, tau xaiv rau kev tshawb xyuas molecular tsom xam. Lub zog siv hluav taws xob tsis muaj nuj nqis nruab nrab ntawm quercetin thiab cov hom phiaj tseem ceeb yog muaj nyob hauvRooj 3Cov. Tsuas yogAKT1 thiab TNF, lub zog siv hluav taws xob rau cov protein uas muaj tas txhuatsawg dua -5, qhia tias ib qho kev sib txuas lus ruaj khov. Docking cov txiaj ntsig nrog kev siv lub zog hluav taws xobtsawg dua -5yog nthuav tawm hauv3D VisualizationsUa piv txwv hauvDaim duab 7.

5 Mus ua haujlwm kev soj ntsuam kev ua haujlwm ntau ntxiv BP, CC, MF peb-hauv-ib daim duab

3 kev sib tham

Ob yambenign prostatic hyperplasia (bpph)thiabErectile kawg li (ED)yog cov etological etological uas cuam tshuam rau qhov ua tau zoo ntawm lub neej ntawm cov neeg laus-hnub nyoog thiab cov laus. Txo cov tshuaj tiv thaiv kab mob qis (Luts) tshwm sim los ntawm BPP tuaj yeem cuam tshuam rau lub neej txhua hnub, thaum Comorbid ed txuas ntxiv ua rau muaj kev puas tsuaj rau lub cev thiab lub hlwb. Cov kev tshawb fawb tau pom tias ntau cov txheej txheem carophysiological, suav nrogTxo tsis-CGMP kev piav qhia, ua kom cov Rauv / pob zeb taw qhia txoj hauv kev, nce kev xav txog kev ua haujlwm ntawm txoj kev ua si, thiab atherosclerosis, pab txhawb rau kev sib koom ua ke ntawm bph thiab ed[19].

Hauv Western tshuaj, kev kho mob rau BPH thiab ed comorbidity feem ntau koom nrogKev siv phosphodiesterase hom 5 tus neeg ua yeeb yam (tadalafil thiab tadalafil) ib leeg lossis hauv kev sib xyaw nrog -Receptor blockers (20-21]Cov. Txawm li cas los xij, cov kev kho no feem ntau phiaj rau ib qho kev piav qhia txoj hauv kev lossis cov phiaj xwm molecular, whereas kev txhim kho ntawm cov kab mob no cuam tshuamNtau yam mechanisms, ntau lub hom phiaj, thiab complex signaling pathwaysCov. Yog li ntawd, kev kho mob niaj hnub no muaj qee qhov kev txwv.

Tsoos suav tshuaj (TCM) muaj cov txiaj ntsig tshwj xeeb thaum nws siv tau los ntawm kev cuam tshuam los ntawmNtau hom phiaj thiab ntau-pathway mechanismsCov. Kev soj ntsuam cov tshuaj ntsuam thiab qhov tseeb hais qhia tias TCM ze ntawm"Tonifying Qi thiab txhawb kev ntshav ncig, nourishing lub raum, thiab thaiv tsis tau meridians"tuaj yeem ua tiav qhov"Kev kho mob ntawm cov kab mob sib txawv nrog tib txoj kev"Rau qee tus neeg mob nrog bph thiab ed comoremidity. Cov kev tshawb fawb tau tshaj tawm[22-23]Ntawd tcm tshuaj ntsuab khaws raws li "Qi-tauv-activing" tuaj yeem tswj hwm cov prot-anteins, yog li txhawb nqa apoptosis thiab inhibiting bph. Ib qho ntxiv, cov tshuaj ntsuab no yuav ua rau muaj kev kho mob extrert siv los ntawm kev tswj hwm covTFF / WNT signaling txoj kevthiab downregulating cov kev qhia ntawmTFF2, WNT4, thiab WNT6.

Peb pab pawg neeg soj ntsuam yav dhau los thov"sib haum xeeb Qi thiab cov ntshav"yog qhov tseem ceeb rau kev ua haujlwm zoo li erectile, thaum"Cov QRARARMONICized QI THIAB NTSHAV"yog lub ntsiab lus edcologism ntawm ed. Thiaj li,TonifyingLev thiab txhawb cov ntshav ncigyog ib lub tswv yim tseem ceeb rau kev kho ed[24]Cov. Cov kev tshawb fawb soj ntsuam tau pom tias ua ke TCM tshuaj ntsuab nrogtadalafilrau kev kho mob ntawm me me mus rau nruab nrab ED tuaj yeem ua tau zooTxo cov tshuaj yuav tsum tau noj ntawm tadalafil, qis dua qhov tshwm sim ntawm kev tsis zoo, thiab txhim kho kev kho kom ntev [25].

Tam sim no, pab pawg tshawb fawb muajClinically thiab simqhia tau tiasQtctuaj yeem txhim khoCov tsos mob thoob ntiaj teb tau qhab nia (iPS) [12]Cov. Tsis tas li ntawd, qtc tseem ceeb inhibitsexogenous Testosterone-induced prostatic hyperplasia hauv nas, txhim kho prostate histosate hloov pauv, thiab suppresses prostate epithelial thickening. Cov txheej txheem tom qab tuaj yeem muaj kev cuam tshuam ntawmBcl -2, PCNA, hif -1, thiab vegf protein qhia, raws li ib tugnce nyob rau hauv bax / bcl -2 piv [26].

Hauv cov ntsiab lus xaus, theoretical, tshuaj ntsuam, thiab cov pov thawj sim qhia tau tiasQTC muaj lub peev xwm los kho ob qho tib si bph thiab ed ib txhijCov. Hauv txoj kev tshawb no, peb ua haujlwmNetwork Partel Pharpacology thiab molecular docking txoj kevrau prelimined tshawb txogKhoom siv hauv paus thiab tej zaumntawmQTC's "Ib qho kev kho rau cov kab mob sib txawv" ua rau bph thiab ed, tsom rau kev tshem tawm ib feem ntawm nws txoj kev tshawb fawb.

Los ntawm kev thov cov kev xaiv tshwj xeeb, peb pomCov tub ntxhais muaj cov tebchaw hauv Qtc rau BPH thiab Ed Kho, suav nrogCrocin, dej cawv, 3, 9- di-o-methyl-nissolin, quercetin, thiab Kaempferol, ntawm cov twgtus yajyog ib feem tiv thaiv hauv ntau cov tshuaj ntsuab TCM.Fu li al. [27]pom tiastus yajtauinhibit bph los ntawm kev tsim txom oxidative kev nyuaj siab thiab ua kom zoo rau kev ua kom pom kevCov. Tsis tas li ntawd,Olabiyi li al. [28]tshawb xyuas lub tshuab uasQrealTin txhim kho kev ua haujlwm erectile hauv ED qauv nasthiab pom tiasquaretin txhim kho erectile muaj nuj nqi los ntawm kev nce nitric oxide (tsis muaj).

Mus thiab Keg GgSricks tsom xam ntawm tusOverlapping cov hom phiaj nruab nrab ntawm cov khoom sib txuas thiab cov kab mobqhia tiasQTC cov kev kho mob kho kom zoo rau BPH thiab Ed Muaj ntau cov txheej txheem biological (BP) thiab kos npe rau txoj kev tswj hwm txoj cai nyuaj.

(1) NF-κb signaling txoj hauv kev (txoj kev 16)

Nf-κb yog aPleioRopic Cov Khoom Sib Sauuas tswj cov kev sib txuas ntawm cov kev ua haujlwm ntawm cov neeg txhawb nqa cuam tshuam nrog cov canniad city.Ko li al. [29]pom tias NF-κB kev ua kom zoo sib xws nrog kev nce qib ntawmBPH, nrog cov neeg mob ua kom pom kev ua haujlwm NF-κb uas qhia tau ntau dua prostate stromal ntau dua li cov tsis muaj kev ua kom. Zoo sib xws,Li li li li al li al. [30]nrhiav tau tiasPseudomonas Aeruginosa Lipopolysaccharide (LPS)tuaj yeem qhib lub NF-κb txoj hauv kev, ua rauOpmation, prooliferation, thiab epithelial-mesenchymal hloov (EMT)Thaum inhibiting apoptis ntawm prostate hlwb, yog li txhawb nqaBph kev vam meej.

Tsis tas li ntawd,Akintunde li al. [31]kawmNtsuas Qe Tawmnyob rau hauv ib qho mobEd much qauvthiab pom tias nwsDownregulated NF-κB, Txhim kho cov kev ua haujlwm endothelial, thiab rov txhim kho erectile muaj nuj nqi. Tshav thiab Al. [32]kho ntshav qab zibEd nasnrogpaaol, qhia tias nws yuav txhim khoEdlos ntawm inhibiting lubHmgb1 / npau taws / NF-κb txoj kevthiab kev tswj hwmO Envothelial tab tom, Fibrosis, thiab ApoptosisCov. Cov kev tshawb pom no qhia tau tias covNf-κb signaling txoj kev ua si lub luag haujlwm tseem ceeb hauv cov pathogenesis ntawm ob qho bph thiab ed.

Quercetin, ib qho ntawm covCov tub ntxhais muaj cov tebchaw hauv QTC, yog dav pom nyob rau hauv ntau cov tshuaj hauv Suav cov tshuaj. Cov kev tshawb fawb tau pom tiasquartin tuaj yeem tswj hwm lub Notx2 / Ros / NF-κb txoj hauv kev hauv lub ntsws epithelial hlwb, liinhibiting lps-induced oxidative kev ntxhov siab thiab phais cov lus teb [33]Cov. Xav txog cov kev tshawb fawb dhau los ntawm cov txiaj ntsig ntawmquercetin hauv bph thiab ed, peb horgothesize ntawdNF-κB taw tes taw qhia lub luag haujlwm tseem ceeb hauv QTC txoj kev kho tshuabRau cov mob no.

(2) Cov kab mob ntshav qab zib ntsig txog txoj kev (txoj kev 2, 13, thiab 20)

Ntau cov phiajcim cov pathwates hauv kev tsom xam muaj feem nrogntshav qab zib, qhia txog lubQhov tseem ceeb ntawm cov ntshav qab zib-ntsig txog txoj hauv kev hauv pathogenesis ntawm bph thiab ed. Ntshav Qab Zib Mellitus (DM)yog aCov teeb meem metabolic tsis sib haum los ntawm hyperglycemia, thiab nrog kev laus thiab lub sijhawm ntev ntawm tus kab mob ntev, nws tuaj yeem ua rau aCov teeb meem ntawm cov teeb meem.

Ed yog ib qho ntawm feem ntau cov teeb meem ntawm cov ntshav qab zib, nrog aKev vam meej thoob ntiaj teb ntawm 65.8% ntawm cov neeg mob ntshav qab zib, cuam tshuam rau lawvlub cev thiab lub hlwb zoo [34]Cov. Cov pathogenesis ntawmkab mob ntshav qab zib Edyog complex, koom nrogOxidative Kev Nyuaj Siab, Atherosclerosis, Apoptosis, Corpus Cavitosum Fibrososum, thiab tej yam zoo nkauj [35].

A meta-tsom xampom tiasBPH cov neeg mob muaj ntshav qab zib muaj ntau dua cov tsos mob thoob ntiaj teb tau ua rau cov menyuam yaus (iPs)piv rau cov uas tsis muaj ntshav qab zib, hais tawm qhov ntawdMob ntshav qab zib tej zaum yuav ua kom lub tsev txiav tawm los ntawm BPH [36]Cov. Tsis tas li ntawd,Wei li al. [37]pom tiasCov qib ntshav siab txhawb BPPLIVATURE LEHYDRODE dehilogenase Kinase 4 (PDK4) qhiaCov. Txoj kev sib raug zoo ntawmBph, Ed, thiab Ntshav Qab Zibqhia tias kev txhim kho ntawm cov xwm txheej no yuav txuas nrog Ntshav Qab Zib nws tus kheej thiab nws cov teeb meem txuam nrog.

Dhananya li al. [38]pom tiasQrealRin tuaj yeem ua tau ntawm ntau cov hom phiaj ntsig txog ntshav qab zib-tswj cov tsos mob tseem ceeb thiab txhim kho hom kab mob ntshav qab zib hom 2Cov. Yog li ntawd,QTC thiab nws cov kev ua haujlwm nquag tuaj yeem tsim kev cuam tshuam rau lawv cov kev kho mob ntawm BPP thiab thiab rau cov kab mob ntshav qab zib ntsig txog cov kev, txhawb lub tswvyim ntawm"Ib txoj kev kho rau cov kab mob sib txawv."

(3) ua rau txoj kev taug qab txoj hauv kev (txoj hauv kev 5)

TusCauna kos npe rau txoj kevyog aCov khoom siv tseem ceeb ntawm cov teeb meem teeb liab teeb meem Transduction [39]Cov. Cov txheej txheem ntawmCenpile erection thiab distrumescencekuj tau tswj hwm los ntawmCauna signaling txoj kevCov. ThaumKev sib deev, Neurons thiab vascular endothelial hlwb nyob rau hauv lub cornus cavernosic tso tawm nitric oxide (tsis muaj), uas qhibGuanallate cyclase nyob rau hauv cov leeg nqaij du, hloov musGuanosine Triphosphate (GTP) rau hauv guanosine monoposphate (CGMP)Cov. CGMP tom qab ua haujlwmprotein kinase g (PKG), txo cov qib intracellular, ua rauKev so ntawm cov leeg nqaij hauv lub cornus cavernosum, ncentshav txaus, thiabtxhim khoCov. Hloov siab,Phosphodiesterase Hom 5 (PDE5) DEGRADES CGMP rau hauv Active GMP, nce ntxivCOUNTERCELLULAR COUNT, ua rauKev mob plab ua kom muaj zogthiab qauteeb meem [40].

WU li al. [41]kawm covPathophysiology ntawm Bphthiab pom tiasInteracellular Cao txoj cai koom nrog hauv Bph txoj kev txhawb nqaCov. Cov kev tshawb pom no qhia tau tias covCau Signaling Txoj Kev Ua Si Lub Luag Haujlwm Tseem Ceeb hauv Bph thiab Ed.

Tam sim no, tsis muaj kev tshawb fawb tau tshaj tawm tiasQTC lossis nws cov chaw ua haujlwm nquag siv exert kev cuam tshuam los ntawm modulating Ca²⁺ taw qhia txoj hauv kev, tab sis qhov no yuav tsum tshawb nrhiav ntxiv ntxiv.

Cov kev nkag siab ntxiv: hi -1 hauv Qtc's "Ib qho kev kho rau cov kab mob sib txawv" mus kom ze

Raws liPPI Network Kev Tshawb Xyuas thiab Cov Tub Ntxhais Tub Ntxhais, peb pom tiashypoxia-inducible factor 1- -1}) tej zaum yuav ua rau lub luag haujlwm tseem ceeb hauv Qtc cov kev kho mob ntawm BPH thiab Ed.

Cov kev tshawb fawb tau pom tiashypoxia tuaj yeem qhib hif -1, ntxiasKev Loj Hlob Cov Khoom zais pa hauv tib neeg prostate stromal hlwb, uas triggersprostate kev loj hlobthiab ua rauBRH kev loj hlob [42]. QTC tau pom tias muaj kev cuam tshuam rau qhov zais ntshis -1 Tshaj tawm hauv BPP cov nas prostate cov ntaub so ntswg, lisuppressing prostatic hyperplasia, txhim kho cov kev hloov keeb kwm kev hloov pauv, thiab tiv thaiv kom tsis txhob muaj epithelial thickening [26].

Hypoxia thiab hif pom zoo kuj ua lub luag haujlwm tseem ceeb hauv Ed pathogenesisCov. Peb Pab Pawg Tshawb Xyuas tshawb xyuasCORPUS CORTOMOSUM Du cov leeg nqaij phenotype hloov hauv ed nasthiab pom tiasNthuav cov Corpus Cavernosum du cov leeg hlwb rau hypoxia rau 24 teev loj nce hi6 {1}} Tshaj tawm [43].

Txawm li cas los xij, nws yog ib qho tseem ceeb kom nco ntsoov tiasNetwork Pharmology Partelezes muab cov lus pom zoo thiab nyuaj, muab tes rau ib tugphau ntawvCov. Deb duasim kev simyog qhov tsim nyog yuav tsum tau rho tawm cov txheej txheem meej los ntawm qhov twgQtc exervts nws "ib txoj kev kho rau cov kab mob sib txawv" tshwm sim rau bph thiab ed.

Tsis tas li ntawd, txoj kev tshawb no sivmolecular docking technologykom paub tseeb lub peev xwm ntawmtus yaj, ib qho ntawm Qtc cov kev ua haujlwm nquag, nrog cov hom phiaj tseem ceeb. Cov txiaj ntsig docking qhia tau tiasquercetin ua yeeb yam zoo khi kev sib luag nrog cov protein feem ntau, tshwj tsis yog rau AKT1 thiab TNFCov. Txawm li cas los xij,AKT1 thiab TNF tseem tuaj yeem cuam tshuam nrog lwm cov chaw ua haujlwm nquagCov. Yog li ntawd, tusPharmacological tshuab thiab kho muaj peev xwm ntawm quercetin hauv BPH thiab Ed lav ntxiv thiab ntsuas kev ntsuas.

Xaus thiab kawm qhov kev txwv

Hauv cov ntsiab lus, qhov kev kawm no ua haujlwmNetwork Pharpacology thiab Molecular dockingraukwv yees cov txheej txheem uas qtc exervts nws "ib txoj kev kho rau cov kab mob sib txawv" tshwm sim rau bph thiab edCov. Cov txiaj ntsig tseem ceebQhov nyuaj thiab ntau haiv neeg ntawm Qtc cov txheej txheem, qhia tias nws kho cov teebmeem koom nrogNtau lub hom phiaj thiab ntau txoj hauv kev.

Txawm li cas los xij, thaum pom kevMuaj nuj nqis pom, txoj kev tshawb no muaj tseebkev txwv:

Muaj peev xwm bias nyob rau hauv kev tshuaj ntsuam- Kev txhais ntawm cov txiaj ntsig network yuav cuam tshuam los ntawm tus kws tshawb fawb lubKawm Tom Qab, ua rauua tau biasesnyob rau hauv cov ntaub ntawv tsom xam.

Cov ntaub ntawv tsis muaj ntaub ntawv- Txij li cov ntaub ntawv hauv txoj kev tshawb fawb no tau txais los ntawmOnline databases, muajcov kev pheej hmoo ntawm cov ntaub ntawv qubVim tias ncua cov ntaub ntawv hloov kho cov ntaub ntawv hloov tshiab.

Yog li ntawd, thaumNetwork Partel Pharpacology thiab molecular docking muab cov kwv yees muaj txiaj ntsig, ntxivCov Kev Qhuab Qhia Ntauthiabsim kev simyog qhov tsim nyog los nkag siab cov elucately lubCov cuab yeej tsis quav ntsej Qtc cov teebmeem kev cuam tshuam ntawm BPH thiab Ed.