Cov txiaj ntsig zoo ntawm Verbascoside Los ntawm Cistanche Tshuaj ntsuab
Mar 08, 2022
Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com
Verbascoside tiv thaiv nas los ntawm Clostridial Gas Gangrene los ntawm inhibiting qhov kev ua ntawm Alpha Toxin thiab Perfringolysin O
Gas gangrene, tshwm sim los ntawm cov kab mob anaerobic Clostridium perfringens (C. perfringens), ua rau tuag hauv 48 teev ntawm qhov pib. Cov tswv yim kho mob txwv tsis pub muaj, thiab nws cuam tshuam nrog kev tuag siab heev. Ob leeg C. perfringens alpha-toxin (CPA) thiab perfringolysin O (PFO) yog ib qho tseem ceeb ntawm kev tsim cov roj gangrene, qhia tias lawv yog cov hom phiaj kho mob. Ntawm no, peb pom qhov ntawdlus verbascoside, a phenylpropanoid glycosidedav faib nyob rau hauv Suav tshuaj ntsuab Cistanche, tuaj yeem cuam tshuam cov kev ua haujlwm lom neeg ntawm ob qho tib si CPA thiab PFO hauv cov tshuaj hemolytic.
Lub oligomerization ntawm PFO tau zoo kawg nkaus inhibited los ntawm verbascoside. Txawm hais tias tsis muaj kev ua haujlwm antibacterial tau pom,lus verbascosidekev kho mob tiv thaiv Caco-2 hlwb los ntawm kev puas tsuaj los ntawm CPA thiab PFO. Tsis tas li ntawd, cov nas mob tau kho nroglus verbascosideqhia tau zoo heevtxo kev puas tsuaj, txo cov kab mob hnyav, thiabtxo kev tuag. Hauv cov ntsiab lus,verbascoside muaj cov nyhuv kho tau zoo tiv thaiv C. perfringens virulence ob leeg hauv vitro thiab hauv vivolos ntawm tib lub hom phiaj CPA thiab PFO. Peb cov txiaj ntsig tau muab lub tswv yim zoo thiab muaj peev xwm ua rau cov kab mob C. perfringens, tshwj xeeb tshaj yog gas gangrene.
Hot Tags: alpha-toxin, tshuaj tiv thaiv kab mob, Clostridium perfringens, gas gangrene, perfringolysin O, verbascoside
Clostridium perfringens (C. perfringens) yog cov kab mob gram-zoo anaerobic uas tau nthuav dav hauv cov xwm txheej thiab hauv tib neeg txoj hnyuv (Fraser thiab Collee, 1975). C. perfringens tuaj yeem tso plaub yam co toxins (, , ε, thiab Ì) thiab muab faib ua tsib serotypes, A–E (Titball, 2005). Nyob rau hauv tib neeg, C. perfringens tuaj yeem ua rau muaj ntau yam kab mob, xws li zaub mov lom thiab gas gangrene, qhov kawg ntawm cov tsiaj kuj tuaj yeem tshwm sim hauv cov tsiaj, xws li miv, nyuj, dev, yaj, nees, thiab tshis (Verherstraeten li al. , 2015). Lub sij hawm incubation ntawm gas gangrene yog luv, thiab tus kab mob tuaj yeem tsim nyob rau hauv 6-8 h (Uzal li al., 2015). Qhov hnyav dua, ntau dua 50 feem pua ntawm cov neeg muaj tus kab mob no tseem yuav tsim cov kab mob toxicosis, thaum kawg ua rau tuag; Yog li, tsis muaj kev tswj xyuas raws sijhawm thiab muaj txiaj ntsig ntawm kev kho mob, gas gangrene tuaj yeem ua rau muaj kev puas tsuaj loj (Low li al., 2018). Txawm li cas los xij, cov kev kho mob ib txwm muaj, xws li kev kho tshuaj tua kab mob thiab kev kho mob phais rau gas gangrene, txhua tus muaj qee yam tsis zoo xws li tab sis tsis txwv rau cov tshuaj tua kab mob thiab kev raug mob rau cov neeg mob (Park et al., 2010; Osman and Elhariri, 2013). Yog li, nws yog ib qho tsim nyog yuav tau nrhiav txoj hauv kev tshiab los yog cov tswv yim rau kev kho cov roj gangrene.
Clostridial gas gangrene yog cov kab mob fulminant kis tau los ntawm kev sib cuam tshuam ntawm C. perfringens toxin (CPA) thiab perfringolysin O (PFO) (Hifumi li al., 2018). CPA, belongs rau tsev neeg ntawm cov kab mob zinc-Metallo phospholipase enzymes, yog tsim los ntawm tag nrho cov C. perfringens, yog encoded los ntawm chromosomes, yog ib tug loj toxin nyob rau hauv C. perfringens, thiab nthuav tawm ob qho tib si phospholipase C thiab sphingomyelinase kev ua ub no (van Bunderen li al. , 2010; Masataka et al., 2015). Xyoo 1990, Awad et al. (1995) siv CPA mutants los kuaj cov roj gangrene nas qauv thiab pom tias hom kab mob tsis muaj CPA noob pom tias txo cov kab mob thiab cov nqaij mos puas tsawg tom qab kis kab mob. Txoj haujlwm no tau lees paub tias CPA yog cov tshuaj lom loj hauv cov roj gangrene. Xyoo 2000, Alberto tau ua qhov kev tshawb fawb tob los ntawm kev tsim cov qauv molecular ntawm a-toxin thiab peb-voj mutants hauv C-terminal domain, thiab cov kev ua ntawm hemolytic thiab cytotoxicity ntawm cov mutants tau txo qis piv rau cov tsiaj qus. Nws tau pom tias kev ua sphingomyelinase thiab C-terminal domain yog tsim nyog rau myotoxicity hauv vivo (Alape-Giron li al., 2000). PFO, cholesterol-dependent cytolysin (CDC), cuam tshuam nrog cov cell membrane li monomer, thiab cov txheej txheem npaj tau muab tso rau hauv daim nyias nyias los ntawm oligomerization, thaum kawg lysing host cells (Johnson thiab Heuck, 2014). Txawm hais tias PFO tsis tsim nyog rau kev tuag, nws tuaj yeem ua rau macrophage cytotoxicity nyob rau theem pib ntawm myonecrosis thiab yog ib qho tseem ceeb rau kev tsim cov thrombus nyob rau theem kawg ntawm kev kis kab mob, pab txhawb rau cov kab mob ntawm cov roj gangrene (Verherstraeten li al., 2015). CPA tuaj yeem ua ke nrog PFO los ua kom puas cov neutrophils khaws cia ntawm qhov chaw muaj kab mob thiab ua rau endothelial cell tsis ua haujlwm, edema, thiab ischemia, thaum kawg ua rau cov ntaub so ntswg hypoxia thiab muab qhov chaw zoo rau kev loj hlob thiab kev loj hlob ntawm C. perfringens (Bryant and Stevens, 1996. ). Yog li, txoj kev tshawb no tsom rau CPA thiab PFO thiab lub hom phiaj los nthuav tawm txoj hauv kev tshiab rau kev kho cov roj gangrene.
Hauv txoj kev tshawb no, ob qho tshuaj tiv thaiv kab mob tau raug tshuaj xyuas los ntawm 17 lub ntuj sib txuas los ntawm hemolysis kom pom qhov muaj peev xwm inhibitor ntawm gas gangrene. Cov ntaub ntawv hemolytic rau ntau lub tebchaw muaj nyob rau hauv Table 1. Ntawm 17 hom natural compounds, verbascoside muaj qhov zoo tshaj plaws inhibitory nyhuv ntawm ob qho tib si co toxins, thiab peb yog li xaiv verbascoside ua lub hom phiaj compound rau txoj kev tshawb no. Verbascoside yog dav faib nyob rau hauv ntau yam tshuaj suav tshuaj ntsuab tshuaj ntsuab xws li cistanche thiab raug cais thiab muab rho tawm los ntawmVerbascosidelos ntawm tus kws tshawb fawb Italian hauv xyoo 1963 (Speranza li al., 2010; Zhu et al., 2016). Cov kev tshawb fawb tau qhia tiasverbascoside muaj ntau yam tshuaj lom neeg thiab tshuaj, zoo lianti-inflammatory, antioxidant, antibacterial, antitumor, antifungal, thiab chelation zog, thiabtuaj yeem siv rau hauv cov tshuaj pleev ib ce ntawm daim tawv nqaijthiabtshuaj npaj.Lwm cov ntawv ceeb toom tau pom tias verbascoside tuaj yeem nqus tau tag nrho hauv 1 h thiab ncav cuag cov ntshav siab thiab tias nws cov bioavailability ntawm kev xa khoom ntawm ntau txoj kev txhaj tshuaj tsis pub tshaj 25 feem pua (Dai li al., 2017; Feng li al., 2018). Raws li cov lus hais saum toj no, txoj kev tshawb fawb no pom thiab kawm txog qhov inhibitorycov teebmeem ntawm verbascosidentawm gas gangrene los ntawm kev sim hauv vitro thiab hauv vivo.
Verbascoside Inhibited Hemolytic Activity ntawm PFO thiab CPA
Qee cov flavonoids tau raug tshaj tawm tias ua tau zoo inhibitors tiv thaiv pore-forming toxins (Li et al., 2013; Wang et al., 2017; Zhou et al., 2017). Ntawm no, verbascoside, ib qho phenylpropanoid, tau pom tias inhibit qhov kev ua ntawm hemolytic ntawm ob qho tib si PFO thiab CPA toxins secreted los ntawm C. perfringens. Thaum cov concentrations ntawm verbascoside ranges ntawm 2 mus rau 32 |ig / mL, verbascoside kev kho mob ho inhibited lub hemolytic kev ua ntawm cov co toxins nyob rau hauv ib tug npaum li cas ntawm cov tshuaj, qhia tias verbascoside yog ib qho zoo inhibitor ntawm PFO thiab CPA.
Verbascoside Tsis cuam tshuam rau kev loj hlob ntawm C. perfringens
We further performed MIC and bacterial growth curve studies to determine the antibacterial activity of verbascoside against C. perfringens, revealing a MIC assay result (Figure 2A) >256|ig/ml. Ib yam li ntawd, qhov tshwm sim ntawm kab mob loj hlob nkhaus (Daim duab 2B) qhia tias verbascoside tsis cuam tshuam rau kev loj hlob ntawm cov kab mob. Ua ke, peb cov txiaj ntsig tau qhia tias kev kho verbascoside tsis muaj kev cuam tshuam rau C. perfringens viability ntawm cov concentrations xav tau rau inhibition ntawm PFO thiab CPA kev ua.
Verbascoside tiv thaiv Cells los ntawm kev puas tsuaj los ntawm PFO lossis CPA
Clostridium perfringens alpha-toxin thiab PFO hauv C. perfringens yog cov co toxins tseem ceeb uas ua rau muaj roj gangrene; Yog li, seb verbascoside tuaj yeem tiv thaiv cov hlwb los ntawm ob qho tshuaj lom no kuj tau kuaj xyuas. Ua ntej, peb tau ua qhov kev sim cytotoxicity nrog cov tshuaj verbascoside, uas tsis ua rau lub hlwb puas (Daim duab 3A). Tom qab ntawd, qhov sib xyaw no tau ntxiv rau kev sib koom ua ke ntawm cov hlwb thiab PFO lossis CPA. Verbascoside inhibited cytotoxicity ntawm ob co toxinshauv Caco{{0}} hlwb. Piv nrog rau cov qauv uas tsis tau kho nrog verbascoside, qhov kev puas tsuaj tshwm sim los ntawm cov co toxins rau Caco-2 hlwb kho nrog verbascoside ntawm 0.5 Jig/mL tau txo qis nyob rau hauv ib koob tshuaj. Tshwj xeeb tshaj yog rau cov protein PFO, cov hlwb tau txais kev tiv thaiv zoo ntawm cov tshuaj concentration ntawm 0.25 ig / mL (P < 0.05).="" kev="" kuaj="" mob="" ntawm="" tes="" tom="" ntej="" kev="" tuag="" (figures="" 3d-k)="" tau="" ua="" haujlwm="" ntxiv="" los="" ua="" pov="" thawj="" qhov="" kev="" tiv="" thaiv="" no.="" raws="" li="" qhov="" xav="" tau,="" kev="" kho="" verbascoside="" pom="" pom="" kev="" tiv="" thaiv="" ntawm="" tes="" raug="" mob="" los="" ntawm="" pfo="" lossis="" cpa.="" noj="" ua="" ke,="" peb="" cov="" txiaj="" ntsig="" tau="" tsim="" tias="" verbascoside="" cuam="" tshuam="" cov="" cell="" puas="" raug="" ntxias="" los="" ntawm="" pfo="" lossis="" cpa="" nyob="" rau="" hauv="" koob="">
Verbascoside Inhibits PFO Hemolytic Kev Ua Si los ntawm Txo Nws Cov Oligomerization
Kev ua haujlwm hemolytic ntawm PFO yuav tsum tau nrog rau qhov tshwm sim ntawm oligomerization thiab pore tsim (Johnson thiab Heuck, 2014). Ntawm no, oligomerization ntawm PFO raug ntxias los ntawm KCl thiab luav cov ntshav, thiab PFO oligomerization tau kuaj pom (Daim duab 4), qhia txog qhov txo qis oligomerization band siv thaum qhov concentration ntawm verbascoside tau nce. Ua ke, peb cov txiaj ntsig tau qhia tias kev kho verbascoside inhibits oligomerization ntawm PFO thiab yog li txo cov kev ua haujlwm hemolytic ntawm cov tshuaj no.
Verbascoside tiv thaiv nas los ntawm C. perfringens Kab mob
Tus nas ceg nqaij qauv ntawm gangrene tau tsim los txiav txim seb qhov kev tiv thaiv tau pom hauv vitro kuj tseem tuaj yeem pom hauv vivo. Ob txhais ceg ntawm ATCC13124-cov nas kis tau zoo sib xws, tus lej ntawm cov kab mob inflammatory hauv pawg tshuaj tau txo qis, thiab cov ntaub so ntswg tsis zoo tom qab kho nrog verbascoside. Tsis tas li ntawd, tus naj npawb ntawm cov kab mob colonized nyob rau hauv cov leeg ceg tau txo qis tom qab kev kho mob nrog verbascoside. Raws li pom nyob rau hauv qhov kev sim tau tshwm sim, 93.33 feem pua ntawm cov nas mob tuag los ntawm 32 teev tom qab kis kab mob. Raws li kev cia siab, qhov ciaj sia taus ntawm cov nas uas tau txais verbascoside nce los ntawm 33.33 feem pua , tsuas yog 60 feem pua ntawm cov nas kis tau tuag (P=0.015 los ntawm kev ntsuas ntsuas ntsuas). Tsis tas li ntawd, kev kho mob verbascoside ncua sij hawm lub sijhawm tuag ntawm ze li ntawm 8 h (los ntawm 32 h rau ATCC 13124-cov nas kis mus rau 40 h rau verbascoside-kho nas) thiab yog li txuas ntxiv lub sijhawm tseem ceeb uas yuav tsum tau muaj rau kev kho mob. Ua ke, peb cov txiaj ntsig tau qhia tias nyob rau hauv cov nas, verbascoside tuaj yeem muab kev tiv thaiv zoo tiv thaiv cov roj gangrene los ntawm C. perfringens.
Raws li cov kab mob gram-zoo anaerobic, C. perfringens tau dav dav hauv cov xwm txheej thiab tuaj yeem tso ntau yam co toxins, uas tuaj yeem ua rau ntau yam kab mob hauv tib neeg thiab tsiaj txhu, suav nrog cov roj gangrene (Fraser thiab Collee, 1975; Verherstraeten li al. ., 2015). Gas gangrene feem ntau tshwm sim los ntawm kev sib xyaw ntawm a thiab theta co toxins secreted los ntawm C. perfringens, uas tuaj yeem ua rau tuag ntawm cov tsiaj txhu, ua rau muaj kev lag luam loj. Txawm li cas los xij, txog niaj hnub no, txoj hauv kev zoo rau kev kho cov roj gas gangrene muaj xws li hyperbaric oxygen, phais, thiab tshuaj tua kab mob. Ntawm lawv, kev phais tuaj yeem ua rau lub cev puas tsuaj rau cov neeg mob thiab muaj kev cuam tshuam tsis zoo rau lub neej tom qab phais. Ntau yam tshuaj tetracycline kuj tau pom nyob rau hauv C. perfringens cais los ntawm Sweden, Norway, Denmark, thiab lwm qhov chaw. Yog li, yuav tsum muaj cov tswv yim tshiab lossis cov neeg sawv cev los tawm tsam cov kab mob no (Park li al., 2010; Osman thiab Elhariri, 2013). Hauv txoj kev tshawb no, phenylpropanoid verbascoside, uas txawv ntawm cov tshuaj tua kab mob ib txwm muaj (cov tshuaj tua kab mob), tuaj yeem cuam tshuam cov kev ua haujlwm hemolytic ntawm CPA thiab PFO, ob qho tseem ceeb pore-forming co toxins uas cuam tshuam rau C. perfringens pathogenicity. Nyob rau theem cellular, verbascoside kuj tseem tuaj yeem tiv thaiv Caco-2 hlwb los ntawm ob co toxins ntawm qhov tsis tshua muaj siab (0.25-2 ig/mL). Hauv particular, verbascoside tuaj yeem txo cov haujlwm ntawm cov co toxins los ntawm inhibiting oligomerization ntawm PFO. Cov txiaj ntsig no tuaj yeem muab cov ntaub ntawv yooj yim txaus rau hauv vivo tshawb fawb.
