Fisetin Attenuates Lipopolysaccharide-Induced Inflammatory Responses hauv Macrophage

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

Ntau qhov kev tshawb fawb tau qhia txog kev ua tau zoo thiab kev nyab xeeb ntawm polyphenols hauv tib neeg kev noj qab haus huv; Txawm li cas los xij, kev txheeb xyuas ntawm lawv cov kev ua tau zoo tseem tsis txaus. Lub hom phiaj ntawm txoj kev tshawb no yog los tshuaj xyuas seb fisetin, ib qho ntawm cov flavonoids uas muaj nyob hauv cov txiv hmab txiv ntoo thiab zaub, tuaj yeem txo cov lipopolysaccharide-(LPS-) ua rau raug mob.mobcov lus teb hauv macrophages. LPS nce proinflammatory mRNA abundance (MCP 1, IL-1ß, thiab iNOS) tab sis raug txwv los ntawm fisetin. Qhov nce ntawm nitric oxide los ntawm LPS, ib qho oxidative kev nyuaj siab, yog attenuated los ntawm fisetin. Tsis tas li ntawd, LPS-enhanced phosphorylation ntawm mitogen-activated protein kinase (ERK thiab JNK) raug txo. Thaum kawg, fisetin tau txo qis qhov kev qhia lossis kev ua haujlwm ntawm uPA, uP AR, MMP-2, thiab MMP-9, uas yog lub npe hu ua cov xwm txheej cuam tshuam ntawm macrophage recruitment lossis infiltration. Hauv kev xaus,fisetinNws yog ib qho kev cog lus kho mob rau cov kab mob macrophage, xws li sepsis thiab atherosclerosis.

Nyem qhov no kom paub ntau ntxiv.

1. Taw qhia

Kev siv tshuaj kho mob ntawm cov khoom ntuj tsim tau tau txais kev mloog ntau dua hauv 2 xyoo dhau los. Raws li lawv cov txiaj ntsig zoo-cacy thiab tsis muaj tshuaj lom, 40 feem pua ​​​​ntawm FDA-pom zoo cov tshuaj kho mob yog cov khoom siv ntuj tsim los yog lawv cov derivatives [1]. Toxicity txuam nrog rau lwm yam tshuaj tau ua tiav kev tiv thaiv los ntawm cov khoom ntuj sib txawv [2]. Yog li ntawd, nws yog ib qho tseem ceeb heev thiab tseem ceeb heev los tshawb nrhiav cov nroj tsuag-derived natural compounds ntxiv.

Polyphenolsyog cov nroj tsuag theem nrab metabolites thiab muaj dav nyob rau hauv cov zaub mov thiab dej haus ntawm cov nroj tsuag keeb kwm, txiv hmab txiv ntoo, zaub, txuj lom, tshuaj yej, thiab caw. Txawm hais tias lawv tsis suav tias yog cov micronutrients tseem ceeb, ntau hom ntaub ntawv evince lawv cov txiaj ntsig zoo rau tib neeg kev noj qab haus huv, tshwj xeeb tshaj yog nyob rau hauv cov khoom noj uas cuam tshuam nrog kev noj txiv hmab txiv ntoo thiab zaub [3-5]. Ntau cov kev tshawb fawb tau ua ntau xyoo dhau los rau kev tshawb fawb txog cov tshuaj pharmacological ntawm polyphenols, qhia txog cov txiaj ntsig zoo rau kev noj qab haus huv. Cov pov thawj loj hlob tau pom tias ob peb polyphenols muajanti-inflammatorykhoom

[6-8].Tsis tas li ntawd, cov kev tshawb fawb tsis ntev los no tau pom tias ntau hom polyphenols tuaj yeem cuam tshuam kev tswj cov enzymes lossis cov txheej txheem hloov pauv uas cuam tshuam nrog kev mob [9].

Kev noj zaub mov cuam tshuam rau theem sib txawv ntawm qhov mob thiab ua kom pom qhov cuam tshuam tseem ceeb ntawm ntau yam kab mob inflammatory[10,11]. Kev mob plab ua lub luag haujlwm tseem ceeb hauv kev txhim kho cov kab mob xws li ntshav qab zib, mob hawb pob, kab mob plawv, thiab mob qog noj ntshav [12]. Yog li ntawd, kev tswj qhov mob tuaj yeem tiv thaiv cov kab mob no. Txij li thaum macrophages yog cov neeg kho mob tseem ceeb ntawm kev mob, lawv muaj ntau yam kev ua haujlwm hauv cov ntaub so ntswg homeostasis thiab o. Yog li, cov neeg ua haujlwm hloov kho lawv cov haujlwm tau zoo yog qhov muaj txiaj ntsig zoo vim tias kev ua kom tsis zoo ntawm macrophages tuaj yeem ua rau lub cev tsis muaj zog. Cov kev tshawb fawb tam sim no qhia meej meej tias cov khoom ntuj yog ib qho tseem ceeb tshaj plaws ntawm cov tshuaj tshiab [13].

Ib qho polyphenol, isetin (3,3',4',7-tetrahydroxyflavone), muaj ntau hauv strawberry, kua, txiv lws suav, dos, txiv kab ntxwv, txiv duaj, txiv hmab txiv ntoo, kiwi, persimmon, tshuaj yej, thiab cawv [14] . Txog tam sim no, fisetin tau tshaj tawm muaj zog tiv thaiv kab mob [15-17],

antioxidant [18], antitumorigenic [19,20, antiangiogenic [21], antidiabetic [22], neuroprotective [23], thiab cov teebmeem cardioprotective [24] ob qho tib si hauv kab lis kev cai ntawm tes thiab hauv cov qauv tsiaj cuam tshuam rau tib neeg cov kab mob. Txawm hais tias fisetin muaj ntau yam teebmeem ntawm lub cev, nws cov nyhuv ntawm macrophages tsis tau tshaj tawm.

Hauv txoj kev tshawb fawb tam sim no, peb tau tshawb xyuas cov txiaj ntsig zoo ntawm fisetin ntawm cov lus teb inflammatory ntawm macrophages qhib los ntawmlipopolysaccharide(LPS).

2. Cov ntaub ntawv thiab cov txheej txheem

2.1. Kev rho tawm ntawm cov neeg nyob hauv Peritoneal Macrophages.

Cov nas BALB / c tau txais los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Kho Mob ntawm University of Tokyo thiab khaws cia hauv Lub Chaw Pabcuam Tsiaj ntawm Okayama University. Tag nrho cov kev sim tsiaj tau ua kom ua raws li NIH cov lus qhia (Cov Lus Qhia rau Kev Saib Xyuas thiab Siv Cov Tsiaj Txhaum Cai). Cov txheej txheem kev sim tau pom zoo los ntawm Pawg Saib Xyuas Kev Ncaj Ncees rau Tsiaj Kev sim ntawm Okayama University Graduate School of Medicine, Dentistry, thiab Pharmaceutical Sciences (OKU-2018449). Tag nrho cov nas tau khaws cia rau hauv qhov chaw thaiv thiab pub noj zaub mov zoo li qub. Txiv neej thiab poj niam BALB / c nas, 16 ± 4 lub lis piam ntawm hnub nyoog tau tshuaj loog nrog isoflurane thiab euthanized ntawm lub ncauj tsev menyuam dislocation. Macrophages tau sau los ntawm peritoneal lavage siv saline (5mL). Cov tshuaj peritoneal lavage tau centrifuged ntawm 1500rpm rau 5 feeb. Cov sediment raug tshem tawm hauv me ntsis DMEM(SIGMA, Cat. No.D6046). Cov qe ntshav liab tau lysed siv cov tshuaj ammonium chloride. Tus naj npawb ntawm macrophages raug xam los ntawm kev siv lub hemocytometer, tom qab ntawd rov muab tso rau hauv DMEM uas muaj cov cua sov tsis ua haujlwm FBS (10 feem pua ​​​​vv), penicillin (10 U / mL), thiab streptomycin (10mg / mL), thiab plated rau hauv 6-zoo daim hlau (Corning Incorporated, Cat. No.3516) [25,26].

2.2. Kab lis kev cai ntawm Cell.

Tom qab hmo ntuj kev tshaib kev nqhis, macrophages tau tsim nrog kev xaiv ntawm fisetin (10, 30, thiab 100 μM; SIGMA, Cat. No. F4043) los yog lub tsheb rau 3 teev thiab incubated nyob rau hauv lub xub ntiag los yog tsis muaj LPS (10ng/mL; SIGMA, Cat. No.L4391) rau lub sij hawm tsim nyog. Tom qab ntawd, qhov nruab nrab thiab cov hlwb raug sau. Qhov nruab nrab yog siv rau kev ntsuam xyuas nitric oxide (NO) thiab gelatin zymography. Cell lysates tau siv rau ntau yam polymerase saw tshuaj tiv thaiv (qPCR) thiab western blotting.

2.3. Real-Time Polymerase Chain Reaction.

mRNAs tau muab rho tawm los ntawm macrophages siv RNeasy Mini Cov Khoom Siv (QIAGEN, Cat. No.74104). Kev hloov pauv rov qab tau ua tiav siv iScript cDNA Synthesis Kit (Bio-Rad, Cat. No. 1708891). qPCR tau ua tiav nrog ABI Kauj Ruam Ib Lub Sijhawm PCR System (Applied Biosystems, QuantStudio 3) siv Fast SYBR Green Real-time PCRMixture (Applied Biosystems, Cat. No.4385612)[27). Primers rau monocyte chemotactic protein 1(MCP-1)(Takara Bio Inc, Cat. No. MA066003), interleukin 1 beta(IL-1 )(Takara Bio Inc., Cat. No. MA025939), inducible nitric oxide synthase (iNOS)(Takara Bio Inc, Cat. No. MA083369), matrix metalloproteinase-(MMP-)2(Takara Bio Inc., Cat. No. MA127110), MMP-9(Takara Bio Inc. ., Cat. No.MA031311), thiab 18S ribosomal RNA(18S)(Takara Bio Inc., Cat. No. MA050364) tau muag khoom. Txhua tus qauv tau ua kom muaj txiaj ntsig zoo rau 18S mRNA qhia (AACT txoj kev) [27].

2.4. Nitric Oxide Assay.

Cov tib neeg kab lis kev cai supernatants tau sau thiab centrifuged 10min ntawm 14, 000rpm ntawm 4 degree . Tom qab ntawd, tus supernatant tau siv rau nitric oxide (NO) assay. Tsis muaj qhov kev ntsuam xyuas tau ua raws li tau piav qhia hauv cov khoom siv muag khoom (BioAssay Systems, Cat. No. D2NO-100). BioAssay Systems'QuantiChrom Nitric Oxide Assay Kit yog ib qho kev ntsuam xyuas xim rau kev txiav txim siab tsis muaj ntau lawm tom qab txo cov nitrate rau nitrite siv txoj kev kho Griess.

2.5. Western Blotting.

Tag nrho-cell proteins tau muab rho tawm los ntawm macrophages siv lub lysis buffer (Cell Signaling, Cat. No.9803). Txhua tus qauv tau siv rau hauv 10 feem pua ​​SDS-PAGE thiab pauv mus rau polyvinylidene fluoride membrane, immunoblotted nrog thawj cov tshuaj tiv thaiv (phosphorylation ntawm extracellular signal-regulated kinase (p-ERK); Cell Signaling, Cat. No.9101, phosphorylation ntawm c-Jun N-terminal kinase(p-JINK); Cell Signaling, Cat. No.9251, the urokinase plasminogen activator(uPA); Abcam, Cat. No.

ab20789, urokinase plasminogen activator, thiab receptor (uPAR); R&D, Cat.No.AF534, thiab -actin; Sigma Cat. No. A5441) [28]. Membranes ces incubated nrog tsim nyog lwm yam tshuaj tiv thaiv kab mob, thiab lub cev tiv thaiv complexes pom nyob rau hauv chemiluminescence (Merck Millipore, Cat. no. WBLUF0100, Cat.no. WBLUC0100) thiab quantified siv ib tug General Electric Imager (GE Healthcare, LAS4000 mini)[29].

2.6. Gelatin Zymography

Cell kab lis kev cai supernatants raug daws nyob rau hauv cov xwm txheej tsis txo qis los ntawm SDS-PAGE (10 feem pua ​​wt/vol) polymerized nyob rau hauv lub xub ntiag ntawm gelatin (0.1 feem pua ​​wt/wt) los soj ntsuam cov dej num ntawm MMP{ {4}}. Gels tau ntxuav nrog Triton X-100(2.5 feem pua ​​vol/vo) rau 60 feeb thiab dej distilled rau 15 feeb ob zaug. Gels tau muab tso rau hmo ntuj ntawm 37 degree Cin 50mM Tris tsis muaj calcium chloride (5mM) pH8.0.Tom qab incubation, gels tau stained nrog Coomassie Brilliant Blue R-250(Bio-Rad, Cat. No. {18}}) rau 30min nyob rau hauv chav tsev kub, ces ua raws li los ntawm destaining nrog Coomassie Brilliant Blue R-250 Destaining Solution (Bio-Rad, Cat. Tsis yog.161-0438) kom txog rau thaum cov bands pom tseeb. Cov duab gel tau suav nrog siv General Electric Imager (GE Healthcare, LAS 4000 mini); cov cheeb tsam uas tsis muaj xim, translucent digested sawv cev thaj chaw ntawm MMP kev ua [30].

2.7. Kev txheeb cais.

Txhua qhov kev txheeb xyuas txheeb cais tau ua tiav siv Sigma Plot v14.0(Systat Software Inc, California, USA). Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab ± tus qauv ntawm qhov ntsuas. Kev txheeb xyuas qhov tseem ceeb ntawm ntau pawg tau soj ntsuam los ntawm ib txoj kev lossis ob txoj kev tsom xam ntawm qhov sib txawv ua raws li Holm-Sidak post hoc test lossis Student-Newman-Keuls post hoc test. pab<0.05 was="" considered="" statistically="">

3. Cov txiaj ntsig

3.1. Fisetin Attenuated Inflammatory Mediators hauv Macrophages Stimulated nrog LPS.

Txij li thaum cov macrophages activated tsim proinflammatory cytokines thiab inflammatory mediators xws li NO [8], peb tshuaj xyuas cov teebmeem ntawm fisetin ntawm inflammatory mediators hauv macrophages stimulated nrog LPS. Ua ntej, txhawm rau kawm seb fisetin siv cov tshuaj tiv thaiv kab mob ntawm qib transcriptional, peb txiav txim siab mRNA A qhia qib ntawm cov noob caj noob ces xws li MCP-1, IL-1 , thiab iNOS (Daim duab 1(a)). ). Raws li qhov xav tau, cov lus qhia ntawm cov noob caj noob ces tau raug tshem tawm los ntawm fisetin nyob rau hauv koob tshuaj. Tom ntej no, kom paub meej tias fisetin suppresses inflammatory teb nyob rau hauv macrophages, peb soj ntsuam nws lub peev xwm los suppress tsis muaj ntau lawm nyob rau hauv LPS-kho macrophages (Daim duab 1(b)). Raws li kev cia siab, fisetin txo qis qhov tsim ntawm NO nyob rau hauv kev siv tshuaj.

3.2. Fisetin Txo Mitogen-Activated Protein Kinase hauv Macrophages Stimulated nrog LPS.

Txij li thaum fisetin tau tshaj tawm tias inhibit mitogen-activated protein kinase (MAPK) txoj hauv kev hauv ntau hom cell [31, 32], peb tau tshuaj xyuas cov teebmeem ntawm fisetin ntawm MAPKs hauv macrophages. Ua ntej, ua kom cov MAPKs raug ntxias los ntawm LPS hauv macrophages tau pom (Daim duab 2(a)). Qhov nce hauv p-ERK los ntawm LPS nce siab ntawm 15 feeb tom qab kev txhawb nqa, thaum qhov nce ntawm p-JNK los ntawm LPS nce siab ntawm 30 feeb. Yog li, hauv kev sim tom ntej, macrophages tau txhawb nqa nrog LPS rau 30 feeb. Kev kho mob nrog fisetin txo qis LPS-vim kev txhim kho ntawm p-ERK thiab p-JNK (Daim duab 2(b) thiab 2(c)).

3.3. Fisetin Txo uPA thiab uPAR hauv Macrophages Stimulated nrog LPS.

Macrophage activation yog sib raug zoo nrog rau qhov invasiveness ntawm hlwb. Tsis tas li ntawd, uPA thiab uPAR hauv macrophages pab txhawb rau infiltration ntawm hlwb. Yog li, cov nyhuv ntawm fisetin ntawm kev qhia ntawm uPA thiab uPAR tau tshawb xyuas. LPS induced protein ntau ntawm uPA (Daim duab 3(a)) thiab uPAR(Daim duab 3(b)). Cotreatment ntawm fisetin txo qhov nce ntawm uPA(Daim duab 3(a)) thiab uPAR los ntawm LPS (Daim duab 3(b)).

3.4. Fisetin Txo MMP-2 thiab MMP-9 hauv Macrophages Stimulated nrog LPS.

Tsis tas li ntawd, txhawm rau qhia meej txog cov txiaj ntsig ntawm fise-tin ntawm MMPs, peb tau tshuaj xyuas MMP-2 thiab MMP-9 cov lus, cov neeg nruab nrab ntawm uPA/uPAR. Hais txog qib mRNA, LPS tau nce MMP-2 thiab MMP-9 mRNA qhia, piv nrog kev kho tsheb (Daim duab 4(a)). Fisetin txo qhov kev txhim kho ntawm cov noob caj noob ces ntawm MMP-2 lossis MMP9 raug ntxias los ntawm LPS raws li koob tshuaj (Daim duab 4(a)). Ntxiv mus, cov haujlwm protein ntawm MMP-9 raug soj ntsuam los ntawm zymography (Daim duab 4(b)). Cov haujlwm protein ntawm MMP-9(92kDa) tau nce los ntawm LPS stimulation, uas tau txo los ntawm fisetin (Daim duab 4(b)).

4. Kev sib tham

Peb pom ib qho tseem ceeb ntawm fisetin tiv thaiv kev mob hauv macrophages. Txoj kev tshawb fawb tam sim no tau pom tias fisetin txo qis qhov cuam tshuam ntawm cov khoom siv inflammatory xws li MCP-1, IL-1 , iNOS, thiab NO, induced los ntawm LPS hauv macrophages. Tsis tas li ntawd, fisetin inhibited qhov ua kom ntawm MAPK thiab txo qis LPS-induced increment ntawm uPA thiab uPAR qhia. Ntxiv mus, fisetin txo qis qhov nce ntawm mRNA ntau ntawm MMP-2 thiab MMP-9 thiab kev ua ntawm MMP-9.

Hauv kab mob sepsis tshwm sim los ntawm kab mob gram-tsis zoo, LPS feem ntau lees paub tias yog tus kab mob ua rau mob sepsis. Hauv ntau qhov kev tshawb fawb, LPS tau siv los ua tus qauv ntawm sepsis thiab o. Tsis tas li ntawd, mob o ua rau mob qog noj ntshav thaum ntxov los ntawm kev ua kom cov hlwb inflammatory thiab tsis tsim nyog ntawm tus neeg kho mob proinflammatory zoo li iNOS thiab cov ntaub ntawv hloov pauv xws li cov khoom siv hluav taws xob hloov hluav taws xob kappa B (NF-xB) [33]. Tsis tas li ntawd, nws kuj tau tshaj tawm tias oxidative kev nyuaj siab yog txo los ntawm attenuating qhov qhia ntawm iNOS [34]. Peb txoj kev tshawb fawb pom tau hais tias fisetin tuaj yeem ua tau zoo hauv kev tiv thaiv thiab kho mob sepsis thiab septic shock, vim muaj kev cuam tshuam rau mRNA ntau ntawm cov noob caj noob ces pro-inflammatory thiab tsim NO. Hauv txoj kev tshawb no, fisetin sup-nias TSIS MUAJ ntau lawm los ntawm kev txo cov kev qhia ntawm mRNA ntawm proinflammatory gene (iNOS); Yog li, nws zoo li tias fisetin attenuated oxidative kev nyuaj siab. Yog li ntawd, cov txiaj ntsig tau txhawb nqa cov tshuaj tiv thaiv kab mob, tshuaj tua kab mob, thiab tshuaj tiv thaiv antioxidant ntawm fisetin.

Ntau qhov kev tshawb fawb tau tshaj tawm tias LPS tau ntxias cov phosphorylation ntawm MAPKs, suav nrog ERK thiab JNK [35].Ntxiv mus, nws tau raug tshaj tawm tias fisetin inhibits kev tsiv teb tsaws thiab ntxeem tau ntawm tib neeg lub tsev me nyuam hlwb los ntawm kev txo qis kev qhia ntawm uPA los ntawm suppressing MAPK[36].In macro -phages, ob peb daim ntawv tshaj tawm muaj txog kev cuam tshuam ntawm fisetin ntawm kev qhia thiab kev ua haujlwm ntawm uPA thiab uPAR. Peb txoj kev tshawb fawb tau pom thawj zaug uas fisetin txwv tsis pub cov kev qhia ntawm uPA thiab uPAR ntxias los ntawm LPS los ntawm kev tawm tsam MAPK signaling hauv macrophages, raws li yav dhau los qhia hauv cov qog nqaij hlav cancer.

MMPs yog ib tsev neeg ntawm cov proteases uas nws cov lus qhia muaj feem xyuam rau qee yam txheej txheem, xws li kev loj hlob, physiology, thiab pathology. Feem ntau, MMP-9 tau lees paub tias yog tus cim ntawm ntau yam kab mob, xws li atherosclerosis, mob caj dab, thiab kab mob lupus erythematosus [37]. Tsis tas li ntawd, MMP-9 tau sib raug zoo nrog kev tsiv teb tsaws ntawm tes [38,39]. Ntau qhov kev tshawb fawb tshwj xeeb tau tshaj tawm tias MMP-2 thiab MMP-9 tau koom nrog hauv atherogenesis thiab ua lub luag haujlwm tseem ceeb hauv kev ruaj khov ntawm atherosclerotic plaques 40-42].Ntawm qhov no, peb cov txiaj ntsig tau qhia tias inhibitors. ntawm MMP-9 tuaj yeem muab cov lus cog tseg raws li txoj hauv kev kho rau kev ruaj khov ntawm cov plaques yooj yim. Tsis tas li ntawd, kev tshawb nrhiav tsis ntev los no tau pom tias kev kho mob ntawm daim tawv nqaij yog qhov tsis zoo los ntawm kev ua kom ntau dhau ntawm MMP-9 [43]. Yog li ntawd, nws tau pom tias fisetin kuj muaj peev xwm ua ib txoj hauv kev kho mob hauv daim tawv nqaij. Cov kev tshawb fawb yav tom ntej yuav xav tau los piav qhia nws cov ntsiab lus ntawm molecular mechanisms.

Ib qho kev tsis ntev los no hauv kev lag luam kws tshuaj yog nrhiav cov tswv yim los tsim cov nroj tsuag ntuj nws tus kheej ua cov tshuaj tshiab. Tseeb tiag, ob txoj kev tshawb fawb tsiaj tsis ntev los no tau pom tias LPS-induced mob ntsws pulmonary o thiab collagen-induced mob caj dab tau txhim kho los ntawm kev kho fisetin |32,44. Lwm qhov ex vivo txoj kev tshawb fawb kuj tau pom tias fisetin muaj peev xwm txo qis LPS-vim cytokine tso tawm los ntawm leukocytes ntawm cov neeg mob uas muaj kab mob ntsws ntev lossis mob ntshav qab zib hom 2 [45]. Ntau cov tshuaj tiv thaiv kab mob tau tsim los ua kom txo qis cov kab mob autoimmune[46-50]; Txawm li cas los xij, feem ntau com-pounds pom muaj kev phiv loj heev. Txij li thaum polyphenols feem ntau muaj nyob rau hauv cov txiv hmab txiv ntoo thiab zaub, lawv xav tias yuav muaj kev nyab xeeb dua cov tshuaj tiv thaiv kab mob [51, 52]. Txiv hmab txiv ntoo thiab zaub muaj ntau yam phytochemicals xws li sesquiterpene lactones, terpenoids, polysaccharides, thiab phenolic compounds. Peb cov txiaj ntsig, qhia txog kev tiv thaiv kab mob, tshuaj tua kab mob, thiab tshuaj tua kab mob antioxidant ntawm fisetin, qhia tau hais tias nws tuaj yeem tsim los ua cov tshuaj tshiab. Txawm hais tias fisetin yog ib tus neeg sib tw rau kev tiv thaiv kab mob, lub peev xwm ntawm cov khoom ntuj tsim muaj fisetin ua tus neeg sawv cev kho mob rau qee yam kab mob yuav tsum tau txheeb xyuas ntxiv hauv qhov chaw kho mob.

5. Cov lus xaus

Txoj kev tshawb fawb tam sim no tau pom tias fisetin txo qis qhov nce ntxivmobgenes (MCP-1, IL-1b, thiab iNOS), qhov tsim ntawm NO, thiab phosphorylation ntawm MAPK, uPA, uPAR, thiab MMPs, induced los ntawm LPS hauv macrophages. Cov txiaj ntsig no tau qhia tias fisetin tuaj yeem yog tus neeg sawv cev thera-peutic rau ntau yam kab mob macrophage.