Txoj Kev Kawm Ntawm Cistanche Deserticola Extract Regulating M2 Zoo li Macrophage Polarization kom txo cov cell tsiv teb tsaws thiab kev tsim cov kab mob hauv lub mis
Jun 28, 2023
Paub meej: Lub Hom Phiaj Los tshawb nrhiav cov txheej txheem tswj hwm ntawm ethanol extract ntawm Cistanche deserticola epimedium brevican ntawm Macrophage polarization hauv vitro thiab nws cov txiaj ntsig ntawm M{{0}}}zoo li macrophage txhawb 4T1 cell migration thiab colony tsim. Txoj kev CCK-8 txoj kev tau siv los txheeb xyuas cov txiaj ntsig ntawm qhov sib txawv ntawm ethanol extract ntawm Cistanche deserticola deserticola ntawm kev ua haujlwm ntawm cov pob txha pob txha derived macrophages (BMDM), thiab txiav txim siab qhov kev nyab xeeb ntawm ethanol extract ntawm Cistanche deserticola deserticola deserticola; Western blotting thiab qRT PCR tau siv los txheeb xyuas cov txiaj ntsig ntawm ethanol extract ntawm Cistanche deserticola deserticola ntawm kev qhia ntawm arginase-1 (Arg-1) thiab CD163, cov cim ntawm M2 zoo li macrophages; QRT PCR tau siv los txheeb xyuas cov txiaj ntsig ntawm cawv extract ntawm Cistanche deserticola deserticola ntawm inflammatory zone 1 (Fizz1) thiab peroxisome proliferator activated receptor (PPAR) ntawm M2 Tumor-associated macrophage (TAMs) ntsig txog cov noob (peroxisome-proliferator-activated receiver, PPAR) ), Cov teebmeem ntawm Chitinase 3-zoo li 3 (Ym1), chemokine 24 (CCL24), macrophage Galactose type C-type Lectin 2 (MGL2) thiab interferon regulatory factor 4 (IRF4) mRNA qhia; Cov nyhuv ntawm ethanol extract ntawm Cistanche deserticola deserticola ntawm M2 TAMs txhawb 4T1 Cell tsiv teb tsaws tau kuaj pom los ntawm kev kuaj kos; Cov nyhuv ntawm ethanol extract ntawm Cistanche deserticola deserticola ntawm kev loj hlob ntawm 4T1 hlwb txhawb los ntawm M2 TAMs tau kuaj pom los ntawm kev sim colony. Epimedium tsis muaj tshuaj lom lossis phiv rau BMDM hlwb ntawm qhov concentration ntawm 0.015 625 mus rau 2.000 000 mg/mL; Cov ethanol extract ntawm Cistanche deserticola ho inhibits M2 TAMs-txog noob Arg{{ 36}}, CD163, Fizz1, PPAR , Qhov kev qhia ntawm CCL24, Ym1, MGL2, thiab IRF4 (P<0.05, 0.01, 0.001) inhibited the migration and colony formation ability of M2-TAMs in 4T1 cells (P<0.05, 0.001). Conclusion The ethanol extract of Cistanche deserticola can weaken the promotion of M2-like macrophages on 4T1 Cell migration and colony formation, and its mechanism may be related to the inhibition of M2-type polarization of macrophages.
Cov lus tseem ceeb: Cistanche deserticola; Macrophages; M2 polarization; mob cancer mis; Kev tsiv teb tsaws chaw; Kev tsim tsa pawg; Benzoin acid; Coniferyl aldehyde; Emodin; Vanillic acid
Cov teebmeem ntawm Cistanche-Antitumor
Mob qog noj ntshav mis yog cov qog nqaij hlav loj uas ua rau poj niam noj qab haus huv, thiab tseem yog qhov thib ob ua rau mob qog noj ntshav hauv ntiaj teb [1-2]. Nyob rau theem kawg ntawm kev mob qog noj ntshav mis, muaj lub ntsws thiab lub siab metastasis. Thaum lub cev metastasis tshwm sim, qhov ciaj sia taus thiab lub neej zoo ntawm cov neeg mob yuav raug txo kom tsawg [3]. Thawj kab kev kho mob cancer mis feem ntau yog nyob ntawm kev kho mob ntawm anthracycline, paclitaxel, thiab lwm yam tshuaj cytotoxic, tab sis cov tshuaj tiv thaiv feem ntau tshwm sim thaum kho. Yog li ntawd, nws yog ib qho tseem ceeb heev uas yuav tau tshawb nrhiav cov txheej txheem pathological ntawm mob qog noj ntshav mis thiab nrhiav kev kho mob zoo. Macrophages yog qhov tseem ceeb rau qhov tshwm sim thiab kev loj hlob ntawm ntau yam qog [4-5], thiab biomarkers ntawm macrophages tuaj yeem ua qhov ntsuas ntsuas. Tus nqi siab ntawm macrophage infiltration yog cuam tshuam nrog qhov tsis zoo ntawm kev mob qog noj ntshav mis. Tumor-associated macrophages (TAMs) yog hom qog-infiltrating lub cev tiv thaiv kab mob. Lawv ua lub luag haujlwm tseem ceeb los ntawm kev mob qog noj ntshav thaum ntxov ntawm lub mis mus rau kev loj hlob, tshwj xeeb tshaj yog metastasis [6]. TAMs koom nrog hauv metastasis, angiogenesis, matrix remodeling, ntxeem tau, thiab tiv thaiv kab mob qog noj ntshav. Cov tshuaj suav tshuaj niaj hnub ua lub luag haujlwm tseem ceeb hauv kev kho mob cancer ntawm lub mis tag nrho. Cov tshuaj suav tshuaj suav tshuaj muaj cov yam ntxwv ntawm ntau yam, txoj hauv kev, thiab lub hom phiaj, uas tuaj yeem txo qhov rov tshwm sim thiab metastasis ntawm cov neeg mob qog, txhim kho lawv lub neej zoo, thiab ua kom lawv lub neej muaj sia nyob ntev. Cistanche deserticola deserticornu Maxim. Nws yog tsob ntoo Berberidaceae ntawm Ranunculales. Nws yog qab zib thiab qab zib hauv saj, sov hauv qhov, thiab ua raws li ob txoj hauv siab thiab lub raum. Nws muaj cov txiaj ntsig ntawm kev ntxiv dag zog rau cov leeg thiab pob txha, tonifying raum yang, tiv thaiv kab mob plawv [7], txhawb kev tsim cov pob txha [8], tswj kev tiv thaiv kab mob [9], thiab inhibiting cancer [10]. Kev tshawb fawb qhia tau hais tias cov cawv extract ntawm Cistanche deserticola tuaj yeem cuam tshuam kev loj hlob ntawm cov qog nqaij hlav cancer ntawm lub mis [11], tab sis kev tshawb fawb txog yuav ua li cas cov cawv extract ntawm Epimedium cuam tshuam rau cov qog tiv thaiv kab mob microenvironment ntawm mob qog noj ntshav mis tsis tau tshaj tawm. Yog li, txoj kev tshawb fawb no npaj siab los tshawb txog cov txiaj ntsig ntawm cawv extract ntawm Cistanche deserticola deserticola ntawm M2-zoo li macrophages thiab nws cov kev cai ntawm 4T1 mob qog noj ntshav cell migration thiab colony tsim, muab kev sim hauv paus thiab theoretical kev taw qhia rau kev taug qab. Kev kho mob ntawm Epimedium.
Cistanche hmoov cov txiaj ntsig kev noj qab haus huv-Antitumor
Nyem qhov no mus saib Cistanche cov khoom
【Nug ntxiv】 Email: cindy.xue@wecistanche.com / Whats App: 0086 18599088692 / Wechat: 18599088692
1. Khoom siv
1.1 Tsiaj thiab Cell
SPF Qib Poj Niam C57BL/6 Nas, hnub nyoog 8 lub lis piam, yuav los ntawm Sibeifu (Beijing) Biotechnology Co., Ltd., nrog daim ntawv pov thawj tsiaj tus lej 110324210105240115. Cov nas tau raug tsa los ntawm Animal Experimental Center of the Fifth Medical Center of the General Hospital of Cov Neeg Liberation Army. Thoob plaws lub sijhawm sim tag nrho, cov nas tau muab zaub mov dawb thiab dej thiab tau muab sijhawm rau 12- teev lub teeb / 12- teev tsaus ntuj. Cov kev sim tsiaj tau ua los ntawm cov lus qhia rau kev saib xyuas thiab siv cov tsiaj sim thiab tau pom zoo los ntawm Lub Tsev Kho Mob Thib tsib ntawm General Tsev Kho Mob ntawm Cov Neeg Liberation Army. Tus lej pom zoo rau kev sim tsiaj yog IACUC-2021-0007. 4T1 hlwb tau yuav los ntawm Shanghai Fuheng Biotechnology Co., Ltd.
Kev Tshawb Fawb Txog Cistanche deserticola
1.2 Cov tshuaj
Cistanche deserticola tau txheeb xyuas los ntawm tus kws tshawb fawb Xiao Xiaohe li Epimedium E., ib tsob nroj ntawm Berberidaceae qhuav nplooj los ntawm Brevicornum Maxim. Noj Cistanche deserticola deserticola nplooj, zuaj lawv, thiab hla lawv los ntawm No. 4 sieve, precisely luj lawv, ntxiv dilute ethanol, ua cov kev kho mob ultrasonic (hwj chim 400 W, zaus 50 kHz) rau 1h, txias lawv, hnyav lawv dua, siv dilute ethanol los ua kom poob phaus, co lawv, lim lawv, coj mus ntxiv filtrate, khov thiab qhuav kom tau Cistanche deserticola deserticola extract. 1.3 Tshuaj thiab reagents arginase-1 (Arg-1) antibody (batch tooj: 93668) tau muas los ntawm CST Tuam Txhab Tebchaws Meskas; - Cov tshuaj tiv thaiv actin (batch tooj 20536 1-AP) tau yuav los ntawm Protentech Company; HRP sau npe tshis los tiv thaiv luav IgG theem nrab antibody (batch naj npawb J111-035-003) tau yuav los ntawm Jackson Immuno Research; Trizol reagent (batch tooj BSC51M1) tau yuav los ntawm lub tuam txhab Biolux; CCK-8 reagent (batch tooj KTA1020-1000T) tau yuav los ntawm Abbkine Company; Interleukin 4 (IL{18}}) qhov tseem ceeb (batch tooj 96-214-14-20) tau yuav los ntawm Peprotech.
1.4 Kev ntsuas
QB-9002 Seismic Plate Instrument (Haimen Qilin Tswb Company); Epoch enzyme-linked immunosorbent assay thiab P100 plus nucleic acid concentration analyzer (Bio Tek Company, USA); Quantstudio 6 Flex fluorescence quantitative PCR instrument (Thermo Fisher Scientific, USA); MINI6K xibtes centrifuge (Hangzhou Aosheng tuam txhab); Vortex-Genie 2 vibrator (Scientific Industries, USA).
2 Txoj kev
2.1 Cheebtsam tsom xam ntawm cawv extract ntawm Cistanche deserticola
2.1.1 SampleKev npaj Ntxiv methanol rau cov cawv extract ntawm Cistanche deserticola los npaj 5 mg / mL ncua kev kawm ntawv, rho tawm los ntawm ultrasound rau 40 min, noj 1 mL thiab centrifugate nws ntawm 12 000 r / min rau 10 min , coj tus supernatant tom qab centrifugation, dhau 0.22 μ M lim membrane, coj mus kuaj rau UPLC-MS / MS. Cov Cheebtsam ntawm Cistanche deserticola tau sau los ntawm cov tshuaj suav tshuaj suav tshuaj tshuaj database thiab tsom xam platform (TCMSP). MS cov txiaj ntsig tau raug tshuaj xyuas siv Progression QI cov ntaub ntawv platform (raws li NPATLAS thiab GNPS databases), thiab cov txiaj ntsig tau muab piv nrog Cistanche deserticola tivthaiv retrieval rau nontargeted tivthaiv tsom xam.
2.1.2 Chromatographic tej yam kev mob:
Tau txais UPLC BEH C18 chromatographic kem (100 mm × 2.1 mm, 1.7 µ m), theem mobile yog ob chav dej distilled (A) - acetonitrile (B), gradient elution: 0-3 feeb, 5% B; 3 mus rau 35 feeb, 5% mus rau 95% B; 35-42 feeb, 95 feem pua -5 feem pua B. Lub volumetric flow rate yog 0.3 mL/min; Qhov ntim txhaj tshuaj yog 5 μL; Qhov kub ntawm lub thawv kub yog 40 degree. 2.1.3 Mass spectrometry tej yam kev mob: electrospray ion qhov chaw (ESI) yog siv los kuaj pom nyob rau hauv zoo ion hom, thiab lub capillary kub yog 275 degree; Sheath gas ntim ntws tus nqi 20 Arb; Pab roj ntim ntws tus nqi 5 Arb; Lub zog hluav taws xob ion yog 5 kV. 2.2 Cell kab lis kev cai Pob txha pob txha-derived macrophages (BMDM) raug cais tawm ntawm cov pob txha femoral ntawm 8-cov poj niam hnub nyoog C57BL/6 nas. Lawv tau coj mus kuaj hauv DMEM nruab nrab uas muaj 10 feem pua Fetal bovine serum, 1 feem pua penicillin / Streptomycin, thiab nas macrophage colony-stimulating factor M-CSF (50 ng / mL), thiab muab tso rau hauv qhov cub ntawm 37 degree thiab 5% CO2 rau 6. hnub.
Digest cells nrog 0.25 feem pua trypsin EDTA (2:1) ntawm tus nqi ntawm 1.2 × Inoculate 106/mL ceev nyob rau hauv ib lub tais dej thaum hmo ntuj. Hnub ob, tom qab ntxiv cov cawv cawv ntawm Cistanche deserticola rau 1h, cov hlwb tau txhawb nqa nrog IL-4 (20 ng / mL) rau 24 teev.
2.3 CCK{{0}} txoj kev tau siv los txheeb xyuas cov cytotoxicity ntawm cawv extract ntawm Cistanche deserticola deserticola rau BMDM hlwb × Inoculate 106/mL ntom nyob rau hauv 96 zoo daim hlau, tso rau hauv lub incubator thaum hmo ntuj, kho cov hlwb nrog ntau qhov sib txawv (0, 0.015 625, {{10}}}031 25, 0.{{ 9}}, 0.125, 0.25, 0.5, 1, 2, 4 mg / mL) ntawm cawv extract ntawm Cistanche deserticola rau 24 teev. Muab pov tseg cov kab lis kev cai nruab nrab, ntxiv CCK-8- kab lis kev cai nruab nrab (1:10) tov, incubate nyob rau hauv lub incubator rau 1h, ntsuas lub absorbance (A) ntawm 450 nm nrog ib tug microplate nyeem ntawv, thiab xyuas cov toxicity ntawm cawv extract ntawm Cistanche deserticola deserticola rau cov hlwb.
2.4Western blotting tau siv los txheeb xyuas qhov kev qhia ntawm Arg {{0}} protein hauv BMDM hlwb. Cov pab pawg tswj hwm, pawg qauv, thiab pawg neeg haus cawv ntawm Cistanche deserticola nrog ntau qhov sib txawv (0062 5, 0.125, 0.25 mg/mL) tau teeb tsa. Cov tshuaj tau ua raws li txoj kev hauv qab "2.2". Cells tau sau thiab RIPA lysate tau ntxiv rau extract protein. Cov qauv protein tau raug rau 10 feem pua Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, xa mus rau PVDF membrane, kaw hauv TBST uas muaj 5 feem pua skim mis nyuj rau 1h, ntxiv nrog cov tshuaj tiv thaiv thawj zaug, thiab incubated thaum hmo ntuj ntawm 4 degree; Tom qab ntxuav nrog TBST, incubate nrog lwm cov tshuaj tiv thaiv kab mob thiab txhim kho kev siv cov tshuaj kho qhov muag pom reagent.
2.5 qRT PCR tau siv los txheeb xyuas BMDM cell chemotactic factor 24 (CCL24), inflammatory zone 1 (Fizz1), Chitinase 3-zoo li 3 (Ym1), macrophage galactose type C-type Lectin 2 (MGL2), thiab Peroxisome proliferator- activated receptor (peroxisome-proliferator-activated receiver , PPAR ), Interferon regulatory factor 4 (IRF4), Arg-1 thiab CD163 mRNA qhia tau teeb tsa hauv pawg tswj hwm, pawg qauv, thiab ntau qhov sib txawv (0 }.
2.6Kev npaj ntawm conditioned nruab nrab Reference method [12]: BMDM yog cultured raws li txoj kev nyob rau hauv "2.2". Tom qab lub cell noob phaj txuas, ib qho nruab nrab uas tsis muaj ntshav qab zib muaj Cistanche deserticola cawv extract (0.25 mg/mL) ntxiv, thiab IL-4 (20 ng/mL) ) tau ntxiv 1 teev tom qab. Tom qab 24 teev, sau cov supernatant raws li qhov nruab nrab conditioned. Qhov nruab nrab nruab nrab yog centrifuged ntawm 2000 r / min kom precipitate cov fragments, aspirated, thiab khaws cia ntawm - 80 degree rau Cell migration thwmsim. BMDM tau coj mus kuaj raws li txoj kev hauv qab "2.2", thiab DMEM nruab nrab uas muaj cawv extract ntawm Cistanche deserticola (0.25 mg / mL) tau ntxiv tom qab lub cell noob phaj txuas rau phab ntsa, thiab IL-4 (20 ng / mL) tau ntxiv ib teev tom qab. Tom qab 24 teev, sau cov supernatant raws li qhov nruab nrab conditioned. Centrifuge qhov nruab nrab nruab nrab 2000 kom ua rau tawg tawg, nqus cov supernatant, thiab khaws cia ntawm -80 degree rau kev sim ntawm tes.2.7 Kev sim migration ntawm tes Muab qhov {{0}}} qhov plug-in rau kev kho qhov txhab rau hauv 12- qhov phaj, thiab 4T1 hlwb raug kho nrog 3.6 × 105/mL txhaj tshuaj . Tom qab cov hlwb lo rau ntawm phab ntsa thaum hmo ntuj, tshem tawm cov plugin thiab ntxuav cov hlwb uas ploj lawm nrog PBS. Ntxiv cov tshuaj dawb dawb uas muaj 50 feem pua qhov nruab nrab. Incubate nyob rau hauv ib tug incubator rau 24 teev. Thaum 0 thiab 24h, thaij duab nrog lub tshuab ntsuas inverted, txheeb xyuas cov duab nrog Image J, thiab xam cov cell tsiv teb tsaws. Cell migration rate=(0 h cheeb tsam qhov txhab -24 h cheeb tsam qhov txhab)/0 h cheeb tsam qhov txhab
2.8Cell colony xyaum ua tej yam 1000 4T1 hlwb raug inoculated rau hauv txhua lub qhov dej ntawm 6 qhov zoo daim hlau, thiab incubated nrog nruab nrab muaj 50 feem pua conditioned nruab nrab rau 8 hnub. Kho nrog 2 feem pua Paraformaldehyde, dye nrog 1 feem pua Crystal violet, thaij duab, thiab tshuaj xyuas cov duab nrog Image J.
2.9Kev txheeb xyuas kev txheeb xyuas tau ua los ntawm GraphPad Prism 8 software, nrog rau kev ntsuas cov ntaub ntawv qhia raws li xs ±, thiab kev sib piv ntawm pab pawg siv ib txoj kev ANOVA.
3 Kev tshwm sim
3.1 Kev txheeb xyuas muaj pes tsawg leeg ntawm cawv extract ntawm Cistanche deserticola deserticola yog qhia nyob rau hauv daim duab 1 thiab Table 2. Cov cawv extract ntawm Cistanche deserticola deserticola muaj benzoic acid, coniferyl aldehyde, Emodin, vanillic acid, hyaline, thiab lepirudin A.
Table 1 Primer sequences
Daim duab 1 Kev tshuaj xyuas cawv ntawm Cistanche deserticola deserticola
Table 2 Cheebtsam tsom xam ntawm cawv extract ntawm Cistanche deserticola deserticola
3.2Cytotoxicity ntawm Cistanche deserticola cawv extract ntawm BMDM Cov txiaj ntsig tau pom tias 0.015 625 - 2 mg/mL ntawm Cistanche deserticola cawv extract tsis muaj tshuaj lom rau BMDMs hlwb tom qab kho BMDMs hlwb nrog ntau ntau ntawm Cistanche deserticola cawv extract. rau 24 teev (Daim duab 2).
Daim duab 2 Cytotoxicity ntawm cawv extract ntawm Cistanche deserticola deserticola rau BMDM (xs ±, n=3)
3.3 Ethanol extract ntawm Cistanche deserticola inhibits M2 polarization ntawm macrophages hauv vitro. Hauv BMDM M0 macrophages, cov cim Arg-1 thiab CD163 ntawm M2-zoo li macrophages yog qhov qis, thiab cov lus qhia tau nce ntxiv tom qab induction los ntawm IL-4, qhia tias BMDM ua tiav polarizes rau hauv M2-zoo li macrophages. Western blotting thiab qRT PCR cov tswv yim tau siv los xyuas kom meej tias cov cawv extract ntawm Cistanche deserticola tuaj yeem hloov kho qhov kev qhia ntawm Arg-1 thiab CD163 induced los ntawm IL-4 nyob rau hauv ib koob tshuaj (Daim duab 3), qhia. tias cov cawv extract ntawm Cistanche deserticola tuaj yeem cuam tshuam ncaj qha rau M2 zoo li polarization ntawm macrophages. Txhawm rau tshawb nrhiav ntxiv cov txiaj ntsig ntawm cawv extract ntawm Cistanche deserticola deserticola ntawm M2 polarization ntawm macrophages, qRT PCR tau siv los kawm M2 xws li macrophage ntsig txog cov noob Fizz1 thiab PPAR, Cov qib hloov pauv ntawm Ym1, CCL24, MGL2, thiab IRF4 tau qhia hauv daim duab. 4. Piv nrog rau pawg qauv, mRNA qhia theem ntawm Fizz1, Ym1, CCL24, thiab IRF4 hauv cawv extract ntawm Cistanche deserticola (0.062 5, 0.125, { {29}}.25 mg/mL) pawg poob qis (P<0.05, 0.01, 0.001), and the PPAR in the alcohol extract of Cistanche deserticola (0.125, 0.25 mg/mL) group γ The mRNA expression level decreased significantly (P<0.01, 0.001), and the MGL2 mRNA expression level in the alcohol extract of Cistanche deserticola deserticola (0.25 mg/mL) group decreased significantly (P<0.001).
3.4 Cov ethanol extract ntawm Cistanche deserticola tsis muaj zog rau kev txhawb nqa ntawm M2-zoo li macrophages ntawm 4T1 cell migration. Kev kuaj khawb tau siv los soj ntsuam cov txiaj ntsig ntawm supernatant ntawm Cistanche deserticola ethanol extract ntawm lub peev xwm tsiv teb tsaws ntawm cov qog nqaij hlav cancer mis. BMDM tau incubated nyob rau hauv ib tug ntshiab ntshiab nruab nrab uas muaj IL-4 thiab cawv extract ntawm Cistanche deserticola deserticola rau 24 teev, thiab cov supernatant tau sau raws li ib tug conditioned nruab nrab. 4T1 yog kab lis kev cai hauv nruab nrab tsis muaj ntshav qab zib uas muaj 50 feem pua txheej txheem nruab nrab, raws li qhia hauv daim duab 5, cov khoom nruab nrab uas tau sau los ntawm BMDM kho nrog IL-4 ib leeg txhawb nqa kev tsiv teb tsaws ntawm 4T1 hlwb (P<0.05), while the conditioned medium of BMDM treated with alcohol extract of Cistanche deserticola significantly inhibited the migration of 4T1 cells (P<0.05). 3.5 Cistanche deserticola alcohol extract weakens the promotion of M2-like macrophages on 4T1 cell colony formation Use colony formation experiment to evaluate the effect of Cistanche deserticola alcohol extract on M2-like macrophages promoting 4T1 cell colony formation. As shown in Figure 6, the conditioned medium treated with IL-4 significantly promoted the colony formation of 4T1 cells (P<0.05), while the conditioned medium treated with alcohol extract of Cistanche deserticola significantly inhibited the colony formation of cells (P<0.001)
4 Kev sib tham
Cov txiaj ntsig ntawm cistanche tubulosa-Antitumor
Tam sim no, mob qog noj ntshav mis tseem yog teeb meem kev noj qab haus huv thoob ntiaj teb. Qhov tshwm sim ntawm mob qog noj ntshav mis yog nce xyoo los ntawm ib xyoos thiab cov tub ntxhais hluas, uas cuam tshuam rau poj niam txoj kev noj qab haus huv [13]. Cov tshuaj suav tshuaj suav hais tias nyob rau theem pib ntawm cov qog, vim qhov tsis muaj peev xwm ntawm lub cev kom dissipate qi vim yang deficiency, yin qi tsis txaus thiab tsis tuaj yeem tsim cov phev tsub zuj zuj. Txawm li cas los xij, qhov txawv txav ua rau cov khoom siv pathological xws li phlegm turbidity thiab ntshav stasis, ua rau hloov cov co toxins mus rau hauv cov qog nqaij hlav [14]. Cistanche deserticola deserticola, ua ib yam tshuaj tseem ceeb rau tonifying yang, muaj cov teebmeem ntawm tonifying tseem ceeb lub zog thiab lub raum yang thiab tswj kev tiv thaiv. Nws yog ib qho siv raum tonifying Suav tshuaj hauv kev kho mob. Tam sim no nws feem ntau siv los kho mob qog noj ntshav mis thiab feem ntau yog siv los ua cov tshuaj sib xyaw ua ke. Ib qho ntawm cov yam ntxwv ntawm kev mob qog noj ntshav yog lub cev tsis muaj zog. Lub cev tiv thaiv kab mob uas yuav tsum tau tawm tsam cov qog nqaij hlav tshwj xeeb Kev sib deev inhibition los ntawm cov ntaub so ntswg nyob ib puag ncig thiab Tumor microenvironment, uas ua rau kev loj hlob tsis muaj zog thiab kis ntawm cov qog [15]. Ntau thiab ntau cov pov thawj qhia tau hais tias thaum nws muaj nyob rau hauv cov qog microenvironment, innate immune cells (macrophages, neutrophils, dendritic cells, innate lymphoid cells, pob txha pob txha-derived Sexual inhibition cells thiab NK cells) thiab adaptive immune cells (T cells thiab B cells). ) pab txhawb qog nqaij hlav [16]. Macrophages yog qhov tseem ceeb ntawm cov neeg kho mob ntawm cov ntaub so ntswg homeostasis, thiab lawv cov polarization ntawm lwm txoj kev qhib macrophages (M2 hom) tuaj yeem txhawb kev loj hlob ntawm cov qog nqaij hlav cancer, angiogenesis, thiab metastasis. Yog li ntawd, tswj TAMs thiab tswj lawv cov homeostasis tau dhau los ua qhov tseem ceeb ntawm kev kho mob qog nqaij hlav [17]. TAMs koom nrog hauv metastasis, angiogenesis, matrix remodeling, ntxeem tau, thiab tiv thaiv kab mob qog noj ntshav. TAMs feem ntau yog muab faib ua ob hom phenotypes, uas yog classic activated M1-zoo li macrophages thiab lwm qhov qhib M2-zoo li macrophages [18]. Hauv cov qog nqaij hlav tsis zoo lossis tsis ua haujlwm, feem ntau TAMs yog classical activated M1-zoo li macrophages, uas yog Interferon- , IFN- ) Los yog lipopolysaccharide (LPS) ua kom, yog li txhawb TAMs los tsim cov tshuaj tiv thaiv thiab phagocytosis ntawm cov qog hlwb. M2-zoo li macrophages tuaj yeem qhib tau los ntawm Th2 cytokines xws li IL-4 los tsim ntau cov tshuaj tiv thaiv kab mob, uas ncaj qha txhawb kev loj hlob ntawm mob qog noj ntshav [19]. Yog li ntawd, thim rov qab los yog inhibiting polarization ntawm M2-zoo li macrophages yog lub tswv yim ntawm kev tiv thaiv kab mob cancer mis. Arg-1 yog ib qho cim ntawm M2-zoo li macrophages, thiab nws qhov kev nthuav qhia ntau dhau yog cuam tshuam nrog kev pom tsis zoo hauv cov neeg mob qog noj ntshav [20].
Suav tshuaj ntsuab cistanche-Antitumor
CD163 yog ib qho cim tshwj xeeb ntawm M2-zoo li macrophages [21], uas cuam tshuam nrog cov qog metastasis. CD163 ntxiv rau TAM induces epithelial-mesenchymal hloov pauv (EMT) thiab txhawb nqa qog noj ntshav cell migration [22]. Cov txiaj ntsig ntawm txoj kev tshawb no qhia tau hais tias cov extract ntawm Cistanche deserticola deserticola plays lub luag haujlwm hauv kev tswj kev tiv thaiv kab mob rau qee yam, inhibiting kev qhia ntawm Arg-1 thiab CD163, cov cim saum npoo ntawm M2-zoo li macrophages, thiab inhibiting M2- hom polarization ntawm macrophages. PPAR Nws yog ib qho kev ntsuas metabolic uas tswj cov lipid homeostasis los ntawm kev ua kom muaj ntau yam fatty acids thiab fatty acid derivatives (xws li Palmitic acid) [23]. PPAR Muaj feem xyuam rau M2 polarization ntawm macrophages, PPAR tau dhau los ua tus tswj hwm lub ntsiab ntawm M2 polarization hauv macrophages [24], PPAR Ligands tau pom tias muaj zog inhibitory cuam tshuam rau cov qog loj hlob hauv vivo [25]. Fizz1 thiab Ym1 yog ob qho tib si M2-zoo li macrophage marker genes, thiab Fizz1 thiab Ym1 koom nrog fibrosis thaum kho cov nqaij mos [26]. M2-zoo li macrophages tsim ntau ntau ntawm CCL24 hauv vitro [27], thiab kev nthuav qhia ntau ntxiv ntawm CCL24 tuaj yeem txhawb cov qog loj hlob, tsiv teb tsaws, thiab ntxeem tau [28]. IRF4 yog ib tug tswv cuab ntawm tsev neeg IRF. Nws koom nrog M2 polarization txheej txheem ntawm macrophages thiab ua raws li qhov tsis zoo regulator ntawm Hu-zoo li receptor signals los ntawm kev sib txuas nrog MyD88 adapter molecule [29]. MGL2 yog ib tug tswv cuab ntawm Galactose hom C hom Lectin tsev neeg ntawm macrophages, thiab nws kuj tau qhia nyob rau hauv macrophages stimulated nyob rau hauv lwm yam kev ua kom ua hauj lwm tej yam kev mob [30]. Cov txiaj ntsig ntawm txoj kev tshawb no qhia tau hais tias cov extract ntawm Cistanche deserticola deserticola inhibits M2 zoo li macrophage ntsig txog noob PPAR, Cov lus qhia ntawm Fizz1, Ym1, CCL24, IRF4, thiab MGL2 inhibits M2 hom polarization ntawm macrophages, qhia tias Epimedium tuaj yeem ua haujlwm tau zoo. inhibitor ntawm M2 zoo li macrophages. Ntau thiab ntau cov pov thawj qhia tias M2-zoo li macrophages tuaj yeem txhawb kev mob qog noj ntshav thiab kev loj hlob [31]. Cov xov xwm zoo los ntawm M2-zoo li macrophages tuaj yeem simulate Cov Tumor microenvironment thiab ua rau cov qog nqaij hlav thiab kev loj hlob, uas zoo ib yam li macrophages cais los ntawm cov qog nqaij hlav malignant [12]. IL-4 tuaj yeem txhawb cov macrophage polarization ntawm M2 hom, thiab txhawb cov qog proliferation thiab angiogenesis [18]. Txoj kev tshawb no tau qhia txog kev sib raug zoo ntawm macrophage polarization thiab cov nyhuv tiv thaiv qog ntawm Cistanche deserticola deserticola. Cov xov xwm kho mob los ntawm IL-4- qhib cov macrophages txhawb kev tsiv teb tsaws thiab kev loj hlob ntawm 4T1 hlwb, thiab tom qab kev koom tes nrog Cistanche deserticola, thim qhov M2- ua kom cov qog ua haujlwm txhawb nqa, qhia tias IL{{55} }activated M2 polarization raug tshem tawm los ntawm Cistanche deserticola.
Txoj kev tshawb no tau qhia txog kev sib raug zoo ntawm macrophage polarization thiab cov nyhuv tiv thaiv qog ntawm Cistanche deserticola deserticola. Cov xov xwm txias los ntawm IL-4- qhib cov macrophages txhawb kev tsiv teb tsaws thiab kev loj hlob ntawm 4T1 hlwb, thiab tom qab kev sib koom tes nrog Cistanche deserticola, thim qhov M2- ua kom cov qog ua haujlwm txhawb nqa, qhia tias IL{{7} }activated M2 polarization raug tshem tawm los ntawm Epimedium. Txoj kev tshawb no pom tias Cistanche deserticola extract inhibits Cell migration thiab colony tsim ntawm mob cancer mis los ntawm kev tswj lub polarization ntawm macrophages nyob rau hauv vitro, qhia tias Cistanche deserticola txoj kev kho mob cancer mis yuav muaj feem xyuam rau cov kev cai ntawm cov qog microenvironment, thiab Epimedium yuav ua raws li. Tus tswj hwm ntawm Tumor microenvironment ntawm qhov chaw metastasis los ntawm kev cuam tshuam cov macrophages, uas muab cov tswv yim tshiab rau kev tiv thaiv qog ua haujlwm ntawm Cistanche deserticola, Nws nthuav tawm lub peev xwm tshiab ntawm Cistanche deserticola rau kev kho mob qog noj ntshav, uas yuav pab txo qis qhov tshwm sim ntawm mob qog noj ntshav thiab mob qog noj ntshav cuam tshuam txog kev tuag. Nyob rau hauv lub neej yav tom ntej, pab neeg tshawb fawb yuav ntxiv kev tshawb fawb txog cov txiaj ntsig ntawm Cistanche deserticola ntawm kev loj hlob thiab metastasis ntawm mob qog noj ntshav tom qab inhibiting M2 polarization ntawm macrophages hauv vivo, los piav qhia ntxiv txog kev tiv thaiv qog nqaij hlav ntawm Cistanche deserticola thiab muab lub hauv paus rau kev siv tshuaj kho mob. Cistanche deserticola hauv kev kho mob qog nqaij hlav.
Cov ntaub ntawv
Cov ntaub ntawv
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