Onco-immunity Thiab Therapeutic Application Of Amygdalin: Kev Ntsuam Xyuas Ntu 2
Jun 13, 2023
6. Pharmaceutical applications ntawm amygdalin
Amygdalin txoj kev tawg, uas tsim cov hydrocyanic acid, tuaj yeem ua rau lub ntsws ua pa qeeb thiab kho mob hawb pob los ntawm kev thaiv cov kab mob ua pa.54 Ib qho kev sim tsiaj txhu nrog cov kab mob ua pa pom tau tias muaj kev nce hauv cov synthesis ntawm pulmonary surfactant.55 Amygdalin tau pom tias tiv thaiv hom II. alveolar epithelial cells (AECIIs) sib cais los ntawm cov nas me hauv lub ntsws thaum raug hypoxia.56 Qhov xwm txheej no txwv tsis pub AECII cov hlwb los ntawm kev loj hlob thiab txo qis lub ntsws surfactant mRNA qib hauv vitro, ua rau lub ntsws raug mob hauv cov tsiaj yug ntxov ntxov.57 Ntawm qhov concentration ntawm 200 μmol / L. , amygdalin txhawb kev loj hlob ntawm AECII hlwb hauv cov nas ua ntej thiab nce qib ntawm SP mRNA.58
Hydrocyanic acid yog cov tshuaj lom neeg, thiab kev noj ntau npaum li cas tuaj yeem ua rau tib neeg lub cev muaj kev phom sij, nrog rau kev lom neeg, kev puas tsuaj rau cov hlab ntsws thiab cov hlab plawv, thiab lwm yam. Vim hydrocyanic acid yog cov tshuaj muaj zog acidic, nws muaj kev ncaj ncees. corrosion cuam tshuam rau tib neeg lub hlwb, uas yuav ua rau cell membrane rupture thiab poob ntawm cell function, yog li cuam tshuam rau tib neeg noj qab haus huv.
Raws li kev sib raug zoo ntawm hydrocyanic acid thiab kev tiv thaiv kab mob, tsis muaj cov pov thawj ncaj qha los txhawb qhov kev xav no. Txawm li cas los xij, kev raug mob mus ntev rau cov tshuaj lom xws li hydrocyanic acid tuaj yeem ua rau lub cev tsis muaj zog, yog li txo qis kev tiv thaiv kab mob thiab ua rau muaj kev pheej hmoo ntawm kev kis kab mob. Yog li ntawd, kev zam kom tsis txhob raug tshuaj lom yog ib qho tseem ceeb rau kev tswj kev noj qab haus huv thiab kev tiv thaiv kab mob. Yog li ntawd, peb yuav tsum txhim kho peb txoj kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv. Cistanche kuj muaj cov tshuaj tiv thaiv kab mob thiab tiv thaiv kab mob qog noj ntshav, uas tuaj yeem ntxiv dag zog rau lub cev tiv thaiv kab mob muaj peev xwm tiv thaiv thiab txhim kho lub cev tiv thaiv kab mob.
Nyem qhov txiaj ntsig kev noj qab haus huv ntawm cistanche
Tsis tas li ntawd, Semen Armeniacae Amarum (SAA), uas muaj amygdalin ua ib qho tseem ceeb, muaj cov tshuaj tiv thaiv kab mob hawb pob hauv cov qauv ua xua los ntawm inducing ovalbumin (OVA).59 SAA yog xav kom txo hom 2 pab T cell muaj nuj nqi thiab txo qis interleukin. (IL-4) production.60 Qhov tshwm sim ntawm kev mob ntsws asthma, xws li kev mob ntsws asthma (AHR) thiab cov hlab ntsws o, raug txo vim yog hloov pauv Th2 cov lus teb rau qhov ua xua.
Kev txo qis ntawm cov hlab ntsws hyperactivity thiab o, uas yog ob qho tib si mob hawb pob, yuav tshwm sim los ntawm kev hloov pauv Th2 cov lus teb rau cov allergen.61 Tsis tas li ntawd, amygdalin suppresses mob ntsws puas tsim los ntawm lipopolysaccharide. Amygdalin kuj tseem tuaj yeem siv los kho tus kab mob ntsws ntev (COPD).62 Ntau qhov kev tshawb fawb qhia tias amygdalin tuaj yeem cuam tshuam ib feem ntawm kev sib kis ntawm epithelial-mesenchymal uas tau tsim los ntawm kev haus luam yeeb.63 Qhov kev cuam tshuam no yuav yog vim amygdalin lub peev xwm los txo TGF-B1 qhia thiab smad2/ 3 phosphorylation, txuas rau TGF/Smad pathway suppression.64
7. Amygdalin thiab lub cev tiv thaiv kab mob
Amygdalin qhia txog kev tiv thaiv atherosclerotic los ntawm kev txo qis cov lus teb los tiv thaiv kab mob thiab txhawb lub cev tiv thaiv kab mob los ntawm kev hloov kho T hlwb kev ua haujlwm (Tregs), ua rau cov quav hniav tshem tawm thiab nthuav dav lumen.65,66 Psoriasis tuaj yeem kho tau zoo nrog T- peptide (PT), ib qho octapeptide uas qee zaum hu ua amygdalin analog vim yog sib piv peptide chains.67
Hauv tib neeg keratinocytes, PT tau pom tias nce TGF- , HSP70, thiab -v integrin qhia thaum txo ICAM-1 expression.68 Tsis tas li ntawd, peb cov amygdalin-derived analogs nrog cov tshuaj sib piv hauv tib lub peptide saw tab sis tsis muaj cyanide pawg. tau pom tias muaj cov dej num lom neeg zoo ib yam li PT.69 Lawv ob leeg hloov kho lub cev tiv thaiv kab mob hauv tib neeg keratinocytes, qhia tias lawv yuav raug siv los kho psoriasis.70
Amygdalin nce kev loj hlob ntawm tib neeg peripheral ntshav T hlwb hauv vitro (25–80{{10}} ug/mL, 0.055–1.75{ {22}} mmol/L).35 Nws tuaj yeem txhawb IL-2 thiab interferon-secretion nyob rau hauv thaj tsam ntawm 25-400μ g/mL (0.055–0.875 mmol/L).71 Amygdalin (100). -400 mg/L; 0.219–0.875 mmol/L) ntxias T cells kom proliferate hauv kev sim ntxiv, nrog rau feem ntau ntawm 200 mg/L (0.437 mmol/L). Amygdalin (10 mg/kg) txo cov kev loj hlob ntawm lub cev tiv thaiv kab mob, suppresses lub cev tiv thaiv kab mob, thiab ua kom cov ciaj sia taus ntawm lub raum hloov nas nyob rau hauv vivo.72 Immune cells muaj lub luag haujlwm tseem ceeb hauv kev loj hlob thiab kev loj hlob ntawm endometriosis. Amygdalin (5 mg/kg) txo qis endometriosis foci los ntawm kev cuam tshuam rau lub cev tiv thaiv kab mob hauv zos ua haujlwm.48 Cov kev tshawb pom no qhia tias amygdalin tuaj yeem txhawb kev loj hlob ntawm cov kab mob hauv lub cev hauv kev tshawb fawb, thiab ib txhij, nws tuaj yeem cuam tshuam kev loj hlob ntawm lub cev tiv thaiv kab mob thiab txhim kho kev hloov hauv nruab nrog cev. kev vam meej nyob rau hauv lub cev hloov cov kev xeem.55
Ob qhov kev tshawb pom no zoo li tsis sib haum xeeb taw qhia txog qhov muaj peev xwm amygdalin-mediated immune system tswj kev tswj hwm ntawm ob tog.64 Lwm qhov zoo ntawm amygdalin txoj kev kho zoo li yog qhov ua tau ntawm qhov mob thiab mob nyem.56 Chang li al.68 tsim amygdalin cov tshuaj tiv thaiv thiab tshuaj tua kab mob. siv hauv vitro cog qoob loo ntawm nas BV2 microglial hlwb hauv xyoo 2005. Huang tau lees paub cov teebmeem no hauv vitro ntawm LPS-kho RAW 264.7 hlwb thiab hauv vivo tshawb nrhiav ntawm cov nas uas muaj carrageenan-induced inflammatory.73 TNF-a thiab IL-1b transcription yog inhibited los ntawm 1 mM amygdalin nyob rau hauv vitro.74 Txoj kev tshawb no theem tom ntej koom nrog txhaj tshuaj carrageenan rau hauv tus nas lub pob taws sib koom ua ke hauv ib qho hauv vivo test.75 Qhov hnyav faib piv (WDR), pob taws ncig, thiab qhia theem ntawm peb qhov ntsuas molecular ntawm qhov mob thiab o (c-Fos, TNF-a, thiab IL-1b) tau siv los tshuaj xyuas qhov cuam tshuam ntawm amygdalin.76 Carrageenan tau pom tias ua rau edema thiab qis WDR, ua rau nws muaj kev kwv yees zoo ntawm qhov mob.77 Kev tswj hwm ntawm amygdalin ua rau muaj kev txo qis hauv WDR, uas tej zaum yuav qhia tau tias amygdalin muaj cov yam ntxwv ntawm cov tshuaj tua kab mob.78 Ntau yam kab mob sib kis tuaj yeem ua rau mob pob taws ntawm cov tsiaj sim.79
Qhov kev qhia ntawm c-Fos, TNF-a, thiab IL-1b nyob rau hauv tus txha caj qaum tau txiav txim siab los ntawm kev tswj hwm amygdalin hauv cov leeg ntawm 0.005 mg/kg.80 Qhov txo qis ntawm Fos (carrageenan-induced) qhia nyob rau hauv tus txha caj qaum los ntawm amygdalin ua rau nws ib tug txaus nyiam kev xaiv rau kev kho mob o thiab mob alleviation nyob rau hauv txoj kev tshawb no.81 Kev kho nrog amygdalin tau pom los txo LPS-induced cell o nyob rau hauv vitro thiab carrageenan-induced o. thiab edema nyob rau hauv nas.82 Lub c-Fos, TNF-a, thiab IL-1b qhia nyob rau hauv tus txha caj qaum yog txiav txim siab los ntawm qhov kev kho no.19 Yog li ntawd, amygdalin qhov kev txiav txim yog txuas mus rau ib tug txo nyob rau hauv proinflammatory cytokine. output.83 Hauv lipopolysaccharide (LPS)-induced cell kab thiab tus qauv nas ntawm carrageenan-induced mob caj dab, amygdalin's analgesic thiab anti-inflammatory zog tau tshawb xyuas.84
Amygdalin, ib qho chaw sib cais los ntawm cov noob txiv rosemary, txo qis hyperalgesia los ntawm inhibiting qhov mob loj thiab cov kab mob inflammatory molecular xws li necrosis factor (TNF-) thiab interleukin-1 (IL-1).85 Amygdalin cais. los ntawm Prunus Armeniacae kuj tau pom tias txo cov formalin-induced mob nyob rau hauv nas ntawm ntau npaum li cas tsawg tshaj li 1 mg / kg, uas tej zaum yuav yog vim nws cuam tshuam rau zus tau tej cov inflammatory cytokines xws li interleukin -1 beta (IL{ {7}} ), thiab qog necrosis factor (TNF -), ob hom cytokines uas tsim los ntawm lub cev tsis muaj zog. (iNOS), txo qis E2 prostaglandins thiab nitric oxide ntau ntau, ua rau muaj kev tiv thaiv kab mob thiab tshuaj tua kab mob.87
8. Amygdalin cov nyhuv ntawm lub plab zom mov
Lub luag haujlwm ntawm amygdalin nyob rau hauv lub plab hnyuv phab ntsa thiab nrog kev pheej hmoo ntawm kev noj zaub mov tau pom los ntawm degrading amygdalin hauv tib neeg txoj hnyuv thiab nws cov metabolite nqus hauv cov hnyuv hauv GIT plab hnyuv thiab kab lis kev cai ntawm tib neeg txoj hnyuv hlwb. tuaj yeem cuam tshuam nrog kev ua haujlwm hauv plab hnyuv los ntawm inhibiting pepsin action.89 Ntawm qhov tsis sib xws, pepsin suppresses ALT thiab txhim kho lub sijhawm thoob ntiaj teb hauv CCl4-kho nas thaum muab ntawm qhov ntau npaum li 500 mg / kg AST.90 Ntxiv mus, nyob rau hauv lub xub ntiag ntawm pepsin hydrolysis ntawm cov kua txiv almond, nas daim siab txuas cov ntaub so ntswg proliferates tsawg, txawm tias qhov no tsis muaj kev cuam tshuam los ntawm kev loj hlob vim qhov kev rov zoo ntawm AST thiab ALT91 qib tom qab di-galactosamine induction.30 Amygdalin kuj tau pom tias muaj txiaj ntsig zoo kho mob gastritis hauv nas nrog atrophic. gastritis.92 Los ntawm kev ua cov qauv kuaj ntawm tib neeg lub plab zom mov, Shim thiab al.51 tuaj yeem simulate amygdalin digestion. Cov enzymes digestive degraded qhov ncauj-administered amygdalin rau prunasin thiab qabzib.93 Tom qab ntawd, prunasin tau tawg mus rau hauv mandelonitrile hauv tib neeg cov hnyuv, muaj beta-glucosidase, los tsim hydroxy-mandelonitrile yam tsis muaj benzaldehyde, raws li cov kws tshawb fawb pom tias. kab mob hauv plab tuaj yeem cuam tshuam rau amygdalin toxicity.47
9. Cov nyhuv ntawm amygdalin rau cov kab mob neurodegenerative
Raws li Cheng et al., 49 amygdalin tuaj yeem ua tau zoo hauv kev kho cov kab mob neurodegenerative zoo li Parkinson tus kab mob. Ntxiv nrog rau kev tiv thaiv lub hlwb tiv thaiv 6-hydroxydopamine-induced neurotoxicity, nws txhim kho neuronal kev loj hlob los ntawm Calreticulin qhia stimulation.48
10. Cov nyhuv ntawm amygdalin ntawm lub genitourinary system
Amygdalin paub zoo txog nws cov khoom muaj zog tiv thaiv fibrotic, thiab nws tuaj yeem siv los kho cov neeg mob raum fibrosis. Thaum kab lis kev cai interstitial fibroblasts tau muab amygdalin, lawv lub peev xwm los proliferate raug txo, thiab lawv cov tiam ntawm kev loj hlob (TGF- 1) yog hloov.49 Tsis tas li ntawd, thaum amygdalin tau muab rau cov tsiaj nrog obstructive neuropathy, tsim ntawm cov extracellular matrix tom qab tso zis txhaws tau sai heev. Hnub tim 21, amygdalin kuj tshwm sim kom txo tau lub raum puas.48 Yog li ntawd, amygdalin tuaj yeem ua rau lub raum fibroblasts tsis muaj zog thiab ua rau lub raum fibrosis interstitial hauv nas.30 Estradiol-17 beta raug tso tawm ntawm zes qe menyuam granulosa hlwb thaum raug ntau npaum li cas ntawm amygdalin, tab sis progesterone secretion tsis tau pom.41 Nyob rau hauv npua zes qe menyuam, amygdalin kuj tswj steroid ntau lawm.47
Tsis tas li ntawd, cov khoom siv tshuaj ntawm cov khoom siv raw Keishi-bukuryo-gan, tshuaj ntsuab Japanese siv los txhawb ovulation hauv cov poj niam cev xeeb tub, suav nrog amygdalin. Hauv ob qho tib si hauv vivo thiab hauv vitro, Keishi-bukuryo-gan txhawb steroidogenesis nyob rau hauv pre-ovulatory follicles thiab corpus luteum nyob rau hauv nas zes qe menyuam.46 Li no, tej yam ntuj tso tshuaj muaj nyob rau hauv iab almond kernels yuav txo FSH thiab tej zaum yuav ua si lub luag hauj lwm nyob rau hauv folliculogenesis nyob rau hauv lub cev. luav ovaries.45 Txawm li cas los xij, intramuscular thiab qhov ncauj kev tswj hwm ntawm amygdalin cuam tshuam rau qee qhov endocrine regulators 'plasma qib (progesterone, estradiol-17 beta, testosterone), thyroid (triiodothyronine, thyroxine, stimulating thyroid hormone), thiab cov tshuaj hormones (triiodothyronine, thyroxine, stimulating thyroid hormone).44 Qhov nruab nrab lub cev hnyav thiab cov qog anterior pituitary (prolactin, luteinizing hormone) ntawm luav siv hauv kev tshawb nrhiav tsis muaj kev cuam tshuam.43
11. Amygdalin cov tshuaj tiv thaiv kab mob
Amygdalin xav tias muaj nyob rau hauv ntau cov nroj tsuag cov noob, uas yog apricots, almonds, txiv apples, thiab txiv duaj, tso cai rau nws mus kuaj ntawm ntau hom qog nqaij hlav cancer.32 Chen li al.49 pom tias amygdalin muaj kev cuam tshuam rau lub ncauj tsev menyuam. mob qog noj ntshav Hela thawj zaug. Amygdalin-kho txiv duaj kab ntawm tes tau stained nrog 4, 6-diamino-2-phenyl indole (DAPI) ua ntej raug kho nrog annexin V-FITC thiab propidium iodide.42 Yog li, BCL-2 Anti-apoptotic protein muaj nuj nqi txo qis, tab sis Bax protein muaj nuj nqi nce.41 Kuj tseem muaj kev nce hauv caspase kev ua thiab kev pib ntawm innate apoptotic pathways.40 Lub neej ntev ntawm HeLa hlwb hauv vitro tau txo qis vim siv amygdalin, qhia tias nws yuav ua tau. muaj kev kho mob rau cov qog nqaij hlav qog noj ntshav. Ib qho kev tshawb pom zoo ib yam kuj tau pom hauv vivo.39
Tsis tas li ntawd, qhov cuam tshuam ntawm amygdalin cais tawm ntawm Armenlacae phev, ib tus neeg hauv tsev neeg prunasin, tau kawm txog cov qog nqaij hlav prostate DU 145 thiab LN CAT.37 Nrog rau kev txo qis ntawm cov tshuaj tiv thaiv apoptotic BCL-2 protein thiab nce Bax protein qhia. , qhov nce hauv caspase-3 enzyme tau pom.94 Raws li anti-apoptotic BCL-2 protein qhia tau txo qis thiab Bax protein qhia tau nce, qhov nce hauv caspase-3 enzyme tau pom. .84 Amygdalin extract yog xav tias yuav ua rau mob qog nqaij hlav qog noj ntshav hauv tib neeg los ntawm apoptosis.85
Amygdalin cov tshuaj inhibitory muaj peev xwm kuj tau kawm hauv vitro hauv cov qog nqaij hlav cancer mis. Nws tseem tuaj yeem tsim cov tshuaj cytotoxicity hauv MCF7 (ER) hlwb, MDA MB-231 hlwb, thiab Hs 578T hlwb (triple-negative mob qog noj ntshav mis kab mob hlwb (TNBC)). BCL-2, Bax thiab caspases tau pom tias muaj cov teebmeem zoo sib xws. Kev kho mob nrog amygdalin.87 Amygdalin qhia txog cov tshuaj tiv thaiv kab mob ntawm cov qog nqaij hlav cancer ntawm lub mis.30 Ib qho piv txwv zoo sib xws ntawm cov qauv adhesion tau pom hauv cov qog nqaij hlav zais zis. Tsis tas li ntawd, UMUC-3 cov qog hlwb, RT112 hlwb, thiab TCCSUP cov hlwb txhua tus tau pom qhov txo qis hauv adhesion tom qab 24 teev lossis ob lub lis piam ntawm kev tswj hwm amygdalin.79 Thawj ob kab mob qog noj ntshav tau nthuav tawm txo qis kev tsiv teb tsaws, qhov TCCSUP nthuav tawm kev hloov pauv hloov pauv tau zoo. . Nws tau thov tias amygdalin cov tshuaj tiv thaiv kab mob tsuas yog txwv rau qee hom mob qog noj ntshav.78 Ib yam zoo sib xws tau tshwm sim nrog cov qog nqaij hlav qog noj ntshav, qhov twg amygdalin muaj kev cuam tshuam rau HeLa cell kab tab sis tsis nyob rau hauv FL hlwb. Nws tau pom tias hloov amygdalin mus rau neo-amygdalin hauv cov tshuaj aqueous inhibits nws cov nyhuv anticancer hauv promyelocytic leukemia hlwb. Lub amygdalin extract los ntawm Persicae phev tau pom tias yog daim ntawv nquag ntawm D los ntawm HPLC chromatography. Yog li, cov extract tau boiled kom tsis txhob muaj epimerization ua ntej siv rau promyelocytic leukemia hlwb (HL-60). Kev tuag ntawm tes kuj tau sau tseg, qhia tias apoptosis tau tshwm sim.77
Tsis tas li ntawd, kev hloov pauv ntawm lub cev hauv lub cev, nrog rau DNA tawg ntawm tes, tau kuaj pom. Tsis tas li ntawd, amygdalin txoj kev kho mob ntawm H1299 thiab PALM hlwb uas tsis yog me me ntawm lub ntsws cancer (NSCLC) tau pom nyob rau hauv vitro.76 Inhibition ntawm cell proliferation tshwm sim nyob rau hauv siab concentrations ntawm amygdalin, thiab inhibition ntawm cell migration thiab ntxeem tau tshwm sim ntawm tsawg concentrations. . Amygdalin tau pom tias txo cov microtubules paub tab nyob rau hauv lub nplhaib aortic ntawm amygdalin-kho mob ntshav nas nas, inhibiting streptozotocin-induced endothelial hlwb nyob rau hauv streptozotocin-induced mob ntshav qab zib nas endothelial hlwb.75 Tom qab xya hnub ntawm incubation, cov nas thiab nas. multiplied yam tsis muaj amygdalin kho. Nws kuj tau pom zoo tias amygdalin's anti-angiogenic zog tuaj yeem ua rau nws cov qog-suppressive zog thiab lub peev xwm kho lub luag haujlwm ntawm amygdalin tau qhia hauv daim duab 3. 92.
12. Cov nyhuv ntawm plab hnyuv microbial flora ntawm amygdalin
GIT, lumen, plab hnyuv, thiab plab hnyuv microorganisms cuam tshuam cov metabolism ntawm cov tshuaj thiab lwm yam tshuaj txawv teb chaws uas nkag mus rau hauv lub cev, tshwj xeeb tshaj yog thaum noj qhov ncauj. Firmicutes, bacteroids, thiab actinobacteria yog cov kab mob anaerobic ntau tshaj plaws uas pab tso tawm cyanide hauv plab.30 Nucleases, lipases, transferases, peptidases, thiab microflora enzymes yog cov enzymes ntau hauv cov hnyuv. Nws tau tshawb pom tias plab hnyuv beta-glucosidase thiab microbial beta-glucosidase tsim cov khoom sib txawv.79 Beta-glucosidase, tseem hu ua lactase fluorescein hydrolase (LPH) thiab cytosolic beta-glucosidase (CBG), yog lwm cov glycosidic bond destroyer uas ua haujlwm ntawm tshuaj, nrog rau cov kua tsib. Tsis muaj hydrocyanic acid yog tsim thaum amygdalin hloov mus rau prunasin los ntawm plab hnyuv beta-glucosidase. Lwm lub plab microbe, beta-glucosidase, converts amygdalin rau HCN.75 Cov kab mob plab hnyuv tau pom nyob rau hauv ntau qhov kev tshawb fawb, uas amygdalin yog hydrolyzed rau cyanide, uas yog proportional rau cov microbial muaj pes tsawg leeg hauv plab.74 Tsis tas li ntawd, thaum txoj hnyuv microbial loj hlob. txhawb cov nas nkag ntawm 300 mg / kg, amygdalin hydrolysis toxicity yog txo, tab sis nws tsim toxicity thiab kev tuag ntau dua hauv cov nas tsis kho.68
Muab piv rau nas thiab liab, tib neeg cov quav tau pom tias hydrolyze kwv yees li 50 feem pua ntawm amygdalin rau cyanide vim tias muaj ntau cov kab mob microbial. Bacteroids feem ntau yog siv los tsim glucosidase. Cov kab mob hauv lub plab yog cuam tshuam thiab tswj hwm los ntawm prebiotics thiab probiotics.64,73,74 Tsis tas li ntawd, prebiotics yog cov khoom siv roj ntsha, hos probiotics yog cov kab mob uas tswj cov kev ua ntawm lub plab microbiota rau tus tswv tsev cov txiaj ntsig. Prebiotics tuaj yeem khi lossis nqus cov carcinogens, txo qis qhov txaus ntshai ntawm amygdalin-induced cyanide lom. Bactericidal beta-glucosidase kev ua haujlwm raug txo los ntawm Lactobacillus thiab Bifidobacterium.56,85,90
13. Amygdalin cuam tshuam rau lub voj voog ntawm tes thiab apoptosis
Amygdalin kuj muaj cov tshuaj tiv thaiv kab mob vim tias nws cuam tshuam lossis hloov cov proteins uas koom nrog hauv lub voj voog ntawm tes. Ib cag los ntawm kev ua rau apoptosis hauv PC3 thiab LNCaP hlwb hauv prostate cancer tom qab 24 teev thiab ob lub lis piam ntawm kev kho mob, amygdalin kuj tau pom tias nce G0}/G1 theem hlwb thiab txo G2/M theem hlwb. Kev hloov pauv ntawm qee lub voj voog ntawm tes, xws li cyclin-dependent kinases (Cdks), kuj tau tshaj tawm.35,70,71 Hauv amygdalin-kho SNu-C4 hlwb, kab mob qog nqaij hlav hauv lub cev, qhov xwm txheej zoo ib yam tau pom, uas qee yam Lub voj voog cov protein, feem ntau exonuclease, topoisomerase, thiab khi cov protein, tau tswj hwm. Cov kws tshawb fawb tau txo cov protein qhia siv cDNA microarray tsom xam, thiab lawv kuj tau pom qhov txo qis hauv mRNAs qhia qib siv RT-PCR tsom xam.64,65,72 Amygdalin tau raug pov thawj kom txo qis kev qhia ntawm cov kab mob ntsig txog ntawm tes hauv SNU-C4 kab mob plab. mob qog noj ntshav, xws li exonuclease 1 (EXO1), topoisomerase (DNA) I (TOP1), subfamily F, thiab ATP binding cassette. Yog li ntawd, nws tuaj yeem cuam tshuam cov qog cell voj voog, tiv thaiv cell proliferation thiab qhia nws cov nyhuv los tiv thaiv qog. Nws tuaj yeem txiav txim siab tias amygdalin tuaj yeem tswj lub voj voog ntawm tes thiab txwv kev loj hlob ntawm tes los ntawm kev hloov pauv cov kab mob ntawm tes los yog cov noob, thiab tshwj xeeb tshaj yog, amygdalin tuaj yeem txo cov qog nqaij hlav qog nqaij hlav, tshwj xeeb tshaj yog nyob rau hauv prostate thiab mob qog noj ntshav.55,64-66.
Chen et al.49 tau tshawb pom tias amygdalin tuaj yeem ua rau apoptosis hauv DAPI-impregnated HeLa hlwb los ntawm kev txhawb nqa caspase -3 kev qhia, uas txo qis qhov kev qhia ntawm BCL-2 thiab txhawb nqa kev qhia ntawm Bax hauv HeLa hlwb kho los ntawm amygdalin. , qhia txog txoj hauv kev tseem ceeb koom nrog hauv kev pib amygdalin-based apoptosis. Nws kuj tuaj yeem ua rau apoptosis hauv cov qog nqaij hlav qog nqaij hlav prostate.14,16,17 Tom qab kho nrog amygdalin, Chang li al. tshawb pom tias Bax enzyme qhia thiab caspase-3 kev ua haujlwm tau nce siab, qhov BCL-2 qhia tau poob hauv DU145 thiab LNCaP hlwb, ua rau apoptosis hauv cov qog nqaij hlav qog nqaij hlav prostate.8 Lee thiab al.15 soj ntsuam apoptotic proteins qhia hauv amygdalin kho mob qog noj ntshav mis nrog ntau npaum li cas. Lawv tshawb pom tias amygdalin tsa qhov kev qhia ntawm proapoptotic Bax protein thaum txo qis kev qhia ntawm anti-apoptotic protein BCL-2 Procaspase 3. PARP degradation kuj tau pom hauv amygdalin-kho cov qog nqaij hlav mis tib lub sijhawm.8 Cov no Kev tshawb pom pom tau hais tias amygdalin inhibits qog loj hlob los ntawm inducing apoptosis thiab modulating apoptosis-related proteins, uas yog ib qho tseem ceeb nyob rau hauv prostate thiab qog nqaij hlav qog noj ntshav (Fig. 4).74–77.
14. Kev sib koom ua ke ntawm amygdalin thiab В-glucosidase
Beta-glucosidases (-D-glucopyrranoside glucohydrolase) [EC3.2.1.21] yog cov enzymes uas hydrolyze carbohydrates 'glycosidic bonds, tso end-glycosyl residues, glycosides, thiab oligosaccharides. Lawv muaj nyob hauv ntau hom, suav nrog eukaryotes, archaea, thiab cov kab mob.30 Lawv kuj tau koom nrog cov haujlwm tseem ceeb xws li kev hloov pauv biomass, glycolipid tawg, lignification, tiv thaiv kab tsuag, phytohormone ua kom, thiab cell phab ntsa catabolism. Gaucher kab mob (vim los ntawm beta-glucosidase deficiency), nyob rau hauv uas glycosides sau nyob rau hauv cov ntaub so ntswg lysosomal, zoo li kho nrog beta-glucosidases. Beta-glucosidases feem ntau yog siv los ua cov nroj tsuag ntawm tes rau cellulose hydrolysis ntawm kev lag luam scale.90 Ntawm qhov kub txog li 90 ◦C, kub-resistant glucosidases yog siv los tsim cov piam thaj los ntawm cellulose, thiab isoflavones tuaj yeem ua tau zoo aglycones. Beta-glucosidase, tseem hu ua emulsion, muaj nyob rau hauv cov nroj tsuag noj tau xws li apricot kernels (uas kuj muaj cov antioxidants siab), almond kernels, nceb, lettuce, thiab ntsuab kua txob, thiab yog tsim los ntawm cov kab mob xws li dub aspergillus, nthuav tawm hauv lub plab microbiota.
Nroj tsuag, fungi, thiab kab mob txhua tus muaj beta-glucosidase zoo tib yam hauv cov kab ke thiab cov qauv. Cov kev ua ntawm cov substrate los yog tus kheej ntawm lawv cov nucleotide sequences yuav siv tau los faib lawv.88 Beta-glucosidases tuaj yeem muab faib ua peb pawg raws li cov txheej txheem substrate: (1) aryl beta-glucosidases (uas muaj kev nyiam rau aryl. -beta-glucosides), (2) cellulose (uas hydrolyzes nkaus xwb disaccharides), thiab (3) glucosidases nrog Extensive Specificity (qhia kev ua ntawm ntau hom substrates thiab yog beta-glucosidases). Beta-glucosidases tau muab faib ua ob lub tsev neeg raws li kev sib koom ua ke: BGA, uas suav nrog beta-glucosidases thiab phospho-beta-glucosidase (los ntawm cov kab mob mus rau tsiaj), thiab BGB, uas tsuas muaj beta-glucosidases (los ntawm cov poov xab, pwm, thiab kab mob. ). Enzymes nyob rau hauv ib tsev neeg uas muaj cov amino acid sib npaug sib npaug thiab muaj kev tiv thaiv tag nrho raug soj ntsuam hauv txoj kev no.87 Cov Carbohydrate Active enzyme (CRAZY) lub vev xaib (http://www.cazy.org) tam sim no teev 133 glycoside hydrolase (GH) tsev neeg. .84 Feem coob ntawm cov tsev neeg no tau muab faib ua pab pawg. Ib pawg muaj cov tsev neeg uas muaj kev tiv thaiv catalytic amino acids, zoo tib yam catalytic domain qauv, thiab sib koom catalytic haiv neeg thiab mechanism. Tsev neeg GH-A muaj cov tswv cuab feem ntau, suav nrog beta-glucosidases los ntawm GH1, GH5, thiab GH30 tsev neeg.81
GH1 tsev neeg muaj cov npe beta-glucosidases. Glucosidases los ntawm cov kab mob, cov nroj tsuag, thiab tsiaj txhu muaj nyob hauv GH1 tsev neeg, thaum glucosidases los ntawm cov kab mob, pwm, thiab cov poov xab yog GH3 tsev neeg.73 GH tsev neeg tau muab faib ua cov tsev neeg los ntawm International Union of Biochemistry thiab Molecular Biology. Raws li nws nyuaj los txheeb xyuas tag nrho cov spectrum ntawm substrates rau cov enzymes tshwj xeeb, cov txheej txheem categorization no, raws li cov enzymes 'structural nta, muaj txiaj ntsig ntau dua li cov khoom siv substrate.74 Siv cov cuab yeej bioinformatics thiab cov txheej txheem lom neeg ntawm cov qauv thib peb, cov qauv zoo. ntawm ib tsev neeg pab txheeb xyuas cov qauv ntawm lwm cov tswv cuab ntawm tib tsev neeg, tshwj xeeb tshaj yog nyob rau hauv txoj hauj lwm nquag, enzyme mechanism, thiab cov yam ntxwv substrate. Lub evolution ntawm glycoside hydrolase kuj piav qhia los ntawm categorization ntawm enzyme tsev neeg.73 tsim, uas txwv cellular respiration thiab ua rau cell tuag (Fig. 2). Cov qog nqaij hlav qog nqaij hlav muaj cov tshuaj sulfur hydroxylase qis dua li cov neeg noj qab haus huv. Yog li ntawd, cov hlwb no lub peev xwm los detoxify lub amygdalin hydrolysis-tso tawm hydrocyanic acid yog txwv. Cov tshuaj tiv thaiv kab mob qog noj ntshav ntawm amygdalin tau txhim kho thaum nws ua ke nrog beta-glucosidase.56 Hauv cov qog nqaij hlav cancer, anaerobic glycolysis yog txoj hauv kev ntau tshaj. Cov xwm txheej acidic txhawb kev ua haujlwm ntawm beta-glucosidase, uas ua rau ntau dua hydrocyanic acid thiab benzaldehyde tsim nyob rau hauv cov qog nqaij hlav cancer, ua rau muaj kev phom sij txaus ntshai. Hydrocyanic acid yog ib tus neeg tsis muaj npe tshwj xeeb piv rau lwm cov tshuaj uas tsis muaj qhov hnyav vim nws diffuses vim muaj toxicity ntawm cyanide thiab ua rau nws tshem tawm.76 Raws li Makarevi'c li al.,29 zais zis qog nqaij hlav tsis cuam tshuam los ntawm amygdalin concentrations tsawg. ntau dua 15 mmol / L. Txawm li cas los xij, stimulation ntawm beta-glucosidase txo cov cell loj hlob thiab tsiv teb tsaws. Apoptosis nce nyob rau hauv koob tshuaj, thiab cov hlwb raug txiav tawm hauv S theem.77
15. Amygdalin thiab beta-glucosidase hauv kev kho mob qog noj ntshav
Amygdalin tau ua hauj lwm raws li kev kho mob cancer adjuvant vim nws cov khoom tiv thaiv qog. Amygdalin tau pom zoo los pab cov neeg mob qog noj ntshav thiab ua kom lawv lub neej ntev. Amygdalin tuaj yeem tswj hwm thiab txo cov kab mob pleural lossis lateral carcinoma rau qee qhov.76 Hauv vitro, amygdalin hydrolytic cov khoom, hydrocyanic acid, thiab benzaldehyde qhia cov tshuaj tiv thaiv kab mob. Hydrocyanic acid rhuav tshem cov qog hlwb los ntawm kev tiv thaiv kev tsim ntawm adenosine triphosphate thiab inhibiting CCO, lub davhlau ya nyob twg enzyme nyob rau hauv mitochondrial electron thauj saw, vim yog kev ua haujlwm ntawm beta-glucosidase ntawm amygdalin.77 Kev siv kev sib xyaw ua ke ntawm cov beta-glucosidase activators tshwj xeeb nrog. amygdalin tau raug soj ntsuam los kho cov nas nrog cov qog nqaij hlav.76 Amygdalin kuj tuaj yeem siv ua ke nrog lwm cov tshuaj los kho mob qog noj ntshav. Kev kho cov hlwb LoVo nrog kev sib xyaw ntawm amygdalin (0.1, 0.5, thiab 1.1 mmol/L) thiab beta-glucosidase (250 nmol / L) rau 24 teev txhawb kev apoptosis thiab necrosis, raws li ib qho kev tshawb fawb. Cov yam ntxwv morphological alterations uas tshwm sim thaum lub sij hawm apoptosis tau lees paub tias siv DNA gel electrophoresis thiab ntws cytometry.75 Yog li ntawd, amygdalin tej zaum yuav yog ib qho tseem ceeb tshiab hauv kev kho mob qog los ntawm kev txhawb nqa apoptosis. Amygdalin kuj tau siv los kho mob qog noj ntshav raws li cov tshuaj. Amygdalin raug suav hais tias yog ib qho kev tsim tawm ntuj tsim cyanide uas txhawb nqa Bax qhia thiab caspase-3 kev ua haujlwm hauv LoVo hlwb, ob qho tib si cuam tshuam hauv apoptosis.90
Lub tswv yim tseem ceeb ntawm kev kho enzyme nrog kev kho mob prodrug hauv kev kho mob qog noj ntshav siv cov tshuaj tiv thaiv kab mob-beta-glucosidase complex siv tus neeg sawv cev sib txuas thiab ua kom muaj enzyme hauv vitro yog siv cov tshuaj tiv thaiv kab mob-beta-glucosidase complex nrog rau kev ua kom cov enzyme thiab ib qho tshuaj tiv thaiv kab mob. cross-linking agent.89 Cancer cell surface antigens yuav raug kuaj pom los ntawm beta-glucosidase siv cov tshuaj tiv thaiv kab mob thaum qhov kev sib xyaw no tau muab tso rau hauv cov hlab ntsha. Lub prodrug Amygdalin yog qhib los ntawm beta-glucosidase thiab txuas rau lub qog lub hom phiaj qhov chaw, muab lub peev xwm los rhuav tshem nws. Lian thiab cov npoj yaig tau tsim tus qauv nas ntawm tib neeg mob qog noj ntshav. Ib qho tshuaj tiv thaiv-CEA McAb beta-glucosidase molecule tau txhaj rau hauv cov nas 'tail leeg leeg, ua raws li 50 mg / kg amygdalin peb zaug hauv ib lub lis piam rau rau lub lis piam.19,84–86,88 Ua ntej thiab tom qab txhaj tshuaj, qog inhibition, thiab qog ntim tau txiav txim siab. Yog li, cov kev hloov pauv pathological hauv cov qog nqaij hlav nas thiab cov kabmob tseem ceeb tau txheeb xyuas.90 Lawv qhov kev tshawb pom hauv cov qauv nas ntawm kab mob qog noj ntshav qhia tau hais tias ib qho kev sib txuas ntawm amygdalin prodrug system ua ke nrog cov tshuaj tiv thaiv CEA McAb beta-glucosidase molecule txo qis xenograft txoj kev loj hlob. Lub cev, ntawm qhov tod tes, tsis pom cov tsos mob ntawm cytotoxicity. Cell membrane peptides yog polypeptides1 nrog 30 amino acids los yog tsawg dua uas yuav thauj tau ntau yam kab mob lom mus rau hauv lub cell.88 Vim li ntawd, cov cell membrane peptides them nyiaj rau qhov tsis txaus ntawm kev kho enzyme-prodrug.90 Kev khi ntawm cell membrane peptides rau beta-glucosidase txhawb nqa cov enzyme nkag mus rau hauv cov hlab ntsha endothelial thiab cov qog nqaij hlav sib sib zog nqus, ua rau cov qog cell tuag.87
16. Xaus
Amygdalin tau raug qhia tias yog kev kho mob rau ntau yam teeb meem kev kho mob, suav nrog leukoderma, mob ruas, mob ntsws, xeev siab, thiab hnoos. Cov kev tshawb fawb hauv chav kuaj thiab tsiaj txhu tau lees paub cov txiaj ntsig rau kev zom zaub mov thiab kev yug me nyuam, nrog rau kev txo qis hauv neurotoxicity, plawv hypertrophy, thiab qib qabzib. Cov kev tshawb fawb yav dhau los tau tsom mus rau amygdalin cov tshuaj siv tshuaj thiab kev nyab xeeb, yog li peb qhov kev paub txog cov txheej txheem molecular hauv qab nws cov yeeb yam tseem nyob hauv nws cov me nyuam mos. Raws li tam sim no tsis muaj cov ntaub ntawv rov qab kho qhov kev kho no, nws yuav tsum tau ua raws li kev ceev faj. Me ntsis paub txog amygdalin's pharmacokinetics lossis nws cov kab mob toxicity. Cov kev tshawb fawb tshiab yuav tsum tau txiav txim siab txog qhov sib xyaw ua ke kho qhov muaj peev xwm, kev nyab xeeb, thiab kev cuam tshuam tsis zoo. Yuav tsum tau kawm ntxiv kom nkag siab txog kev noj qab haus huv. Qee qhov piv txwv muaj xws li lub siab lub ntsws, ntshav qab zib, o, teeb meem digestive, neurodegeneration, thiab kev yug me nyuam. Txawm hais tias tam sim no muaj cov ntaub ntawv siv tau ntau dua li yav dhau los, nws tseem tsis tau tsim nyog rau kev txheeb xyuas qhov tseeb. Kev tshawb fawb tsis ntev los no tau pom tias noj amygdalin qhov ncauj yog qhov txaus ntshai dua li kev txhaj tshuaj. Txawm hais tias tau cog lus hauv vitro tau los ntawm amygdalin-nanocarrier coupling, ntxiv rau hauv vivo kev pom zoo ntawm cov kev tshawb pom no yuav tsum tau. Kev sim tshuaj ntsuam xyuas tau pom tias amygdalin/-Glu MDEPT yog ib lub tswv yim zoo. Amygdalin cov txiaj ntsig kho mob thiab cov kev mob tshwm sim tuaj yeem txhim kho nrog kev tshawb fawb ntxiv rau hauv nws cov encapsulation thiab tiv thaiv qog noj ntshav.
Cov ntaub ntawv muaj
Cov ntaub ntawv siv los txhawb qhov kev tshawb pom ntawm qhov kev tshawb fawb no muaj los ntawm tus neeg sau ntawv raws li qhov kev thov tsim nyog.
Tshaj tawm ntawm kev sib tw txaus siab
Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab.
Kev lees paub
Qhov kev tshawb fawb no tau txais kev txhawb nqa los ntawm ntu immunogenetic ntawm Department of Immunology thiab Allergy, Kws Qhia Ntawv ntawm Tshuaj, Mashhad University of Medical Science.
Cov ntaub ntawv
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