Aescineyog ib chav kawm ntawm triterpenoid saponin tebchaw muab rho tawm los ntawm qhuav, mature noob ntawm nees chestnut ntoo (Aesculus hippocastanum), ib txwm suav tshuaj. Kev npaj nrog aescine raws li cov khoom xyaw nquag muaj xws li sodium aescinate lyophilized hmoov rau kev txhaj tshuaj, sodium aescinate liniment, compound sodium aescinate gel, thiab sodium aescinate ntsiav tshuaj. Cov kev kho mob tam sim no rau kev npaj aescine yog cerebral edema, o tshwm sim los ntawm kev raug mob los yog kev phais, thiab cov kab mob uas cuam tshuam nrog venous rov qab. Nrog rau kev nce qib ntawm kev tshawb fawb nyob rau hauv xyoo tas los no, kev npaj cov tshuaj intravenous aescine yog tam sim no dav siv nyob rau hauv kev kho mob ntawm cov kab mob xws li cerebral hemorrhage thiab cervical spondylosis. Kuj tseem muaj cov lus ceeb toom txog nws txoj kev siv hauv kev kho mob edema tshwm sim los ntawm lymphatic kua dej tsis zoo, nrog kev ua tau zoo dua thaum siv nrog rau lwm cov tshuaj.
1. Kev tiv thaiv -Cov teebmeem thiab cov txheej txheem
Cov tshuaj tiv thaiv - cov teebmeem ntawm aescine zoo ib yam li cov dexamethasone, tab sis nws lub sijhawm ua haujlwm ntev dua. Nws tsis muaj qhov cuam tshuam loj rau tus kab mob poov xab (SI), thymus index (TI), spleen cell proliferation capacity (PS), lymphocyte count (LC), los yog cov qog nqaij hlav necrosis factor- (TNF-) qib hauv cov tsiaj sim. aescine tsis ua rau kom cov ntshav corticosteroid secretion ntau ntau, thiab nws tsis txhawb apoptosis ntawm lub cev tiv thaiv kab mob hauv tus po thiab thymus; Yog li ntawd, nws cov tshuaj tiv thaiv - cov nyhuv inflammatory tsis yog nyob ntawm corticosteroid secretion.
Hauv kev tshawb fawb txog kev cuam tshuam ntawm aescine ntawm kev ciaj sia ntawm cov nas nrog lipopolysaccharide-induced endotoxemia, aescine inhibited qhov kev tso tawm ntawm siab-mobility pawg box 1 (HMGB1) los ntawm macrophages, txo cov qib ntawm TNF- , IL{{7}6 {9} crophages, thiab NF-κB ua kom muaj zog, thiab txhim kho qhov ciaj sia taus ntawm cov nas. Tsis tas li ntawd, cov tshuaj tiv thaiv antioxidant ntawm aescine txhim kho nws txoj kev tiv thaiv - muaj peev xwm ua mob. aescine tuaj yeem ua rau muaj kev ua haujlwm ntawm myeloperoxidase, superoxide dismutase (SOD), thiab glutathione peroxidase (GSH{15}}Px), txo cov qib ntawm cov kab mob xws li NO, TNF- , thiab IL-1 hauv cov ntshav, nce kev qhia thiab kev ua haujlwm ntawm glucocorticoid mob ntsws ntev receptors, txo cov ntshav qab zib mellitus. lub sij hawm ciaj sia. Tshuaj pleev ib ce ntawm aescine ho inhibits carrageenan -induced paw edema nyob rau hauv nas, nrog ib tug ntau pronounced nyhuv tom qab pretreatment nrog dexamethasone; nws tuaj yeem cuam tshuam xylene-induced pob ntseg edema hauv nas, nrog kev ua tau zoo dua li dexamethasone ib leeg; nws muaj peev xwm inhibit histamine-induced nce nyob rau hauv daim tawv nqaij vascular permeability, tab sis nrog tsawg npaum li cas dexamethasone; Nws cuam tshuam cov paj rwb pob-induced subacute granulomatous o, nrog kev ua tau zoo dua li dexamethasone. Cov kev sim qhia tau hais tias aescine tuaj yeem cuam tshuam qhov nce ntawm cov kab mob inflammatory xws li PGE2, TNF-, thiab IL-1, thiab nws cov nyhuv yuav cuam tshuam nrog kev koom tes ntawm glucocorticoid receptors.
aescine tuaj yeem cuam tshuam exudation hauv cov ntaub so ntswg inflammatory thiab txo lawv cov permeability, uas qhia cov teebmeem tseem ceeb ntawm edema thiab kev puas tsuaj hauv ntau cov ntaub so ntswg. Cov kev tshawb fawb tau lees paub tias qhov siab - koob tshuaj aescine tuaj yeem cuam tshuam qhov nce hauv cov ntshav- retinal barrier permeability tshwm sim los ntawm ischemia / reperfusion hauv cov nas, txo cov retina edema, thiab inhibit retinal edema thiab qhov muag tsis pom kev. Kev sib xyaw ua ke ntawm aescine thiab triamcinolone muaj kev sib koom ua ke tiv thaiv kab mob ischemia/reperfusion raug mob rau cov ntshav-retinal barrier; kev sib xyaw ua ke txo cov permeability ntawm cov ntshav-retinal barrier tom qab ischemia, thaum qis - koob tshuaj aescine lossis triamcinolone ib leeg tsis muaj qhov zoo li no. Tsis tas li ntawd, daim ntawv thov sib xyaw ua ke tuaj yeem txhawb nqa qhov kev qhia ntawm cov protein occludin nruj, tiv thaiv kev puas tsuaj rau cov ntshav -retinal barrier thiab txhim kho cov txiaj ntsig kho mob.
Hauv kev kho mob ntawm kev tsis haum tshuaj, kev sim tau pom tias qis - koob tshuaj prednisone ua ke nrog kev kho mob aescine tuaj yeem txo qis paw o nyob rau hauv cov tsiaj cov qauv ntawm kev mob caj dab, txo cov synovial inflammatory cell infiltration, inhibit synovial hyperplasia thiab pob txha yaig, txo cov ntshav qib ntawm TNF- , IL, {{4} IL, {6} thiab 1} siab -cov tshuaj hormones. aescine tuaj yeem txhaj koob tshuaj - nyob ntawm qhov cuam tshuam ntawm daim tawv nqaij ua xua. Hauv kev sim tsiaj hauv qhov ncauj tau noj 5 mg / kg ntawm aescine, kev ua xua ntawm daim tawv nqaij raug txo qis rau hnub 2, nrog rau qhov txo qis ntawm daim tawv nqaij liab thiab o. Nws cov tshuaj tiv thaiv kev ua xua tuaj yeem cuam tshuam rau txoj hauv kev glucocorticoid receptor. Hais txog kev ua xua rau hauv cov hlab ntsws, sodium -aescinate tuaj yeem cuam tshuam qhov ua kom thiab degranulation ntawm mast hlwb hauv cov tawv nqaij nas, tiv thaiv cov kua dej nkag mus rau hauv cov ntaub so ntswg, thiab txo cov tshuaj tiv thaiv hom I hypersensitivity; Nws kuj inhibits lub ntsws cov ntaub so ntswg o, txo cov tsub zuj zuj ntawm leukocytes, eosinophils, IL-5, thiab IL-13 nyob rau hauv lub alveoli, txo cov hlab cua inflammatory teb, thiab txo cov kev siv ntawm ncua sij hawm hom I hypersensitivity tshua.
2. Cov nyhuv Antitumor thiab Mechanisms
Cov ntaub ntawv pov thawj ntau ntxiv qhia tias ntau lub me me, xws li ntau yam inflammatory molecules, transcription yam, adhesion molecules, activator protein 1 (AP-1), chemokines, CRP, COX-2, ILs, 5-lipoxygenase (5-LOX), MMPs, NF-κB, transcription (TNF3), activator (TNF-κB) thiab transcription thiab VEGF, ua lub luag haujlwm tseem ceeb hauv kev txhim kho cov kab mob ntev xws li o thiab qog. aescine tuaj yeem tiv thaiv lossis ncua qhov tshwm sim ntawm cov kab mob ntev xws li qog los ntawm inhibiting cov kab mob inflammatory. Ntau qhov kev tshawb fawb tseem ceeb tau lees paub tias aescine tuaj yeem tua cov qog nqaij hlav cancer los ntawm ntau lub tswv yim.
2.1 Synergistic Antitumor Effects of Chemotherapy Drugs
Cov kev tshawb fawb tau pom tias aescine tuaj yeem txhim kho cov nyhuv antitumor ntawm cov tshuaj chemotherapeutic thiab thim rov qab multidrug resistance. aescine tuaj yeem ua rau muaj kev nkag siab zoo ntawm cov qog nqaij hlav cancer rau cytokines thiab cov tshuaj chemotherapeutic, induce cell voj voog ntes, txhawb apoptosis nyob rau hauv pancreatic cancer hlwb, txhim khu kev loj hlob -inhibiting nyhuv ntawm gemcitabine rau pancreatic cancer hlwb, thiab zoo inhibit cancer cell proliferation thiab ntxeem tau. Nws cov txheej txheem yuav cuam tshuam nrog kev cuam tshuam ntawm NF-κB kev ua haujlwm thiab nws cov khoom lag luam tswj hwm. aescine kuj tseem tuaj yeem txhim kho kev ua tau zoo ntawm cov tshuaj khomob tiv thaiv kabmob kheesxaws kabmob kheesxaws los ntawm glycogen synthase kinase-3 / -catenin (GSK3 / -}catenin) txoj hauv kev, thiab thim rov qab P-glycoprotein-dependent multidrug resistance.
2.2 Induction of Tumor Cell Cycle Arrest thiab Apoptosis aescine tuaj yeem ua rau muaj cov pa oxygen reactive, txo cov mitochondrial membrane muaj peev xwm, thiab nce cytochrome C tso tawm, yog li inducing apoptosis nyob rau hauv lub zais zis qog nqaij hlav thiab inhibiting zais zis qog. Tsis tas li ntawd, nws tuaj yeem thaiv txoj kev taw qhia STAT3, inhibit upstream JAK1 thiab JAK2 ua kom muaj zog, txo qis STAT3- tswj cov khoom lag luam xws li cyclin D1, B-cell lymphoma/leukemia-2 noob (Bcl-2), B{15} qog ntshav qog ntshav. (Bcl-XL), survivin, myeloid leukemia gene-1 (Mcl-1), thiab VEGF, txhawb cov cleavage ntawm poly (ADP-ribose) polymerase (PARP), inhibit qhov kev loj hlob ntawm thawj lub siab mob qog noj ntshav, thiab txhawb cov qog nqaij hlav cancer apoptosis. aescine tuaj yeem ua rau apoptosis hauv cholangiocarcinoma hlwb los ntawm cov txheej txheem xws li cuam tshuam nrog lub voj voog ntawm tes thiab mitochondrial caspase-dependent txoj hauv kev, nce Bax / Bcl-2 piv, thiab txhim kho kev ua haujlwm ntawm cov pa oxygen reactive. aescine tuaj yeem ntes G2-M theem hloov pauv, nce kev sib sau ntawm cov qog nqaij hlav qog noj ntshav nyob rau theem ua ntej G1 thiab annexin V binding, qhib caspase-9/3, nce PARP cleavage thiab Bax protein ntau ntau, thiab txo cov qib ntawm anti-apoptotic proteins xws li Bcl-2, apoptosis inhibitory proteins, thiab survivin. Nws kuj tseem tuaj yeem ua rau cov cim ntawm cov pa oxygen reactive (ROS), ua rau muaj qhov txawv txav mitochondrial membrane muaj peev xwm thiab thaum kawg inducing apoptosis hauv tib neeg lub raum cell carcinoma hlwb.
2.3 Inhibition of Tumor Angiogenesis Sodium aescine tuaj yeem inhibit endothelial cell proliferation thiab migration, suppress endothelial cell viability, thiab induce endothelial cell apoptosis. Nws cov tshuaj tiv thaiv - cov nyhuv angiogenic yuav muaj feem cuam tshuam rau nws qhov kev txiav txim ncaj qha ntawm cov hlwb endothelial. Hauv cov hlwb endothelial, aescine tuaj yeem tsim cov roj cholesterol synthesis, ua rau txo qis kev ncaj ncees ntawm actin cytoskeleton. Qhov kev hloov pauv no txo qis cov lus teb ntawm tes rau TNF- stimulation, txo cell migration, txo cov permeability ntawm monolayer endothelial hlwb, thiab inhibits cov transcription ntawm NF-κB txoj kev taw qhia, yog li ua rau txo qis hauv kev qhia ntawm TNF- -induced effector proteins.
2.4 Inhibition of Tumor Invasion thiab Metastasis aescine muaj cov nyhuv inhibitory ntawm kev ntxeem tau thiab metastasis ntawm ntau cov qog nqaij hlav cancer, suav nrog triple-mob qog noj ntshav tsis zoo. aescine tuaj yeem cuam tshuam kev cuam tshuam thiab metastasis ntawm cov hlwb melanoma, txo qhov kev qhia ntawm phosphorylated extracellular teeb liab- tswj kinase (p-ERK), thiab inhibit qhov kev qhia ntawm NF-κB thiab cov khoom siv hluav taws xob κB repressor (IκB). Exogenous supplementation ntawm macrophage chemokine ligand 16 (CXCL16) tuaj yeem txo cov nyhuv inhibitory ntawm aescine ntawm cov qog nqaij hlav qog nqaij hlav. aescine tuaj yeem cuam tshuam cov phosphorylation ntawm focal adhesion kinase (FAK) / serine / threonine protein kinase (Akt), txo qhov ua kom CXC-hom chemokine receptor 6 (CXCR6) / CXCL16, txo qis kev qhia theem ntawm CXCL16, thiab inhibit CXCL16 TM 15 kev qhia. sCXCL16 secretion, thaum kawg inhibiting migration thiab ntxeem tau ntawm gastric adenocarcinoma AGS hlwb.
3. Cov teebmeem ntawm Neuroprotective: aescine tuaj yeem tshem tawm cov pa dawb radicals, tiv thaiv ischemic/reperfusion-cov paj hlwb puas, thiab txhawb nqa nws txoj haujlwm zoo. Sodium aescine ua ke nrog cov txheej txheem fibroblast kev loj hlob tuaj yeem nce Bcl -2 kev qhia, inhibit neuronal apoptosis, txo kev puas tsuaj rau cov paj hlwb, paj hlwb, thiab myelin sheaths, txhawb kev ua haujlwm zoo tom qab raug mob txha caj qaum, txhim kho lub cev muaj zog, thiab muaj kev sib koom ua ke tiv thaiv tus txha caj qaum paj hlwb. aescine tuaj yeem txo cov theem ntawm TNF- , MMP-9, COX-2, thiab prostaglandin E2 (PGE2), txhim kho cov ntshav-hlwb barrier permeability, txo cerebral edema, thiab muaj kev kho mob zoo ntawm cerebral edema nyob rau hauv nas nrog mob dimethoate lom.
4. Kev tiv thaiv kab mob plab: aescine tuaj yeem cuam tshuam cov kua qaub hauv plab thiab tiv thaiv plab hnyuv mucosa. Nws tuaj yeem inhibit H + / K + ATPase, txo cov kua qaub hauv plab, nce SOD, catalase (CAT), thiab GSH-Px kev ua ub no, nce qib ntawm TNF-, P-selectin, thiab vascular cell adhesion molecule-1 (VCAM-1) nyob rau hauv cov ntaub so ntswg mucosa. Li et al. pom tias aescine tuaj yeem ua rau kom muaj kev nthuav qhia ntawm cov kab nrib pleb nruj nreem claudin-5, txo cov endotoxin-vim lub siab puas tsuaj thiab plab hnyuv mucosal puas tsuaj, thiab txo cov hnyuv epithelial barrier tsis ua haujlwm.
Tsis tas li ntawd, aescine tuaj yeem ua kom lub plab zom mov, txhawb kev zom zaub mov, thiab txo cov adhesions tom qab. Matsuda et al. pom tias aescine tuaj yeem ua kom lub plab zom mov hauv cov nas. Cov txheej txheem yuav koom nrog kev txhawb nqa cov synthesis ntawm serotonin (5-HT), cuam tshuam nrog 5-HT2 receptors, ua rau muaj kev tso tawm ntau ntxiv ntawm NO thiab endogenous prostaglandins (PGs). aescine tuaj yeem txo qis kev ua haujlwm ntawm plab hnyuv adhesions, inhibit mob o, txo cov vascular permeability, rov ua kom lub plab zom mov, ua kom lub plab zom mov, inhibit granuloma tsim, inhibit adhesion ntau lawm, thiab txhawb kev rov ua haujlwm ntawm lub cev muaj zog.
5. Cov tshuaj tua kab mob, tshuaj tua kab mob, lub zog metabolism tswj, thiab vascular tone txhim kho cov teebmeem: Intrathecal txhaj ntawm aescine tuaj yeem thaiv formaldehyde, inhibit formaldehyde, inhibit formaldehyde -induced induced in c-fos thiab phosphorylated p36} mitogen{3{8} mitogen{3} MAPK), txo cov mob inflammatory thiab nociceptive hnov nyob rau hauv lub dorsal horn ntawm tus txha caj qaum, thiab inhibit qhov mob -txog kev coj cwj pwm. aescine derivatives ho inhibit porcine epidemic diarrhea tus kab mob, txo nws cov kab mob replication ua si thiab nthuav tawm cytotoxicity tsawg. aescine pom zoo inhibitory thiab txawm tua cov teebmeem tawm tsam tus kab mob herpes simplex virus type 1 (HSV-1), as well as enveloped negative-sense RNA viruses and enveloped positive-sense RNA viruses (xws li dengue virus type 2). Txawm li cas los xij, nws tsis muaj qhov cuam tshuam rau cov kab mob DNA uas tsis yog lub hnab ntim khoom (xws li adenovirus-5), yog li muaj cov kab mob dav dav.
aescine tuaj yeem cuam tshuam lub plab zom mov, kev thauj cov piam thaj los ntawm lub plab mus rau cov hnyuv me thiab nyob rau hauv qhov txhuam ntawm cov hnyuv me, yog li ncua kev nqus cov piam thaj, tab sis nws tsis txo cov ntshav qabzib. Nws tseem tuaj yeem ua rau cov ntshav qabzib nce ntxiv, nce kev siv cov piam thaj hauv insulin- cov ntaub so ntswg rhiab heev, thiab txo qis cov ntshav qabzib ntau ntxiv los ntawm kev noj zaub mov muaj roj ntau. Nws tuaj yeem txo cov qib leptin hauv cov ntshav, tswj cov khoom noj kom tsawg thiab lub zog metabolism hauv nruab nrab thiab peripheral tshwj xeeb receptor txoj hauv kev, txo qis qab los noj mov, thiab nce tus nqi ntawm lub zog metabolism. Los ntawm kev txo qis thyroxine dawb (FT4) qib thiab nce qib triiodothyronine (T3) hauv cov tib neeg ntawm kev noj zaub mov muaj roj ntau, nws txo qis ATP synthesis thiab nce ATP noj hauv cov thyroid hormone- nyob ntawm cov txheej txheem los muab lub zog, yog li tswj qhov hnyav. Tsis tas li ntawd, nws tuaj yeem ua rau siab -cov roj lipoprotein ntom ntom (HDL{11}}C) qib tab sis tsis cuam tshuam rau cov metabolism hauv cov ntshav qis- ntom lipoprotein cholesterol (LDL-C) thiab triglycerides.
aescine muaj cov txiaj ntsig tseem ceeb ntawm kev txo cov qe ntshav edema tshwm sim los ntawm varicocele hauv nas. Nws tuaj yeem txo qhov ntom ntawm polymorphonuclear leukocytes hauv cov kab mob qog nqaij hlav, ua kom cov phev nce ntau, thiab thaum kawg thim rov qab cov qog nqaij hlav los ntawm varicocele. Nws tuaj yeem txhim kho extracellular Ca2+-dependent venous contraction thiab yog li nce venous tone, tab sis nws cuam tshuam nrog endogenous vasoconstrictors xws li -adrenergic receptor agonists thiab angiotensin II (Ang II) receptor agonists nrog rau vasoconstriction tshwm sim los ntawm daim nyias nyias depolarization. Yog li, qhov ua tau zoo ntawm kev siv sijhawm ntev - rau cov neeg mob varicocele yuav tsis zoo tagnrho.
