Imikhiqizo

Incazelo:i-tanshinone I iwuhlobo lwe-IIA oluhlanganisa umuntu lwe-sPLA2 kanye ne-Rabbit Recombinant cPLA2 inhibitor ene-IC50 ye-11 ngokulandelanayo μ M kanye no-82 μ M.

Izigaba Ezihlobene:izindlela zokubonisa > > ama-enzymes we-metabolic /
amaprotheni > > ama-phospholipids
Umkhakha wocwaningo > > isifo senhliziyo
Imikhiqizo Yemvelo > > Ama-Quinones

Ithagethi:I-IC50: 11 μM (sPLA2), 82 μM (cPLA2)[1].

Isifundo se-In Vitro:i-tanshinone ngivimbele ukwakhiwa kwe-PGE2 nge-LPS eyenza ama-macrophages aluhlaza (IC50 = 38 μ M) Lapho i-tanshinone I ne-LPS yengezwa ngesikhathi esifanayo, i-compound ivimbele kakhulu ukukhiqizwa kwe-10-100 μ PGE2 ye-M (IC50 = 38 μ M) ）. Uma sengezwe ngemva kokungeniswa okuphelele kwe-COX-2, i-tanshinone ngiphinde nganciphisa ukukhiqizwa kwe-PGE2 (IC50 = 46) μ M）。 Iqiniso lokuthi i-tanshinone I ivimbela ukukhiqizwa kwe-PGE 2 ngokusebenzisa i-COX-2 eyenziwe ngaphambilini iphakamisa ngokuqinile ukuthi i-compound ingakwazi. ivimbela ngokuqondile umsebenzi we-COX-2 kanye / noma ithinte Umsebenzi we-PLA2. Lapho i-tanshinone ifakwe izinhlobo ezimbili ezihlukene ze-phospholipase A2 (PLA2), yayivimbela kakhulu i-sPLA2 ngendlela encike ekugxilweni (IC50 = 11) μ M). amandla, tanshinone Ngiphinde ngavimbela i-cPLA2 (IC50 = 82) μ M) [1]

Esifundweni Se-Vivo:i-tanshinone Ngabonisa umsebenzi wokulwa nokuvuvukala ku-carrageenan eyenza i-paw edema kanye ne-adjuvant eyenzelwe i-arthritis kumagundane.Ukuze kusungulwe umsebenzi wokulwa nokuvuvukala we-tanshinone I, izibonelo zezilwane zakudala zokuvuvukala okunamandla nokungapheli [i-rat carrageenan (CGN) - i-paw edema eyenziwe nge-rat kanye ne-rat adjuvant induced arthritis (AIA)] yasetshenziswa.Lapho i-tanshinone yomlomo I, ibonise umsebenzi obalulekile wokulwa nokuvuvukala ngokumelene ne-CGN eyenza i-paw edema (i-47% inhibition ku-160 mg / kg), kuyilapho i-IC50 ye-indomethacin yayingu-7.1 mg / kg.Ku-AIA, i-tanshinone nginikeze ukuvinjelwa kwe-27% yokuvuvukala kwesibili ngosuku lwe-18 kumthamo womlomo we-50 mg / kg / ngosuku, kuyilapho i-prednisolone (5 mg / kg / ngosuku) ibonise ukuvinjelwa okusebenzayo (65%) [1]

Ukuhlolwa kwe-Kinase:njengomthombo we-PLA2, i-sPLA2 ye-recombinant yomuntu (uhlobo lwe-IIA) yahlanzwa kumaseli e-CHO afakwe isakhi sofuzo se-PLA2, futhi i-platelet ye-rabbit recombinant cPLA2 yatholwa ngokuvezwa kwayo ku-baculovirus.Ingxube yokusabela evamile (200) μ 50) Yayiqukethe i-100 mm Tris HCl buffer (pH 9.0), 6 mM CaCl2 kanye nama-nmol angu-20 we-1-acyl - [1-14C] - arachidonyl Sn glycerol phosphate ethanolamine (2000 CPM / nmol).Noma ibingekho i-tanshinone I. ukusabela kwaqalwa ngokungeza i-50NG purified sPLA2 noma i-cPLA2.Ngemuva kwemizuzu engama-20 ku-37 ℃, ama-fatty acids amahhala akhiqizwayo ahlaziywa.Ngaphansi kwalezi zimo ezijwayelekile, cishe i-10% yama-fatty acids amahhala akhululwa ku-substrate ye-phospholipid eyengeziwe kungxube yokusabela ngaphandle kwe-tanshinone I [1].

Ukuhlolwa Kweseli:amaseli aluhlaza angama-264.7 akhuliswe nge-DMEM yengezwe ngo-10% FBS kanye no-1% wemithi elwa namagciwane ku-37 ℃ ngaphansi kuka-5% CO2.Ngamafuphi, amaseli ahlwanyelwe kumapuleti angama-96 (2) × 10 (amaseli angu-5 / kahle).Ngaphandle kwalapho kuboniswe ngenye indlela, i-LPS (1ug / ml) ne-tanshinone ngangezwa futhi ngafukanyelwa amahora angama-24.Ukugxiliswa kwe-PGE2 phakathi nendawo kukalwe kusetshenziswa ikhithi ye-EIA ye-PGE2.Ukuze unqume umphumela we-tanshinone I ekukhiqizeni kwe-PGE 2 ngemuva kokungeniswa kwe-COX-2, amaseli ahlanganiswe ne-LPS (1 μ G / ml) amahora angu-24 futhi ageza kahle.Ngemuva kwalokho, i-tanshinone ngengezwa ngaphandle kwe-LPS futhi amaseli akhuliswa amanye amahora angama-24.Ukugxiliswa kwe-PGE2 kukalwe kusuka kokumaphakathi.Ukuhlolwa kwe-MTT kwasetshenziswa ukuhlola i-cytotoxicity ye-tanshinone I kumaseli aluhlaza.I-Tanshinone I ku-100 μ M ayizange ibonise noma iyiphi i-cytotoxicity [1].

Ukuhlolwa Kwezilwane:ukuze kuhlolwe umsebenzi ovimbelayo we-tanshinone I kumamodeli wezilwane ezivuthayo nezingapheli, i-rat carrageenan (CGN) - i-paw edema eyenziwe nge-paw edema kanye namamodeli we-adjuvant induced arthritis (AIA) asetshenzisiwe.Ngamafuphi, i-1% ye-CGN encibilikisiwe ku-saline yamahhala we-pyrogen (0.05 ml) yajova esidladlani sangemuva esingakwesokudla samagundane ukuze kuhlolwe i-paw edema.Ngemuva kwamahora ama-5, ukuvuvukala kwezinzipho ezilashiwe kukalwa kusetshenziswa i-plethysmograph.I-Tanshinone I encibilikile ku-0.5% CMC yaphathwa ngomlomo ihora elingu-1 ngaphambi komjovo we-CGN.Ocwaningweni lwe-AIA, ukuvuvukala kwe-arthritic kudalwe ngokujova i-Mycobacterium lactis (0.6ml / rat) encibilikiswe kuwoyela wamaminerali odlalweni lwangemuva olungakwesokudla lwamagundane.I-Tanshinone nganginikezwa ngomlomo nsuku zonke.Ukunwetshwa kwezinzipho ezilashiwe nezinganakiwe kukalwa kusetshenziswa i-plethysmograph.

Izithenjwa:[1] UKim SY, et al.Imiphumela ye-Tanshinone I ehlukanisiwe ne-Salvia miltiorrhiza bunge ku-arachidonic acid metabolism kanye nezimpendulo ezivuvukalayo ze-vivo.I-Phytother Res.2002 Nov;16(7):616-20.