I-ARA-290 iyi-peptide yokwenziwa eyakhiwe 11 ama-amino acid, ethathwe kumodeli yesakhiwo enezinhlangothi ezintathu zehomoni engapheli i-erythropoietin (I-EPO). Ilingisa isixhumi esibonakalayo esibophezelayo se-β-co-receptor ye-erythropoietin (βcR), ngokukhetha kusebenze iphrotheni ye-receptor yokulungisa. Okubaluleke nakakhulu, le nqubo igwema izingozi ezikhulayo ezingase zihlotshaniswe nama-receptors endabuko e-EPO.
Kuqale kwabikwa ngo 2008, ukuvela kwe-ARA-290 kusho uguquko lwamasu ocwaningweni lwe-EPO lusuka ekwelashweni kwe-hematopoietic luye ekulungiseni okuhlosiwe kwezicubu kanye i-immunomodulation.
Ngomshini, ngokubophezela ngokuhambisana okuphezulu ku-IRR, I-ARA-290 ngokukhetha ivula izindlela zokusayina eziwukhiye ezansi nomfula, kuhlanganise I-JAK2-STAT3 futhi I-PI3K-Act, okuyinto ekugcineni modulators ezibucayi like I-NF-kB.
Ngale kwalokhu, I-ARA-290 ibonisa imiphumela enamandla yokulwa nokuvuvukala kanye ne-immunomodulatory, ikhuthaza ukulungiswa kwe-neural futhi inciphise ubuhlungu be-neuropathic, ilawula imetabolism, futhi ikhombisa amandla okwelapha okwelapha i-fiber neuropathy encane, Isifo sikaCharcot-Marie-Tooth, kanye ne-diabetesic neuropathy.
Ukulandelana
H-Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser-OH
Inombolo ye-CAS
1208243-50-8
I-Molecular Formula
I-C51H84N16O21
Isisindo samangqamuzana
1257.3
Ucwaningo lwe-ARA-290
1.Ukuthuthukisa Amandla e-Angiogenic kanye Namakhono Okuhlala we Amaseli E-Endothelial Progenitor Ejikelezayo:
- Okokuqala, Izifo ze-ischemic zibonisa ukuphazamiseka okulimazayo kwe-vascular. Ngokudlanga kokukhuluphala kanye nesifo sikashukela, isibalo seziguli ezithintekile siyaqhubeka nokukhuphuka. Ngenxa yalokho, kubantu abanesifo esibi se-vascular, ukunqunywa kwesitho kusasele kuyinketho yokwelapha eyinhloko.
- Ocwaningweni olufanele, I-ARA-290 inikezwe amagundane nge i-ischemia yesitho esingamahlalakhona (I-CLI). Imiphumela yabonisa ukuthi i-ARA-290 ithuthukisa kakhulu ukwanda/ukufuduka futhi imelane ne-apoptosis eyenziwe nge-hydrogen peroxide..
- Ukwengeza, umjovo owodwa we-ARA-290 uthuthukise ukugeleza kwegazi kwezitho kanye nokuminyana kwe-capillary.
Ngokuhlangene, Lokhu okutholakele kubonisa ukuthi ukusebenzisa i-ARA-290 njenge-adjuvant kungathuthukisa izakhiwo ze-angiogenic zangaphakathi. I-Endothelial colony forming cell(Ama-ECFCs) kanye ne-vivo yabo ukuya ezindaweni ze-ischemic, ngaleyo ndlela ivuselela i-angiogenesis. Ngakho, lokhu kunikeza indlela entsha yokwelapha esebenzayo yezifo ezingapheli ze-ischemic.
2.Ukwenza ngcono ukukhishwa kwe-insulini kanye nokubekezelela i-glucose ohlotsheni 2 Iziguli Zesifo Sikashukela:
Esizindeni se-metabolic, I-ARA-290 ithuthukisa kakhulu ukubekezelelwa kweglucose kumagundane anesifo sikashukela ngaphandle kokuthinta amagundane angenasifo sikashukela.. Ngokuqondile, ivuselela ukuphakama I-GSIS(Ukukhiqizwa kwe-insulin ekhiqizwa yi-glucose) amazinga, ekugcineni kuthuthukisa i-glucose oxidation futhi I-Adenosine triphosphate(I-ATP) ukukhiqiza. Ngalo mshini, ngokuthonya Isiteshi se-potassium esizwela i-ATP(IKATI) ukuvalwa kwesiteshi, ekugcineni kuba nomthelela ekukhiqizweni kwe-insulin.
3.I-Anti-inflammatory kanye Neuroprotective Effects:
Ukuhlola i-neuroinflammation, ocwaningweni lokwelapha olubandakanya amagundane ka Lewis nge ukuhlolwa kwe-autoimmune encephalomyelitis (I-EAE), ukuphathwa okuqhubekayo kwemijovo ye-ARA-290 kunciphisa kakhulu ukuqina kwe-EAE kumagundane. Ngokuqondene, lokhu kwelashwa kunciphisa ukuqoqwa kwamangqamuzana okuvuvukala emthonjeni womgogodla we-EAE futhi kwacindezela ukwanda nokuvezwa kwama-cytokines njenge-interleukin., I-tumor necrosis factor-α, kanye ne-inducible i-nitric oxide synthase ku-EAE rat umgogodla womgogodla.
Ngaphezu kwalokho, izifundo ze-in vitro zibonise ukuthi i-ARA-290 ivimbela Iseli le-Th1 ne-Th7 i-polarization kuma-EAE lymphocyte. Ndawonye, lokhu kuhlola kubonisa ukuthi i-ARA-290 inevelu yokwelapha engaba khona ye-multiple sclerosis.
4.Ukukhuthaza Ukulungiswa Kwemizwa Nokunciphisa Ubuhlungu Be-Neuropathic:
Ngokuphawulekayo, I-ARA-290 ingawela ngokuqondile umgoqo wegazi-ubuchopho, ukuyivumela ukuthi isebenze ngokuqondile i-ganglia yezimpande zomgogodla futhi i-microglia. Lapho, icindezela ukukhishwa okungavamile ohlelweni lwezinzwa olumaphakathi lobuchopho, kunciphisa ukuzwela okuphakathi, futhi ishintshe ngenkuthalo izici ze-neurotrophic ngenkathi kunciphisa ukuvuvukala ku-dorsal root ganglia ukulungisa isimiso sezinzwa esimaphakathi..
5.Ukuthuthukisa Ukulungiswa Kwezicubu Nokuvuselela Amandla:
Ekugcineni, I-ARA-290 isebenza kumaseli omzimba azalwa nawo aveza i-IRR, okukhuthaza ngamandla ukuhlukaniswa kwabo kusuka ku-phenotype ye-M1 e-pro-inflammatory kuya ku-phenotype elwa nokuvuvukala kanye ne-pro-repair M2. Ngenxa yalokho, icindezela izimpendulo ezivuvukalayo ngokwedlulele ngenkathi ivuselela ukugcinwa kwezici eziningi zokukhula, ukuhlanza amaseli e-apoptotic, kanye nokwakha imithambo yegazi emisha. Ekugcineni, lokhu kuthuthukisa ubuqotho besakhiwo kanye nezakhiwo zemishini yezicubu ezilungisiwe.
I-COA
I-HPLC
MS
