Molecular mechanisms of the antioxidative effect of centaury (Centaurium erythraea Rafn) extract in the experimental model of diabetes in rats

Abstract

Kičica se u Srbiji tradicionalno koristi za lečenje različitih oboljenja, uključujući i dijabetes. Cilj ovog rada bio je rasvetljavanje mehanizama antioksidativnog i protektivnog dejstva ekstrakta kičice (EK) koji doprinose očuvanju strukture i funkcije β-ćelija pankreasa i ublažavanju komplikacija u dijabetesu. Efekti EK analizirani su na eksperimentalnom modelu dijabetesa pacova izazvanom streptozotocinom (STZ) kao i na Rin-5F β-ćelijama izloženim oksidativnom stresu primenom vodonik peroksida, natrijum nitroprusida ili STZ-a. EK je ispoljio antidijabetogeno dejstvo uočeno kao sniženje nivoa glukoze/glikohemoglobina, poboljšanje lipidnog statusa i povećanje nivoa insulina u cirkulaciji dijabetičnih pacova što se može pripisati detektovanom uticaju EK na oc uvanje strukture Langerhansovih ostrvaca i povec anju mase β-c elija koje produkuju insulin. ntioksidativni efekat EK na β-c elije ogledao se u redukovanju oksidativnih os tec enja, modulisanju aktivnosti i ekspresije enzima antioksidativne zaštite (C T, SOD, GPx i GR) i uravnotežavanju aktivnosti redoks-senzitivnih faktora (NFκB, Nrf-2, Sp1, FOXO3 ) uključenih u regulaciju transkripcije gena za antioksidativne enzime. Dodatni doprinos EK boljem preživljavanju β-ćelija i sekreciji/ekspresiji insulina ostvaren je finim promenama u aktivnosti Akt, ERK i p38 kinaza kao i PDX-1 i MafA proteina. Pored toga, antioksidativni efekat EK kod dijabetičnih životinja ogledao se u zaštiti eritrocita, jetre i bubrega od gliko-oksidativnih oštećenja što je doprinelo poboljšanju njihovih funkcionalnih parametara. Opisani efekti EK ukazuju na značaj daljeg razjašnjavanja mehanizama antioksidativnog i protektivnog dejstva EK i njegovih komponenti u cilju potencijalnog terapijskog delovanja u dijabetesu.Centaury is traditionally used in Serbia for treating different diseases, including diabetes. This study aimed to elucidate the mechanisms of the antioxidant and protective effects of the centaury extract (CE) that preserve the structure and function of pancreatic β-cells and alleviate diabetic complications. The effects of the CE were analyzed on the experimental model of streptozotocin (STZ)-induced diabetic rats and in Rin-5F β-cells exposed to oxidative stress after exposure to hydrogen peroxide, sodium nitroprusside or STZ. The CE exhibited an anti-diabetic effect, observed as a decrease in hyperglycemia and glycohemoglobin concentration, an improved lipid status, and as increased insulin level in the circulation of diabetic rats. These effects can be attributed to the detected impact of the CE on the preservation of the structure of the islets of Langerhans, and on the increase in insulin producing β-cell mass. The antioxidant effect of the CE on β-cells was manifested as a reduction in oxidative damage, changed activities and expression of antioxidant enzymes, CAT, SOD, GPx and GR, and as a readjustment of the activities of redox-sensitive factors, NFκB, Nrf-2, Sp1, FOXO3A, involved in the regulation of gene transcription of antioxidant enzymes. Additional contributions of the CE to improved β-cell survival and insulin secretion/expression were achieved by the fine-tuning of the activities of Akt, ERK and p38 kinases and transcription regulators, PDX-1 and MafA. The antioxidant effect of the CE in diabetic animals was also reflected on increased protection of erythrocytes, liver and kidneys from glyco-oxidative damage, which contributed to the improvement of their functional parameters in diabetic rats. The described effects of the CE point to the importance of further clarification of the mechanisms of the antioxidant and general protective effects of the CE and its components in view of its potential use for therapeutic intervention in diabetes