Activité biochimique des extraits flavonoïdiques de la plante Ranunculus repens L.

Abstract

In the present study, the antihyperglycemic, anti-diabetic and antioxidant effects of the n-Butanol extract (BE) obtained from air part of Ranunculus repens L plant and quercetin were investigated in normal glucose-fed hyperglycemia, in alloxan induced diabetes and in epirubicin (EPI) toxicity of the rats. The results of this study show antihyperglycemic and antidiabetic activity of the phenolic compounds. And to elucidate a possible mechanism of action of this plant extract, the glycogen liver rate, insulin secretion and the in vitro chelating effect of glucose by plant compounds were also investigated. The flavonoids reduced significantly blood glucose in a dose-dependant manner (200,400,600 mg/kg) in both hyperglycemic and diabetic rats after oral administration as oral hypoglycemic drug, glibenclamide (2.5 mg/kg). We show that flavonoids extracts was able significantly to complex the glucose in vitro, induce insulin secretion of beta cells and to active glycogenesis in liver as shown by the abundance of glycogen granulation in liver histochemical preparation after administration of flavonoids extract. In addition these flavonoids extract and quercetin possess a chemoprotector power against malondialdehyde formation (MDA, lipid peroxidation product) and reduction of antioxidant systems such SOD, CAT and GSH in alloxaninduced diabetic rats. The equilibrium disorder of redox status after alloxan administration is reestablished by flavonoids pretreatment of alloxanised rats. The flavonoids markedly inhibited lipid peroxidation process in pancreatic cells and the proportioning of cytosolic SOD, CAT and GSH showed a significant elevation to establish equilibrium of redox status and consequently protect beta cells and prevent diabetes. The anticancer therapy with EPI produces acute hepatotoxicity by generation of free radicals. However, the oxidative status of the liver cells and mitochondria has been investigated in EPI toxicity of the rats. In this present study, we investigated in first the prooxidant effect of EPI and its implication on both hepatic cells and mitochondria function. EPI injection in rats at dose of 9 mg/kg induced hepatic dysfunction revealed by a significant increase in serum of glutamate oxaloacetate transaminases and glutamate pyruvate transaminases. Oxidative stress in liver cells and mitochondria was provoked by EPI since a statistically significant reduction of CAT, SOD and GSH levels, and significant increase of MDA level, indicator of lipid peroxidation which could perforate the biologic

membranes, were observed. In second, the protective effect of quercetin (33 mg/kg) and flavonoids extract of RRL (100 mg/kg) against oxidative stress induced by EPI was also investigated. Indeed, the pretreatment of rats with flavonoids protected liver cells and mitochondria from oxidative stress permitting, on one hand, the prevention of hepatic dysfunction on maintaining the normal level of serum transaminases following inhibition of their hepatic leakage by preventing lipid peroxidation Thus, the prevention of the cellular membranes perforation, and in the other hand maintaining also antioxidant defense system in mitochondria and cytosol of hepatocytes. Taken together, this data reveal that flavonoids extract of Ranunculus repens L extract and quercetin possess an interesting virtue to be antihyperglycemic and antidiabetic with positive action on liver glycogenesis and insulin secretion. These phenolic compounds have also antiradical and antioxidant power that confers them chemoprotection role against oxidative stress generated in pancreas cells and liver respectively by alloxan and epirubicin.