EFFECTS OF ACUTE CHRONIC ADMINISTRATION OF ETHANOL EXTRACT OF Cola nitida SCHOTT AND ENDLICHER (KOLANUT) AND CAFFEINE ON GLUCOSE METABOLISM IN RATS

Abstract

Cola nitida is known for its high caffeine content. Caffeine administration has been shown to cause glucose intolerance and insulin resistance. However, few studies on the effect of kolanut and decaffeinated kolanut on glucose metabolism. This study was designed to investigate the effect of acute and chronic administration of Ethanol Extract of Kolanut (EEK) and Decaffeinated Ethanol Extract of Kolanut (DEEK) on glucose metabolism in Wistar rats. Kolanut was obtained from Ilobu, Osun State and authenticated at Department of Applied Biology, LAUTECH, Ogbomoso with herbarium number LHO 442. The seeds (500 g) were air-dried, powdered and macerated in cold ethanol. Decaffeination was achieved by soaking equal amount of the seeds in distilled water and adding dichloromethane. Caffeine content of EEK and DEEK was analysed using Gas Chromatography-Mass Spectrometry (GC-MS). In acute studies, 24 Wistar rats (235-300 g) divided into 4 groups were orally administered single dose of caffeine (6 mg/Kg), EEK (6 mg/Kg), DEEK (6 mg/Kg), and 0.3 mL distilled water (control). Sample collection commenced 30 minutes after administration. In chronic studies, the same doses were orally administered daily for eight weeks to another set of 24 rats (240-310g). Samples were collected a day after the final dose was given. In both phases, oral glucose tolerance test was carried out using standard procedure and the Areas Under Curve (AUC) calculated. Blood samples (0.2 mL) and liver biopsies were taken from each animal to determine insulin levels. Liver Glycogen Synthase (LGS), and phosphorylase activities using ELISA. Plasma glucose was determined using glucose oxidase method. Glycogen level was determined spectophotometrically by anthrone method. Data were subjected to descriptive statistics and analysed using ANOVA and Student t-test at α0.05. The GC-MS revealed caffeine content of 17.5% and 3.3% in the EEK and DEEK respectively. In the acute study, AUCᵍˡᵘᶜᵒˢᵉ. AUCᶦⁿˢᵘˡᶦⁿ increased by 19.0% and 11.8% for caffeine and EEK, respectively while DEEK had no effect on AUCᵍˡᵘᶜᵒˢᵉ. The AUCᶦⁿˢᵘˡᶦⁿ increased by 66.6%, 21.5% and 10.6% for caffeine, EEK, and DEEK, respectively. The liver glycogen content significantly decreased from 2.4±0.1 (control) to 1.1±0.1 and 1.3±0.2g/100g for caffeine and EEK, respectively while DEEK showed no effect. Acute administration of caffeine and EEK significantly decreased the activities of LGS and phosphorylase while DEEK had no effect. Chronic caffeine treatment increased AUCᵍˡᵘᶜᵒˢᵉ by 9.2% while EEK reduced AUCᵍˡᵘᶜᵒˢᵉ by 3.2% and DEEK had no effect. Caffeine increased AUCᶦⁿˢᵘˡᶦⁿ from 131.4±5.2 to 157.1±6.9 ng.min/mL, while EEK reduced AUCᶦⁿˢᵘˡᶦⁿ to 114.5±5.6 ng.min/mL, DEEK had no effect on AUCᶦⁿˢᵘˡᶦⁿ. Caffeine and DEEK had no significant effects on LGS and phosphorylase activities. On the contrary, EEK increased liver glycogen content from 1352.0±253.1 to 1987.8±304.9 mg/100g, and LGS activities from 1270.0±154.4 to 2470.0±229.9 ng/mg protein while the phosphorylase activities reduced from 21.3±1.1 to 17.6±0.9 ng/mg protein. Chronic administration of ethanol extract of kolanut enhanced glucose tolerance and insulin sensitivity while its acute administration resulted in glucose intolerance and insulin resistance. Decaffeination had no effect on insulin sensitivity and glucose tolerance.