Mohamed Zaffar Ali Mohamed Amiroudine

Friedelin and lanosterol from Garcinia prainiana stimulated glucose uptake and adipocytes differentiation in 3T3-L1 adipocytes

Friedelin and lanosterol have been isolated from twigs of Garcinia prainiana. Their structures were elucidated by spectroscopic methods. The compounds were examined for their effects on 3T3-L1 adipocytes. In the MTT assay, it was found that the compounds had no cytotoxic effects up to 25 µM. Adipocyte differentiation analysis was carried out by Oil Red O staining method. In the presence of adipogenic cocktail (MDI), it was found that friedelin and lanosterol enhanced intracellular fat accumulation by 2.02 and 2.18-fold, respectively, compared with the vehicle-treated cells. Deoxyglucose uptake assay was used to examine the insulin sensitivity of adipocytes in the presence of the compounds. It was found that friedelin was able to stimulate glucose uptake up to 1.8-fold compared with insulin-treated cells. It was suggested that friedelin and lanosterol may be beneficial to mimic insulin action that would be useful in the treatment of diabetes type 2 patients.

α-Mangostin Improves Glucose Uptake and Inhibits Adipocytes Differentiation in 3T3-L1 Cells via PPARγ, GLUT4, and Leptin Expressions.

Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes. In this study, we investigated the activity of α-mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. α-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[3H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM. In addition, α-mangostin increased the amount of free fatty acids (FFA) released. The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by α-mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin. These evidences propose that α-mangostin might be possible candidate for the effective management of obesity in future.

Phytochemical Investigation of the Leaves of Tetracera scandens Linn. and In Vitro Antidiabetic Activity of Hypoletin

Tetracera scandens Linn. (Dilleniaceae), locally known as Mempelas Kasar, is traditionally used in folk remedies by various indigenous people in different countries including Malaysia for the treatment of rheumatism, inflammatory diseases, hepatitis, internal pains, urinary disorders, dysentery, sore throat, gout and diabetes infirmities; for lowering hypertension; and for child birth. In this study, phytochemical analysis of T. scandens leaf methanol (MeOH) extract was carried out for the first time and afforded three terpenoids (stigmasterol, betulinic acid and an isomeric mixture of sitosterol (∆5) glycoside and stigmasterol (∆5,22) glycoside) and six flavonoids (namely, kaempferol, quercetin, isoscutellarein, hypoletin, astragalin and kaempferol-3-O-(6″-O-p-trans-coumaroyl) glucoside, a rare compound which has been isolated for the first time from family Dilleniaceae). Structures of all compounds were elucidated through extensive UV–Vis, mass, IR and NMR spectral analysis. The occurrence of all these compounds is being reported for the first time from this plant. Due to the rare occurrence of hypoletin (3′,4′,5,7,8-pentahydroxyflavone) in plants, its in vitro antidiabetic effect was explored. Hence, the treatment of hypoletin in a dose-dependent manner was examined on the induction of lipid accumulation by using Oil Red O staining and glucose regulation in 3T3-L1 adipocytes in vitro with regard to its preventive role in the management of diabetes. After 8 days, morphological changes and high lipid accumulation activity were observed in cells treated with 10 μg/mL of hypoletin concentration (P < 0.01). In addition, the intracellular fat accumulation increased by up to 79.7 % relative to MDI-treated control cells at a dose of 10 μg/mL. Furthermore, insulin-induced 2-deoxy-d-[3H] glucose uptake was significantly increased (P < 0.001) in hypoletin-treated cells as compared to control (DMSO cells). Our results suggest that hypoletin could be useful for the management of type 2 diabetes due to its adipocyte stimulation and glucose uptake activity.