Antidiabetic Effects of Corosolic Acid in KK-Ay Diabetic Mice

Abstract

Despite considerable progress in the management of diabetes mellitus with synthetic drugs, the search for indigenous natural antidiabetic agents is ongoing. The plant kingdom offers a wide field to search for effective oral hypoglycemics. More than 400 species have been reported to exhibit hypoglycemic effects, but only a few have been investigated. [1][2][3][4][5] The leaf of Banaba (Lagerstroemia speciosa L.) has been used as a traditional Oriental medicine to treat diabetes (polyuria and polydipsia). It contains polyphenol compounds and corosolic acid (CA) (Fig. 1).6) In a previous study, it was reported that polyphenol compounds have antidiabetic effects.7) We found a new antidiabetic compound, CA of Banaba leaf, for single oral administration. 8) However, there is no experimental evidence detailing improved hyperglycemia after repeated administration. In the present study, we examined the antidiabetic effects of CA in KK-Ay diabetic mice, an animal model of type 2 diabetes. MATERIALS AND METHODSMaterials CA was donated by Use Techno Corporation Co. Ltd. (Kyoto, Japan). CA was stored at room temperature until use. For oral administration, CA 0.4, 2 and 10 mg/kg was suspended in distilled water 20 ml. For subcutaneous administration, insulin 0.5 U/kg was dissolved in saline 10 ml.Animals and Treatments KK-Ay strain male mice (6 weeks old, weighing 39-43 g) (Clea, Tokyo, Japan) with a blood glucose level greater than 300 mg/dl and considered to be diabetic were used. The mice were housed in an air-conditioned room at 22Ϯ2°C with a 12-h light and 12-h dark cycle. The animals were kept in the experimental animal room for 7 d with free access to food and water. Blood samples were withdrawn from the cavernous sinus with a capillary for glucose determinations. The experiments were started between 10:00 and 11:00 am.Effects of a Single Dose of CA on Blood Glucose Levels in KK-Ay Mice CA (0.4, 2, 10 mg/kg) dissolved in 20 ml of distilled water was administered orally to the mice. The control group received an equal volume (20 ml/kg) of distilled water. Blood samples were taken for glucose determination 2, 4, and 7 h later. This experiment was performed under nonfasting conditions.Effects of 2-Week Repeated Administration of CA on Blood Glucose Levels in KK-Ay Mice CA 2 mg/kg suspended in 20 ml of distilled water was administered orally once a day for 2 weeks to the mice. The control group received an equal volume (20 ml/kg) of distilled water. Blood samples were taken for glucose determination every week. This experiment was performed under nonfasting conditions. Insulin Tolerance Test An insulin tolerance test was performed at the end of the repeated administration period. After overnight fasting, an insulin solution 0.5 U/kg was injected subcutaneously into the mice and blood samples were obtained for glucose determinations 0, 30, 60, and 120 min later.Determination of Blood Glucose and Insulin Levels Blood glucose levels in both normal and diabetic animals were determined using the glucose oxidase method 9) and pl...

Effect of Corosolic Acid on the Hydrolysis of Disaccharides

“…1), a compound which prevents oxidative stress, inflammation, hypertension and so on ( 1 ). The hypoglycemic effect of CA has been reported by various experiments (2)(3)(4)(5). The decrease in insulin resistance due to the increase in GLUT4 translocation has been reported as a mechanism of action ( 6 ).…”

Hypoglycemic activity of Lagerstroemia speciosa L. extract on streptozotocin-induced diabetic rat: Underlying mechanism of action

“…This anti-oxidant effect results from elevated serum glucose. Corosolic acid helps to reduced blood glucose level by activating the transport of glucose across the cell membranes, in short, corosolic acid has insulin-like effect (Liu et al, 2001;Miura et al, 2006;Fukushima et al, 2006). Table II showed that oral administration of extract significantly increased (31.3%, p<0.02) the depressed blood glutathione (a tripeptide of glycine, cystein and glutamic acid, GSH) level of chemically induced diabetic rats.…”

Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice

“…In Wistar fatty rats, a model for non-insulin-dependent diabetes mellitus, enhanced ACAT activity in the small intestine and hypercholesterolemia were observed when an atherogenic diet containing 1% cholesterol, 0.5% cholic acid, emia. Since excessive plasma insulin levels in KKAy mice decreased after repeated administration of CA (22), improvement in insulin resistance by CA may have reduced blood cholesterol levels and liver cholesterol contents in the long-term. On the other hand, increased cholesterol absorption in the small intestine has been reported in patients with both type 1 and type 2 diabetes (10, 17,18).…”

“…Two kinds of specific diet were prepared for this study. One was a high cholesterol diet made of CE-2 (Clea, Japan), 1% cholesterol and 0.5% cholic acid, while the other was the same high cholesterol diet containing 0.023% CA, a dosage similar to that used in previous studies (22,30).…”

“…1), a compound which consists of pentacyclic triterpene. The hypoglycemic effect of CA has been noted in various experiments (7,14,22,25,29). In addition to the hypoglycemic effect, Yamaguchi et al reported its lowering effect on serum fatty acids in SHR/NDmcr-cp rats (31), while Yamada et al observed that CA reduced fasting plasma and liver triglyceride contents in KK-Ay mice (30).…”