Of the more than 360 Aloe species known, Aloe barbadensis MILLER (Aloe vera) is the most widely used. Aloe vera contain two major parts: firstly, leaves containing a high concentration of anthraquinone compounds that have been used throughout the centuries as a cathartic and for medicinal purges; and secondly, a clear gel that has been used as a food and to treat burns and other wounds. 1,2) Several chemical components of the Aloe gel are thought to be responsible for its wound healing and immunostimulatory properties. For example, glycoprotein Aloectin A is reported to have anti-tumor and anti-ulcer effects, 3) and a 29 kDa glycoprotein has been found to increase proliferation of normal human dermal cells. 4) Most of these polysaccharides are glucomannans, mannans, or pectins with a range of molecular weights. A major focus of research has been on the carbohydrate fraction isolated from Aloe gel known as "acemannan," which comprises a polydispersed b-(1,4)-linked acetylated mannan interspersed with O-acetyl groups. 5)As a result of these studies, there have been numerous reports of Aloe having diverse biological activities, including anti-tumor activity, anti-acid activity, 6) tyrosinase inhibiting activity, 7) and antioxidant activity. 8)Two clinical trials are available from the same research group that reported hyperglycemic effects on fasting blood glucose as well as on HbA1c levels 9,10) with Aloe vera gel. Hikino et al. isolated two hyperglycemic polysaccharides from Aloe arborescens at 1985. 11) Beppu et al. separated two different anti-diabetic components from the leaf pulp and leaf skin of the same plant. A previous study made with Kidachi Aloe (Aloe arborescens var. naralensis) in streptozotocin (STZ)-induced diabetic rats confirmed its efficacy through administration, 12) contrary to Koo who reported hyperglycemic effects in diabetic rats in acute phase with a product containing Aloe vera gel. 13)In this study, we sought to determine the constituents of Aloe vera gel extract that normalize hyperglycemia in the diabetic mouse strain BKS.Cg-m ϩ/ϩ Lepr db/J (db/db), which exhibits many of the metabolic disturbances of human type 2 diabetes including hyperglycemia, obesity, and insulin resistance. Hemoglobin A1c (HbA1c), a binding product of glucose and hemoglobin, increases depending on the severity of hyperglycemia in a glucose level-dependent manner, and the level of HbA1c reflects the past blood glucose control conditions over a long period. Therefore, we tried to isolate the bioactive compounds from Aloe vera gel based on their ability to decrease the HbA1c level of db/db mice. Finally, we examined whether phytosterols and fractions isolated from Aloe vera gel play an important role in anti-hyperglycemic activity. MATERIALS AND METHODS General ProcedureMelting points were determined on a micro melting point apparatus (Yanako MP-3) without correction. NMR spectra were recorded using a Varian Unity-500 spectrometer ( C: 125 MHz). Positive APCI-MS was taken with LC-MS 2000 (Shimadzu).Preparation of Ext...

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We investigated the effects of the oral administration of lophenol (Lo) and cycloartanol (Cy), two kinds of antidiabetic phytosterol isolated from Aloe vera , on glucose and lipid metabolism in Zucker diabetic fatty (ZDF) rats. We demonstrated that the administrations of Lo and Cy suppressed random and fasting glucose levels and reduced visceral fat weights significantly. It was also observed that treatments with Lo and Cy decreased serum and hepatic lipid concentrations (triglyceride, nonesterified fatty acid, and total cholesterol). Additionally, Lo and Cy treatments resulted in a tendency for reduction in serum monocyte chemotactic protein-1 (MCP-1) level and an elevation in serum adiponectin level. Furthermore, the expression levels of hepatic genes encoding gluconeogenic enzymes (G6 Pase, PEPCK), lipogenic enzymes (ACC, FAS), and SREBP-1 were decreased significantly by the administrations of aloe sterols. In contrast, Lo and Cy administration increased mRNA levels of glycolysis enzyme (GK) in the liver. It was also observed that the hepatic β-oxidation enzymes (ACO, CPT1) and PPARα expressions tended to increase in the livers of the Lo- and Cy-treated rats compared with those in ZDF-control rats. We therefore conclude that orally ingested aloe sterols altered the expressions of genes related to glucose and lipid metabolism, and ameliorated obesity-associated metabolic disorders in ZDF rats. These findings suggest that aloe sterols could be beneficial in preventing and improving metabolic disorders with obesity and diabetes in rats.

p56dok‐2 acts as a multiple docking protein downstream of receptor or non‐receptor tyrosine kinases. However, the role of p56dok‐2 in biological functions of cells is not clear. We found that transcription of the p56dok‐2 gene in macrophages was increased markedly in response to cytokines such as macrophage colony‐stimulating factor (M‐CSF), granulocyte/macrophage‐CSF and interleukin‐3 (IL‐3). Forced expression of p56dok–2 inhibited M‐CSF‐, granulocyte‐CSF‐, IL‐3‐ and stem cell factor‐induced proliferation of myeloid leukemia cells, M‐NFS‐60. The p56dok‐2‐overexpressing cells showed an impaired induction of c‐myc but not of c‐jun, junB or c‐fos when stimulated with M‐CSF. Consistent with these results, the peritoneal cavity of the hairless (hr/hr) strain of mutant mice, whose cells expressed less p56dok‐2 than wild‐type mice, contained more macrophages than that of +/hr mice. Moreover, the inhibition of endogenous p56dok‐2 expression in macrophage‐like tumor cells, J774A.1, by stable expression of antisense p56dok‐2 mRNA accelerated cell proliferation. The study identifies a novel role for p56dok‐2 as a molecule that negatively regulates signal transduction and cell proliferation mediated by cytokines in a feedback loop.

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