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...

Bovine lactoferrin is produced on an industrial scale from cheese whey or skim milk. The safety of purified lactoferrin has been confirmed from the results of a reverse mutation test using bacteria, a 13-week oral repeated-dose toxicity study in rats, and clinical studies. In order to apply active lactoferrin to various products, a process for its pasteurization was developed. Subsequently, lactoferrin has been used in a wide variety of products since it was first added to infant formula in 1986. A pepsin hydrolysate of lactoferrin is also used in infant formula. This hydrolysate contains a potent antimicrobial peptide named lactoferricin that is derived from the lactoferrin molecule by pepsin digestion. Semilarge-scale purification of lactoferricin can be performed by hydrophobic interaction chromatography. Lactoferricin also exhibits several biological actions and appears to be the functional domain of lactoferrin. Recent studies have demonstrated that oral administration of lactoferrin or lactoferricin exerts a host-protective effect in various animals and in humans. The results of these studies strongly suggest that the effects of oral lactoferrin are mediated by modulation of the immune system. Further elucidation of the clinical efficacy and mechanism of action of lactoferrin will increase the value of lactoferrin-containing products.

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N-acylated or d enantiomer peptide derivatives based on the sequence RRWQWRMKK in lactoferricin B demonstrated antimicrobial activities greater than those of lactoferricin B against bacteria and fungi. The most potent peptide, conjugated with an 11-carbon-chain acyl group, showed two to eight times lower MIC than lactoferricin B.

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.