Diabetes mellitus is a potentially life-threatening disease affecting major populations worldwide. Epidemiological studies and clinical trials strongly support that hyperglycemia is the principal cause of microvascular (retinopathy, neuropathy, nephropathy) and macrovascular (heart disease, stroke, amputations) complications, 1) suggesting effective blood glucose control as the key to preventing or reversing diabetic complications and improving quality of life in patients with diabetes.2,3) In order to control hyperglycemia, oral hypoglycemic agents such as, sulfonylureas, meglitinides, biguanides, thiazolidinediones, a-glucosidase inhibitors, glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-IV) inhibitors are currently used. Having different classes of anti-diabetic drugs with their sites of action being different, accumulating evidences suggests that combination therapy using these agents may be highly effective in achieving and maintaining target blood glucose levels. [4][5][6] The root of ginseng has been used for remedies in traditional Chinese medicine. The pharmacological properties of ginseng are mainly attributed to ginsenosides, which are the active components found in the extracts of different species of ginseng. 7) Numerous studies have been conducted and found the anti-diabetic effects of ginsenosides, [8][9][10][11] however, the active component responsible for this anti-diabetic action has yet been unknown. Compound K (CK), a final metabolite of protopanaxadiol ginsenosides, 12,13) is known to have anticancer, anti-pruritic, apoptotic and hepatoprotective effects.14-18) Despite these various effects CK possesses, antidiabetic effect has not been studied as of this writing. In our preliminary studies with protopanaxadiols, CK enhanced insulin secretion presumably by acting directly on the pancreas.Biguanides are used worldwide for the treatment of diabetes. With the liver being the site of action, metformin (MET) decreases a hepatic glucose production and increases muscle glucose uptake and disposal, thereby lowering hyperglycemia. 19,20) Therefore, CK and MET are both effective in lowering plasma glucose level via different mechanisms of action. In this study, we compared the efficacy of CK and MET in diabetic db/db mice. Furthermore, we assessed the effects of a combination of CK and MET to examine the possibility that this combination may be valuable for reducing hyperglycemia efficiently. MATERIALS AND METHODSDrugs and Chemicals CK used in this study was obtained from Central Research Center, Ilhwa Pharmaceutical Co. (Guri-Si, Korea) in the form of a dried powder. Metformin, diazoxide and nifedipine were purchased from Sigma (St. Louis, MO, U.S.A.). Mouse insulin enzyme immunoassay ELISA kit was purchased from Shibayagi (Gunma, Japan). Plasma triglyceride (TG), total cholesterol, HDL cholesterol (HDL-C) and hemoglobin Alc kits were purchased from Asan Pharmaceutical Co. (Seoul, Korea) and the mouse adiponectin ELISA kit was purchased from Adipogen (Seoul, Korea). Tween...

No abstract

The fruit of Actinidia polygama (AP) has long been used as a folk medicine in Korea for the treatment of pain, rheumatoid arthritis and inflammation. In the present study, bioassay-guided fractionation of AP led to the separation and identification of a polyunsaturated fatty acid, alpha-linolenic acid (ALA), which was found to show anti-inflammatory activity. The anti-inflammatory effects of ALA, using acetic acid or carrageenan-induced inflammation models, were investi gated in mice or rats, respectively. ALA significantly inhibited the acetic acid-induced vascular permeability in a dose dependent manner (34.2 and 37.7% inhibition at doses of 5 and 10 mg/ kg, respectively). ALA also significantly reduced a rat paw edema induced by a single treatment of carrageenan. To investigate the mechanism of the anti-inflammatory action of ALA, the effects of ALA on lipopolysaccharide (LPS)-induced responses in the murine mac rophages cell line, RAW 264.7, were examined. Exposure of LPS-stimulated cells to ALA inhibited the accumulation of nitrite and prostaglandin E2 (PGE2) in the culture medium. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were markedly inhibited by ALA in a dose dependent manner. These results suggest that the anti-inflammatory activity of ALA might be due to the suppression of the expressions of iNOS and COX-2 mRNA.

No abstract

Recently, intratympanic injection of gadolinium-based contrast agent (GdC) is growing in use to visualize the endolymphatic hydrops. Although GdC has been quite safely used over 20 years through intravenous injection, the biological influence of GdC on sensory hair cells needs to be thoroughly assessed for wider clinical application of it through intratympanic injection. In this in vivo experimental study, the summated number of sensory hair cells (SO1, SO2, O1 and OC1 neuromasts) showed a steep decrease in the group exposed to 10% and 20% GdC (35.7 ± 7.3, 15.09 ± 10.82, respectively, P < .01) compared with the control group (47.18 ± 2.30). An increase in apoptosis was also observed in the group exposed to 20% gadolinium (7.20 ± 5.56), as compared with the control group (0.08 ± 0.72) or the group exposed to 10% gadolinium (3.48 ± 3.32). A significant reduction in the viable cytoplasmic mitochondria was observed in embryos exposed to 20% GdC (369 ± 124 μm , P = .01) as compared with control embryos (447 ± 118 μm ) or embryos exposed to 10% GdC (420 ± 108 μm ). GdC administration did not impact peripheral neural structures. GdC caused a significant reduction in sensory hair cell counts in response to high concentrations along with increased apoptosis and mitochondrial damage. However, it may not be likely that GdC will lead to hair cell toxicity, as the estimated concentration in the inner ear after clinically tried intratympanic injection is far more diluted than the non-toxic concentration (0.625%) that was tested in this study.