Kohji Yamaguchi

Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice.

Nobiletin is a polymethoxylated flavone found in certain citrus fruits that exhibits various pharmacological effects including anti-inflammatory, antitumor and neuroprotective properties. The present study investigated the effects of nobiletin on insulin sensitivity in obese diabetic ob/ob mice, and the possible mechanisms involved. The ob/ob mice were treated with nobiletin (200mg/kg) for 5 weeks. Nobiletin significantly improved the plasma glucose levels, homeostasis model assessment index, glucose tolerance in an oral glucose tolerance test and plasma adiponectin levels. In white adipose tissue (WAT), nobiletin significantly decreased the mRNA expression levels of inflammatory adipokines such as interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 and increased the mRNA expression levels of adiponectin, peroxisome proliferator-activated receptor (PPAR)-gamma and its target genes. At the same time, nobiletin increased the glucose transporter (Glut) 4 expression levels in the whole plasma membrane, and Glut1 and phospho-Akt expression in the whole cell lysates in WAT and muscle. Nobiletin also increased Glut4 protein expression level in the whole cell lysates of the muscle. Taken together, the present results suggest that nobiletin improved the hyperglycemia and insulin resistance in obese diabetic ob/ob mice by regulating expression of Glut1 and Glut4 in WAT and muscle, and expression of adipokines in WAT.

Effects of Fenugreek Seed Extract in Obese Mice Fed a High-Fat Diet

It was found that fenugreek seed extract reduced the body weight gain induced by a high-fat diet in obese mice. The extract decreased plasma triglyceride gain induced by oil administration. The major component of the extract, 4-hydroxyisoleucine, also decreased plasma triglyceride gain. Consequently, fenugreek seed extract is expected to prevent the obesity induced by a high-fat diet.

ABSOLUTE CONFIGURATION OF NORZOANTHAMINE, A PROMISING CANDIDATE FOR AN OSTEOPOROTIC DRUG

Abstract The absolute configuration of norzoanthamine ( 1 ) was determined to be 2 R 4 S , 6 S , 9 S , 10 R , 12 S , 13 R , 18 S , 21 S , and 22 S based on 1 H NMR spectral data of the MTPA esters of norzoamthamine derivatives. The possible biogenesis of zoanthamines is also proposed.

Suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption in vitro and in vivo

The suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption was examined in vitro and in vivo. This synthetic peptidyl aldehyde was found to be a potent and selective cathepsin L inhibitor in our screening for cysteine protease inhibitors. In the pit formation assay with unfractionated rat bone cells, 1.5 nM of this compound markedly inhibited parathyroid hormone-stimulated osteoclastic bone resorption. In addition, intraperitoneal administration of this peptidyl aldehyde (2.5-10 mg/kg) for 4 weeks suppressed bone weight loss dose dependently in the ovariectomized mouse, experimental model of osteoporosis. Hydroxyproline measurement of the decalcified femurs from these ovariectomized mice suggested that this compound acts as a bone resorption suppressor through the inhibition of collagen degradation.

4-Phenylthiazole derivatives inhibit IL-6 secretion in osteoblastic cells and suppress bone weight loss in ovariectomized mice

A series of 4-phenylthiazole derivatives were synthesized and tested their inhibitory effect on the interleukin-6 secretion stimulated by PTH in osteoblastic cells. SCRC2941-18, 2-amino-4-(4-chlorophenyl)-5-methylthiazole, was found to be the most potent inhibitor in the derivatives. Furthermore, SCRC2941-18 significantly suppressed the bone weight loss in the ovariectomized mice, an osteoporosis model.

Peptidyl aldehyde derivatives as potent and selective inhibitors of cathepsin L

Abstract A series of peptidyl aldehyde derivatives were synthesized and tested for their inhibitory effects on several cysteine proteases and a serine protease. These componds showed no inhibition for α-chymotrypsin at the concentration less than 1000 ng/ml, while they exhibited prominent inhibition for calpain II and cathepsins, especially cathepsin L.

Inhibitory effects of bakuchiol, bavachin, and isobavachalcone isolated from Piper longum on melanin production in B16 mouse melanoma cells.

An EtOH extract of fruits of Piper longum was found to exhibit a potent inhibitory effect against α-melanocyte-stimulating hormone (α-MSH)-induced melanin production in B16 mouse melanoma cells. Bioassay-directed fractionation led to the isolation of prenylated phenolic compounds bakuchiol, bavachin, and isobavachalcone. These compounds and the crude extract of the fruits of P. longum may have suppressive effects against pigmentation by melanin in the skin.

Chaxine A, an Osteoclast-Forming Suppressing Substance, from the Mushroom Agrocybe chaxingu

A novel compound, chaxine A, (1), and a known one (2) were isolated from the mushroom Agrocybe chaxingu. These compounds suppressed the formation of osteoclast.

Hepatoprotective Effect of a Hot-Water Extract from the Edible Thorny Oyster Spondylus varius on Carbon Tetrachloride-Induced Liver Injury in Mice

The edible thorny oyster, Spondylus varius (Mizuiri-shoujou), was found to suppress the carbon tetrachloride-induced increase in serum aspartate and alanine aminotransferase activities in mice. Significant suppressive effects on these enzyme activities were found in the fraction eluted with 75% ethanol from polystyrene gel in a dose-dependent manner. These results suggest that S. varius exerts a protective effect against liver injury.

Suppressive effects of Anoectochilus formosanus extract on osteoclast formation in vitro and bone resorption in vivo.

Anoectochilus formosanus, a plant native to Taiwan, is used as a folk medicine. It was found that oral administration of A. formosanus extract (AFE) (500 mg/kg) for 4 weeks suppressed bone weight loss and trabecular bone loss in ovariectomized mice, an experimental model of osteoporosis. Although AFE at 12.5 and 25 μg/ml inhibited osteoclast formation in co-culture of osteoblasts and bone marrow cells, AFE did not inhibit the formation of osteoclast progenitor cells and preosteoclast cells in bone marrow cells and RAW264 cells. However, AFE (at 12.5 and 25 μg/ml) decreased RANKL expression. These results suggested that AFE might suppress the bone loss caused by estrogen deficiency through suppression of RANKL expression required for osteoclast formation.