Toshichika Takita

Inhibition of increases in blood glucose and serum neutral fat by Momordica charantia saponin fraction.

Focusing on a functional component of Momordica charantia, saponin, we investigated its effects on serum glucose and neutral fat levels. Saponin was extracted as a butanol-soluble fraction (saponin fraction) from hot blast-dried Momordica charantia powder. The disaccharidase-inhibitory activity and the pancreatic lipase-inhibitory activity of the saponin fraction were measured, and in vivo sugar- and lipid-loading tests were performed. The saponin fraction inhibited disaccharidase activity and elevation of the blood glucose level after sucrose loading. The fraction also markedly inhibited pancreatic lipase activity and elevation of the serum neutral fat level after corn oil loading. Based on these findings, the main active component related to the anti-diabetic effect of Momordica charantia is present in the butanol fraction, and it may be saponin. The blood glucose and serum neutral fat-lowering effects of Momordica charantia were closely associated with its inhibitory activity against disaccharidase and pancreatic lipase.

Effect of Caffeine on the Body Fat and Lipid Metabolism of Rats Fed on a High-Fat Diet

The intake of caffeine (CF) at 0.025, 0.05 or 0.1% for 21 days progressively reduced the body fat mass and body fat percentage in Sprague-Dawley (SD) rats fed on a high-fat diet with increasing administration level. Moreover, CF increased the serum concentrations of catecholamines and free fatty acids in SD rats orally administered with CF (5 mg/kg). These results suggest that the intake of CF reduced body fat by lipolysis via catecholamines. CF has potential as a functional food ingredient with an anti-obesity action.

Effects of dietary n‐3‐to‐n‐6 polyunsaturated fatty acid ratio on mammary carcinogenesis in rats

We investigated the effects of the dietary n-3-to-n-6 polyunsaturated fatty acid (PUFA) ratio (n-3/n-6 ratio) on mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in rats by feeding them several types of dietary fat with a fixed PUFA-to-saturated fatty acid ratio. Dietary fat was fed to the rats as 10% of the total feed weight, starting two weeks before the initiation. An increase in the n-3/n-6 ratio did not suppress the incidence or reduce the latency of mammary tumor development. The number and weight of mammary tumors per tumor-bearing rat tended to be large in the group with an n-3/n-6 ratio of 7.84 compared with those in the other groups. As the n-3/n-6 ratios were elevated, the total number and weight of tumors increased gradually. The prostaglandin E2 (PGE2) concentration in mammary tumor tissue was markedly low in the group with an n-3/n-6 ratio of 1.03 compared with the group with an n-3/n-6 ratio of 0.01. In addition, PGE2 concentrations were almost constant when n-3/n-6 ratios were > 1.03. These results suggested that the increase in the n-3/n-6 ratio of dietary fat with the fixed PUFA-to-saturated fatty acid ratio cannot suppress the mammary carcinogenesis but can promote development of tumors, despite reduced PGE2 concentration in the tumor.

Effects of dietary docosahexaenoic acid on surface molecules involved in T cell proliferation.

It is known that n-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) suppress immunity as compared with n-6 PUFA such as linoleic acid (LA), but the mechanism involved in this phenomenon is still unclear. The present study was designed to assess the effect of dietary DHA on the surface molecules involved in T cell proliferation. Weanling male C57BL/6 mice were divided into four dietary groups that were fed a 10% fat diet for 4 weeks varying in amounts of DHA and LA. As the dietary DHA concentration increased, the surface expression of CD4 and CD8 on splenic T cells decreased, while that of CD28 increased. The surface expression of CD3, however, was invariable in all dietary groups. DNA synthesis of splenic T cells, induced by CD3 crosslinkage with anti-CD3 epsilon monoclonal antibody in the presence of CD28-mediated costimulation, increased as the DHA concentration was elevated. These observations suggest that diets rich in DHA exert some of their immunomodulatory effects by a downregulation of surface expression of CD4 and CD8 and by an upregulation of CD28-mediated costimulatory signal.

Orally administered apple procyanidins protect against experimental inflammatory bowel disease in mice

Apple procyanidins (ACT) is a natural biologically active compound extracted from apple. Our recent studies have shown that ACT ameliorates the symptoms of atopic dermatitis and inhibits food-allergen-induced oral sensitization. The aim of this study was to investigate the potential protective effect and mechanism of action of ACT in a murine model of inflammatory bowel disease. We investigated the preventive effects of ACT in experimental models of colitis induced by dextran sulfate sodium (DSS) or oxazolone. Oral administration of ACT before DSS treatment attenuated the DSS-induced mortality rate and decreased body weight loss. ACT also prevented the body weight loss associated with oxazolone-induced colitis. Next we examined the effect of ACT on intraepithelial lymphocytes (IEL), which is a major T cell population in the intestine. Oral administration of ACT increased the proportions of TCRgammadelta and TCRalphabeta-CD8alphaalpha T cells in IEL and suppressed interferon gamma synthesis in stimulated IEL. In addition, ACT inhibited phorbol 12-myristate 13-acetate-induced secretion of interleukin 8 (IL-8) in intestinal epithelial cells. The combined anti-inflammatory and immunomodulatory effects of ACT on intestinal epithelial cells and IEL suggest that it may be an effective oral preventive agent for inflammatory bowel diseases.

The hypocholesterolemic activity of Momordica charantia fruit is mediated by the altered cholesterol- and bile acid–regulating gene expression in rat liver

Although many studies have demonstrated the hypocholesterolemic activity of Momordica charantia, also called bitter gourd fruit (BGF), the relative hypocholesterolemic mechanism is not fully understood. In the present study, we hypothesized that BGF alters hepatic gene expression of cholesterol- and bile acid-regulating proteins to improve blood cholesterol profiles. To clarify the mechanism, we fed 7-week-old male Wistar rats a high-cholesterol (HC) diet containing 5% BGF for 4 weeks and determined the cholesterol levels in the serum, liver and feces, concentrations of the fecal total bile acid, and the expression level of cholesterol- and bile acid-regulating genes. The HC diet with BGF supplementation showed a significant serum hypocholesterolemic activity compared with the HC diet without BGF. BGF intake also significantly increased the levels of fecal total bile acid, suggesting that BGF inhibited the reabsorption of bile acids into the intestine. Hepatic messenger RNA (mRNA) levels of small heterodimer partner (SHP) and liver receptor homolog-1, which are both involved in cholesterol 7α-hydroxylase (CYP7A1) regulation, were significantly decreased and increased, respectively, by BGF intake. In addition, BGF tended to increase the hepatic CYP7A1 mRNA level. Taken together, these results suggest that BGF not only decreases the reabsorption of bile acids into the intestine but also increases the conversion of cholesterol to bile acids by CYP7A1 up-regulation through the down-regulation of the hepatic farnesoid X receptor/SHP pathway.

Regulation of the Body Fat Percentage in Developmental-Stage Rats by Methylxanthine Derivatives in a High-Fat Diet

We investigated the regulatory effects of structural differences among methylxanthine derivatives on the elevation of body fat percentage in developmental-stage rats. Caffeine, theophylline and theobromine were used as the methylxanthines. High-fat diets (20% lard) containing each methylxanthine (0.025%) were administered to male Sprague-Dawley rats for 12 weeks, with the result that the body fat percentage was generally reduced in each methylxanthine-fed group. The abdominal adipose tissue weight in the caffeine group was also significantly lower than that in the control group, the serum cholesterol and triglyceride levels in the caffeine group also being significantly lower than the levels in the control group. The study results suggest that caffeine could contribute most to preventing arteriosclerotic diseases.

Hypocholesterolemic Effect of Peanut Skin and Its Fractions: A Case Record of Rats Fed on a High-Cholesterol Diet

Peanut skin (PS) is characterized by almost exclusively consisting of polyphenols and fiber. We fractionated PS into a water-soluble fraction (WSF) and water-insoluble fraction (WIF), and further fractionated WSF into a soluble dietary fiber fraction (DF) and dietary fiber-free, water-soluble fraction (DFF-WSF). Male Sprague-Dawley rats were fed on high-cholesterol diets supplemented with PS and its fractions. PS, WSF, and DFF-WSF decreased the serum lipid and cholesterol levels and increased those in feces. This effect was probably due to the polyphenols that inhibited intestinal cholesterol absorption.

Dietary n–3 Polyunsaturated Fatty Acid and Status of Immunocompetent Cells Involved in Innate Immunity in Female Rats

The aim of this study was to estimate the contributions of dietary n–3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n–6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n–3 PUFA (n–3 diet) and the other an n–6 PUFA (n–6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor α in the rats fed the n–3 diet, compared with rats fed the n–6 diet. NK cell activity was reduced by consumption of the n–3 diet. This study suggests that consumption of n–3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM.

High-fat diet reduces levels of type I tropocollagen and hyaluronan in rat skin.

Although it is known that nutritional conditions affect the skin function, little information is available on the effect of a high-fat (HF) diet on skin. In this study, Sprague-Dawley rats were fed HF diets for 28 days, and we investigated the effect of this diet on type I tropocollagen and hyaluronan in rat skin. The HF diets reduced the levels of type I tropocollagen, COL1A1 mRNA, hyaluronan, and rat hyaluronan synthase (rhas)2 mRNA, which play a primary role in hyaluronan synthase in the dermis. However, rhas3 mRNA level in the skin was increased. The HF diets also decreased the skin mRNA expression of transforming growth factor (TGF)-beta1, which enhances the expression of COL1A1 and rhas2 mRNA and decreases rhas3 mRNA expression, and decreased the hepatic mRNA expression of insulin-like growth factor (IGF)-I, which enhances COL1A1, rhas2, and TGF-beta1 mRNA expression. The serum level of adiponectin, which promotes the syntheses of type I collagen and hyaluronan, was decreased in the HF diet groups. These findings suggest that an HF diet reduces the levels of type I tropocollagen and hyaluronan in the skin by suppressing the action of TGF-beta1, IGF-I and adiponectin, and these effects are deleterious for skin function.