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Weight-loss drugs and supplements: Are there safer alternatives?

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Abstract

Obesity is a major cause of health complaints in western developed countries. Problems ranging from apnea to joint pain have been associated with excess weight. Many factors have been attributed to the epidemic of obesity including sedentary lifestyle, high-fat diets and consumption of large amounts of processed foods. Pharmacies and health-food store shelves abound with a vast selection of products promoted for weight-loss. Some of these have made headlines recently for the damaging effect they have on such things as cardiac valvular function. Unfortunately, others will probably follow and original data is presented on potentially dangerous natural products. Alternatives are presented and discussed below. These natural alternatives include such things as digestive enzyme inhibitors (e.g. L-arabinose, hibiscus tea, marine algae, Nomame Herba, etc), anorexics (e.g. monoterpenes such as d-limonene and perillyl alcohol), glucose-uptake inhibitors (e.g. phlorizin), and probiotics as adjuvants. These all-natural products are presented as some possible alternatives to those that could be potentially lethal and are not meant as the only options.

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... Conclusive, difficult-to-refute results concerning the inhibitory and/or hypoglycemic effects of natural constituents such as bean extract, hibiscus extract, and L-arabinose are limited. Bean and hibiscus extracts have been reported to inhibit amylase202122232425, while L-arabinose inhibits sucrase262728. The major purpose of the present study is to examine the potential of certain natural substances alone and combined in a formula to decrease or at least slow the gastrointestinal absorption of CHO. ...
... These data suggest that there is a dose-response with bean and hibiscus extracts on circulating glucose after rice starch challenge. Just as postulated, we believe that changes in the appearance of circulating glucose are due to the effects on CHO breakdown in the gut202122232425262728. This concept was strengthened when it was shown that these natural ingredients did not affect circulating glucose levels unless the rats were challenged with rice starch or sucrose, i.e., these natural ingredients did not affect circulating glucose levels after a water challenge (Fig. 2). ...
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Rapid gastrointestinal absorption of refined carbohydrates (CHO) is linked to perturbed glucose-insulin metabolism that is, in turn, associated with many chronic health disorders. We assessed the ability of various natural substances, commonly referred to as "CHO blockers," to influence starch and sucrose absorption in vivo in ninety-six rats and two pigs. These natural enzyme inhibitors of amylase/sucrase reportedly lessen breakdown of starches and sucrose in the gastrointestinal tract, limiting their absorption. To estimate absorption, groups of nine SD rats were gavaged with water or water plus rice starch and/or sucrose; and circulating glucose was measured at timed intervals thereafter. For each variation in the protocol a total of at least nine different rats were studied with an equal number of internal controls on three different occasions. The pigs rapidly drank CHO and inhibitors in their drinking water. In rats, glucose elevations above baseline over four hours following rice starch challenge as estimated by area-under-curve (AUC) were 40%, 27%, and 85% of their internal control after ingesting bean extract, hibiscus extract, and l-arabinose respectively in addition to the rice starch. The former two were significantly different from control. L-Arabinose virtually eliminated the rising circulating glucose levels after sucrose challenge, whereas hibiscus and bean extracts were associated with lesser decreases than l-arabinose that were still significantly lower than control. The glucose elevations above baseline over four hours in rats receiving sucrose (AUC) were 51%, 43% and 2% of control for bean extract, hibiscus extract, and L-arabinose, respectively. Evidence for dose-response of bean and hibiscus extracts is reported. Giving the natural substances minus CHO challenge caused no significant changes in circulating glucose concentrations, indicating no major effects on overall metabolism. A formula combining these natural products significantly decreased both starch and sucrose absorption, even when the CHO were given simultaneously. These results support the hypothesis that the enzyme inhibitors examined here at reasonable doses can safely lower the glycemic loads starch and sucrose.
... Unlike the challenges with rice starch and sucrose, glucose challenge was not affected by the formulation of natural products, suggesting little direct effect on exogenous glucose absorption or endogenous metabolism (Fig. 5) [28]. The latter finding in vivo again supports an effect of the natural products on the enzymes amylase and sucrase rather than on glucose absorption or metabolism293031323334353637. After nine weeks of daily intake of carb blockers, there was a significant lowering of circulating glucose levels in the test compared to the control rats. ...
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Acute oral consumption of various natural inhibitors of amylase (bean and hibiscus extracts) and sucrase (L-arabinose) reduce absorption of starch and sucrose respectively in rats and pigs measured by lessened appearance of circulating glucose levels. The present subchronic study was designed to determine whether these selected inhibitors of gastrointestinal starch and sucrose absorption (so-called "carb blockers") remain effective with continued use and to assess their metabolic influences after prolonged intake. Sprague-Dawley rats were gavaged twice daily over nine weeks with either water or an equal volume of water containing a formula that included bean and hibiscus extracts and L-arabinose. To estimate CHO absorption, control and treated Sprague-Dawley rats were gavaged with either water alone or an equal volume of water containing glucose, rice starch, sucrose, or combined rice starch and sucrose. Circulating glucose was measured at timed intervals over four hours. The ability to decrease starch and sucrose absorption use. No toxic effects (hepatic, renal, hematologic) were evident. Blood chemistries revealed significantly lower circulating glucose levels and a trend toward decreased HbA1C in the nondiabetic rats receiving the natural formulation compared to control. Subchronic administration of enzyme inhibitors was also associated with many metabolic changes including lowered systolic blood pressure and altered fluid-electrolyte balance. We postulate that proper intake of natural amylase and sucrase inhibitors may be useful in the prevention and treatment of many chronic disorders associated with perturbations in glucose-insulin homeostasis secondary to the rapid absorption of refined CHO.
... However, this is not only a question of calories. (Brudnak, M. A. 2002). Physical activity has an effect on how your hormones work, and hormones have an effect on how your body deals with food. ...
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Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. More recent guidelines for obesity use a measurement called BMI (body mass index). BMI of 25.9-29 is considered overweight; BMI over 30 is considered obese. Measurements and comparisons of waist and hip circumference can also provide some information regarding risk factors associated with weight. The higher the ratio, the greater the chance for weight - associated complications. The amount of fat in a person's diet may have a greater impact on weight than the number of calories it contains. Obesity can also be a side effect of certain disorders and conditions, including: Cushing's syndrome, hypothyroidism, neurologic disturbances, such as damage to the hypothalamus, a structure that helps regulate appetite, consumption of such drugs as steroids, antipsychotic medications or antidepressants. The aim of this study was to understand the actual situations of weight in young people between the ages of eighteen and twenty-three and also to explain the reasons of weight gain in cases of obesity and overweight. In this study, the methodology applied was that of gathering information through a questionnaire. It was randomly distributed to a number of 200 students, 80 males and 120 females, from Korça and Tirana Universities. The participants ranged as it follows: 18 years old - 12%, 19 years old - 18%; 20 years old - 20,5%; 21 years old - 18%; 22 years old - 13% and 23 years old - 18,5%. The subjects were also questioned about their life – style as it is considered as one of the important factors on rating the body weight. According to the results, it was found that only 1,5% of the respondents were obese; 13,5% were overweight, 73% had a normal weight and 12% were underweight. None of them declared to suffer from any diseases and a total of 77% indicated to live a moderate lifestyle. DOI: 10.5901/mjss.2014.v5n19p33
... However, the general public may use low-cost methods for weight reduction such as non-prescription weight-loss products (e.g., herbs, vitamins, and nutritional supplements; Udani, Hardy, & Madsen, 2004) because diet-and exercise-related habits are difficult to initiate and maintain (Aarts, Paulussen, & Schaalma, 1997; Holland, Aarts, & Langendam, 2006). Pharmacies and health-food stores offer vast selections of products promoting weight loss (Brudnak, 2002), many of which suggest that significant weight loss can be achieved without diet or exercise (Ashar, Miller, Getz, & Pichard, 2003). Supplements are an appealing alternative or adjunct for weight management for many individuals (Blanck et al., 2007 ). ...
... Perhaps as many as 60% of Americans are overweight and this has given rise to interest in compounds that can reduce dietary sugar absorption in vivo. One such compound is lectin from the kidney bean (Phaseolus vulgaricus Linn.), a glycoprotein that is well known for its ability to bind sugars at low levels, thus impairing their intestinal absorption [7] . However, lectins are potent mitogens and can even become cytotoxic at higher levels of intake, which become necessary if they are to be effective as sugar blockers. ...
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Problem statement: Increasing interest from the general public to use herbal remedies, exposes a considerable need to document ancient medical practices, as well as to investigate the efficacy of "ancient" compounds currently reputed t o have medicinal benefits for such diseases as diabetes and obesity. Approach: In order to investigate the efficacy of "karkadeh " Roselle- Hibiscus sabdariffa tea as a means of reducing post-prandial blood glu cose levels in human subjects, 10 g of dried karkadeh was brewed in 500 mL of water, allowed to infuse for 60 min and imbibed along with a high glycemic index food. Results: Data showed that in one individual, karkadeh tea taken in connection with a carbohydrate based break fast meal resulted in a significant increase (17%; p
... Released L-arabinose may cause lowering of insulin and triacylglycerol concentrations (Osaki et al 2001). Also, it may inhibit small intestinal sucrase in an uncompetitive manner and consequently decrease digestion and absorption of sucrose in foods ( Seri et al 1996;Brudnak 2002). ...
Article
Cereal Chem. 80(3):252–254 Arabinofuranosyl groups are present in many hemicelluloses as single or multiple units attached to the main xylan or galactan chain where they are sensitive to acid hydrolysis. Under acidic conditions of the human stomach, up to 10% of the L-arabinose is released from the hemicellulose of corn hull, larch wood, and banana peel hemicellulose. Arabinoxylans occur in a wide variety of cereal crops such as corn, wheat, barley, rye, rice, and sorghum (Izydoczyk and Biliaderis 1995; Doner and Hicks 1997). Insolated corn hull arabinoxylan is water-soluble with a bland flavor. It is useful as a food thickener, emulsifier, and stabilizer (Whistler 1993). The arabinoxylans contain numerous arabinofuranosyl units attached to the main xylan chain. Arabinofuranosyl units are also found linked in the same way but to galactans chains to form the structures of arabinogalactans of larch wood, which may have health benefits (Kelly 1999) as an immune enhancer. Physiological effects of hemicelluloses appear relevant to gastrointestinal function, to lipid and glucose metabo-lism, and to trace mineral homeostasis (McPherson 1993). Because L-arabinofuranosyl groups are sensitive to hydrolysis under acid condition (Whistler and Corbett 1955), the present work was undertaken to determine the possible extent of hemicellulose hydrolysis during passage through the human stomach where acidi-ties of pH 1–3 are present over one to several hours (Green 1976). Released L-arabinose is poorly absorbed in the intestine and may cause lowering of insulin and triacylglycerol concentrations (Schutte et al 1992; Osaki et al 2001). Distribution of arabinosyl units along the xylan backbone affects chain conformation (Andrewartha et al 1979) and the capacity of arabinoxylan molecules to interact (Dea et al 1973). Also, chain conformation and intermolecular associ-ations alter physical and functional properties (Izydoczyk and Biliaderis 1995). Because arabinoxylans are a significant portion of normal human dietary fiber, the present work was undertaken to examine the possible loss of the labile L-arabinose from corn hull arabinoxylan as well as two other hemicelluloses as they may pass through the human stomach.
... with the livestock industry in the case of ecosystems; Park and Choi, 2008) and chemicals (including herbicides and pesticides in the case of ecosystems) that destroy the microbiome, unless this is strictly necessary, and (iii) promoting practices that favor the system's ability to self-regenerate, something that living systems do wonderfully well, and that increase its resilience against pathogens and extreme events could be part of the solution, if not all, of the problem. Of course, there are opportunities to aid in the recovery of our damaged and degraded ecosystems as well as there are possibilities to recover the lost or damaged intestinal flora (Brudnak, 2002;Sheth et al., 2016). This can be achieved by the use of properly designed probiotics or fecal transplants or, in the case of ecosystems, inocula assembled in the lab from pure cultures or soil samples obtained in the field from healthy ecosystems (Bowker, 2007;Chiquoine et al., 2016;Wubs et al., 2016) in conjunction with a balanced nutrient supply (i.e., organic matter inputs, the equivalent to prebiotics; Mathur and Barlow, 2015;Sheth et al., 2016). ...
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The importance of the gut and the soil microbiomes as determinants of human and ecosystem health, respectively, is gaining rapid acceptation in the medical and ecological literatures. This suggests that there is a wealth of highly transferable knowledge about the microbial ecology of human and non-human ecosystems that is currently being generated in parallel, but mostly in isolation from one another. I suggest that effectively sharing this knowledge could greatly help at more efficiently understanding and restoring human health and the functioning of ecosystems, which are currently under wide-spread pressure. I illustrate this by comparing the effects of nitrogen deposition on ecosystem carbon sequestration with unhealthy dietary habits and human disease. The deposition of N, a key nutrient for plant growth, may increase carbon sequestration (equivalent to obesity) through several mechanisms, including a reduction in the ability of soil microbes to process organic matter, which some argue could help mitigate climate change. However, this usually results in a degradation of ecosystem health and, thus, cannot represent a real solution. Similarly, human obesity is linked to an alteration of the composition and functioning of microbial communities inhabiting the gut, which is often attributed to unhealthy dietary habits, including ingesting high amounts of simple sugars and processed foods. Finally, I advocate for the explicit recognition of the many commonalities between the functioning of the gut and ecosystems and a broader multidisciplinary collaboration among experts in ecology and human health, including the engineering of soil microbial communities designed ad-hoc to restore ecosystem health.
... It also suppresses increase of blood glucose after sucrose loading in a dose-dependent manner, but shows no effect after starch loading in mice [5] . These observations have suggested the possibility of application of L-arabinose, mixed with small quantities of sucrose, in controlled diets such as those for weight-loss or for dia- betics [6]. Commercial production of L-arabinose consists of an initial step of acid hydrolysis of gum arabic, followed by its purification through multiple procedures such as neutralization reaction, ion exchange and other chromatographic separations. ...
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L-arabinose is an important intermediate for anti-virus drug synthesis and has also been used in food additives for diets-controlling in recent years. Commercial production of L-arabinose is a complex progress consisting of acid hydrolysis of gum arabic, followed by multiple procedures of purification, thus making high production cost. Therefore, there is a biotechnological and commercial interest in the development of new cost-effective and high-performance methods for obtaining high purity grade L-arabinose. An alternative, economical method for purifying L-arabinose from xylose mother liquor was developed in this study. After screening 306 yeast strains, a strain of Pichia anomala Y161 was selected as it could effectively metabolize other sugars but not L-arabinose. Fermentation in a medium containing xylose mother liquor permitted enrichment of L-arabinose by a significant depletion of other sugars. Biochemical analysis of this yeast strain confirmed that its poor capacity for utilizing L-arabinose was due to low activities of the enzymes required for the metabolism of this sugar. Response surface methodology was employed for optimization the fermentation conditions in shake flask cultures. The optimum conditions were: 75 h fermentation time, at 32.5°C, in a medium containing 21% (v/v) xylose mother liquor. Under these conditions, the highest purity of L-arabinose reached was 86.1% of total sugar, facilitating recovery of white crystalline L-arabinose from the fermentation medium by simple methods. Yeast-mediated biopurification provides a dynamic method to prepare high purity of L-arabinose from the feedstock solution xylose mother liquor, with cost-effective and high-performance properties.
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Phase2, which has been reported to reduce body weight by its inhibition of a-amylase, was evaluated for toxicity in young adult male and female Wistar rats (10 animals/dose group). Evaluations included mortality, change in body weight, food consumption pattern, organ weight, and other adverse side reactions as well as hematological, biochemical, and histopathological analyses. Acute toxicity was determined after a single dose of Phase2 by oral gavage at doses of 5.0, 1.0, and 0.5 g/kg body weight. Animals were sacrificed on fourteen days after Phase2 administration. Subchronic toxicity was determined by administering Phase2 daily for 90 days to rats, at doses of 1.0, 0.5, and 0.2 g/kg body weight. These animals were sacrificed on day 90. Acute and subchronic administration of Phase2 did not produce any adverse reactions or any significant change in the loss of body weight as compared to untreated controls, organ weight, and mortality. Administration of Phase2 did not alter the hepatic and renal function, and did not produce any change in the hematological parameters and in lipid profile. Subchronic administration produced a reduction in the food consumption after 77 days (1.0 g/kg body weight). These data indicate that acute and subchronic administration of Phase2 did not produce any toxicity to rats as evident from weight change, mortality, and limited biochemical and histopathological analyses.
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This study was designed to investigate the effect of hibiscus (Hibiscus sabdariffa) on adipogenic differentiation of 3T3-L1 cells at the cellular and molecular levels. Various concentrations of hibiscus extract were added to confluent 3T3-L1 preadipocytes at the outset of the differentiation program and further incubated for 36 hours. Cells were maintained in postdifferentiation medium containing insulin with hibiscus extract in complete culture medium. Hibiscus extract inhibited the adipocyte differentiation of 3T3-L1 preadipocytes induced by insulin, dexamethasone, and isobutylmethylxanthine (IBMX) in a dose-dependent manner. Hibiscus blocked the cytoplasmic lipid accumulation when administered at the onset of differentiation and 4 days after induction of differentiation. The inhibitory effect of hibiscus on adipogenic lipid accumulation of preadipocytes was significant (p < 0.01) between control cells and cells treated with hibiscus. Hibiscus extract significantly attenuated the expression of key adipogenic transcription factors, including CCAAT element binding protein (C/EBP)alpha and peroxisome proliferator-activated receptor (PPAR)gamma at protein levels. These results suggest that hibiscus extract blocks adipogenesis, in part, by its suppression on the expression of adipogenic transcription factors, including C/EBPalpha and PPARgamma.
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Hen eggs represent an easily available and inexpensive source of glycoproteins expressing a variety of sugars. Egg glycoproteins might therefore be exploited to purify by affinity chromatography carbohydrate-binding proteins (lectins) with different specificities. A method to generate an affinity matrix from hen eggs is described. The matrix was assayed for its ability to purify in a single step biologically active phytohemagglutinin, wheat germ agglutinin, lentil lectin, and peanut agglutinin. Milligrams of purified lectins per gram of matrix was obtained, with the only exception of peanut agglutinin that was not efficiently retained into the affinity column. Hen egg chromatography is a relatively simple, fast, and reproducible method to purify high amount of plant lectins.
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Many believe that excessive intake of refined carbohydrates (CHO) plays a major role in the development of obesity/overweight, type 2 diabetes mellitus and insulin resistance, a collection of events commonly referred to as "diabesity," and have sought natural means to overcome these linked perturbations. As a first approach, planned diets with low portions of refined CHO have become popular. However, these diets do not satisfy everyone; and many are concerned over replacing CHO with more fats. As a second option, addition of soluble fiber to the diet can slow absorption of refined CHO, i.e., lower the glycemic index of foods and overcome or at least ameliorate many of the adverse reactions resulting from increased refined CHO ingestion. Unfortunately, the general public does not favor diets high in fiber content, and various fibers can lead to gastrointestinal problems such as gas and diarrhea. A third choice to favorably influence CHO absorption is to use natural dietary supplements that block or slow CHO absorption in the gastrointestinal tract via inhibiting enzymes necessary for CHO absorption -amylase and alpha-glucosidases. Although a number of natural supplements with anti-amylase activity have been recognized, the most studied and favored one is white kidney bean extract. Animal and human studies clearly show that this agent works in vivo and has clinical utility. This paper reviews many aspects of diabesity and the use of "carb blockers" to prevent and ameliorate the situation. In many respects, carb blockers mimic the beneficial effects of fibers.
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The optimum conditions for the production of L-arabinose from debranched arabinan were determined to be pH 6.5, 75°C, 20 g l(-1) debranched arabinan, 42 Um l(-1) endo-1,5-α-L-arabinanase, and 14 U ml(-1) α-L-arabinofuranosidase from Caldicellulosiruptor saccharolyticus and the conditions for sugar beet arabinan were pH 6.0, 75°C, 20 g l(-1) sugar beet arabinan, 3 U ml(-1) endo-1,5-α-L-arabinanase, and 24 U ml(-1) α-L-arabinofuranosidase. Under the optimum conditions, 16 g l(-1)l-arabinose was obtained from 20 g l(-1) debranched arabinan or sugar beet arabinan after 120 min, with a hydrolysis yield of 80% and a productivity of 8 g l(-1)h(-1). This is the first reported trial for the production of L-arabinose from the hemicellulose arabinan by the combined use of endo- and exo-arabinanases.
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We describe an ELISA assay to measure the active lectin content in dietary supplements containing protein extracts from Phaseolus vulgaris. Phytohemagglutinin (PHA) is known to induce serious consequences for metabolism and health when consumed raw or only lightly cooked. The ELISA was performed using plates preliminarily coated with porcine thyroglobulin, which has high specificity binding to active lectin. The bound active lectin was detected by a rabbit anti-PHA IgG and a secondary antibody enzyme conjugate. An assessment of linearity and analytical range were also performed. The data obtained showed good repeatability, specificity and a limit of quantification of 15 ng of PHA. The sensitivity of the method corresponds to 30 ppm.
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To find whether green tea has anti-obesity effects in mice, female ICR mice were fed on diets containing 1, 2 and 4% green tea powder for 16 weeks and the body weight and food intake were weighed. After the administration of green tea, the ovaries, kidneys, adrenals, liver, spleen, brain, pituitary and intraperitoneal adipose tissues in the mice were weighed and lipid levels in the serum and in the liver and serum leptin levels were measured. It was found that body weight increase and intraperitoneal adipose tissues were remarkably suppressed by the administration of diets containing 2 and 4% green tea powder. Food intake was suppressed by feeding the 4% green tea diet. Concentrations of total cholesterol in the liver, triglycerides in serum and liver and nonestrified fatty acids in serum from mice which were administered green tea diet were lower than those in the controls. Leptin levels in serum showed a decrease with green tea treatments. These results indicated that lipid metabolism in mice was suppressed by the administration of green tea powder and thereby the fatty accumulation and body weight increase was suppressed.
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To explore the underlying molecular mechanism whereby nutrients modulate the expression of intestinal digestion/absorption-related genes, we have cloned the 5' flanking regions of two representing disaccharidase genes, i.e. sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH), and investigated whether the binding activity of putative common nuclear factor(s) binding to the cis-elements located in these regions is altered by dietary manipulations. Oro-gastric feeding of a sucrose-containing diet to rats caused parallel increases in SI mRNA and LPH mRNA levels within 3 h. Among the monosaccharides tested, fructose gave rise to the most prominent increase in the mRNA levels of SI and LPH genes, which were accompanied by a coordinate rise in the mRNA levels of two microvillar hexose transporters, i.e. SGLT1 and GLUT5. Nuclear run-on assays revealed that fructose, but not glucose, increased the transcription of SI, LPH and GLUT5. DNase I footprinting analysis of the rat LPH gene showed that the protected region conserved the same sequence as the cis-element (CE-LPH1) reported in the pig LPH gene. Electrophoretic mobility shift assay using CE-LPH1 and the related cis-element of SI gene (SIF1) revealed that nuclear extracts from the jejunum of rats fed the high-starch diet gave greater density of retarded bands than those of rats fed the low-starch diet. Force feeding a fructose diet gave rise to an increase in the binding of the dimeric nuclear protein (Cdx-2) to the SIF1 element. These results suggest that the cis-elements of CE-LPH1 and SIF1 might be involved in the carbohydrate-induced increases of the transcription of LPH and SI, presumably through a change in the expression and/or binding activity of Cdx-2.
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小腸スクラーゼ活性を選択的に阻害するL-アラビノースを14C-スクロースとともにラットに投与し, 6時間までの呼気14CO2排出量および消化管内14C-残存量を測定した。その結果,1) 14C-スクロース摂取後6時間までの呼気14CO2排出量は, 同時に投与したL-アラビノースによって有意に抑制された。L-アラビノースの作用は用量依存的であり, 50mg/kgおよび250mg/kg投与群の抑制率はそれぞれ31.7%, 45.6%であった。2) ラットにおけるスクロース負荷後の血糖上昇も同時に投与したL-アラビノースによって有意に抑制された。3) 呼気14CO2排出量および血糖上昇に対して, L-アラビノース50mg/kgは作用比較物質アカルボース1.5mg/kgと同等の抑制作用を示した。4) L-アラビノース投与群では14C-スクロース摂取から6時間後において盲腸および結腸部に多量の残存14Cが認められた。以上の結果から, L-アラビノースはスクロースとともに摂取した場合, スクロースの消化吸収を抑制し, そのエネルギー利用を低下させると結論された。
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A roselle (Hibiscus sabdariffa Linn.) tea extract was found to have high inhibitory activity against porcine pancreatic or-amylase. Hibiscus acid and its 6-methyl ester were respectively isolated as active principles from the 50% methanol and acetone extracts of roselle tea. The activity of each isolate was compared to that of structurally related citric acid, a previously known inhibitor of fungal alpha-amylase.
Article
Use of fenfluramines, either alone or co-administered with phentermine (“fen-phen”) as anorexic agents in obesity, has been associated with the development of clinically significant cardiac valve disease. We present the macroscopic and histologic findings in cardiac valves explanted from three patients who presented with valvular disease after fenfluramine or fenfluramine-phentermine use and underwent single valve replacement surgery. Paraffin sections were prepared with hematoxylin and eosin, trichrome, elastic–van Gieson, and Giemsa stains, as well as immunostains using antibody to CD3 and CD20. All three patients (two females, ages 37 and 43, and a 49-year-old male) developed progressively symptomatic mitral (2 patients) or aortic (1 patient) valvular insufficiency following dexfenfluramine (2 patients) or fenfluramine-phentermine (1 patient) use. Macroscopic changes included irregular leaflet thickening, accompanied by chordal fusion in the mitral valves, but without vegetations, commissural fusion, or evidence of annular dilation. Histologically, fibromyxoid plaques and nodules just below the valve surface, superficial to a generally intact elastic fiber layer, were associated with CD3-positive lymphocytes. Valves from all three patients had central myxoid degenerative changes, which were focal/mild in one mitral valve, diffuse/moderate in one mitral valve, and diffuse/marked in one aortic valve. Focal areas of superficial fibromyxoid change or intimal thickening may also be seen in cardiac valves from patients with drug-unrelated processes leading to symptomatic or asymptomatic valvulopathy. Therefore, when valve tissue is available for histopathologic examination, valvular disease can be attributed to use of fenfluramines only if the following criteria are satisfied: (i) the macroscopic and microscopic features are consistent with fenfluramine-related valvulopathy, (ii) clinical, echocardiographic, and intraoperative findings support the diagnosis, and (iii) the history of drug exposure predates the development or exacerbation of valvular dysfunction.
Article
In rats fed on beans (Phaseolus vulgaris) the poorly digestible lectins were shown to react with intestinal cells in vivo and to cause a disruption of many of the brush borders of duodenal and jejunal enterocytes. Although depressed to a certain extent, absorption still occurred, probably through the non-disrupted cells of the small intestine. In addition, abnormal absorption of potentially harmful substances, lectin-related or of bacterial origin, could also occur, possibly as a direct effect of the disruption caused by the lectins on the enterocytes. It is suggested that toxicity was the result of ensuing systemic effects, such as for example the observed high N excretion possibly through increased tissue catabolism.
Article
A low-metastatic, glycosylation-defective variant of the B16 murine melanoma was obtained by Tao and Burger (1977) through selection with wheat germ agglutinin. We found that variant and parental (wild-type) cell lines were equally invasive when confronted with precultured embryonic chick heart fragments in vitro. Also, a short-term in vivo arrest assay showed no significant differences. After intravenous injection, wild-type cells killed the recipient mice faster than did the variant cells. We were able to confirm the changes in glycosylation at the enzyme level. In addition, we showed that the pattern of endogenous lectins was strikingly different, at least at the quantitative level. We also looked at another set of receptor proteins, namely receptors for neurotransmitters coupled to adenylate cyclase. The response to the vasoactive intestinal peptide and prostaglandins was lower in the variant cells, which also had a delayed response to cholera toxin. Although most of the data can be explained by altered glycosylation in the variant cells, the large number of differences between variant and parent cells makes it difficult to identify the biochemical basis of altered metastatic behaviour. This might also be the case with other pairs of cells differing in metastatic activity.
Article
Spontaneous wheat germ agglutinin (WGA)-resistant mutants of the MeWo human malignant melanoma line were isolated after sequential selection in increasingly toxic concentrations of WGA, without prior mutagenesis. They were isolated in an attempt to obtain "membrane glycosylation mutants" having significantly altered metastatic properties when grown in nude mice, and to characterize the biochemical (oligosaccharide) changes associated with altered metastatic behavior. The lines were assessed for their sensitivity to other lectins, membrane glycoprotein profiles, ploidy levels, and their ability to produce "artificial" metastases in nude mice after i.v. inoculation. One mutant, called 70-W, manifested a 3- to 4-fold resistance to WGA compared with wild-type cells. When inoculated into NIH Swiss nude mice, 70-W cells not only produced extensive lung colony formation but also showed an extraordinary ability to disseminate widely and extensively in a clinical fashion to many extrapulmonary sites such as the subcutis, mesentery, muscle, and brain. Moreover the majority of these metastases were deeply pigmented facilitating visual identification of very small visceral metastases. A second mutant called 3S5 was isolated and found to be highly resistant to WGA (greater than 20-fold resistance). This line was virtually devoid of metastatic ability and was found by biochemical analysis to be phenotypically similar to the class I WGA resistant non-metastatic mutants previously isolated from the highly metastatic murine tumor MDAY-D2 which are known to be deficient in sialic acid and galactose. The similarity between these and earlier results using lectin resistant mutant rodent cell lines strongly suggests that sialylated glycoconjugates contribute to the metastasis of both animal and human tumors of different tissue origin. These new spontaneously derived WGA resistant MeWo mutants should be valuable new tools for the study of human tumor progression in vivo and factors involved in metastasis, especially the contribution of oligosaccharide moieties of cell surface glycoconjugates.
Article
1. Inclusion of raw kidney bean ( Phasealus vulgaris ) proteins in the diet for rats was shown to affect the weight of some internal organs. Of these, in addition to the well-known hypertrophy of the pancreas attributable to dietary trypsin inhibitors, the observed atrophy of the thymus and the doubling in weight of the small intestine are related to the protein or lectin content of the bean diet, or both. 2. Changes in tissue composition of the small intestine were also recorded. Its protein content increased by about 40–50% and carbohydrate content doubled suggesting the occurrence of increased mucinous glycoprotein secretion. Increased DNA content (by about 30–40 %) however also indicated mucosal hyperplasia. 3. Changes were also observed in mineral content, urea concentration and some enzyme activities in sera and urine, possibly as a result of disturbances in systemic metabolism or hormone levels, or both. 4. The results gave further support to previous suggestions that the oral toxicity of kidney-bean lectins involves local reactions in the small intestine in combination with their effects on the systemic immune system and general metabolism.
Article
We investigated the effects of mitogenic stimulation on the cytotoxicity and mutagenicity of X-rays and ethylnitrosourea (ENU) in human peripheral blood lymphocytes using a cloning technique. Resistance to 6-thioguanine (TG) served as the genetic marker. Day 0 (unstimulated) lymphocytes were about two times more radiosensitive than day 3 (stimulated) lymphocytes to the cytotoxicity when compared for the D0 value (0.72 Gy vs. 1.54 Gy), and about five times more radiosensitive to its mutagenicity when compared for the frequency of TG-resistant cells following exposure to 4 Gy of X-rays (25.5 x 10(-6) vs. 126.0 x 10(-6). On the other hand, day 3 (stimulated) lymphocytes were about three times more sensitive to ENU with a D37 value of 1.03 mM compared with 2.82 mM for day 0 (unstimulated) lymphocytes, but as sensitive as day 0 lymphocytes to its mutagenic effect. These results indicate that the sensitivity of lymphocytes for cytotoxicity and mutagenicity is modified by mitogen stimulation, when lymphocytes are exposed to carcinogens or mutagens in vitro.
Article
The aim of this study was to examine the afferents to the rat locus coeruleus by means of retrograde and anterograde tracing experiments using cholera-toxin B subunit and phaseolus leucoagglutinin. To obtain reliable injections of cholera-toxin B in the locus coeruleus, electrophysiological recordings were made through glass micropipettes containing the tracer and the noradrenergic neurons of the locus coeruleus were identified by their characteristic discharge properties. After iontophoretic injections of cholera-toxin B into the nuclear core of the locus coeruleus, we observed a substantial number of retrogradely labeled cells in the lateral paragigantocellular nucleus and the dorsomedial rostral medulla (ventromedial prepositus hypoglossi and dorsal paragigantocellular nuclei) as previously described. We also saw a substantial number of retrogradely labeled neurons in (1) the preoptic area dorsal to the supraoptic nucleus, (2) areas of the posterior hypothalamus, (3) the Kölliker-Fuse nucleus, (4) mesencephalic reticular formation. Fewer labeled cells were also observed in other regions including the hypothalamic paraventricular nucleus, dorsal raphe nucleus, median raphe nucleus, dorsal part of the periaqueductal gray, the area of the noradrenergic A5 group, the lateral parabrachial nucleus and the caudoventrolateral reticular nucleus. No or only occasional cells were found in the cortex, the central nucleus of the amygdala, the lateral part of the bed nucleus of the stria terminalis, the vestibular nuclei, the nucleus of the solitary tract or the spinal cord, structures which were previously reported as inputs to the locus coeruleus. Control injections of cholera-toxin B were made in areas surrounding the locus coeruleus, including (1) Barrington's nucleus, (2) the mesencephalic trigeminal nucleus, (3) a previously undefined area immediately rostral to the locus coeruleus and medial to the mesencephalic trigeminal nucleus that we named the peri-mesencephalic trigeminal nucleus, and (4) the medial vestibular nucleus lateral to the caudal tip of the locus coeruleus. These injections yielded patterns of retrograde labeling that differed from one another and also from that obtained with cholera-toxin B injection sites in the locus coeruleus. These results indicate that the area surrounding the locus coeruleus is divided into individual nuclei with distinct afferents. These results were confirmed and extended with anterograde transport of cholera-toxin B or phaseolus leucoagglutinin. Injections of these tracers in the lateral paragigantocellular nucleus, preoptic area dorsal to the supraoptic nucleus, the ventrolateral part of the periaqueductal gray, the Kölliker-Fuse nucleus yielded a substantial to large number of labeled fibers in the nuclear core of the locus coeruleus.(ABSTRACT TRUNCATED AT 400 WORDS)
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Article
Liver insulin resistance and glucagon-stimulated hepatic glucose production are characteristics of the diabetic state. To determine the potential role of glucose toxicity in these abnormalities, we examined whether phlorizin treatment of streptozotocin-diabetic rats resulted in altered expression of genes involved in key steps of hepatic glucose metabolism. By inhibiting renal tubular glucose reabsorption, phlorizin infusion to diabetic rats induced normoglycaemia, did not significantly alter low circulating insulinaemia, but caused a marked decrease in hyperglucagonaemia. Glucokinase and L-type pyruvate kinase mRNA levels were reduced respectively by 90% and 70% in fed diabetic rats, in close correlation with changes in enzyme activities. Eighteen days of phlorizin infusion partially restored glucokinase mRNA and activity (40% of control levels), but had no effect on L-type pyruvate kinase mRNA and activity. In contrast to the glycolytic enzymes, mRNA and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase were increased (10- and 2.2-fold, respectively) in fed diabetic rats. Phlorizin administration decreased phosphoenolpyruvate carboxykinase mRNA to values not different from those in control rats, while phosphoenolpyruvate carboxykinase activity remained 50% higher than that in control rats. The 50% rise in liver glucose transporter (GLUT 2) mRNA and protein, produced by diabetes, was also corrected by phlorizin treatment. In conclusion, we propose that phlorizin treatment of diabetic rats may induce a partial shift of the predominating gluconeogenesis, associated with hepatic glucose overproduction, into glycolysis, by correction of impaired pre-translational regulatory mechanisms. This could be essentially mediated through improved pancreatic alpha-cell function and subsequent lowering of hyperglucagonaemia. These observations suggest that glucagon-stimulated hepatic glucose production may result, in part, from glucose toxicity.
Article
Limonene and related monoterpenes display compelling anticarcinogenic activity. The mechanism(s) that underline this activity is/are as yet unknown. One attractive possibility is that the monoterpenes interact with the RAS signal transduction pathway. The monoterpenes have been shown to impair incorporation of mevalonic acid-derived isoprene compounds, that is farnesyl pyrophosphate, into RAS and RAS-related proteins. As farnesylation is critical for RAS's membrane localization and function, the isoprenylation pathways have received attention as potential targets of anti-RAS pharmacological maneuvers. We have expanded on prior studies and demonstrate that one of limonene's metabolic derivatives, perillyl alcohol, decreases the levels of antigenic RAS in the human-derived myeloid THP-1 and lymphoid RPMI-8402 leukemia cell lines. Both limonene and perillyl alcohol decrease levels of 35[S] methionine labeled RAS proteins in cells that have been pulsed with radiolabeled methionine for four hours. In contrast, lovastatin, which inhibits hydroxymethylglutaryl coenzyme A reductase and thus depletes cells of farnesyl pyrophosphate, does not diminish levels of total antigenic RAS but rather results in a shift in the RAS protein; levels of farnesylated RAS decrease whereas levels of unmodified/unfarnesylated RAS increase. As limonene and perillyl alcohol do not induce such a shift we conclude that these monoterpenes decrease farnesylated RAS protein levels by a mechanism that is clearly distinct from that of either depleting cells of farnesyl pyrophosphate or inhibiting the enzyme farnesyl protein transferase that catalyzes the posttranslational farnesylation of RAS. These findings are discussed with respect to implications for the monoterpenes to alter RAS protein synthesis and degradation. The results of these studies will likely impact the inclusion of the monoterpenes in clinical anticancer trials.
Article
The objective of this study was to investigate the effects of L-arabinose on intestinal alpha-glucosidase activities in vitro and to evaluate its effects on postprandial glycemic responses in vivo. L-Arabinose inhibited the sucrase activity of intestinal mucosa in an uncompetitive manner (Ki, 2 mmol/L). Neither the optical isomer D-arabinose nor the disaccharide L-arabinobiose inhibited sucrase activity, whereas D-xylose was as potent as L-arabinose in inhibiting this activity. L-Arabinose and D-xylose showed no inhibitory effect on the activities of intestinal maltase, isomaltase, trehalase, lactase, and glucoamylase, or pancreatic amylase. In contrast, a known alpha-glucosidase inhibitor, acarbose, competitively inhibited (Ki, 1.1 mumol/L) sucrase activity and also inhibited intestinal maltase, glucoamylase, and pancreatic amylase. L-Arabinose suppressed the increase of blood glucose after sucrose loading dose-dependently in mice (ED50, 35 mg/kg), but showed no effect after starch loading. The suppressive effect of D-xylose on the increase of blood glucose after sucrose loading was 2.4 times less than that of L-arabinose, probably due to intestinal absorption of the former. Acarbose strongly suppressed glycemic responses in both sucrose loading (ED50, 1.1 mg/kg) and starch loading (ED50, 1.7 mg/kg) in mice. L-Arabinose suppressed the increase of plasma glucose and insulin in rats after sucrose loading, the suppression of the former being uninterruptedly observed in mice for 3 weeks. Thus, the results demonstrated that L-arabinose selectively inhibits intestinal sucrase activity in an uncompetitive manner and suppresses the glycemic response after sucrose ingestion by inhibition of sucrase activity.
Article
Bovine pancreatic trypsin inhibitor (BPTI) was secreted by Aspergillus niger at yields of up to 23 mg l-1 using a protein fusion strategy. BPTI was linked to part of the fungal glucoamylase protein (GAM) with a dibasic amino acid (KEX2) processing site at the fusion junction. Electrospray ionisation mass spectrometry and N-terminal protein sequencing revealed that, although biologically active in vitro, the purified products from a number of independent transformants consisted of a mixture of BPTI molecules differing at the N-terminus. Approximately 35-60% of this mixture was processed correctly. Aberrant processing of the GAM-BPTI fusion protein by the A. niger KEX2-like endoprotease was the most likely cause of this variation although the involvement of other fungal endoproteases could not be ruled out. In vitro studies have highlighted a weak interaction between BPTI and the Saccharomyces cerevisiae KEX2 endoprotease, suggesting that BPTI is not a potent inhibitor of KEX2p. A small proportion of the recombinant BPTI (10%) showed 'nicking' of the K15-A16 bond, indicating an interaction with a fungal trypsin-like enzyme. Mutant BPTI homologues designed to have anti-elastase activity, BPTI(K15V), BPTI(K15V,P13I) and BPTI(K15V,G12A), have also been expressed and secreted by A. niger. They also showed a similar spectrum of aberrant N-terminal processing but no 'nicking' of the K15-V16 bond was observed. Comparison of A. niger with other expression systems showed that it is an effective system for producing BPTI and its homologues, although not all molecules were correctly processed. This variation in processing efficiency may be useful in understanding the important determinants of protein processing in this fungus.
Article
Monoterpenes are nonnutritive dietary components found in the essential oils of citrus fruits and other plants. A number of these dietary monoterpenes have antitumor activity. For example, d-limonene, which comprises >90% of orange peel oil, has chemopreventive activity against rodent mammary, skin, liver, lung and forestomach cancers. Similarly, other dietary monoterpenes have chemopreventive activity against rat mammary, lung and forestomach cancers when fed during the initiation phase. In addition, perillyl alcohol has promotion phase chemopreventive activity against rat liver cancer, and geraniol has in vivo antitumor activity against murine leukemia cells. Perillyl alcohol and d-limonene also have chemotherapeutic activity against rodent mammary and pancreatic tumors. As a result, their cancer chemotherapeutic activities are under evaluation in Phase I clinical trials. Several mechanisms of action may account for the antitumor activities of monoterpenes. The blocking chemopreventive effects of limonene and other monoterpenes during the initiation phase of mammary carcinogenesis are likely due to the induction of Phase II carcinogen-metabolizing enzymes, resulting in carcinogen detoxification. The post-initiation phase, tumor suppressive chemopreventive activity of monoterpenes may be due to the induction of apoptosis and/or to inhibition of the post-translational isoprenylation of cell growth-regulating proteins. Chemotherapy of chemically induced mammary tumors with monoterpenes results in tumor redifferentiation concomitant with increased expression of the mannose-6-phosphate/insulin-like growth factor II receptor and transforming growth factor beta1. Thus, monoterpenes would appear to act through multiple mechanisms in the chemoprevention and chemotherapy of cancer.
Article
The possible presence of an inhibitor of pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) was screened in 54 marine algae. An active inhibitor, caulerpenyne, was purified from an extract of Caulerpa taxifolia, using ethyl acetate extraction, followed by successive chromatographies on ODS and silica gel columns. The purified inhibitor was identified by thin-layer chromatography, infrared and nuclear magnetic resonance spectroscopy. Caulerpenyne competitively inhibited lipase activities using emulsified triolein and dispersed 4-methylumbelliferyl oleate (4-MU oleate) as substrates. The concentrations producing 50% inhibition against triolein and 4-MU oleate hydrolysis were 2 mM and 13 microM, respectively. In vivo, oral administration of corn oil with or without caulerpenyne to rats demonstrated a reduced and delayed peak plasma triacylglycerol concentration with caulerpenyne.
Article
We conducted a phase I dose-escalation trial of perillyl alcohol (POH; NSC 641066) given p.o. on a continuous four times a day basis to characterize the maximum tolerated dose, toxicities, pharmacokinetic profile, and antitumor activity. Sixteen evaluable patients with advanced refractory malignancies were treated at the following doses: level 1 (L1), 800 mg/m2/dose; L2, 1200 mg/m2/dose; L3, 1600 mg/m2/dose. POH was formulated in soft gelatin capsules containing 250 mg of POH and 250 mg of soybean oil. The predominant toxicities seen were gastrointestinal (nausea, vomiting, satiety, and eructation), which were dose limiting. There appeared to be a dose-dependent increase in levels of the two main metabolites, perillic acid and dihydroperillic acid. No significant differences were seen whether the drug was taken with or without food. There was a trend toward decreasing metabolite levels on day 29 compared with days 1 and 2. Peak metabolite levels were seen 1-3 h post ingestion. Metabolite half-lives were approximately 2 h. Approximately 9% of the total dose was recovered in the urine in the first 24 h, the majority as perillic acid. Evidence of antitumor activity was seen in a patient with metastatic colorectal cancer who has an ongoing near-complete response of > 2 years duration. Several other patients were on study for > or = 6 months with stable disease. The maximum tolerated dose of POH given continuously four times a day was 1200 mg/m2/dose. Gastrointestinal toxicity was dose limiting, although significant interpatient variability in drug tolerance was seen.
Article
Sixty-five strains of obligately and facultatively heterofermentative sourdough lactic acid bacteria were screened for their capacity to grow optimally in the presence of arabinose, ribose and xylose as carbon sources. Lactobacillus alimentarius 15F, Lact. brevis 10A, Lact. fermentum 1F and Lact. plantarum 20B showed higher growth rate, cell yield, acidification rate and production of acetic acid when some pentoses instead of maltose were added to the SDB medium. Lactobacillus plantarum 20B used arabinose also in a synthetic medium where complex growth factors such as yeast extract were omitted. Other Lact. plantarum strains did not show the same property. Pentosan extract was treated with alpha-L-arabinofuranosidase from Aspergillus niger or endo-xylanase from Bacillus subtilis to produce hydrolysates containing mainly arabinose and xylose, respectively. In particular, the hydrolysate containing arabinose substantiated the growth and the production of lactic acid and, especially, of acetic acid by Lact. plantarum 20B. Sourdough fermentation by Lact. plantarum 20B with addition of pentosan extract and alpha-L-arabinofuranosidase increased the acidification rate, titratable acidity and acetic acid content compared with traditional sourdough. A facultatively heterofermentative strain, Lact. plantarum 20B, also produced a sourdough with an optimal fermentation quotient.
Article
Type 2 diabetes generally develops in persons older than age 45 and comprises more than 90% of the estimated 15 million diabetes cases identified in the United States. Due to the burgeoning population of older Americans and the increased prevalence of obesity and sedentariness, type 2 diabetes is nearing epidemic proportions. Tight glycemic control combined with good diet and regular exercise can reduce the incidence of complications associated with unchecked disease. To help physicians and patients achieve such objectives, the American Diabetes Association publishes clinical practice recommendations that propose the most effective methods for screening, diagnosis, and disease management. The position statements presenting the standard of care for treatment of diabetes are reviewed and critiqued from an evidence-based medicine perspective.
Article
To investigate the inhibitory effects of CT-II, extract of Nomame Herba, on lipase activity in vitro and on obesity in rats fed a high-fat diet in vivo. The assay for the inhibitory effect of CT-II on lipase activity was performed by measuring released free fatty acids after the incubation of the medium with CT-II, porcine pancreatic lipase and triolein (experiment 1). In vivo experiments, lean rats or obese rats (570-718 g) were fed a high-fat diet containing 60% fat with or without CT-II for 8 weeks (experiment 2), for 14 days (experiment 3) or for 12 weeks (experiment 4), respectively. The time course of body weight, food intake, organ weight (parametrial fat, liver, heart and kidney) and plasma parameters (triglyceride, total cholesterol, glucose, AST, ALT and insulin), fecal output of total fat and total cholesterol were measured. Hepatic histological examinations were also performed. CT-II inhibited the porcine lipase activity dose-dependently in vitro (experiment 1). Body and liver weight were reduced and hepatic histological examination showed an amelioration of fatty liver in CT II treated animals (experiment 2). CT-II significantly inhibited body weight gain and plasma triglyceride elevation in a dose-dependent manner, without affecting food intake in lean rats fed the high-fat diet. Elevated plasma AST and ALT were also decreased (experiment 3). When obese rats fed the high-fat diet were treated with CT-II for up to 6 months, body weight was initially reduced and thereafter weight gain was significantly suppressed. Total body fat was also significantly reduced and significant reduction of plasma AST and ALT was observed (experiment 4). These results demonstrated that the lipase inhibitor CT-II is effective in preventing and ameliorating obesity, fatty liver and hypertriglyceridemia in rats fed a high-fat diet.
Article
Mitogenic activity of a lectin, purified from Parkia speciosa seeds, on the isolated peripheral blood lymphocytes taken from normal blood donors and patients with esophageal carcinoma was examined using [3H]thymidine incorporation. The lectin increases the incorporation of [3H]thymidine into DNA of human lymphocytes. The activity of the lectin increased as its concentration was increased and then declined once the concentration passed an optimum point. The stimulant effect was also expressed using a proliferation index (PI): the ratio of [3H]thymidine incorporated into lymphocytes in the presence and absence of the lectin. The mitogenic activity of the lectin is comparable to those of the known T-cell mitogens, such as concanavalin A, phytohaemagglutinin, and pokeweed mitogen. Only slightly less responsiveness was observed in the case of lymphocytes from esophageal cancer compared to lymphocytes from normal donors.
Article
L-Arabinose is a natural, poorly absorbed pentose that selectively inhibits intestinal sucrase activity. To investigate the effects of L-arabinose feeding on lipogenesis due to its inhibition of sucrase, rats were fed 0-30 g sucrose/100 g diets containing 0-1 g L-arabinose/100 g for 10 d. Lipogenic enzyme activities and triacylglycerol concentrations in the liver were significantly increased by dietary sucrose, and arabinose significantly prevented these increases. Arabinose feeding reduced the weights of epididymal adipose tissue. Moreover, plasma insulin and triacylglycerol concentrations were significantly reduced by dietary L-arabinose. These findings suggest that L-arabinose inhibits intestinal sucrase activity, thereby reducing sucrose utilization, and consequently decreasing lipogenesis.
Article
Traditionally, the pharmaceutical and natural products industries have looked for products, which affect some biochemical or cellular pathway in either a positive or negative manner. While both industries have enjoyed success with this approach, there is a vast area that as of yet has remained relatively untapped: the genome. The following work explores how both industries can benefit from the burgeoning area of nutrients directed toward the genome. Nutritional supplements capable of altering the integrity, expression, or fidelity of genes are herein referred to collectively as 'genomeceuticals' for their ability to acting on the genome in a manner related to pharmaceuticals acting on biochemical pathways. Central to the paper is the finding that glucosamine can up-regulate the obese (ob) gene by acting on a 'nutrient-sensing' pathway (1). An explanation of how nutrient-sensing pathways might be exploited at the genetic level is presented. Discussion is given to how such genomeceuticals can not just replace substances, which may be missing (e.g., an enzyme diminished by mutation), but actually alter the expression and functionality of gene products in, and resulting from, genomic nutrient-sensing pathways.
Article
Autism is a developmental disease affecting as many as 1 in 300 children and is often characterized as a mental disorder originating in infancy that is associated with self-absorption, inability to interact socially, behavior, and language dysfunction (e.g. echolalia). Current theories indicate an important role of diet in the development of disease. It is thought that, as a result of maldigestion of casein and gluten, opioid-type peptides, or exorphins, are produced. Additionally, because of the time-frame of development of the disease, there has been an association with childhood vaccination. Consequently, prevailing therapies attempt to address these causes in one, or a combination, of three ways: diet restriction (removing casein and gluten); supplementation with exogenous enzymes; and probiotic bacteria. Until recently, none of the therapies addressed the molecular mechanisms that may be at work in the development and progression of autism. This paper presents potential molecular and cellular mechanism related to autism as well as discusses their application to the treatment of the disease through the application of genomeceuticals. Additionally, a link between developmentally associated aberrant immune and inflammatory responses, and autism is suggested and explored.
Cancer preventing properties of essential oil monoterpenes D-limonene and perillyl alcohol
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Brudnak M. A. 2000. Cancer preventing properties of essential oil monoterpenes D-limonene and perillyl alcohol. Poss Health 53: 23±25.
Regulation of the expression of carbohydrate digestion/absorption-related genes): S245±S248. beta 1-6 branched oligosaccharides in mouse mammary cancer cells
  • T Goda
Goda T. Regulation of the expression of carbohydrate digestion/absorption-related genes. Br J Nutr 2000; 84(suppl 2): S245±S248. beta 1-6 branched oligosaccharides in mouse mammary cancer cells. Glycobiology 1999;