Prolonged Treatment with Grains of Paradise (Aframomum melegueta) Extract Recruits Adaptive Thermogenesis and Reduces Body Fat in Humans with Low Brown Fat Activity.

Increasing adaptive thermogenesis through the activation of brown adipose tissue (BAT) is a promising practical strategy for preventing obesity and related disorders. Ingestion of a single dose of 40 mg of an extract of Grains of Paradise (GP), a ginger family species, reportedly triggers BAT thermogenesis in individuals with high but not in those with low BAT activity. We hypothesized that prolonged treatment with GP might revive BAT in individuals who have lost active BAT. In the present study, we recruited 9 healthy young male volunteers with reduced BAT that was assessed by fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) following 2-h cold exposure at 19ºC. The subjects ingested GP extract (40 mg/d) or placebo every day for 5 wk. Before and after the treatment with either GP or placebo, their body composition and BAT-dependent cold-induced thermogenesis (CIT)-a non-invasive index of BAT-were measured in a single-blinded, randomized, placebo-controlled cross-over design. Their whole-body resting energy expenditure at a thermoneutral condition remained unchanged following GP treatment. However, CIT after treatment was significantly higher in GP-treated individuals than in placebo-treated individuals. Body weight and fat-free mass did not change significantly following GP or placebo treatment. Notably, body fat percentage slightly but significantly decreased after GP treatment but not after placebo treatment. These results suggest that repeated ingestion of GP elevates adaptive thermogenesis through the re-activation of BAT, thereby reducing body fat in individuals with low BAT activity.

1-Ethyl-ß-N-acetylglucosaminide increases hyaluronan production in human keratinocytes by being converted to N-acetylglucosamine via ß-N-acetylglucosaminidase-dependent manner.

Regulation of hyaluronan (HA) is important for the maintenance of epidermal homeostasis. Here, we examined the mechanism by which 1-ethyl-ß-N-acetylglucosaminide (ß-NAG2), a newly developed N-acetylglucosamine (NAG) derivative, increases HA production in cultured human epidermal keratinocytes. When keratinocytes were treated with ß-NAG2, mRNA expression of HA synthase 3, which is responsible for HA production in human keratinocytes, was not influenced, but the intracellular level of UDP-NAG, a substrate used for HA synthesis, was increased. By using a synthetic substrate for ß-N-acetylglucosaminidase (ß-NAGase), keratinocytes were found to possess ß-NAGase activity, and treatment of o-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of ß-NAGase, abolished the release of NAG from ß-NAG2 in keratinocytes. Furthermore, PUGNAc attenuated the ß-NAG2-induced intracellular UDP-NAG and HA production in keratinocytes. These results suggest that ß-NAG2 is converted to NAG by endogenous ß-NAGase in keratinocytes, and the resulting NAG is further metabolized to UDP-NAG and utilized for HA production.

Daily ingestion of grains of paradise (Aframomum melegueta) extract increases whole-body energy expenditure and decreases visceral fat in humans.

We reported previously that a single ingestion of an alcohol extract of grains of paradise (GP, Aframomum melegueta), a species of the ginger family, increases energy expenditure (EE) through the activation of brown adipose tissue, a site of sympathetically mediated metabolic theromogenesis. The present study aimed to examine a daily ingestion of GP extract on whole-body EE and body fat in humans. Whole-body EE and body fat content were measured before and after daily oral ingestion of GP extract (30 mg/d) for 4 wk in 19 non-obese female volunteers aged 20-22 y in a single-blind, randomized, placebo-controlled, crossover design. Four-week daily ingestion of GP and a placebo decreased and increased slightly the visceral fat area at the umbilicus level, respectively. The GP-induced change was significantly different from that induced by the placebo (p<0.05), and negatively correlated with the initial visceral fat area (r=-0.64, p<0.01). Neither GP nor placebo ingestion affected subcutaneous or total fat. The daily ingestion of GP, but not the placebo, increased whole-body EE (p<0.05). These results suggest that GP extract may be an effective and safe tool for reducing body fat, mainly by preventing visceral fat accumulation.

Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men.

Brown adipose tissue (BAT) is responsible for cold- and diet-induced thermogenesis, and thereby contributes to the control of whole-body energy expenditure (EE) and body fat content. BAT activity can be assessed by fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) in human subjects. Grains of paradise (GP, Aframomum melegueta), a species of the ginger family, contain pungent, aromatic ketones such as 6-paradol, 6-gingerol and 6-shogaol. An alcohol extract of GP seeds and 6-paradol are known to activate BAT thermogenesis in small rodents. The present study aimed to examine the effects of the GP extract on whole-body EE and to analyse its relation to BAT activity in men. A total of nineteen healthy male volunteers aged 20-32 years underwent FDG-PET after 2 h of exposure to cold at 19°C with light clothing. A total of twelve subjects showed marked FDG uptake into the adipose tissue of the supraclavicular and paraspinal regions (BAT positive). The remaining seven showed no detectable uptake (BAT negative). Within 4 weeks after the FDG-PET examination, whole-body EE was measured at 27°C before and after oral ingestion of GP extract (40 mg) in a single-blind, randomised, placebo-controlled, crossover design. The resting EE of the BAT-positive group did not differ from that of the BAT-negative group. After GP extract ingestion, the EE of the BAT-positive group increased within 2 h to a significantly greater (P<0·01) level than that of the BAT-negative group. Placebo ingestion produced no significant change in EE. These results suggest that oral ingestion of GP extract increases whole-body EE through the activation of BAT in human subjects.

Extract of grains of paradise and its active principle 6-paradol trigger thermogenesis of brown adipose tissue in rats.

Grains of paradise (GP) is a species of the ginger family, Zingiberaceae, extracts of which have a pungent, peppery taste due to an aromatic ketone, 6-paradol. The aim of this study was to explore the thermogenic effects of GP extracts and of 6-paradol. Efferent discharges from sympathetic nerves entering the interscapular brown adipose tissue were recorded. Intragastric injection of a GP extract or 6-paradol enhanced the efferent discharges of the sympathetic nerves in a dose-dependent manner. The enhanced nerve discharges were sustained for as long as 3h. The rats did not become desensitized to the stimulatory effects these compounds on sympathetic nerve activity. The tissue temperature of brown adipose tissue showed significant increase in rats injected with 6-paradol. These results demonstrate that GP extracts and 6-paradol activate thermogenesis in brown adipose tissue, and may open up new avenues for the regulation of weight loss and weight maintenance.

Successful treatment of acute myelogenous leukemia with favorable cytogenetics by reduced-intensity stem cell transplantation.

Acute myelogenous leukemia (AML) with favorable cytogenetics responds well to chemotherapy. If the leukemia relapses, allogenic hematopoietic stem transplantation (allo-HSCT) is considered as a treatment option. Since the efficacy of reduced-intensity stem cell transplantation (RIST) for AML with favorable cytogenetics has not been established, we retrospectively analyzed the outcomes of allo-HSCT in AML patients according to cytogenetic risks. The outcome of allo-HSCT for AML patients with favorable cytogenetics seemed to be superior to that for AML patients with intermediate cytogenetics. In AML patients with favorable cytogenetics, the 3-year overall survival (OS) and relapse-free survival (RFS) rates were 88 and 76%, respectively, in the RIST group. Both the 3-year OS and RFS rates were 81% in the conventional stem cell transplantation (CST) group. The outcome of RIST for AML patients with favorable cytogenetics was comparable to that for patients who received CST despite the more advanced age and greater organ dysfunction in RIST group than in CST group. None of the patients died within 90 days after RIST. Moreover, there was no relapse in patients with favorable cytogenetics who were in hematological remission prior to RIST. Thus, RIST for AML patients with favorable cytogenetics in remission is safe and effective.

Granulocyte-colony stimulating factor-producing pancreatic cancer: report of a case.

A 74-year-old man was hospitalized for the investigation of fever and severe general fatigue. Laboratory examinations revealed severe leukocytosis, with a leukocyte count of 29 500/mm(3). Computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography showed a pancreatic tumor with a diameter of 70 mm. We performed distal pancreatectomy with splenectomy and gastrectomy because there was invasion of the posterior wall of the stomach. The leukocyte count decreased to 16 900/mm(3) immediately following the operation, but it began to increase again a week later, ultimately reaching 213 000/mm(3). We measured the serum granulocyte-colony stimulating factor (G-CSF) concentration and the G-CSF expressions in the resected specimens with immunohistochemistry, the findings of which confirmed the diagnosis of G-CSF-producing pancreatic cancer. G-CSF-producing tumors are considered to be in a category of rare malignant diseases originating in various organs, which carry a poor prognosis. However, G-CSF-producing pancreatic cancer is extremely rare. On postoperative day (POD) 35, an intraabdominal recurrence was detected with marked leukocytosis, and on POD 42 the patient died without receiving postoperative cancer therapy.

Plasma kinetics and urine profile of ethyl glucosides after oral administration in the rat.

In this in vivo study, the time course of plasma concentration and the urinary excretion of ethyl alpha-D-glucoside (alpha-EG) and ethyl beta-D-glucoside (beta-EG) were investigated in rats after a single oral dose of 4 mmol/kg body weight. Maximal plasma concentrations of both alpha-EG and beta-EG (EGs) reached approximately 3 mM at 1 h after oral administration and then decreased rapidly. Approximately 80% of EGs administered were excreted into the urine during the first 6 h. Within 24 h, cumulative urinary alpha-EG and beta-EG excretions were estimated to be 87.2+/-7.9% and 85.4+/-5.0%, respectively. Traces of both EGs were detected in plasma and urine 24 h after oral ingestion. The results of this study indicate that almost all of both EGs was rapidly absorbed into the blood stream and easily excreted into the urine after oral administration, and that a small amount of them remained in the rat body 24 h after administration.

Studies on absorption and hydrolysis of ethyl alpha-D-glucoside in rat intestine.

Ethyl alpha-D-glucoside (alpha-EG) is normally contained in Sake, which has been taken by Japanese people since ancient times. In this study, the intestinal absorption of alpha-EG was investigated using rat everted intestinal sac. Furthermore, the alpha-EG hydrolytic activity in rat intestine was compared with disaccharides hydrolytic activities, and the effects of alpha-EG on disaccharides hydrolysis were examined using crude enzyme preparation from rat intestinal acetone powder. Glucose liberated from alpha-EG was detected in a serosal solution of everted rat intestinal sac, but it was only less than 4% of absorbed intact alpha-EG. alpha-EG absorption into small intestinal tissue was reduced by elimination of sodium ion from the mucosal solution or under the presence of phlorizin. The hydrolytic activity for alpha-EG was detected in crude enzyme preparation from rat intestinal acetone powder, but it showed a low value as compared to those for disaccharides. alpha-EG showed mixed type inhibition for maltose and sucrose hydrolysis, but inhibitory concentrations of alpha-EG required for 50% inhibition for the maltose and sucrose hydrolysis were higher than those of arabinose and acarbose. In conclusion, a small amount of alpha-EG was hydrolyzed and most of it was absorbed via SGLT1 as an intact form in the rat small intestine, and the inhibitory effect of alpha-EG on disaccharides hydrolysis was weak.

Effect of ingested concentrate and components of sake on epidermal permeability barrier disruption by UVB irradiation.

Daily topical applications of the concentrate of sake (CS) have been shown to reduce epidermal barrier disruption in murine skin caused by ultraviolet B (UVB) radiation, while one of the components of sake, ethyl alpha-D-glucoside (alpha-EG), also reduces barrier disruption. We confirmed the effect of oral ingestion of various doses of CS on epidermal barrier disruption caused by UVB irradiation in hairless mice. Then, to identify the effective components, we quantitatively analyzed alpha-EG, organic acids, and glycerol, the main components of CS, and examined the effect of various concentration of each on barrier disruption. alpha-EG and organic acids showed comparable results to CS itself, and transepidermal water loss levels in murine skin were significantly decreased as compared with the control. Furthermore, an investigation of the dose dependency of these agents was performed and the results showed the significant effectiveness of alpha-EG. In addition, red wine concentrate (WC) and beer concentrate (BC) were examined in order to confirm the unique effects of CS. Similar effects were not found with WC and BC.