Administration of mucuna beans (Mucuna pruriences (L.) DC. var. utilis) improves cognition and neuropathology of 3 × Tg-AD mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of extracellular amyloid-beta peptides (Aß) resulting in senile plaques and intracellular hyperphosphorylated tau protein resulting in neurofibrillary tangles (NFTs). Mucuna beans (Mucuna pruriences (L.) DC. var. utilis) are unique plants containing 3-9% L-3,4-dihydroxyphenylalanine (L-DOPA). Here we investigated the effect of the administration of Mucuna beans on AD prevention by feeding triple-transgenic mice (3 × Tg-AD mice) with a diet containing Mucuna beans for 13 months. The levels of Aß oligomers and detergent-insoluble phosphorylated tau decreased in the brain of mice fed with Mucuna beans (Mucuna group) compared to those of the Control group. Aß accumulation and phosphorylated tau accumulation in the brain in the Mucuna group were also reduced. In addition, administration of Mucuna beans improved cognitive function. These results suggest that administration of Mucuna beans may have a preventive effect on AD development in 3 × Tg-AD mice.

Beneficial effects of Chlorella on glucose and lipid metabolism in obese rodents on a high-fat diet.

BACKGROUND: Obesity-induced glucose and lipid metabolism disorders have become risk factors for lifestyle diseases. Powderized Parachlorella beijerinckii (BP) and its hot water extract (BCEx) are believed to be useful for preventing common diseases such as hypertension, arteriosclerosis, and hyperlipidemia. The present study investigated how chlorella components influence common diseases in obese mice and rats on a high-fat diet. METHODS: We fed C57BL/6J mice a high-fat diet containing 5% BP, and then weighed their organs, tested their glucose tolerance and insulin sensitivity, and analyzed their serum. Further, we fed Sprague-Dawley rats with a high-fat diet containing 1% BCEx, and then weighed their organs and analyzed their serum parameters. RESULTS: BP administration had no effect on high-fat diet-induced obesity. However, compared with high-fat diet group, BP group had improved glucose tolerance and insulin sensitivity and inhibited the hypertrophic growth of visceral fat cells. In addition, BP group had improved serum adiponectin, leptin and monocyte chemoattractant protein-1 (MCP-1) levels. The MCP-1 expression level at epididymal fat was decreased at BP group. BCEx administration reduced amount of peritesticular fat and serum triglyceride (TG) levels. CONCLUSIONS: The results suggest that the antihyperinsulinemic effects of BP are due to the modulation of adipose tissue hypertrophy and adipocytokine secretion. BCEx inhibited the accumulation of visceral fat and serum TG. The study showed that BP and BCEx improve glucose and lipid metabolism disorders caused by a high-fat diet.

Preventive effects of Chlorella on cognitive decline in age-dependent dementia model mice.

Oxidative stress is one of the major causes of age-dependent memory loss and cognitive decline. Cytotoxic aldehydes are derived from lipid peroxides and their accumulation may be responsible for age-dependent neurodegeneration, including Alzheimer's disease. Since aldehyde dehydrogenases detoxify such aldehydes, we constructed transgenic mice with mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity deficiency (DAL101 mice) as an age-dependent dementia model. This model animal is age-dependently progressed by persistent oxidative stress, and thus enables us to investigate foods that prevent dementia. Since Chlorella, a kind of alga, exhibits various anti-oxidative effects, we investigated whether Chlorella has the potential to prevent age-dependent cognitive impairment. We fed Chlorella to DAL101 mice and investigated its effects on oxidative stress and the progression of cognitive decline using the Morris water-maze and object recognition tests. The diet with Chlorella tended to reduce oxidative stress and significantly prevented the decline of cognitive ability, as shown by both methods. Moreover, consumption of Chlorella decreased the number of activated astrocytes in the DAL101 brain. These findings suggest that the prolonged consumption of Chlorella has the potential to prevent the progression of cognitive impairment.

Anti-androgen effects of extracts and compounds from Ganoderma lucidum.

The 30% EtOH extracts of Ganoderma lucidum Fr. Karst (Ganodermateceae) showed weak 5alpha-reductase inhibitory activity and binding ability to androgen receptor. When LNCaP (lymph-node carcinoma of the prostate) cells were treated with the EtOH extracts, cell proliferation was inhibited. Treatment with the extracts significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats. These results showed that G. lucidum might be a useful ingredient in the treatment of androgen-induced diseases, such as benign prostatic hyperplasia or prostate cancer. From the 30% EtOH extracts, we isolated ganoderiol F, which showed binding activity to androgen receptor and inhibited LNCaP cell proliferation, as one of the active compounds in the 30% EtOH extracts.

Effect of an extract of Ganoderma lucidum in men with lower urinary tract symptoms: a double-blind, placebo-controlled randomized and dose-ranging study.

AIM: To conduct a double-blind, placebo-controlled randomized and dose-ranging study to evaluate the safety and efficacy of the extract of Ganoderma lucidum (G. lucidum) in men with lower urinary tract symptoms (LUTS). METHODS: We enrolled male volunteers (> or = 50 years) with an International Prostate Symptom Score (IPSS; questions 1-7) > or = 5 and a prostate-specific antigen (PSA) value < 4 ng/mL. Volunteers were randomized into groups of placebo (n = 12), G. lucidum of 0.6 mg (n = 12), 6 mg (n = 12) or 60 mg (n = 14), administered once daily. Efficacy was measured as a change from baseline in IPSS and the peak urine flow rate (Q(max)). Prostate volume and residual urine were estimated by ultrasonography, and blood tests, including PSA levels, were measured at baseline and at the end of the treatment. RESULTS: The overall administration was well tolerated, with no major adverse effects. Statistical significances in the magnitude of changes between the experimental groups were observed at weeks 4 and 8. No changes were observed with respect to Q(max), residual urine, prostate volume or PSA levels. CONCLUSION: The extract of G. lucidum was well tolerated and an improvement in IPSS was observed. The recommended dose of the extract of G. lucidum is 6 mg in men with LUTS.

Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms.

AIM: To evaluate the safety and efficacy of an extract of Ganoderma lucidum that shows the strongest 5alpha-reductase inhibitory activity among the extracts of 19 edible and medicinal mushrooms by a double-blind, placebo-controlled, randomized and dose-ranging study in men with lower urinary tract symptoms (LUTS). METHODS: In this trial, we randomly assigned 88 men over the age of 49 years who had slight-to-moderate LUTS to 12 weeks of treatment with G. lucidum extract (6 mg once a day) or placebo. The primary outcome measures were changes in the International Prostate Symptom Score (IPSS) and variables of uroflowmetry. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, laboratory values and the reported adverse effects. RESULTS: G. lucidum was effective and significantly superior to placebo for improving total IPSS with 2.1 points decreasing at the end of treatment (mean difference, -1.18 points; 95% confidence interval, -1.74 to -0.62; P < 0.0001). No changes were observed with respect to quality of life scores, peak urinary flow, mean urinary flow, residual urine, prostate volume, serum prostate-specific antigen or testosterone levels. Overall treatment was well tolerated with no severe adverse effects. CONCLUSION: The extract of G. lucidum was well tolerated and improved IPSS scores. These results encouraged a further, large-scale evaluation of phytotherapy for a long duration using the extract of G. lucidum on men with LUTS.

The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum.

The anti-androgenic activity of the ethanol extract of the fruiting body of Ganoderma lucidum has been previously reported. Ganoderol B with 5alpha-reductase inhibitory activity and the ability to bind to androgen receptor (AR) can inhibit androgen-induced LNCaP cell growth and suppress regrowth of the ventral prostate induced by testosterone in rats. The down-regulation of AR signaling by ganoderol B provides an important mechanism for its anti-androgenic activity. In view of the fact that PSA (prostatic specific antigen, a well-accepted prognostic indicator of prostate cancer) is down-regulated, an important implication of this study is that ganoderol B intervention strategy aimed at toning down the amplitude of androgen signaling could be helpful in controlling morbidity of prostate cancer. In conclusion, our result suggests that ganoderol B might be useful in prostate cancer and benign prostatic hyperplasia (BPH) therapy through suppressing the function of androgen and its receptor.

Anti-androgenic activities of Ganoderma lucidum.

The inhibitory effects of methanol extracts of 19 edible and medicinal mushrooms on 5alpha-reductase activity were examined. The extract of Ganoderma lucidum Fr. Krast (Ganodermataceae) showed the strongest 5alpha-reductase inhibitory activity. The treatment of the fruit body of Ganoderma lucidum or the extract prepared from it significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats. These results showed that Ganoderma lucidum might be a useful ingredient for the treatment of benign prostatic hyperplasia (BPH).

Role of endothelin B receptor in the pathogenesis of ischemic acute renal failure.

This study evaluated the role of endothelin B (ET ) receptor-mediated action in the development and maintenance of ischemic acute renal failure (ARF), using the spotting-lethal ( ) rat that carries a naturally occurring deletion in the ET receptor gene. Because homozygous ( ) rats die shortly after birth due to congenital distal intestinal aganglionosis, genetic rescue of rats from the developmental defect using a dopamine-beta-hydroxylase (DbetaH)-ET transgene was performed to produce ET -deficient adult rats. Rescued homozygous (DbetaH-ET ) and wild-type (DbetaH-ET +/+) rats were subjected to ischemic ARF by clamping the renal pedicle for 45 min followed by reperfusion. At 24 h after the reperfusion, renal glomerular dysfunction and histologic damage, such as proteinaceous casts in tubuli, were markedly and observed equally in homozygous and wild-type groups, and these renal injuries gradually recovered. However, when the ischemia/reperfusion-induced renal injury was examined 7 days after the reperfusion, the recovery in homozygous ARF rats was obviously delayed compared with the wild-type animals. Two of the eight homozygous ARF rats died within 3 days after the reperfusion. Increment of renal endothelin-1 content after the ischemia/reperfusion was more marked in homozygous than in wild-type rats. Thus, ET receptor-mediated actions do not play an important role in the development of ischemic ARF but may be involved in the recovery process from ischemia/reperfusion-induced renal injury.

Role of endothelin ET(B) receptors in the renal hemodynamic and excretory responses to big endothelin-1.

We determined the role of endothelin ET(B) receptor in the renal hemodynamic and excretory responses to big endothelin-1, using A-192621, a selective endothelin ET(B) receptor antagonist and the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the endothelin ET(B) receptor gene. An intravenous injection of big endothelin-1 produced a hypertensive effect, which is greater in wild-type (+/+) rats pretreated with A-192621 and in homozygous (sl/sl) rats. Big endothelin-1 markedly increased urine flow, urinary excretion of sodium and fractional excretion of sodium in wild-type rats treated with the vehicle. These excretory responses to big endothelin-1 were markedly reduced by pharmacological endothelin ET(B) receptor blockade. On the other hand, big endothelin-1 injection to the endothelin ET(B) receptor-deficient homozygous animals resulted in a small diuretic effect. When renal perfusion pressure was protected from big endothelin-1-induced hypertension by an aortic clamp, the excretory responses in vehicle-treated wild-type rats were markedly attenuated. In homozygous or A-192621-treated wild-type rats, there was a small but significant decreasing effect in urine flow. In addition, big endothelin-1 significantly elevated nitric oxide (NO) metabolite production in the kidney of wild-type rats but not in the homozygous rats. We suggest that the diuretic and natriuretic responses to big endothelin-1 consist of pressure-dependent and pressure-independent effects and that the increased NO production via the activation of endothelin ET(B) receptors in the kidney is closely related to the big endothelin-1-induced excretory responses.

Effect of docosahexaenoic acid-fortified Chlorella vulgaris strain CK22 on the radial maze performance in aged mice.

Effect of docosahexaenoic acid (DHA) [22: 6(n-3)]-fortified Chlorella oil fraction on radial maze performance was studied in aged mice. Male ICR mice aged 9 months were fed a diet containing 2 g DHA-fortified Chlorella oil fraction/100 g diet or normal diet (Control group) for 2 months. Two months after the start of feeding, the mice were tested for learning ability related to 2 types of memory, reference memory and working memory, with the partially (4 of 8) baited eight-arm radial maze. Reference memory is a kind of information that should be retained until the next trial. Working memory is a kind of information that disappears in a short time. Entry into the unbaited arms and repeated entry into the visited arms were defined as reference memory errors and working memory errors, respectively. DHA-fortified Chlorella oil fraction administration to mice for 2 months resulted in a significant decrease in the number of working memory errors without affecting the number of reference memory errors. A significant increase in the DHA content in the brain was also observed. These results suggest that the intake of DHA-fortified Chlorella oil fraction effectively enhances working memory in maze performance.