Improvement of blood lipid profiles by Goishi tea polyphenols in a randomised, double-blind, placebo-controlled clinical study.

Dyslipidaemia is a risk factor for arteriosclerosis. Recent studies have shown that dyslipidaemia is effectively prevented by various polyphenols. In this clinical study (UMIN trial: 000024028), we evaluated the beneficial effects of polyphenols contained in Goishi tea on blood lipid profiles. Seventy-seven subjects with LDL cholesterol (CHO) ≧120 mg/mL were randomly divided into two groups for 12 weeks of polyphenol intake as follows: the Goishi tea group for daily consumption of Goishi tea containing 122 mg of polyphenols and the placebo group for the corresponding consumption of a placebo drink containing 12.2 mg of polyphenols. Intake of Goishi tea polyphenols tended to increase HDL CHO and suppress the elevation of triglycerides. These effects were particularly notable among the subjects with a body mass index <25 kg/m2. These findings suggest that Goishi tea polyphenols may suppress arteriosclerosis and reduce cardiovascular event risk by improving blood lipid profiles and thereby preventing dyslipidaemia.

Application of Natural Ingredients to Preventive Medicine.

The super-aging society in Japan is currently experiencing growing demand for treatments that improve health and longevity. To develop new high-functional foods and search for pharmaceutical candidates among foods and natural products, it is necessary to promote organic collaboration among researchers in pharmacy, medicine, nutrition, and other fields to encourage joint utilization of their technologies. Recently, attempts have been made to use numerous foods and natural products to prevent or treat diseases based on scientific evidence. We have been endeavoring to develop preventive medicines from foods and natural ingredients by engaging in relevant activities such as screening these substances to determine the structures of their effective ingredients, verifying pharmacological activities, and conducting clinical trials. In this study, the effectiveness of Goishi tea (postfermented tea) and Flos Lonicerae (Japanese honeysuckle) for metabolic syndrome and hepatic disorders, respectively, was explored. Multicomponent foods and natural ingredients have diverse effects produced by the actions of individual components as well as the interactions among different components. Additionally, when using natural ingredients and similar materials, it is necessary to consider the different extraction efficiencies of various methods and their absorption, deposition, metabolism, and excretion after consumption. The influence of intestinal bacteria and other factors is also critical. In our study, the administration of Goishi tea and Flos Lonicerae in animal models of disease demonstrated high functionality. Based on these findings, we plan to conduct further investigations, including clinical studies in human participants, focusing on the potential usefulness of Goishi tea and Flos Lonicerae as functional foods.

Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.

Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8.

Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.

The influence of Goishi tea on adipocytokines in obese mice.

This study investigated the influence of Goishi-tea on visceral fat weight in induced obese mice. Mice were divided into two main groups, normal and obesity. In obesity group, mice were fed with high-fat diet. Goishi-tea including its fractions (ethyl-acetate layer and water layer) was administrated in normal and obesity three sub-groups. Results showed no influence of Goishi-tea in normal group. However, visceral fat weight, size of adipose cell and cholesterol level were significantly decreased in obesity group fed Goishi-tea compared to control group. Moreover, adiponectin levels tended to increase and adipocytokines has significant values lower in obesity group fed Goishi-tea compared to control group. Interestingly, Goishi tea involved in the high-fat diet induced-obese mice can inhibit fat accumulation and maintain adiponectins without increasing tumor necrosis factor-alpha and interleukin-6. It would be beneficial for the prevention of metabolic syndrome and obesity-related disorder.

Eriobotrya japonica seed extract and deep sea water protect against indomethacin-induced gastric mucosal injury in rats.

We have previously reported that Eriobotrya japonica seed extract (ESE) is effective for the treatment of various gastric mucosal injuries. For the pharmaceutical preparation of ESE, we are evaluating deep sea water (DSW), which contains trace elements and has a homeostasis-enhancing effect, as the solvent. In this study, we prepared DSW containing ESE (ESE + DSW) and evaluated its usefulness for the prevention of gastric mucosal injuries using non-steroidal anti-inflammatory drug-induced acute gastric mucosal injury models in male Wistar/ST rats. Gastric mucosal injury models were prepared by administering indomethacin at 30 mg/kg orally to the rats after a 24-h fast. ESE was prepared by a routine procedure and administered at the same concentration as in the administration to humans. The rats were divided into the following 6 groups: ESE, DSW, ESE + DSW, tap water (control), rebamipide (positive control), or untreated. Gastric mucosal injuries were evaluated by measuring the injury area, lipid peroxide (LPO) level, antioxidative enzyme level, and volume of mucus. The injury area and LPO levels in plasma and gastric tissue were significantly reduced in the ESE and ESE + DSW groups compared with the control and DSW group. The plasma and gastric tissue antioxidative enzyme levels were significantly higher in the ESE and ESE + DSW groups than in the control group. These results suggest that DSW, when combined with ESE, inhibits antioxidative enzymes, and enhances the gastric mucosal protecting effect of ESE.

Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non-alcoholic steatohepatitis.

OBJECTIVES: Non-alcoholic steatohepatitis is associated with the deposition of lipid droplets in the liver, and is characterised histologically by the infiltration of inflammatory cells, hepatocellular degeneration and liver fibrosis. Oxidative stress may play an important role in the onset and deterioration of non-alcoholic steatohepatitis. We previously reported that an Eriobotrya japonica seed extract, extracted in 70% ethanol, exhibited antioxidant actions in vitro and in vivo. In this study, we examined the effect of this extract in a rat model of non-alcoholic steatohepatitis. METHODS: The seed extract was given in the drinking water to fats being fed a methionine-choline-deficient diet for 15 weeks. KEY FINDINGS: Increases in alanine aminotransferase and aspartate aminotransferase levels were significantly inhibited in rats fed the seed extract compared with the group on the diet alone. Formation of fatty droplets in the liver was also inhibited. Antioxidant enzyme activity in liver tissue was higher than in the diet-only group and lipid peroxidation was reduced compared with rats that also received the extract. Expression of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal was lower in the rats given the seed extract than in the diet-only group. In the former, liver tissue levels of transforming growth factor-beta and collagen were also decreased. CONCLUSIONS: Thus, the E. japonica seed extract inhibited fatty liver, inflammation and fibrosis, suggesting its usefulness in the treatment of non-alcoholic steatohepatitis.

Metabonomics study of the protective effects of Lonicera japonica extract on acute liver injury in dimethylnitrosamine treated rats.

A metabonomics approach, consisting of gas chromatography coupled to mass spectrometry (GC/MS) and a multivariate statistical technique, was developed to estimate the protective effects of Lonicera japonica extract (LJE) on acute liver injury. A high dose of dimethylnitrosamine (DMN) was used to induce an acute stage of hepatic injury in 21 male Wistar rats. The rats were divided into three groups: normal, model and treatment. Pathological changes, particularly fibrosis, were also examined by Azan staining. The results indicate that clear and consistent biochemical changes occur. Nine candidate biomarkers for DMN treatment and LJE intervention under controlled conditions were identified using chemometric analysis. Pathological analysis suggests that LJE has a protective effect to the liver. This work suggests that a metabonomics approach can be used to estimate pharmacodynamic action of naturally occurring drugs in a dynamic and non-invasive way.

Protective effects of Flos lonicera extract on acute liver injury by dimethylnitrosamine-induced in rats.

The aim of this study is to investigate effects of Flos lonicera extract (FLE) on acute liver injury model rats which induced by 35 mg/kg dimethylnitrosamine (DMN). Model rats were divided into hepatic injury control group (administrated with water), FLE group (administrated with FLE) and silymarin group (administrated with silymarin which is hepatotherapeutic drug) as positive control. They were examined including ALT, AST, ALP, gamma-GT, ALB and TP levels in serum, and MDA, GPx levels in liver tissue. In addition, pathologic changes, particularly fibrosis, were examined by Azan staining. The results revealed that the ALT, AST, ALP, gamma-GT, MDA GPx and liver fibrosis degree in the LJE group were lower than the silymarin group and control group, ALB and TP were higher than the silymarin group and control group. These results suggested that LJE may help in inhibiting of acute liver injury greater than silymarin.

Animal studies supporting the inhibition of mast cell activation by Eriobotrya japonica seed extract.

OBJECTIVES: The potent antioxidant activity of Eriobotrya japonica seed extract (ESE) and its usefulness in the prevention and treatment of various disorders has been reported previously. Its antioxidant activity associated with beta-sitosterol and polyphenols contained in the extract was also validated. In this study, anti-allergic activity of Eriobotrya japonica seed extract was investigated. METHODS: The inhibition of histamine release-mediated type 1 allergy by Eriobotrya japonica seed extract was used as an index. KEY FINDINGS: The administration of this extract inhibited histamine release from rat mast cells, suggesting its usefulness in allergic disease treatment. In an experiment using a guinea-pig allergic rhinitis model, this extract reduced the frequency of sneezing and nose-scratching. CONCLUSIONS: These results suggest that Eriobotrya japonica seed extract may contribute to the relief of allergic disease-related symptoms.

[Inhibitory effects of "Goishi-tea" as a post-fermented-tea on dietary-induced hypercholesteremia and atherosclerosis in rabbits].

Since lipid oxidation is involved in the deterioration of hypercholesterolemia-related atherosclerosis, ingestion of drinks and foods with antioxidant actions is useful for preventing lipid oxidation. Goishi-tea is a post-fermented-tea manufactured by a unique method in Japan, and may be useful for preventing various disorders. However, there is no scientific evidence. In this study, we compared the radical scavenging activity of goishi-tea with that of other teas, and administered this tea to a rabbit model of hypercholesteremia to evaluate its usefulness in the inhibition of hypercholesteremia and atherosclerosis. The radical scavenging activity of goishi-tea was similar to that of green-tea, and was higher than that of other types of fermented-teas. On the other hand, some difference of components was found between goishi-tea and green-tea. In cholesterol-fed rabbits, low-density lipoprotein (LDL)-cholesterol level in the goishi-tea-group was lower than that in the green-tea-group. Plasma lipidperoxide value was also lower in the goishi-tea-group than in the green-tea and tap-water-groups. On aortic endothelial staining, fat area in the goishi-tea-group was lower than that in the tap-water-group. Furthermore, fat accumulation in the aortic intima in the goishi-tea-group was very low. Goishi-tea has higher antioxidant activities than the other fermented-teas tested, which were generally low, and decreased serum lipid levels, suggesting that goishitea is a very peculiar fermented-tea with usefulness in the prevention of hypercholesterolemia and atherosclerosis.

Gastroprotective activity of Eriobotrya japonica seed extract on experimentally induced gastric lesions in rats.

The effect of Eriobotrya japonica seed extract (ESE) prepared with 70% ethanol on gastric mucosal injury was investigated. Six experimental models with different action mechanisms were used for the evaluation. Three concentrations of ESE were prepared for each model. ESE administration was initiated 14 days before induction of gastric mucosal injury, and its effect was investigated. ESE inhibited formation of gastric mucosal injury.

Effect of Eriobotrya japonica seed extract on 5-fluorouracil-induced mucositis in hamsters.

In this study, we investigated the effects of an Eriobotrya japonica seed extract (ESE) on mucositis using a 5-fluorouracil (5-FU)-induced mucositis hamster model. This model was prepared by intraperitoneally administering 90 mg/kg of 5-FU to hamsters on Day 1, scratching 1 cm(2) of the left cheek pouch of hamsters with a wire brush on Days 2, 3, and 4, and intraperitoneally administering 60 mg/kg of 5-FU on Day 5. Mucositis was evaluated based on the mucositis score at the mucositis site, left cheek pouch thickness, histological findings on HE staining, and plasma lipid peroxide levels. On Day 10, the mucositis score and left cheek pouch thickness in the ESE group were significantly lower than those in the tap water group. Histologically, the two groups showed a defect of the cheek pouch epithelium on Day 6. On Day 10, epithelial injury and bacterial infection were noted in the tap water group. However, in the ESE group, similar findings were not observed. On Day 6, the plasma lipid peroxide level in the tap water group was significantly higher than that in the normal group. In the ESE group, the plasma lipid peroxide level was significantly lower than that in the tap water group. These results suggest that ESE is useful for treating chemotherapy-induced mucositis.

Effect of orally administered Eriobotrya japonica seed extract on allergic contact dermatitis in rats.

The anti-allergic activity of Eriobotrya japonica seeds extract (ESE) was investigated. Oral administration of ESE dramatically inhibited ear swelling due to allergic contact dermatitis caused by repeated application of two antigens, 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (oxazolone) and dinitrofluorobenzene (DNFB), respectively. The increase of histamine content in inflamed ear tissue induced by oxazolone and DNFB was significantly antagonized by orally administered ESE. Eosinophil peroxidase and myeloperoxidase activity in both models was suppressed by orally administered ESE. Tumour necrosis factor-alpha in the inflamed region caused by repeated application of DNFB was also significantly suppressed. The findings suggest that ESE may be effective for treating allergic contact dermatitis.

Scavenging of reactive oxygen species by Eriobotrya japonica seed extract.

We have clarified that Eriobotrya japonica seed extract has strong antioxidative activity, and is effective for the prevention and treatment of various diseases, such as hepatopathy and nephropathy. In this study, to investigate the influences of components of Eriobotrya japonica seed extract on its antioxidative activity, extracts were prepared using various solvents (n-hexane (Hex), ethyl acetate (EtOAc), n-butanol (n-BuOH), methanol (MeOH) and H2O) and the antioxidative activity of the solvent fractions and components was evaluated based on the scavenging of various radicals (DPPH and O2(-)) measured by the ESR method and the inhibition of Fe3+-ADP induced NADPH dependent lipid peroxidation in rat liver microsomes. The radical scavenging activities and inhibitory activities on lipid peroxidation differed among the solvent fractions and components. In the n-BuOH, MeOH and H2O fractions, radical scavenging activity and inhibitory activity on lipid peroxidation were high. In addition, these fractions contained abundant polyphenols, and the radical scavenging activity increased with the polyphenol content. In the low-polar Hex and EtOAc fractions, the radical scavenging activity was low, but the lipid peroxidation inhibition activity was high. These fractions contained beta-sitosterol, and the inhibitory activity on lipid peroxidation was high. Based on these findings, the antioxidative activity of Eriobotrya japonica seed extract may be derived from many components involved in a complex mechanism, resulting in high activity.

The effect of Eriobotrya japonica seed extract on oxidative stress in adriamycin-induced nephropathy in rats.

Eriobotrya japonica has been used as a medicinal plant for a long time, and its leaves are known to have many physiological actions such as anti-inflammatory, antitussive, and expectoran. In contrast, Eriobotrya japonica seeds are only known to contain amygdalin, and almost no investigations of its pharmacological action have been performed. Moreover, some anticancer agents such as adriamycin cause renal disorders as an adverse effect, and the mechanism of the adverse effect is considered to involve oxidative stress. We have reported that Eriobotrya japonica seed extract has an inhibitory effect on liver disorders. In this study, we prepared a 70% ethanol extract of Eriobotrya japonica seeds and administered the extract to rats with renal disorder induced by a single administration of 7 mg/kg body weight adriamycin, and investigated the usefulness of the extract. Increases in indices of renal function, plasma urea nitrogen, were significantly inhibited in rats treated with the Eriobotrya japonica extract compared to rats treated with tap water. In addition, the renal tissue level of reduced glutathione was significantly high in rats that ingested the extract, while the lipid peroxide levels in plasma and renal tissue were significantly low. However, no effect on renal tissue antioxidative enzymes was observed, suggesting that Eriobotrya japonica seed extract has direct antioxidative action. Based on these findings, Eriobotrya japonica seed extract may be effective in reducing the oxidative stress of adriamycin-induced renal disorder. Therefore, ingestion of Eriobotrya japonica seed extract may contribute to a reduction of the adverse effects of adriamycin.