The discovery of microRNAs (miRNAs) and following studies reporting that miRNAs are stably present in the circulation, paved the way for possible use of miRNAs as biomarkers. Identification of circulating miRNAs that are functional upon delivery to the recipient cells, suggests miRNAs play roles in cell-to-cell communication as well as hormones and cytokines. This review provides a basic understanding of miRNAs and the current understanding of circulating miRNA as biomarkers and focuses on their putative roles and regulation under stressed conditions including physical exercise.

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We evaluated the safety of Ashitaba (Angelica keiskei) in bacterial reverse mutation test as well as single and 13-weeks oral toxicity tests. In the bacterial reverse mutation test, ethanol extract of Ashitaba had no reverse mutation inducing activity on five bacterial strains with or without S9 metabolic activation. In the single oral toxicity test, Ashitaba powder (3,500 mg/kg/day) showed no adverse effects in male and female SD rats. In the 13-week repeated oral toxicity test, Ashitaba powder (875 and 1,750 mg/kg/day) showed no adverse effects on body weight, food consumption, blood biochemistry, hematology, urinalysis, ophthalmoscopy, organ weight and histopathology in male and female SD rats. These results indicate that Ashitaba is very safe foodstuff under the conditions of this study.

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Objective: “Ashitaba” (Angelica keiskei) is a traditional vegetable peculiar to Japan. Ashitaba contains vitamins, dietary fiber and polyphenols such as chalcones abundantly. We previously reported anti-diabetic action of Ashitaba in an animal model as well as in diabetics. In this study, we evaluated the safety of Ashitaba green juice in healthy and borderline mildly diabetic subjects.
Methods: Japanese adult subjects (n = 24) ingested Ashitaba green juice (31.5 g granulated powder) for 4 weeks. For evaluation of safety, blood chemistry analysis, hematological analysis and urinalysis were conducted.
Result: On excessive ingestion of Ashitaba green juice for 4 weeks, there were no adverse clinical changes in blood analysis and urinary analysis and no serious symptom was observed.
Conclusion: These results indicate that excessive ingestion of Ashitaba green juice is safe in healthy and borderline mildly diabetic subjects.

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Objective: The overproduction of reactive oxygen species leads to oxidative stress, which is related to lifestyle-related disease and cancer. Although antioxidants are considered as one of the countermeasures to oxidative stress, it is necessary to develop the assessment methodology for the antioxidant capacity which is closer to the inner body conditions. In this study, we examined antioxidant actions of plant extracts by using newly-developed neutrophil activity measurement system.
Method: Lemon verbena, Green tea, Camellia japonica and Antiallerge^® were used as plant extracts, and were diluted to medium in wide-range concentrations. Each solution was added on modified Mebiol Gel^® (hydrogel), and the mixture of blood and luminol were set onto the hydrogel in each tube. The amount of reactive oxygen species were measured by luminol-dependent chemiluminescence, whereas the cell count in the hydrogel was quantified as migratory activity of neutrophils.
Result: Lemon verbena and Green tea significantly inhibited reactive oxygen species in a concentration-dependent manner, whereas Camellia japonica and Antiallerge^® did not. The migratory activity of neutrophils was not affected by those plant extracts. Also, damaged cells were not detected.
Conclusion: It was suggested that Lemon verbena and Green tea scavenged reactive oxygen species without causing cell death of neutrophils. This new method for measuring neutrophil activities can be applied not only for assessing the status of inflammation and oxidative stress but also as the screening system for predicting the effectiveness of antioxidant and anti-inflammatory substances.

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Objective: We studied the effect of long-term the reduced form of coenzyme Q10 (H₂CoQ10: QH) consumption and exercise training (EX) with SAMP1 mice on senescence, exercise capacity, and an oxidative stress regulation system.
Methods: The subjects of this study were 50 SAMP1 mice for accelerated senescence, sorted at random into four groups: one which consumed QH, one which consumed QH and performed EX, one which performed EX, and a control group. The experiment started when the mice were 8 weeks old and the consumption of QH continued for 12 months (12M). The measurement for the oxidative stress regulation system was performed at the start of this study and 12M later. Running time for exercise capacity, senescence grading scores, and body weight were each measured at the start of the study, 6 months (6M) and 12M later. For the oxidative stress regulation system, we used reactive oxygen and free radical analysis equipment, with which we measured plasma oxidative stresses (d-ROM test) and plasma anti-oxidant potential (BAP test), and calculated the ratio of d-ROM to BAP.
Result: A combination of QH consumption and EX showed, at a later stage, an inhibiting effect on the increase in senescence grading scores and on the decrease in running time. For the oxidative stress regulation system, the combination showed a decrease in latent anti-oxidant potential caused by the rise of plasma oxidative stresses.
Conclusion: Results of this study suggest that a combination of QH consumption and EX is effective in delaying aging, inhibiting the decline of exercise capacity, and decrease in latent anti-oxidant potential.

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Objective: In general, antiallergic drugs, steroids, and autonomic drugs are administered for patients with allergic diseases, but the chronic administration of these medicines may occasionally induce side effects. As such, several complementary and alternative medicine (CAM) are used, even though their effectiveness has not been established by a significant amount of evidence. Health food, herbal medicines, herbal tea, and aromatherapy, etc., are used for the treatment of allergic rhinitis (AR) as CAM. Rosmarinic acid is a type of polyphenol, and is reported to have antiallergic, antioxydative and anti-inflammatory properties. Rosmarinic acid is included in Perilla Herbs, which are used in health foods and herbal medicines (Kampo medicines), Rosemary and Lemon balm, which are used as herbal teas and essential oils of aromatherapy. This study was performed to evaluate the effect of rosmarinic acid on AR using AR model rats.
Methods: Six-week-old male Sprague-Dawley rats were sensitized with toluene 2,4-diisocyanate (TDI) to induce AR. Rosmarinic acid (1 mg/kg i.p. or 3 mg/kg i.p.) is administrated for 21 days. On day 22, the symptom of nasal allergy was evaluated by counting the number of sneezes within 10 minutes. Substance P (SP), calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) in the nasal lavage fluids were also measured.
Result: SP and CGRP take part in the exacerbation of rhinitis symptoms, and are secreted from the nerve ending following nerve stimulation by chemical mediators such as histamine. The administration of Rosmarinic acid had no effect on NGF, but significantly suppressed increases of sneezes, SP and CGRP dose-relatedly. Conclusion: Rosmarinic acid could control the symptom of nasal allergy, and one of the mechanisms was suppressing of the secretion of SP and CGRP.

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Objective: Although there are numerous epidemiological studies on supplement use, only a small number of studies focused on the issue of the subjective health perception and the clinical laboratory data. The aim of this study was to determine the relation between supplement use and the subjective health perception and the clinical laboratory data.
Method: The participants were asked to complete a self-administered questionnaire on supplement use, and subjective health perception (“overweight”, “easy fatigability”, “lower tolerance”, and “anxiety about bone and joints”) during the previous one month. The clinical laboratory data (blood pressure, fasting blood glucose, LDL-C), demographic information, smoking status and drug use were collected from the record at the medical checkup center.
Results: 608 men and 500 women were enrolled. A total of 30.3% of participants were found to use supplements. Logistic regression analysis revealed that supplement users were more likely to be women, older than 40 years, with lower or higher BMI, and with the normal laboratory data. However, the four items of subjective health perception and the three laboratory data were not individually associated with the supplement use.
Conclusion: Supplement use was associated with middle aged women with low or high BMI and normal clinical laboratory data.

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Objective: We investigated subjective effects of a lactoferrin (LF) -containing supplement on cold-like symptoms and gastroenteritis symptoms.
Method: Healthy women were divided into a LF-consumption group and a non-consumption group. The former intaked LF-containing tablets for 90 days. Subjects filled out questionnaires about cold-like symptoms, gastroenteritis symptoms, and drug use.
Results: Significant decreases were found in the onset of cold-like symptoms and gastroenteritis symptoms in the LF-consumption group compared with non-consumption group.
Conclusion: These results suggest the possibility that LF intake inhibits the onset of common cold and gastroenteritis.

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Objective: The purpose of this study was to confirm the effect of Okara-puree (okara after the sub-critical water reaction) on antitumor and antipromoter activity.
Method: The antipromoter activity was investigated by colony method using JB6 Cl 41 cells and 3-3 MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method. We examined the antitumor effect by measuring the survival days and the bodyweight of the mice in which colon cancer cells had been transplanted in the soles of the left foot.
Result: Okara-puree DMSO extract inhibited EGF(epidermal growth factor)-induced colonization of JB6 Cl 41 cells. In the mice transplanted with cancer cells, more survivors were seen in the Okara-puree group compared to control during the period day 10 to day 20. Furthermore,the mice in the Okara-puree group showed a longer survival time compared to control even after day 22.
Conclusion: Unlike unprocessed okara, Okara-puree shows promise for development as a functional food material with antitumor and antipromoter effects.

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Objective: We conducted a clinical study to investigate the effects of newly developed LED lighting on living comfort in an indoor environment.
Design: Twenty healthy subjects participated in a randomized crossover trial. They performed a mental task for 4 hours under ordinary lighting, and then rested for 1 hour under newly developed lighting or ordinary lighting. Sixteen of the subjects (8 males, 8 females) completed the trial. We evaluated subjective comfort using a visual analogue scale (VAS) and measured autonomic nervous system effects by the frequency analysis of a-a intervals on accelerated plethysmography (APG) waves.
Result: The subjects’ VAS evaluations showed that the newly developed lighting increased their comfort, while frequency analysis of APG during the rest period was found to activate the parasympathetic nerve system.
Conclusion: This newly developed LED lighting produces suitable illumination and color temperature and is useful for improving living comfort in an indoor environment during a rest period after daytime work.

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Objective: Gagome kombu (Kjellmaniella crassifolia), an edible brown seaweed grown around the southern area of Hokkaido, is known to abundantly contain fucoidan. Previous studies show that on animals, fucoidan from Gagome kombu (GKF) exhibits immune-enhancing, anti-cancer and anti-influenza virus capabilities. In this study, we focused on the elderly and evaluated the safety and immune-efficacy of GKF.
Methods: Eighteen (18) Japanese elderly subjects were chosen to ingest the test samples (3 tablets/day containing 50 mg GKF and lactic acid bacteria) for 8 weeks. Before ingestion and every 4 weeks thereafter (4^th and 8^th week), blood chemistry analysis, hematological analysis, urinalysis and immune analysis were conducted.
Result: Test results showed no adverse clinical changes in blood and urinary analysis. In addition, no serious symptoms were observed. Moreover, GKF markedly decreased serum IgE levels.
Conclusion: These results indicate that in the case of elderly, GKF is a safe functional food ingredient.

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