Effects of a Standardized Oligomerized-Polyphenol from Litchi chinensis Fruit Extract and Mixed Plant Extract Supplementation on Peripheral Circulation and Cold Sensitivity.

Certain individuals tend to suffer from a cold sensation-particularly in the lower extremities-despite most people not suffering from the same sensation. In Japan, this phenomenon is called "hie-sho" and reduces quality of life for several people, particularly women. A previous study has shown that a standardized oligomerized-polyphenol from Litchi chinensis fruit extract (OPLFE) reportedly causes a significant increase in body surface temperature. The present study aimed to investigate whether supplementation with OPLFE affected peripheral circulation and cold sensitivity. This randomized, double-blind, placebo-controlled trial was performed including 25 participants (age, 45.0±10.4 y; 3 males and 22 females) who were assigned to consume OPLFE, mixed plant extract with OPLFE, or placebo capsules for 14 d. Participants were instructed to relax for 60 min in a temperature-controlled room prior to obtaining measurements. Changes in skin temperature and peripheral blood flow of the middle finger were assessed immediately before and 1, 5, 10, 20, and 30 min after immersion in cold water (10ºC). Participants' height, weight, skin temperature, and blood flow in peripheral tissue were measured; furthermore, their "hie-sho" was measured using the Visual Analog Scale (VAS). Skin temperature and blood flow in peripheral tissue increased in the OPLFE and mixed plant extract with OPLFE groups on day 14 compared with those on day 1. In addition, cold sensitivity in these two groups significantly improved between day 1 and day 14. These findings suggest that OPLFE improves "hie-sho" by increasing peripheral blood flow and skin temperature.

Safety Assessment of Bangle (Zingiber purpureum Rosc.) Rhizome Extract: Acute and Chronic Studies in Rats and Clinical Studies in Human.

Bangle (Zingiber purpureum Rosc.) rhizome extract (BRE) contains phenylbutenoid dimers (banglenes), which exert neurotrophic effects and possess the potential capability to regenerate hippocampal neurons in mice. The acute and chronic oral toxicities of BRE powder were evaluated in Sprague-Dawley rats. A dose of BRE powder was estimated to be higher than 2000 mg/kg containing BRE 534 mg/kg as minimum lethal dose in a single-dose oral toxicity study. The no-observed-adverse-effect-level for the BRE powder was 1000 mg/kg/day (BRE 267 mg/kg) in the 90 day oral toxicity study. Four week clinical studies of BRE tablets in humans suggested that the ingestion of BRE tablets within 850 mg/man/day (BRE 227 mg/man/day) was safe for at least 1 month and in a usual manner. The C max, t max, and AUC of cis- and trans-(E)-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-enes (c- and t-banglenes) were calculated after the ingestion of BRE tablets (BRE 227 mg) and were 17.73 and 22.61 ng/mL, 1.8 and 1.8 h, and 71.47 and 95.53 ng/mL/h, respectively.

Effects of AHCC® on Immune and Stress Responses in Healthy Individuals.

AHCC® is a functional food from the basidiomycete Lentinula edodes. We evaluated the effects of AHCC® on subjects under different kinds of stress and at rest. Physical stress was imposed using an active standing test, known as Schellong's test. Sympathetic nervous activity in the standing position was significantly greater in AHCC®-treated subjects than in a placebo group. In contrast, AHCC® significantly increased parasympathetic nervous activity at rest. Under mental stress, AHCC® increased sympathetic nervous activity, with no difference in the parasympathetic nervous system. In subjects with chronic mental stress, self-reported "initiation and maintenance of sleep" was significantly greater in the AHCC®-intake period than in the placebo intake period, and natural killer cell activity also increased after AHCC® intake, suggesting a possible mechanism of action of AHCC®. Our findings indicate that AHCC® is potentially effective in stress management and may be useful in the treatment of depression.

Effects of electroacupuncture to the trigeminal nerve area on the autonomic nervous system and cerebral blood flow in the prefrontal cortex.

BACKGROUND: The autonomic nervous system and trigeminal nerve are involved in adjusting flow through diverging cerebral arteries in the prefrontal cortex. The purpose of this study was to examine the effect of 100 Hz electroacupuncture (EA) to the trigeminal nerve area on cerebral blood flow and autonomic nervous system function. METHOD: This was a randomised crossover study of 16 healthy volunteers who were assigned to an EA or control group. Stimulation (in the EA group) was performed five times, each after 1 min of rest. Needles were inserted at the inner edge of the eyebrows and 1 cm from the front hairline midpoint. We used high-frequency (HF) and low-frequency (LF) components of heart rate (HR) variability to assess autonomic nervous system function. HF and LF/HF ratio were taken as indicators of parasympathetic and sympathetic nervous system activity, respectively. We measured cerebral blood flow using a two-channel near-infrared spectroscope. RESULTS: In the EA group, HR significantly decreased (p=0.004) and HF significantly increased (p=0.006) relative to baseline. By contrast, there were no significant changes in HR or HF within the control group (p>0.05). Accordingly, HR tended to be lower (p=0.087) and HF greater (p=0.071) in the EA group versus the control group. There were no significant differences in LF/HF ratio within/between groups. Compared with the control group, cerebral blood flow was significantly greater in the left (p=0.048) and right (p=0.016) prefrontal cortex in the EA group. CONCLUSIONS: Delivery of 100 Hz EA to the trigeminal nerve area reduces HR and increases parasympathetic nervous activity and cerebral blood flow.

Effect of Enzyme-Treated Asparagus Extract (ETAS) on Psychological Stress in Healthy Individuals.

The aim of this study was to examine the effectiveness of Enzyme-Treated Asparagus Extract (ETAS) on improving stress response. A randomized, double-blind, placebo-controlled cross-over trial was undertaken in healthy volunteers. ETAS (150 mg/d) or a placebo was consumed for 28 d, with a washout period. Psychological parameters were examined using a self-report scale questionnaire and psychological stress was applied using the Uchida-Kraepelin (U-K) test. During the stress load, autonomic nervous function was analyzed. After the stress load, a profile of mood states (POMS) psychological rating was performed, and serum cortisol, plasma catecholamine, salivary secretory immunoglobulin A (sIgA), and salivary cortisol were analyzed. ETAS intake improved the self-reported rating for the items "Feel tired," "Hard to get up," and "Feel heavy" in the psychological questionnaire; ameliorated the self-reported rating for the items "Depression-Dejection" and "Fatigue" in the POMS questionnaire; and increased salivary sIgA levels after the U-K test. In contrast, serum and salivary cortisol levels, and plasma catecholamine did not change. During the U-K test, ETAS significantly upregulated the sympathetic nerve activity. Furthermore, ETAS intake significantly increased the number of answers and the number of correct answers in the U-K test, suggesting that it might improve office work performance with swiftness and accuracy under stressful conditions. In conclusion, ETAS supplementation reduced feelings of dysphoria and fatigue, ameliorated quality of sleep, and enhanced stress-load performance as well as promoted stress response by increasing salivary sIgA levels. These data suggest ETAS intake may exert beneficial effects, resulting from well-controlled stress management, in healthy individuals.

Physical and Psychological Effects of Head Treatment in the Supine Position Using Specialized Ayurveda-Based Techniques.

OBJECTIVE: To clarify the physical and psychological effects of head massage performed in the supine position using Ayurveda-based techniques (head treatment). DESIGN: Twenty-four healthy female students were included in the study. Using a crossover study design, the same participants were enrolled in both the head treatment intervention group and control group. There was an interval of 1 week or more between measurements. OUTCOME MEASURES: The physiologic indices measured included blood pressure and heart rate fluctuations (high frequency and low frequency/high frequency). The psychological markers measured included liveliness, depression, and boredom using the visual analogue scale method. State anxiety was measured using the State-Trait Anxiety Inventory method. RESULTS: The parasympathetic nerve activity increased immediately after head treatment. Upon completion of head treatment, the parasympathetic nerve predominance tended to gradually ease. Head treatment boosted freshness and relieved anxiety. CONCLUSIONS: The results suggest that head treatment has a relaxing and refreshing effect and may be used to provide comfort.

Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans.

PURPOSE: The purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans. METHODS: Study 1: SFPP tape-type patch (2-60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics. Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch. RESULTS: Study 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4-72.2 %. Cmax and AUC0-∞ were dose-proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7-fold (p < 0.001) higher, respectively, than those achieved by the FP patch. CONCLUSIONS: Sustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA.

Astaxanthin and Corni Fructus protect against diabetes-induced oxidative stress, inflammation, and advanced glycation end product in livers of streptozotocin-induced diabetic rats.

This study was conducted to compare the protective effects of astaxanthin (ASX) with Corni Fructus (CF) against diabetes-induced pathologies such as oxidative stress-induced inflammation and advanced glycation end product (AGE) formation in the liver of type 1 diabetic rats. ASX (50 mg/kg body weight/day) or CF (200 mg/kg body weight/day) was orally administered every day for 18 days to streptozotocin (STZ)-induced diabetic rats, and their effects were compared with nondiabetic and diabetic control rats. The administration of CF, but not ASX, decreased both the elevated serum and hepatic glucose concentration in diabetic rats. In diabetic rats, increased levels of AGE, reactive oxygen species, and lipid peroxidation were significantly decreased by treatment with both ASX and CF in the liver of diabetic rats. STZ treatment markedly augmented the protein expressions of AGE, and both ASX and CF efficiently attenuated these increases in hepatic protein expressions. In addition, oxidative stress and proinflammatory protein expressions were upregulated in the diabetic rats. On the contrary, these upregulations of protein expressions were decreased by the administration of ASX or CF. These results suggest that the inhibitory effect of ASX on diabetes-induced hepatic dysfunction could be derived from the blocking of AGE formation and further anti-inflammation and that CF exhibited beneficial effects through the attenuation of hyperglycemia, and thus the inhibition of AGE formation and the inflammatory responses. Therefore, ASX as well as CF may help prevent ongoing diabetes-induced hepatic injury.

Efficacy of oral administration of Lentinula eododes mycelia extract for breast cancer patients undergoing postoperative hormone therapy.

Extract of Lentinula edodes mycelia (LEM) is currently utilized as an oral biological response modifier (BRM) medicine for cancer patients. However, its effectiveness for breast cancer patients with postoperative adjuvant hormone therapy has not yet been scientifically verified. In this study, we investigated the influence of LEM on the quality of life (QOL) and immune response in breast cancer patients undergoing postoperative adjuvant hormone therapy. Twenty patients were studied in total. They received only hormone therapy in the first 4 weeks followed by hormone therapy and LEM during the next 8 weeks. Laboratory tests, QOL score and peripheral blood cytokine production levels were evaluated during the study period. No changes in QOL or cytokines were noted after the first 4 weeks. In contrast, during the following combined therapy period, improvements were noted in QOL and cytokine levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant use of LEM with postoperative adjuvant hormone therapy improves the QOL and immune function of patients.

The effects of corni fructus extract and its fractions against α-glucosidase inhibitory activities in vitro and sucrose tolerance in normal rats.

Corni fructus (Cornus officinalis Sieb. et Zucc.) is a traditional medicine exerting multifaceted protective effects against diabetes and its complications. In this study, to further identify the physiological effects of corni fructus against diabetes and its complications, we investigated α-glucosidase inhibitory activities in vitro and employed the sucrose tolerance test as an indicator of the control of the postprandial blood glucose level. In vitro assays showed that corni fructus extract has a higher inhibitory activity than its major components. Then, corni fructus extract was fractionated again to screen the fractions showing a strong inhibitory activity against α-glucosidase. Of the tested fractions, five showed a rate of α-glucosidase inhibition of over 80%. Next, the four abundant fractions were evaluated their IC(50) values, as well as the inhibition mode in vitro and plasma glucose level after sucrose loading in normal Wistar rats. As a result, the IC(50) values of these fractions were between 1.1-2.1 µg/ml. Among the four fractions, three showed mixed inhibition, while one (Fr. 4-9) showed the competition-independent inhibition of α-glucosidase. In addition, Fr. 4S-1 significantly inhibited the rise in the plasma glucose levels at a dose of 20 mg/kg body weight after sucrose loading. These results indicate that Fr. 4S-1 from corni fructus has a potential to control postprandial hyperglycemia by α-glucosidase inhibition.

Increase in plasma concentrations of geranylgeranoic Acid after turmeric tablet intake by healthy volunteers.

Geranylgeranoic acid (GGA) is one of the most potent cancer-preventive acyclic retinoids. GGA has been shown to induce cell death in human hepatoma-derived HuH-7 cells. We have recently reported the natural occurrence of GGA and its related compounds in several medicinal herbs such as turmeric, basil, rosehip, cinnamon and others [Shidoji and Ogawa, J. Lipid Res., 45: 1092-1103, 2004]. In the present study, we performed oral administration of turmeric tablets to healthy volunteers in order to investigate bioavailability of natural GGA. By using liquid chromatography/mass spectrometry, authentic GGA was eluted at a retention time of around 18 min as a negative ion of m/z 303.4. With healthy volunteers, plasma GGA was detected prior to the tablet intake and its concentrations were increased at 2 h after its intake and maintained at higher level until 4 h, suggesting an efficient bioavailability of preformed GGA in the turmeric tablets through oral administration. These results indicated that GGA in the turmeric tablet was absorbed as an intact form from intestinal mucosa. The present study provides a clue to conduct a research for cancer preventive roles of GGA in a number of spices.

Antioxidative potentiality of a Kampo formulation measured by an ex vivo study.

OBJECTIVES: Antioxidants in herbs or crude herbal formulations are well known. The antioxidative effect of a Kampo formulation, Bofu-tsusho-san (BTS), was studied in healthy human subjects by means of an ex vivo study of the lag time of low-density lipoprotein (LDL) oxidation. METHODS: Eighteen (18) healthy young males (22 +/- 3 years old), who were screened out from 38 males by strict screening tests of serum lipids, were randomly assigned into 3 groups (active BTS 7.5 g/day, placebo of BTS 7.5 g/day, and vitamin E 500 mg and vitamin C 1000 mg/day). The BTS groups were assigned in a double-blind manner. These 3 groups took each test drug, and the antioxidant effects of their plasma were estimated by assessing the susceptibility of LDL to oxidation induced by 2-2'-azobis (4-methoxy-2,4-dimethyl-valeronitrile) via an ex vivo study. The antioxidative activity was evaluated by measuring the lag time of the production of conjugated dienes. Along with lag time, plasma ephedrine, plasma baicalin, serum lipid peroxide, serum free fatty acids (nonesterified fatty acids), urinary 8(OH)dG/creatinine, blood pressure, and heart rate were monitored for 24 hours. RESULTS: Although lag time of the placebo group revealed no significant changes, the active BTS group showed some tendency of prolonged plasma lag time (p = 0.08). However, urinary 8(OH)dG/creatinine and serum lipid peroxide did not show no significant changes. The physiologic changes were compatible with the pharmacokinetic results of ephedrine and its sympathomimetic effect in the active BTS group. CONCLUSIONS: Although the systemic antioxidative effects of BTS have not been ascertained, the antioxidative potentiality on LDL oxidation was suggested by the ex vivo study.

Pharmaco-physio-psychologic effect of Ayurvedic oil-dripping treatment using an essential oil from Lavendula angustifolia.

Ayurvedic oil-dripping treatment, Shirodhara, involves the use of medicated herbal sesame oils. In our previous reports, we found that Shirodhara with plain sesame oil induced anxiolysis and an altered state of consciousness (ASC) in healthy subjects. We studied the pharmaco-physio-psychologic effect of Shirodhara with medicated sesame oil including an essential oil from Lavendula angustifolia (lavender) in the present study. Sixteen (16) healthy females (38 +/- 8 years old) were assigned at random to three treatments applied by a robotic oil-dripping system: plain sesame oil (plain Shirodhara), medicated sesame oil with a 0.3 volume % of lavender essential oil (lavender Shirodhara), or the control supine position. Psychophysiologic parameters including the heart rate, skin temperature of the dorsum of hands and feet, as well as anxiety and ASC were monitored, and the rates of change of these items were calculated to assess the psychophysiologic changes brought about by Shirodhara. Lavender Shirodhara showed potent anxiolytic and ASC-inducing or promoting effects, and induced the largest increase in foot skin temperature. The correlation between anxiolysis and ASC, as well as the correlation between these psychologic effects and the elevated foot skin temperature were larger in the lavender Shirodhara than in the other two conditions. It was speculated that the psycho-physiologic effects of lavender Shirodhara would be brought about by three mechanisms: (1) the well-known relaxing action of essential oils from L. angustifolia mediated by olfactory nerves, (2) the pharmacologic action of substances absorbed through the skin or mucosa in the sesame oil or lavender essential oil, and (3) the physiologic effect of sesame oil dripped on the forehead induced by the somato-autonomic reflex through thermosensors or pressure sensors in the skin or hair follicles via the trigeminal cranial nerve. The complicated pharmaco-physio-psychologic action of Ayurvedic oil treatment may provide a useful model for future pharmaco-physio-psychotherapy.

French maritime pine bark extract significantly lowers the requirement for analgesic medication in dysmenorrhea: a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: A previous open study demonstrated that French maritime pine bark extract (Pycnogenol) may soothe menstrual pain in dysmenorrhea. We thus investigated the effects of Pycnogenol on menstrual pain in a double-blind study. STUDY DESIGN: Subjects were 116 women aged 18-48 years. The first 2 menstrual cycles served as a control period; during the subsequent 2 menstrual cycles women received either a Pycnogenol supplement (60 mg/day) or a placebo in identical capsule form. One further cycle was monitored after cessation of capsule administration. Women were assigned to either a group with low menstrual pain or a group with dysmenorrhea. The criterion for assignment to the first group was absence of analgesic medication. RESULTS: In women with low menstrual pain, no significant difference for lowering of pain scores was found. In contrast, women with dysmenorrhea had a significantly lower pain score and required statistically significantly less analgesic medication during supplementation with Pycnogenol. The number of days women required analgesic medication was likewise found to be statistically significantly lowered in the Pycnogenol group. Even after discontinuation of Pycnogenol supplementation, the required analgesic medication remained significantly decreased. CONCLUSION: The analgesic-sparing effect of Pycnogenol increases with duration of supplementation and benefits persist even after discontinuation.

Psychoneuroimmunologic effects of Ayurvedic oil-dripping treatment.

OBJECTIVE: This study assessed the psychoneuroimmunologic changes achieved by Shirodhara, an Ayurvedic treatment, characterized by dripping oil on the forehead, in a randomized, controlled protocol involving a novel approach using a robotic system. METHODS: In the first experiment for the determination of the most appropriate conditions of Shirodhara, 16 healthy females (33 +/- 9 years old) underwent a 30-minute treatment. In the second study, another 16 healthy females (39 +/- 9 years old) were assigned to either the Shirodhara treatment or control supine position for 30 minutes, with monitoring of physiologic, biochemical, immunologic, and psychometric parameters including anxiety and altered states of consciousness (ASC). RESULTS: The subjects receiving Shirodhara treatment showed lowered levels of state anxiety and higher levels of ASC than those in the control position. Plasma noradrenaline and urinary serotonin excretion decreased significantly more after Shirodhara treatment than in the control. Plasma levels of thyrotropin-releasing hormone, dopamine, and natural killer (NK) cell activity were different between control and Shirodhara treatment. The correlation between anxiolysis and the depth of ASC was significant in the Shirodhara treatment group (r = 0.52, p < 0.05, N = 16), while in the control no correlation was obtained (r = 0.13, p = 0.64, N = 16). The increase in foot skin temperature after Shirodhara showed a significant correlation with anxiolysis and the depth of Trance of ASC (r = 0.58, p < 0.01, r = 0.43, p < 0.01, respectively). NK cell activity after Shirodhara treatment showed a significant correlation with anxiolysis and the depth of Trance of ASC (r = 0.33, p < 0.05, r = 0.56, p < 0.01, respectively). CONCLUSIONS: These results indicate that Shirodhara has anxiolytic and ASC-inducing effects, and it promotes a decrease of noradrenaline and exhibits a sympatholytic effect, resulting in the activation of peripheral foot skin circulation and immunopotentiation.

Comprehensive health education combining hot spa bathing and lifestyle education in middle-aged and elderly women: one-year follow-up on randomized controlled trial of three- and six-month interventions.

BACKGROUND: This study attempted to clarify the duration of effects of 3- and 6-month comprehensive health education programs based on hot spa bathing, lifestyle education and physical exercise for women at 1-year follow-up. METHODS: We examined middle-aged and elderly women who were randomly divided into two groups and followed up them for one year. Spa programmers instructed subjects for one hour in lifestyle education and physical exercise and for one hour in a half bath (salt spring, temperature at 41.5 degrees C) once a week. The program for the 3-month group (n=19) was repeated in the 6-month group (n=14). The evaluation items were body mass index, PWC75%HRmax (by a bicycle ergometer as aerobic capacity), blood profiles (total cholesterol, HDL cholesterol, arteriosclerotic index, uric acid, and hemoglobin A1c), profile of mood states, self-rating depression scale, subjective happiness, pains in the knee and back, and active modification of lifestyle. RESULTS: There were significant interactions between groups and response over time to aerobic capacity, hemoglobin A1c, back pain, vigor, fatigue and self-rating depression (respectively, p<0.05). Duration of effects was longer for the 6-month intervention than for the 3-month intervention. CONCLUSIONS: Beneficial effects of 6-month intervention on hemoglobin A1c, aerobic capacity, pains in the back, vigor, fatigue and depression remained significant at the 1-year follow-up. Duration of effects was longer in the 6-month intervention than in the 3-month intervention.