薬理と治療

Background Accumulating evidence suggested that n︱3 polyunsaturated fatty acids（PUFAs） were associated with reduction of cardiovascular events. However, it remains unclear whether n-3 PUFAs have protective role in abdominal aortic aneurysm（AAA）formation. Methods 6-week-old apolipoprotein E-deficient mice were fed a high n-3 PUFA diet（EPA, EPA＋DHA, and DHA）or normal diet with high cholesterol. AngiotensinⅡ（n＝62）or normal saline（n＝6）were continuously infused from 12 weeks old by implanting osmotic mini-pumps and AAA formation was evaluated at 16 weeks. Results Seventy-five percent of angiotensinⅡ -infused mice with EPA treatment developed AAA formation, 100％ with EPA＋DHA treatment and 88.9％ with DHA treatment. The severity of AAA was slightly reduced in EPA treatment group. The mortality rates of each treatment group （EPA, EPA＋DHA, and DHA）were 12.5％, 25.0％ and 28.6％, respectively. Flow cytometric analyses revealed that EPA treatment increased Foxp3 positive regulatory T cells and effector T cells. The proportions of mature dendritic cells were not significantly different among those three treatment groups. Conclusion This study suggests that dietary supplementation with EPA might potentially have a protective role in AAA formation and reduce the mortality of AAA. More precise mechanisms are elucidated and promotion of n-3 PUFAs intake may represent a novel therapeutic approach to AAA.

Background In recent years, there is greater use of the transdermal delivery system. Oxybutynin　has some interesting properties to treat overactive bladder. However, these medicines have　reportedly caused dermopathy. Methods Oxybutynin chloride tapes were applied to 7︱week︱old male hairless mice. The patches were removed after 24 hours, and the skin was observed after one hour. Dry skin mice are produced by organic agents. Various external medicines are particularly indicated in the management of dry skin applied tapes. The dermopathy was assayed mainly by transepidermal water loss and skin hydration. Results With oxybutynin chloride, greater skin damage was seen with tapes. These are especially for dry skin treatment. However, treatment of heparinoid relieved significant symptoms. Conclusions Experimental investigation has confirmed dermopathy. Even oxybutynin chloride tapes have a stronger effect on the skin than non-patch applications. This suggests that close attention to inflammation is needed in patients with the dry skin characteristics of elderly people. Furthermore clinical research, on the pre-application of moisturizing agents, is needed to identify appropriate tapes for transdermal delivery systems.

We investigated the effect of oral administration of chlorella prepared from Chlorella pyrenoidosa（Chlorophyceae）at doses of 600 or 1200 mg╱kg on hepatic injuries experimentally induced by D-galactosamine in male rats, an animal model of viral hepatitis. Oral administration of chlorella showed significant improvement on the serum-biochemical and histopathological suppressions in D-galactosamine-induced hepatic injury. In the D-galactosamine-treated rats, chlorella significantly prevented the increases in serum aspartate aminotransferase （GOT）, alanine aminotransferase（GPT）and alkaline phosphatase（ALP）activities in a dose-dependent manner, and also apparently improved hepatic cell necrosis. In addition, the chlorella showed the antagonizing effect on the increase of lipid peroxide and the decrease of triglyceride contents in serum. These findings suggest that oral administration of chlorella may have an ameliorating effect on hepatic dysfunction.

Objectives The objective of this study was to investigate the acute effect of Kaempferia parviflora extract on oxygen consumption and respiratory quotient（RQ）during rest and moderate exercise. A randomized double-blind placebo-controlled cross over study was conducted in the case of the single oral intake of Kaempferia parviflora extract in healthy volunteers. Methods We prepared the hard capsules containing a mixed powder of Kaempferia parviflora extract, dextrin and cyclodextrin for this clinical study. A randomized double-blind placebo-controlled cross over trial was conducted on 12 healthy volunteers（age 20 to 29 years old）. The subject ingested placebo or 50 mg Kaempferia parviflora extract（1 cupsule）30 minutes before moderate exercise（70％ stress of anaerobic threshold, 30 minutes）. Results After excluding deviants, the number of subjects analyzed was five. The single oral intake of Kaempferia parviflora extract increased oxygen consumption and significantly decreased RQ during moderate exercise, as compared with placebo. In addition, any clinical adverse events were not found through the study period. Conclusions These results suggest that the single oral intake of Kaempferia parviflora extract increased energy consumption and fat utilization rate without adverse reaction, and might support for prevention and improvement of obesity and metabolic syndrome.

Objective We examined effects of a food containing Shogaol“, Ginger Extract Powder S”, on a cold constitution in volunteers with a subjective symptom of poor circulation. Methods A 4-weeks study with 12 female subjects, whose age was 20-35 years old, was conducted as an open-label trial. At first cold-water exposure test was conducted during the non-ingestion period: core temperature was measured at before exposure, just after exposure, 5, 10, 15, 30 and 60 min after exposure（the non-ingestion period）. After one day washout, subjects ingested test food, participated cold︱water exposure test measured core temperature after single ingestion of the test food as with the case in the non-ingestion period（the single ingestion period）. The third cold-water exposure and measurement for core temperature were conducted after 4-weeks ingestion of the test food（the 4-weeks ingestion period）. Changes of core temperature, and a bodily sensation measured by the Visual Analogue Scale（VAS）were compared in each period. Results A result of analysis of core temperature, there was no significant change in the single ingestion period and the 4-weeks ingestion period compared with that in the non-ingestion period. On a variation of core temperature after cold-water exposure, the 4-weeks ingestion period showed significant inhabitation of decreasing body temperature compared with that in the non-ingestion period at 15, 30, and 60 min after cold-water exposure. On a result of VAS, the 4-weeks ingestion period showed significant improvement with items（“coldness of body”, “leg swelling”“, face swelling”“, bad makeup application”“, poor digestion”, and“ languidness”） compared with those in the non-ingestion period. Conclusion These results imply that a food containing Shogaol would be useful for improving a cold constitution.

The efficacy of long pepper extract as a hypotensive agent in humans was analyzed. The study, designed as a randomized open-label parallel-group study, was conducted in individuals with blood pressure in the high normal range and patients with first-degree hypertension. The subjects ［50 subjects in total（male╱female＝38╱12, age＝29-64 years old）］took either test capsule（capsule containing 150 mg of long pepper extract）or control capsule（placebo; free of long pepper extract）or FOSHU［commercially available food for specified health uses for high blood pressure（efficacy of ACE inhibition）］once daily for 8 weeks. We observed systolic and diastolic blood pressures, pulse rate, side effect, adverse event, laboratory test data, body weight, and abdominal circumference. The test capsule group showed a significant reduction of the systolic and diastolic pressures compared to the placebo group at each time-point of evaluation from Week 1 onward（systolic pressure）and Week 4 onward（diastolic pressures）. Furthermore, the test capsule group showed a significant reduction of the systolic and diastolic pressures compared to the FOSHU group at each time-point of evaluation from Week 2 onward （systolic pressure）and Week 4 onward（diastolic pressure）. 1 side effect which was constipation was seen in 1 subject from FOSHU group. These results confirmed that capsule containing 150 mg long pepper extract exerts a sufficient reduction of both the systolic and diastolic blood pressures.

Objectives The objective of this study was to examine the effect of the beverage containing heat-killed Lactococcus lactis subsp. lactis JCM5805（Lc. lactis JCM5805）on anti-viral immune responses and maintenance of physical conditions. Methods A randomized, double-blind, placebo-controlled, parallel-group trial was conducted. One hundred subjects were divided into 2 groups and took 1 bottle （500 mL）daily of the beverage that did╱did not contain approximately 100 billion heat killed Lc. lactis JCM5805 for 8 weeks. To evaluate anti-viral immune responses, we measured CD86 and HLA-DR expression levels on plasmacytoid dendritic cells（pDC）, which are responsible for regulation of anti-viral immune responses in peripheral blood mononuclear cells（PBMC）and gene expression levels of anti-viral factors in PBMC stimulated by inactivated human influenza A virus（H1N1）. Also, cumulative incidence days of cold︱like symptoms were analyzed to evaluate effects on maintenance of physical conditions. Results After 8 weeks intake period, CD86 and HLA-DR expression levels on pDC in the Lc. lactis JCM5805 group were significantly higher compared to the placebo group. Additionally, gene expression level of ISG15, an anti-viral factor known to be induced by typeⅠ interferon, was significantly higher compared to the placebo group after the intake period. Furthermore, cumulative incidence days of cold-like symptoms during the intake period were significantly lower in the Lc. lactis JCM5805 group compared to the placebo group. Conclusions The beverage containing approximately 100 billion heat-killed Lc. lactis JCM5805 is suggested to be beneficial in enhancing anti-viral immune responses and maintaining physical conditions.

Background Our previous clinical study suggested that the intake of sesame seed oil（Kadoya Pure Sesame Oil, which contains sesamin and sesamolin as active ingredients）resulted in lowering serum low density lipoprotein（LDL）-cholesterol levels in subjects with slightly higher serum cholesterol. Objective The aim of this study was to confirm hypocholesterolemic effect of Kadoya Pure Sesame Oil in larger population. Methods/Study design We conducted a randomized, double-blind, parallel-group, placebo-controlled study with volunteers with slightly higher level of serum cholesterol. Subjects（100 persons aged from 28 to 64）were randomly allocated to 2 groups, placebo（group P）and active food（14 g of Kadoya Pure Sesame Oil daily）（group A）. The period of intake was 12 weeks. Five subjects in group P dropped out, and 95 subjects completed the study. After excluding 11 subjects who fell under the exclusion criteria for evaluation of efficacy, data obtained with 84 subjects were analyzed for efficacy. Results There were significant decreases in serum LDL-cholesterol levels（estimated using the Friedewald formula）in subjects in group A at the 8th and 12th weeks（－3.6±15.0 and －6.4± 14.2 mg╱dL, respectively）compared to the levels in group P（3.6 ±16.1 and 0.6±15.8, respectively）. No serious adverse event was observed during this study. Discussion/Conclusion Our investigation confirms the concept that intake of Kadoya Pure Sesame Oil lowers serum LDL-cholesterol level in populations with slightly higher serum cholesterol level.

Objectives It studied wether cecal fermentation products affect the secretion of glucagon like peptide-1（GLP-1）, peptide tyrosine tyrosine（PYY）and the activity of dipeptidyl peptidase-4 （DPP-4）. Methods Sham-operated rats and cecectomized rats were fed an AIN-93 G diet with or without 5％ partially hydrolyzed guar gum（PHGG）. Male Wistar rats（10 wk old）were fed an experimental diet for 19 days, and blood samples were collected from the portal vein and abdominal artery. Results In rats fed the diet containing PHGG, GLP-1 concentrations in the portal vein blood and arterial blood and DPP-4 activities in the arterial blood were lower in cecectomized rats than in sham-operated rats. PYY concentrations in the portal vein blood and arterial blood were little affected by PHGG ingestion and cecectomy. Glucose and insulin concentrations in the arterial blood were not affected by PHGG ingestion and cecectomy. In sham-operated rats fed the diet containing PHGG, the cecum tissue and cecum content weights increased compared with sham-operated rats fed a fiber-free diet. Short-chain fatty acids （SCFA）were shown that clearly increased by PHGG ingestion in sham-operated rats. It was clearly cecal fermentation products affected the secretion of GLP-1 and the activity of DPP-4 in rats fed a diet containing PHGG. Conclusions The present results show that the effect of SCFA on the metabolism of GLP-1 and DPP-4 was greater than that on PYY secretion.