薬理と治療

Background Several clinical trials have investigated the impact of coffee-derived mannooligosaccharides on the intestinal condition in various kinds of food products, but no systematic review was conducted. Objective The objective was to perform a systematic review with meta-analysis of randomized, placebo controlled trials of coffee-derived mannooligosaccharides to better understand its impact on intestinal condition in the healthy adults or adults with a tendency of constipation. Design A systematic literature search of scientific databases and register databases for clinical trials╱systematic review was conducted. The main outcome measures were defecation days╱week, defecation frequency╱week, fecal Bifidobacterium counts and the occupancy rate of Bifidobacterium in the total fecal microbiota. A random-effects model was used to calculate the standardized mean difference and 95％ CI as the difference between the mean for the treatment and placebo groups. Standard methods for assessing statistical heterogeneity and bias risk were used. The protocol for this study was registered to UMIN-CTR（No. 000025016）. Results Six studies met the inclusion criteria. The use of coffee-derived mannooligosaccharides improved the defecation days╱week［standardized mean difference（SMD）：0.62；95％ CI：0.37, 0.88］, defecation frequency╱week［SMD：0.65；95％ CI：0.40, 0.91］and increased the fecal Bifidobacterium counts［SMD：1.26；95％ CI：0.73, 1.79］and occupancy［. SMD：2.05；95％ CI：1.50, 2.60］ No heterogeneity was observed in the meta-analysis. Bias risk for body of evidence was rated as medium. Conclusion Coffee-derived mannooligosaccharides appears to beneficially affect intestinal condition in the healthy adults and adults with a tendency of constipation.

背景Piperine 90μg を含有するヒハツ抽出物を配合した食品は，正常高値血圧者およびⅠ度高血圧者を対象とした12 週間継続摂取試験において，摂取1週間後という早期から十分な血圧低下作用を示すことが報告されている。Piperine が血管を弛緩させることにより血圧低下作用を示すことが示唆されているが，その作用機序の詳細については不明な点が残されている。目的Piperine の血圧低下作用における詳細な作用機序を明らかにする。方法正常ラットを用いたangiotensinⅠ（ATⅠ）惹起昇圧反応（in vivo 試験）に対するpiperine の作用を評価した。次に，ラット摘出胸部大動脈標本を用いたphenylephrine（PE）惹起血管収縮（in vitro 試験）に対するpiperine の作用を評価し，血管内皮細胞および一酸化窒素合成酵素（NOS）の関与を検討した。最後に，正常ヒト大動脈内皮細胞を用いて，piperine の細胞内一酸化窒素（NO）量に対する作用を評価した。結果Piperine 11.25 mg╱kg の十二指腸内投与は，ATⅠによる昇圧反応を有意に抑制した。また，piperine10，30 および100μmol╱L はPE 惹起血管収縮を濃度依存的かつ有意に抑制し，piperine による血管弛緩作用は，血管内皮細胞除去またはNOS 阻害剤であるL︱NAME 前処理により有意に減弱した。さらにpiperine 30 および100μmol╱L は，細胞内NO量を有意に増加させた。結論Piperine は血管内皮細胞のNO 産生を促進することにより血管を弛緩させ，血圧低下作用を示すことが明らかとなった。

Background Kyushin capsule F is an over the counter drug for amelioration of a palpitation, short of bless and as a restorative. These symptoms are included typical symptoms of menopause. Objectives The aim of this study was to investigate an efficacy and safety of the Kyushin capsule F on aged women experiencing mild to moderate menopausal syndrome. Methods An open trial study was conducted with female volunteers have typical symptom of menopause and some indefinite complains related cardiovascular medicine. Subjects（20 subjects: aged 40 to 62）were orally received 3 capsules Kyushin capsule F daily for 4 weeks, and recorded a score of complaints, in addition, the simplified menopausal index, the POMS test, an autonomic nervous function test, and laboratory examination were conducted. Results Kyushin capsule F showed the significant ameliorating effect in the score of indefinite complaints, simplified menopausal index, and POMS test. No adverse effect was observed during this study. Conclusion These findings suggest that Kyushin capsule F is safe, has a potential for effectiveness on the indefinite complaints related insufficient blood circulation, autonomic nerve dysregulation and mood malaise in aged women have mild to moderate menopausal syndrome. Further investigation with more subjects and placebo or reference controlled studies should be needed.

目的 本研究では，果実や野菜を百数十種類混合して発酵させた植物発酵ペーストAO の抗酸化能を検証するとともに，細胞における酸化ストレスおよび細胞機能に対する効果を調査した。方法 植物発酵ペーストAO の抗酸化能については，各種活性酸素およびラジカルに対する作用を調査した。表皮細胞培養時に植物発酵ペーストAO を加え，過酸化水素（0.25 mM）を添加または紫外線（83.2 mJ╱cm2）を照射し，酸化ストレス耐性を検証した。褐色脂肪細胞または骨格筋細胞，表皮細胞の培養時に植物発酵ペーストAO を添加した後，褐色脂肪細胞または骨格筋細胞におけるミトコンドリア活性および蓄積量の測定，ならびにReal-time PCRを用いて表皮細胞における線維芽細胞成長因子（FGF）および表皮成長因子（EGF）の遺伝子発現量を測定した。結果 植物発酵ペーストAO はスーパーオキシドラジカル消去能，ヒドロキシラジカル消去能，過酸化水素消去能を示した。また，表皮細胞において植物発酵ペーストAO は過酸化水素および紫外線による酸化ストレスから細胞を保護する作用を示した。さらに，植物発酵ペーストAO は褐色脂肪細胞においてはミトコンドリアの活性および量の上昇，骨格筋細胞においてはミトコンドリア量の上昇が認められ，表皮細胞におけるFGF およびEGF の遺伝子発現量を上昇させた。結論 以上の結果から植物発酵ペーストAO の抗酸化能が確認された。また，この抗酸化能によって，酸化ストレスからの細胞保護およびミトコンドリアの賦活性が示された。ミトコンドリアの賦活化により細胞機能が向上することで，皮膚におけるFGF およびEGFの産生を促進し，肌の機能を向上させる可能性があった。

目的　本研究は，健常者を対象に抗酸化能の高い果実や野菜を複数混合して発酵させた植物発酵ペーストAO（試験食品）がヒトの抗酸化能および肌の状態に与える影響を検証した。対象と方法　試験責任医師の判断により，日ごろ疲れやすいと自覚している成人日本人女性27 名を選抜した。試験参加者は試験食品を1 日1 包，8 週間摂取した。摂取前および摂取8 週間後にDNA 酸化損傷マーカーの尿中8︱OHdG と脂質酸化損傷マーカーの尿中PRL，尿中HEL，抗酸化能マーカーの血中PAO を測定した。また，肌の状態，肌や疲労に関する自覚症状，安全性についても評価した。結果　全試験参加者27 名（51.1±9.8 歳）が試験を完遂した。摂取前と比較して，摂取後に尿中8︱OHdG の低下（P＜0.001）および血中PAO の上昇（P＝0.033）が認められた。また，目尻のシワの項目が有意に減少し（P＜0.05），多くの自覚症状が改善した（P＜0.05）。安全性の評価では，試験食品摂取に伴う医学的に問題のある変化は認められなかった。結論　植物発酵ペーストAO の8 週間摂取は，日ごろ疲れやすいと自覚する健常な成人日本人女性の抗酸化能を向上し，肌や疲労に関する自覚症状やシワを改善した。また，本研究の条件下では安全な食品であった。

Objectives The aim of this study was to evaluate the effect of food containing collagen hydrolysates, sphingomyelin, amino acids and glucosamine on skin conditions in healthy female subjects. Methods A randomized double-blind, placebo-control parallel-group study was conducted with 114 healthy female subjects ranging in age from 30 to 49 years old. Subjects ingested the active food including collagen hydrolysates, sphingomyelin, amino acids and glucosamine or the placebo food once a day for 8 weeks. Stratum corneum moisture content, transepidermal water loss（TEWL）, skin assessment by a dermatologist and subjective questionnaire were evaluated at 4 and 8 weeks-ingestion. The incidence of side effects was compared between two groups. Results Stratum corneum water content in the active food group was significantly improved after 4 and 8 weeks-ingestion compared with before-ingestion, however there was no significant difference in the placebo food group. The change of stratum corneum water content of 4 weeks-ingestion was trend to higher active food group compared to placebo food group. Between two groups, there was no significant difference in TEWL and skin assessment by dermatologist in 4 or 8 weeks-ingestion. In an additional analysis excluding subjects suspected of seasonal allergic rhinitis, the change of stratum corneum water content in 4 weeks-ingestion of active food group was significantly increased compared with placebo food group. No adverse effects were observed in both groups. Conclusion These results suggest that ingestion of the food containing collagen hydrolysates, sphingomyelin, amino acids and glucosamine for 4 weeks or more improve moisture content of stratum corneum in healthy female subjects.

Objectives To evaluate the effect of isomaltodextrin（IMD）on the postprandial blood glucose level elevation in healthy subjects. Methods A randomized, placebo -controlled, double-blind crossover study was conducted. Fifty subjects ingested a solution containing 50 g glucose with（test diet）or without（control diet）2.5 g IMD. Blood glucose concentrations were measured before and 30, 45, 60, 90, and 120 minutes after ingestion. Forty-five subjects were included in the analysis because five subjects were withdrawn from the study. Results Analysis of all subjects revealed no significant difference between the control and test diets. However, analysis of the subjects with a tendency for increased postprandial blood glucose levels revealed a significant attenuating effect confirmed by measurements of blood glucose and Δblood glucose levels 45 minutes after ingestion. Furthermore, the maximum blood glucose level（Cmax）and ΔCmax following ingestion of the test diet were significantly lower than those following ingestion of the control diet. Conclusions These results suggest that IMD attenuates postprandial blood glucose levels.