薬理と治療

Objective　We aimed to investigate the psychological stress–reducing effects of oral intake of gamma–aminobutyric acid(GABA)in healthy adults by updating a previous systematic review (SR). Methods　We systematically performed comprehensive and structured literature searches involving six literature databases, four study registration databases, and one Foods with Function Claims database between August 4 and 17, 2023. The research question was“, Does ingestion of GABA reduce psychological stress compared with ingestion of placebo or nonintervention in healthy participants?”The study protocol was registered in the University Hospital Medical Information Network Clinical Trials Registry(No. UMIN000051927). Results　Seven trials evaluated the effect of a single ingestion of GABA on changes in outcomes due to stress induction, such as arithmetic tasks. The total sample size of included studies was 260. A qualitative SR was conducted because a meta–analysis could not be conducted owing to the differences in the methods used in each study. In almost all studies, GABA significantly affected five objective indicators(brain waves, heart rate variability, salivary cortisol, salivary chromogranin A, and salivary Immunoglobulin A). Large variations exist in the effects of GABA on subjective indicators, including the Profile of Mood States(POMS)and Visual Analog Scale(VAS), although GABA had significant effects on POMS(vigor)and VAS (fatigue).Conclusions　This SR suggests that a single oral intake of GABA reduces the psychological stress temporarily induced via arithmetic tasks in healthy adults. The psychological stress–reducing effect of oral GABA intake has a scientific basis because the certainty of evidence is high or medium.(Jpn Pharmacol Ther 2025;53:293‒314)

Objectives　Autophagy is a degradation and recycling system for intracellular components such as the cytoplasm and organelles. It has been reported that activating autophagy suppresses ageing and several diseases. In recent years, lactic acid bacteria(LAB)have been reported to induce autophagy activity, however, the effect of LAB on autophagy flux in intestinal cells is unknown. The aim of this study was to screen of LAB for autophagy–inducing activity in human intestinal cells. Methods　To screen of LAB for autophagy flux–inducing activity, we used intestinal epithelial model cells(Caco–2)expressing a green fluorescent protein(GFP)–microtubule–associated protein light chain 3(LC3)–red fluorescent protein(RFP)probe to measure of autophagy flux. Caco–2 GFP–LC3–RFP cells were treated with each LAB(20, 200, 2000μg/mL)for 24 hours. After that, cellular fluorescence was analyzed by Spectral Cell Analyzer, and the GFP/RFP ratio was calculated. Results　Some LAB decreased the GFP/RFP ratio in a concentration–dependent manner, indicating that they induced autophagy activity. Specifically, Lactiplantibacillus paraplantarum showed potent autophagy inducing activity. Conclusions　This study showed that LAB such as Lactiplantibacillus paraplantarum upregulated autophagy activity in intestinal epithelial–like cells. Our findings will help to develop functional foods that target autophagy.(Jpn Pharmacol Ther 2025;53:315‒20)

Objectives　A randomized, double–blind, placebo–controlled crossover study was conducted to evaluate the impacts of food containing Terminalia bellirica extract on bowel movement and alpha diversity of the gut microbiota in healthy adults with constipation tendency. Methods　Forty–six participants were enrolled and randomly divided into two sequence groups. The subjects consumed either T. bellirica extract containing 20.8 mg of gallic acid or a placebo with a loading diet. The frequency of defecation as the primary outcome and secondary outcomes including fecal characteristics and gut microbiota were evaluated. Results　The consumption of food containing T. bellirica extract significantly increased the number of times, days, and amount of defecation after 4 weeks of ingestion(P<0.05)compared with the placebo. No significant differences were observed in the other fecal characteristics. In addition, the consumption of food containing T. bellirica extract significantly increased the alpha diversity of the gut microbiota in feces after 4 weeks of ingestion(P<0.05)compared to the placebo. 　　No adverse events attributable to the test food were observed during the study period. Conclusions　Overall, these findings indicate that foods containing T. bellirica extract increase the frequency of defecation and the alpha diversity of the gut microbiota in healthy adults with constipation tendency.(UMIN–CTR ID: UMIN000053709)(Jpn Pharmacol Ther 2025;53:321‒9)

Objectives　A randomized, double–blind, placebo–controlled, parallel–group study was conducted to evaluate the impact of food containing the Terminalia bellirica extract on obesity in healthy participants. Methods　One hundred healthy participants(23≤body mass index[BMI]<30)were enrolled in this study and randomly divided into two groups: Test food group, which consumed food containing the T. bellirica extract(41.6 mg/day of gallic acid)for 12 weeks, and the placebo group, which consumed food without the T. bellirica extract for the same duration. Their primary outcomes, visceral fat area, body weight, and BMI, and the secondary outcome, waist circumferences, were evaluated. Results　Following the 12–week intervention, test food group showed significant differences in the visceral fat area, body weight, and BMI(P<0.05)compared to the placebo group. No adverse events attributable to the test food were observed during the study period. Conclusions　Overall, these findings indicate that food containing the T. bellirica extract exert anti–obesity effects in healthy participants(23≤BMI<30).(UMIN–CTR ID: UMIN000053804)(Jpn Pharmacol Ther 2025;53:331‒8)

有効率に関する推測(検定および推定)を例に挙げて,ベイズ流と頻度流の違いを見ていきます.あまりなじみのないベイズ流について,くわしく述べたいと思います.

CONSORT(Consolidated Standards of Reporting Trials: 臨床試験報告に関する統合基準)声明はランダム化比較試験(randomized controlled trial: RCT)の報告を改善するために,世界中で広く用いられている.Kenneth Schulzらは,新たな方法論的エビデンスと蓄積された経験に基づいて改訂した最新版CONSORT 2010を発表した.