薬理と治療

The toxicity of the test substance, a water chestnut extract, was evaluated in male and female Sprague–Dawley（Crl: CD（SD））rats by repeated oral administration for 90 days. Three groups of 10 male and 10 female rats were used per group: 600 and 1200 mg/kg/day, and a control group. During the treatment period, general and detailed observations, functional tests, body weight and food intake measurements, ophthalmologic examinations, and urinalysis were performed. At the end of the treatment period, hematological examinations, blood biochemical tests, necropsy, organ weights, and histopathological examinations were performed. 　　No deaths occurred in either male or female group during the observation period. In the general condition, stools colored with the test substance were observed sporadically in males and females receiving 600 mg/kg/day or more, and post–dose drooling was observed sporadically in males and females receiving 1200 mg/kg/day during the observation period. 　　No toxicological changes were observed during detailed condition monitoring, functional examination, body weight, food intake, ophthalmological examination, urinalysis, hematological examination, hematological biochemical examination, organ weights, necropsy, and histopathological examination. 　　The NOAEL of 1200 mg/kg/day for both males and females was determined to be the nontoxic dose（NOAEL）after repeated oral administration of water chestnut extract for 90 days under the conditions of this study.（Jpn Pharmacol Ther 2023；51：633‒42）

Objectives　Ginger extact contains 6–shogaol, which is suggested to improve bowel movements. This study aimed to examine the effects of a supplement product containing ginger extract powder E on bowel movements. Methods　A randomized, double–blind, placebo–controlled, parallel–group study was conducted in 30 participants. Participants were randomly assigned to receive either the test product containing 100 mg ginger extract powder E or placebo daily for 4 weeks. Assessment items were number of bowel movements, fecal volume, fecal form, fecal odor, refreshing sensation of bowel movements, measurement of fecal water content in stool, and evaluation of Gastrointestinal Symptom Rating Scale（GSRS）and MOS 36–Item Short–Form Health Survey（SF–36）. Results　The number of bowel movements was significantly improved in the test group compered with the placebo group at periodⅥ（22–28 days of ingestion）. Conclusions　The result suggested that ginger extract ingestion improves bowel movement. （UMIN ID: UMIN000048594）（Jpn Pharmacol Ther 2023；51：643‒53）

Methods　A randomized, placebo–controlled, double–blind, parallel–group study was conducted to investigate the usefulness of a food containing the siberian dahurian larch tree（Larix gmelinii（Rupr.）Rupr.）extract, Lavitol®, on cognitive function in healthy Japanese males and females aged 55 to 79 who were aware of memory loss or had been pointed out to be forgetful. 　　Subjects consumed two capsules of the test food（containing taxifolin 48.6 mg/capsule）or the control food daily for 12 weeks. Results　Food containing Lavitol® improved“Motor speed”of Cognitive domain score,“ Correct responses（Immediate memory）”and“Correct responses（Delayed memory）”scores in Visual Memory Test, and“Right taps average”score in Finger Tapping Test at 6 W in Cognitrax. The“Correct responses（Delayed memory）”of Visual Memory Test showed an improvement continuously until 12 W. Furthermore, the Japanese version of POMS2（Profile of Mood States 2nd Edition）showed an improvement in negative mood due to a decrease in T–point of “Total Mood Disturbance（TMD）”at 6 W. In addition, no severe or serious adverse events were observed in this study, and there are no safety issues regarding the continued intake of the test food. Conclusions　Lavitol® intake was effective in improving the ability to recall memorized figures among the cognitive functions of healthy adults who were aware of forget things or who had been pointed out to be forgetful. It may also be effective in improving“Motor speed”and negative mood.（Jpn Pharmacol Ther 2023；51：655‒74）

Objective　The study investigated the effects of supplements include composite functional ingredients（3–O–acetyl–11–keto–beta–boswellic acid, hydroxytyrosol, proteoglycan, undenatured type Ⅱ collagen）on cartilage turnover biomarkers and knee joint function in healthy adults. Methods　A randomized, double–blind, placebo–controlled, parallel–group study was conducted. Healthy subjects aged 30 to 75 years with knee pain were selected. They were randomly assigned into two groups, and ingested either test supplement or placebo for 24 weeks. Primary endpoints were evaluated by cartilage turnover biomarkers for type Ⅱ collagen degradation（C2C）and synthesis（CPⅡ）. Secondary endpoints were evaluated by Visual Analogue Scale（VAS）. Result　CPⅡ and VAS were significantly improved by the ingestion of test supplements. No adverse effects were observed in this study. Conclusion　These results suggest that the ingestion of supplements include composite functional ingredients improves cartilage turnover biomarkers（type Ⅱ collagen synthesis）and knee joint function in healthy adults.（UMIN ID: UMIN000045592）（Jpn Pharmacol Ther 2023；51：675‒84）

Objective　This study aimed to investigate the effects of consuming food containing champignon extract（CME）on halitosis（bad breath）and its related concerns in healthy Japanese adults. Methods　This study was a randomized, double–blind, placebo–controlled, parallel–comparison study involving 66 subjects who met the eligibility criteria. The subjects were assigned to the CME group（n＝33; three tablets of CME［240 mg of CME per day］for 8 weeks）or placebo group（n＝33; placebo once daily for 8 weeks）using a random number generator. The assessment items were subjective symptoms（using a Keio Self–Rating Questionnaire for patients complaining of foul breath, visual analogue scale, and the Profile of Mood States 2nd Edition）, volatile sulfur compounds in the mouth, tongue coating score, oral moisture, and salivary volume at rest. The primary outcome was the total score of the Keio Self–Rating Questionnaire after 8 weeks. Furthermore, safety evaluations for test foods were conducted. Results　The total number of subjects analyzed according to the protocol set was 63 subjects （CME group, 32; placebo group, 31）. After 8 weeks, the total score of the Keio Self–Rating Questionnaire and its changes from baseline were significantly lower in the CME group than in the placebo group. No clinically significant changes caused by the continued consumption of the test food were observed. Conclusions　The 8–week consumption of CME–containing foods was confirmed to improve halitosis（bad breath）in healthy Japanese adults. Trial registration　UMIN000046201 Foundation　Greenhouse Co., Ltd.（Jpn Pharmacol Ther 2023；51：687‒701）

Objectives　A randomized, double–blind, placebo–controlled, parallel–group study was conducted to evaluate the effect of food containing Garcinia indica extract on liver function in healthy subjects. Methods　This study enrolled 60 healthy subjects with a body mass index＜30. The subjects were randomly divided into two groups, and they consumed either food containing G. indica extract or a placebo for 12 weeks. Liver function was evaluated by measuring serum liver enzyme levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, and γ– glutamyl transpeptidase at baseline and 4, 8, and 12 weeks of ingestion. Results　The G. indica extract group showed a significant reduction in ALT and AST levels（P ＜0.05）compared to the placebo group. No adverse effects of the test food on the subjects were observed during the study period. Conclusions　Overall, the findings indicated that foods containing G. indica extract had a positive effect on liver function in healthy subjects.（UMIN–CTR ID: UMIN000047438）（Jpn Pharmacol Ther 2023；51：703‒9）

Inflammation linked to age or physical inactivity has been recognized as a major factor in muscle mass decline. This randomized, placebo–controlled, double–blind, and parallel–group comparison study sought to determine the effects of consuming salmon nasal cartilage–derived proteoglycan complex（SNC–PGs）with anti–inflammatory effects on muscle mass in healthy Japanese adults who felt a muscle strength decline. Fifty–six subjects were randomly designated to the SNC–PGs group（n＝28）or the placebo group（n＝28）and consumed each test product（SNC–PGs 40 mg/day）for 24 weeks. Body composition was measured 12 and 24 weeks after the intervention. Furthermore, the test foodʼs safety was evaluated. The efficacy analysis dataset as per the protocol set（PPS）comprised 24 subjects per group. The SNC–PGs group had significantly higher muscle mass than the placebo group at 12 and 24 weeks. Safety assessment indicated no medically significant changes because of the continued consumption of the test food. Conclusively, SNC–PGs consumption for 24 weeks enhanced the maintenance of muscle mass in healthy Japanese adults who noticed a muscle strength decline （UMIN000042714）.（Jpn Pharmacol Ther 2023；51：711‒47）

Objectives　Lactobacillus delbrueckii ssp. bulgaricus OLL1073R–1 produces the exopolysaccharides（R1–EPS）that have been reported to possess immunomodulatory properties. We previously found that yogurt fermented with L. bulgaricus OLL1073R–1 enhanced natural killer（NK）cell activity. The purpose of this study was to clarify whether R1–EPS in the yogurt enhanced NK cell activity in a dose–dependent manner. Methods　Mice were divided into three groups and orally administered yogurt containing 41.7 μg/mL R1–EPS（normal yogurt group）, containing 80.8μg/mL R1–EPS（high EPS yogurt group）or distilled water（control group）for 3 weeks. Results　NK cell activity was enhanced in the order of control group＜normal yogurt group＜ high EPS yogurt group with statistical differences. In addition, R1–EPS induced IFN–γ production from human peripheral blood mononuclear cells in the presence of concanavalin A in a concentration–dependent manner up to a certain concentration of R1–EPS. Conclusions　These results suggest that R1–EPS intake can induce IFN–γ production and enhance NK cell activity in a dose–dependent manner up to a certain amount.（Jpn Pharmacol Ther 2023；51：751‒6）

Objectives　This study was conducted to compare changes in blood glucose levels when subjects with impaired glucose tolerance ingested a liquid nutrient containing palatinose and partially hydrolyzed guar gum（PHGG）and a medical enternal nutrient. Methods　In this randomized crossover trial, nineteen patients with glucose intolerance were recruited and assigned to two groups ingesting either test food or control food. Test food is a concentrated liquid which contains palatinose（a sugar that is digested and absorbed slowly）, and PHGG（a dietary fiber）. Control food is one of the common medical enteral nutrient. The blood glucose levels of the subjects were measured every 15 minutes from 0 to 150 minutes after ingestion using a commercially available 24–hour continuous self–monitoring blood glucose meter, isCGM. We analysed the difference of the blood glucose trend and iAUC between the test nutrient and control nutrient. Results　The blood glucose levels after ingestion of the test food were significantly lower at 30, 75, and 90 minutes after ingestion compared to the control food. On the other hand, the blood glucose levels at 120 and 135 minutes were significantly higher in test food group. The iAUC in test food was also significantly lower than the control food. Conclusion　The concentrated liquid nutrient containing palatinose and PHGG（test food）can significantly suppress the increase of blood glucose level compared to the medical enteral nutrient（control food）. Trial registration　UMIN–CTR UMIN000048929（Jpn Pharmacol Ther 2023；51：757‒63）