薬理と治療

Background Rosmarinic acid is one type of plant－derived natural polyphenol that is abundantly present in perilla, rosemary, lemon balm, etc., and that has an antioxidant effect, an anti－inflammatory effect, an antibacterial effect, an anti－allergic effect, and an antidepressant effect. In this research, using a rat social isolation stress model, the anti－stress effect of rosmarinic acid was verified from the perspective of the nervous system, the endocrine system and the immune system. Methods Twenty－four male Wistar rats were randomly divided into a non－stress group （Control）, a non－stress, RA administration group（Control＋RA）, a stress group（Stress）, and a stress, RA administration group（Stress＋RA）. For stress loading, each rat was kept in its own cage for a week, while for the Control and Control＋RA groups, rats were kept three to a cage. Intraperitoneal administration of RA was performed daily（3.0 mg／kg）. One week later, aggression was evaluated（stick biting duration）. Blood plasma corticosterone concentration（EIA method）and spleen Natural killer（NK）cell activity（4－hour 51Cr release method）were studied. Results Compared to the Control group, the Stress group showed a significant increase in aggression, and blood plasma corticosterone concentration also increased, but in the Stress+RA group, these were significantly inhibited. In the Stress group spleen NK cell activity decreased, but in the Stress＋RA group this was significantly inhibited. Conclusions The administration of RA controlled the activations of the sympathetic nervous system and the endocrine system caused by stress. The authors concluded that RA had an anti－stress effect.

We examined safety and efficacy of treatment with Caduet 1 Ban（2.5 mg／5 mg, dose of amlodipine／dose of atorvastatin）, 2 Ban（2.5 mg／10 mg）, 3 Ban（5 mg／5 mg）or 4 Ban（5mg／10 mg）combination tablets for 52 weeks in Japanese patients with hypertension and hypercholesterolemia or angina pectoris and hypercholesterolemia. There were no deaths throughout the study period. All serious adverse events which occurred in the study were not related to Caduet. Most adverse events were mild or moderate with only 1 severe event（ischemic colitis）. All treatment－related adverse events were mild and the only event which occurred in more than 2 patients was abdominal pain. In efficacy, Caduet favorably controlled systolic blood pressure（SBP）, as well as diastolic blood pressure（DBP）with lower levels than the baseline throughout the treatment period. The lowdensity lipoprotein cholesterol（LDL－C）level showed approximately 10％ reduction at Week 4 from baseline and maintained its level throughout the period. The LDL－C level in patients who were treated with the same dose of atorvastatin at the observational period（n＝116）maintained the same level at baseline throughout the study period. The LDL－C level in patients without any treatment on hypercholesterolemia （n＝40） greatly reduced. As to changes of the other lipid parameters except LDL－C, the percent changes from baseline of both total cholesterol and apolipoprotein B and both LDL－C and high density lipoprotein cholesterol（HDL－C）and TC, and the change from baseline of HDL－C gradually reduced until Week 4 and then maintained this reduced level. HDL－C level slightly increased throughout the study period except at Week 24. However, the triglyceride level did not show any change until Week 52. From the above results, it is considered the long－term safety of Caduet in Japanese patients is well－tolerated. The controls of BP and LDL－C treated with Caduet are favorable, in particular Caduet showed good improvement of LDL－C levels in patients without any treatment to hypercholesterolemia at baseline. This suggests that Caduet allows patients with hypercholesterolemia further intervention to their serum lipid.

The intake of soy peptide preparations composed mainly of di－ and tri－peptides（Hinute, Fuji Oil Co.）is reported to modulate the levels of certain neuroactive amino acids in the adult mouse brain. The present study examined the effects of soy peptide supplementation on higher brain function. The subjects were 30 patients with mild cognitive impairment（soy peptide group：mean age：58.1±1.7 years, n＝15, placebo group：58.9±1.8 years, n＝15）.Cognitive function was evaluated by the Japanese version of repeatable battery for the assessment of neuropsychological states（RBANS）at two time points：at baseline and after 8－week dietary supplementation of 8 g／day soy peptides or placebo. Soy peptide supplementation significantly improved the delayed memory score and tended to improve immediate memory （score of story memory）, compared with placebo. In addition, soy peptide intake significantly increased serum dopamine, which is associated with memory function, compared with the placebo. The results suggest that soy peptide supplementation can improve aging－related cognitive dysfunction.