The leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) are found in some traditional oriental herbal medicines that are primarily used to treat affective disorders such as depression and anxiety. The aim of the present study was to identify the bioactive component in Perillae Herba that possesses antidepressive activity. The effects of a water extract of Perillae Herba and six fractions therefrom were evaluated in mice by use of the forced-swimming test. An oral administration of a water extract of Perillae Herba significantly reduced the duration of immobility. Moreover, 50% methanol extract of the water extract of Perillae Herba and its 30% methanol extract also reduced the duration of immobility. Three-dimensional high-performance liquid chromatography and FAB-MS and NMR spectral analysis clearly showed that the extracts with anti-immobility effects contained abundant rosmarinic acid. The oral and intraperitoneal administration of rosmarinic acid significantly reduced the duration of immobility. In contrast, a water extract from another species of Perillae Herba, which contains only low levels of rosmarinic acid, had no anti-immobility effect. These results suggest that rosmarinic acid may be the main component involved in the antidepressive effect of Perillae Herba in the forced-swimming test. Thus it may be a novel antidepressive substance.
{"title":"Identification of rosmarinic acid as a novel antidepressive substance in the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba).","authors":"Hiroshi Takeda, Minoru Tsuji, Teruhiko Matsumiya, Masayoshi Kubo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) are found in some traditional oriental herbal medicines that are primarily used to treat affective disorders such as depression and anxiety. The aim of the present study was to identify the bioactive component in Perillae Herba that possesses antidepressive activity. The effects of a water extract of Perillae Herba and six fractions therefrom were evaluated in mice by use of the forced-swimming test. An oral administration of a water extract of Perillae Herba significantly reduced the duration of immobility. Moreover, 50% methanol extract of the water extract of Perillae Herba and its 30% methanol extract also reduced the duration of immobility. Three-dimensional high-performance liquid chromatography and FAB-MS and NMR spectral analysis clearly showed that the extracts with anti-immobility effects contained abundant rosmarinic acid. The oral and intraperitoneal administration of rosmarinic acid significantly reduced the duration of immobility. In contrast, a water extract from another species of Perillae Herba, which contains only low levels of rosmarinic acid, had no anti-immobility effect. These results suggest that rosmarinic acid may be the main component involved in the antidepressive effect of Perillae Herba in the forced-swimming test. Thus it may be a novel antidepressive substance.</p>","PeriodicalId":502118,"journal":{"name":"Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology","volume":"22 1","pages":"15-22"},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
hBmal1 cDNA has been cloned from a human brain cDNA library and revealed that the cDNA encoded a novel bHLH-PAS transcription factor. The rBmal1 mRNA expression was found not only at high levels in the suprachiasmatic nuclei (SCN), but also in the pyriform cortex, hippocampus, and cerebellum. Furthermore, this expression was found in the eyes, pineal body, and peripheral organs, such as the muscle, liver, and heart. Bmal1 mRNA levels reveal a circadian rhythm in the rat SCN, with the highest expression levels at ZT18. The yeast two-hybrid screening have demonstrated that CLOCK forms a heterodimer with BMAL1. CLOCK. BMAL1 heterodimer functions as a positive transcription factor through binding to the E-box in the promoter region of the mPer1. Nuclear translocation is promoted by dimerization among PERs, or between PERs and CRYs, and the complexes inhibit the transcription of their own genes. This feedback loop is used in the clock output system driving the transcription of arginine vasopressin peptide and serotonin N-acetyl-transferase by binding the CLOCK-BMAL1 dimer to an E-box in their promoters.
{"title":"[BMAL1 and circadian rhythm].","authors":"M Ikeda","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>hBmal1 cDNA has been cloned from a human brain cDNA library and revealed that the cDNA encoded a novel bHLH-PAS transcription factor. The rBmal1 mRNA expression was found not only at high levels in the suprachiasmatic nuclei (SCN), but also in the pyriform cortex, hippocampus, and cerebellum. Furthermore, this expression was found in the eyes, pineal body, and peripheral organs, such as the muscle, liver, and heart. Bmal1 mRNA levels reveal a circadian rhythm in the rat SCN, with the highest expression levels at ZT18. The yeast two-hybrid screening have demonstrated that CLOCK forms a heterodimer with BMAL1. CLOCK. BMAL1 heterodimer functions as a positive transcription factor through binding to the E-box in the promoter region of the mPer1. Nuclear translocation is promoted by dimerization among PERs, or between PERs and CRYs, and the complexes inhibit the transcription of their own genes. This feedback loop is used in the clock output system driving the transcription of arginine vasopressin peptide and serotonin N-acetyl-transferase by binding the CLOCK-BMAL1 dimer to an E-box in their promoters.</p>","PeriodicalId":502118,"journal":{"name":"Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology","volume":"20 5","pages":"203-12"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent progress in molecular chronobiology revealed that the clock genes control intracellular feedback loops. CLOCK protein and BMAL1 protein, first discovered as components of the circadian clock in mammals, are known to function as transcriptional activators in the circadian feedback loop of drosophila. PERIOD and TIMELESS proteins work as inhibitors for these activators in drosophila and possibly in mammals. The clock genes described above are also expressed in peripheral tissues with circadian rhythmicity. Cultured rat-1 fibroblast shows circadian expression of clock genes after serum shock or forskolin stimulation. These results indicate that the clock genes function not only as components of the endogenous clock, but also as a coordinator of the circadian activity of peripheral tissues. It will be important to study stress from the aspect of circadian rhythm.
{"title":"[Molecular mechanism of biological clock: for chronobiological approach to stress].","authors":"T Ebisawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recent progress in molecular chronobiology revealed that the clock genes control intracellular feedback loops. CLOCK protein and BMAL1 protein, first discovered as components of the circadian clock in mammals, are known to function as transcriptional activators in the circadian feedback loop of drosophila. PERIOD and TIMELESS proteins work as inhibitors for these activators in drosophila and possibly in mammals. The clock genes described above are also expressed in peripheral tissues with circadian rhythmicity. Cultured rat-1 fibroblast shows circadian expression of clock genes after serum shock or forskolin stimulation. These results indicate that the clock genes function not only as components of the endogenous clock, but also as a coordinator of the circadian activity of peripheral tissues. It will be important to study stress from the aspect of circadian rhythm.</p>","PeriodicalId":502118,"journal":{"name":"Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology","volume":"20 3","pages":"107-11"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}