Biological and epidemiological evidence of anti-allergic effects of traditional Japanese food ume (Prunus mume).

Japanese apricot (Prunus mume; ume) is a traditional food in Japan that has been shown to have various beneficial health effects. There is some evidence to suggest that ume is also effective against allergic disease. Here, we conducted a cross-sectional epidemiological pilot study to examine the association between ume intake frequency and allergic symptoms including rhinitis in 563 adults (288 men and 275 women) who resided in Wakayama, Japan. After adjusting for age, present illness and medication, women with high ume intake had significantly lower odds ratio (OR) for the presence of symptoms of allergy [OR: 0.49 with 95% confidence interval (CI): 0.25-0.97]. Therefore, we investigated the anti-allergic effect of ume on passive cutaneous anaphylaxis (PCA) reaction in immunoglobulin E (IgE)-sensitized mice. The animal study demonstrated that oral administration of ume extract attenuated the PCA reaction and mast cell degranulation. Furthermore, RBL-2H3 mast cells were used to identify anti-allergic ume compounds. The following ume compounds inhibited IgE-mediated mast cell degranulation: vanillin, syringic acid, protocatechuic aldehyde, lyoniresinol and p-coumaric acid. These results suggested that ume has the potential to inhibit mast cell degranulation and may be associated with reduced risk of allergic symptoms in women.

Peach (Prunus persica) extract inhibits angiotensin II-induced signal transduction in vascular smooth muscle cells.

Angiotensin II (Ang II) is a vasoactive hormone that has been implicated in cardiovascular diseases. Here, the effect of peach, Prunus persica L. Batsch, pulp extract on Ang II-induced intracellular Ca(2+) mobilization, reactive oxygen species (ROS) production and signal transduction events in cultured vascular smooth muscle cells (VSMCs) was investigated. Pretreatment of peach ethyl acetate extract inhibited Ang II-induced intracellular Ca(2+) elevation in VSMCs. Furthermore, Ang II-induced ROS generation, essential for signal transduction events, was diminished by the peach ethyl acetate extract. The peach ethyl acetate extract also attenuated the Ang II-induced phosphorylation of epidermal growth factor receptor and myosin phosphatase target subunit 1, both of which are associated with atherosclerosis and hypertension. These results suggest that peach ethyl acetate extract may have clinical potential for preventing cardiovascular diseases by interfering with Ang II-induced intracellular Ca(2+) elevation, the generation of ROS, and then blocking signal transduction events.

A Prunus mume extract stimulated the proliferation and differentiation of osteoblastic MC3T3-E1 cells.

Osteoporosis is a serious disease caused by decreased bone mass. There is constant matrix remodeling in bones, by which bone formation is performed by osteoblastic cells, whereas bone resorption is accomplished by osteoclast cells. We investigated the effect of a Japanese apricot (Prunus mume SIBE. et ZUCC.) extract on the proliferation and osteoblastic differentiation in pre-osteoblastic MC3T3-E1 cells. An alkaline phosphatase (ALP) activity assay, cell proliferation assay, alizarin red staining and expression analysis of osteoblastic genes were carried out to assess the proliferation and osteoblastic differentiation. The water-soluble fraction of Prunus mume (PWF) increased the ALP activity, cell proliferation and mineralization. The gene expression of osteopontin and bone morphogenetic protein-2, which are markers in the early period of osteoblastic differentiation, were significantly enhanced by the PWF treatment. PWF therefore stimulated the proliferation and osteoblastic differentiation of cells and may have potential to prevent osteoporosis.

Increased sensitivity to kainic acid in a genetic model of reduced NMDA receptor function.

The pathophysiology of schizophrenia may involve reduced NMDA receptor function and experimental models of NMDA receptor hypofunction have proven useful for characterizing neurobiological abnormalities potentially relevant to schizophrenia. The present study assessed behavioral responses and induction of Fos after administration of kainic acid to wild type mice (NR1(+/+)) and mice with genetically reduced NMDA receptor expression (NR1(neo/neo)). At a dose of 20 mg/kg, kainic acid induced lethal seizures in 100% of the NR1(neo/neo) mice tested but produced no lethal seizures in the wild type mice. The NR1(neo/neo) mice also exhibited enhanced behavioral responses to kainic acid at a dose of 15 mg/kg but no lethal seizures were produced by this dose. A greater induction of Fos was observed in neocortical and limbic cortical regions of the NR1(neo/neo) compared to NR1(+/+) mice after administration of 15 mg/kg kainic acid. In contrast, there were no differences between the genotypes in kainic acid induced Fos in the amygdala, hippocampus, lateral septum, and nucleus accumbens. In order to determine if altered behavioral phenotypes of the NR1(neo/neo) mice could be related to increased sensitivity of kainate receptors to endogenous glutamate, effects of the highly selective kainate antagonist LY382884 were examined. The kainate antagonist reduced the exaggerated acoustic startle responses, deficits in prepulse inhibition of acoustic startle, and motor hyperactivity in the NR1(neo/neo) mice. These findings suggest that selective kainate receptor antagonists could be novel therapeutic candidates for schizophrenia.

Comparision of the volatile components of unripe and ripe Japanese apricot (Prunus mume Sieb. et Zucc.).

The composition of the volatile components from unripe (I) and ripe (II) Japanese apricot (Prunus mume Sieb. et Zucc.) have been investigated. Seventy-six volatile components were identified, 25 for the first time as volatile constituents of Japanese apricot. The main components were benzaldehyde (I, 59.16%; II, 1.81%), isolongifololyl acetate (II, 19.21%), palmitic acid (I, trace; 10.22%), linalool (I, 9.93%; II, 7.34%), and butyl acetate (II, 8.30%). Unripe Japanese apricot have a green colour due to the main components being aldehydes. On the contrary, ripe Japanese apricot had a fruity note due to the increase of the ratio of esters during ripening.

Neural activation deficits in a mouse genetic model of NMDA receptor hypofunction in tests of social aggression and swim stress.

Mice with reduced expression of the NR1 subunit of the NMDA receptor (NR1 hypomorphic mice) display altered behavioral phenotypes that may relate to behavioral characteristics of schizophrenia. Altered phenotypes in the NR1 hypomorphs include marked deficits in species-typical behavioral interactions in tests of social aggression and social affiliation. To gain insight into neuroanatomical circuits disrupted by reduced NMDA receptor function, the present work compared regional brain activation in NR1 hypomorphic mice and their wild type controls after a resident-intruder test. Induction of Fos protein was used as an index of neuronal activation. Wild type mice exhibited robust induction of Fos in select brain regions, including specific nuclei of the hypothalamus and amygdala, lateral septum, and widespread regions of the cerebral cortex. Although the behavioral patterns were different for male and female mice, neuroanatomical patterns of Fos induction were remarkably similar for the two sexes. To determine socially specific components of Fos induction by the resident-intruder test, responses were compared for mice assessed in a test of general arousal and stress involving forced swim. Some common brain regions were activated by both tests but regionally specific differences were also found. The NR1 hypomorphic mice tested in the resident-intruder procedure displayed distinctly different behavioral interactions compared to the wild type mice and exhibited a significantly blunted Fos response in almost all brain regions. The mutant mice also exhibited reduced Fos in response to swim stress in specific brain regions. These data suggest that the NR1 hypomorphic mice have functional activation deficits in response to social challenge and swim stress.

Seizure responses and induction of Fos by the NMDA agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction.

Effects of the direct NMDA agonist (tetrazol-5-yl)glycine (TZG) were examined in a genetic mouse model of reduced NMDA receptor function. In this model, expression of the NR1 subunit is reduced but not eliminated and the mice are therefore designated as NR1 hypomorphic. Previous work suggested that the reduced NR1 subunit expression produced a functional subsensitivity as judged by a blunted Fos induction response to a sub-seizure dose of TZG. In the present study seizure threshold doses of TZG were tested in the wild type and mutant mice. Surprisingly, there was no difference in the seizure sensitivity between the wild type mice and mice presumed to express very low levels of the NR1 subunit. An extensive neuroanatomical analysis of Fos induction was conducted after the threshold seizure doses of TZG. The results demonstrate that some brain regions of the NR1 -/- mice exhibit much lower Fos induction in comparison to the NR1 +/+ mice. These regions include hippocampus, amygdala, and cerebral cortical regions. However, in other regions, similar induction of Fos was observed in both genotypes in response to the NMDA agonist. Regions showing similar Fos induction in the NR1 +/+ and NR1 -/- mice include the lateral septum, nucleus of the solitary tract, and medial hypothalamic regions. The results suggest that the NMDA receptor hypofunction in the NR1 -/- mice is not global but regionally specific and that subcortical structures are responsible for the seizure-inducing effects of TZG.

Immunohistochemical evaluation of thymidylate synthase (TS) and p16INK4a in advanced colorectal cancer: implication of TS expression in 5-FU-based adjuvant chemotherapy.

BACKGROUND: Our previous analyses on the expression of thymidylate synthase (TS) and p16(INK4a) in colorectal cancer patients administered 5-fluorouracil (5-FU) pre-operatively demonstrated that a high level of TS expression was a predictor of 5-FU resistance, and that the combination of a low level of TS expression and induction of p16(INK4a) after chemotherapy implicated chemosensitivity. The present study aimed to assess the relationship between the biological behavior of advanced colorectal cancer treated post-operatively by 5-FU-based chemotherapy and the expression of TS and p16(INK4a) in primary tumors. METHODS: Formalin-fixed, paraffin-embedded specimens from 132 colorectal cancers (Dukes' B, 36 cases; Dukes' C, 60 cases; and Dukes' D, 36 cases) treated by 5-FU post-operatively were immunostained for TS and p16(INK4a). Antigenicities were suitably retrieved. RESULTS: Primary tumors expressing high levels of TS in the Dukes' C group showed a significantly shorter recurrence-free interval (RFI) (P = 0.0002). The overall survival (OS) was shorter in high TS expressors than in low TS expressors (P = 0.001). A high level of TS expression also correlated with advanced Dukes' staging and the severity of nodal metastasis (Dukes' B versus Dukes' D, P = 0.001; Dukes' C versus Dukes' D, P = 0.008; N0 versus N2, P = 0.002; N1 versus N2, P = 0.03). p16(INK4a) expression was not correlated with the prognosis or clinicopathological features. CONCLUSIONS: Appropriate immunohistochemical evaluation is essentially important. We suggest that, in the Dukes' C group, a 5-FU-based regimen can be chosen as a first-line chemotherapy for low TS expressors. TS-high cancer should be treated with anti-cancer agents acting through different mechanisms. Further research should be conducted on applying TS immunostaining to the treatment strategy.