Mao-to Prolongs the Survival of and Reduces TNF-alpha Expression in Mice with Viral Myocarditis.

Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg(-1) kg(-1) day(-1)) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each, P < 0.05). HW and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-alpha (TNF-alpha) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-alpha. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis.

Pueraria mirifica phytoestrogens improve dyslipidemia in postmenopausal women probably by activating estrogen receptor subtypes.

Impaired lipid metabolism is an important health problem in postmenopausal women with insufficient estrogens, because dyslipidemia is a risk factor for development of atherosclerosis and the incidence of cardiovascular disease markedly increases after menopause. Pueraria mirifica (PM), a Thai herb, has been noticed as a source of phytoestrogens, estrogen-mimicking plant compounds. However, the clinical effects of PM on lipid metabolism and the underlying molecular mechanisms remain undetermined. Therefore, we examined the effects of PM on serum lipid parameters in a randomized, double-blind, placebo-controlled clinical trial. Nineteen postmenopausal women were randomly assigned to receive oral administration of PM powder or placebo. After 2 months of treatment, the PM group showed a significant increase in serum concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-1 (34% and 40%, respectively), and a significant decrease in low-density lipoprotein (LDL) cholesterol and apo B (17% and 9%, respectively), compared with baseline measurements. Moreover, significant decreases were observed in the ratios of LDL cholesterol to HDL cholesterol (37%) and apo B to apo A-1 (35%). Next, we determined the effects of PM phytoestrogens on the activation of estrogen receptor (ER)-mediated transactivation by transient expression assays of a reporter gene in cultured cells. Among PM phytoestrogens, miroestrol and coumestrol enhanced both ERalpha- and ERbeta-mediated transactivation, whereas other phytoestrogens, including daidzein and genistein, preferentially enhanced ERbeta-mediated transactivation. In conclusion, PM has a beneficial effect on lipid metabolism in postmenopausal women, which may result from the activation of gene transcription through selective binding of phytoestrogens to ERalpha and ERbeta.

Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of Hochu-ekki-to (TJ-41).

Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of chronic fatigue syndrome (CFS) and neuron apoptosis. Nevertheless, no study has been performed directly to explore the relationship between CFS, BDNF and neuron apoptosis. We induced a CFS model by six injections of killed Brucella abortus antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running activity, body weight (BW), ratio of cerebral weight to BW (CW/BW) and expression levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily activity and CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA expression levels in the hippocampus were suppressed in the CFS model and TJ-41 treated mice, while no significant difference was found between them. We improved a murine model to investigate the relationship between CFS and brain dysfunction. In this model, reduced daily activity might have been associated with decreased hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41 increased the daily running activity of the model, which was independent of brain recovery.

Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with first acute myocardial infarction.

UNLABELLED: Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, reduces plasma norepinephrine concentration in patients with ischemic heart disease. However, long-term effects on cardiac sympathetic nerve activity (CSNA) as evaluated by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy have not been determined for patients with acute myocardial infarction (AMI). METHODS: We studied 40 patients with their first AMI who were treated with intravenous nicorandil before and after primary coronary angioplasty. After suspension of the initial intravenous nicorandil treatment, 20 patients were randomized to receive oral nicorandil (15 mg/d) (group A) and the other 20 patients received a placebo (group B). All patients were also treated with an angiotensin-converting enzyme (ACE) inhibitor or beta-blockers. The delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score (TDS), and washout rate (WR) were determined from (123)I-MIBG scintigraphy 3 wk and 6 mo after angioplasty. The left ventricular (LV) end-diastolic volume (EDV), LV end-systolic volume (ESV), and LV ejection fraction (EF) were determined by contrast left ventriculography, whereas plasma procollagen type III amino-terminal peptide (PIIINP) concentrations were also measured at the same time points. RESULTS: Three weeks after angioplasty, TDS, H/M ratios, WR, LVEDV, LVESV, and LVEF were similar in both groups. After 6 mo, all of these parameters had improved in both groups. However, the extent of change in TDS was -9 +/- 6 in group A and -5 +/- 6 in group B (P < 0.05), whereas that in the H/M ratio was 0.15 +/- 0.13 and 0.07 +/- 0.11 (P < 0.05) and that in the WR was -12% +/- 8% and -5% +/- 11% (P < 0.05). The extent of change in LVEDV, LVESV, and LVEF in group A tended to exceed that in group B, but these changes were not statistically significant. We found significant correlations between the percent change in PIIINP and that of TDS from baseline to 6 mo in group A (r = 0.456, P < 0.05). CONCLUSION: Long-term nicorandil therapy can be more beneficial for CSNA and LV remodeling than short-term therapy in patients with AMI.

Beneficial effect of brewers' yeast extract on daily activity in a murine model of chronic fatigue syndrome.

The aim of this study was to assess the effect of Brewers' yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area. There were suppressed IFN-gamma and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses.

Effects of hormone replacement therapy on circulating docosahexaenoic acid and eicosapentaenoic acid levels in postmenopausal women.

Hormone replacement therapy (HRT) has antiatherosclerotic effects of which the mechanism remains unclear. The ingestion of fish oil or other sources of n-3 polyunsaturated fatty acids has been included in comprehensive strategies to prevent atherosclerosis. Many epidemiologic studies have shown that the dietary intake of docosahexaenoic acid and eicosapentaenoic acid has antiatherosclerotic effects. We investigated the effect of HRT on plasma docosahexaenoic acid and eicosapentaenoic acid concentrations in postmenopausal women. Fifty-nine postmenopausal women, who received conjugated estrogens (0.625 mg/day) and medroxyprogesterone (2.5 mg/day) for 12 months, and 45 control postmenopausal women, who did not receive HRT, volunteered to participate in this study. Plasma docosahexaenoic acid and eicosapentaenoic acid concentrations were measured at baseline and at 6 and 12 months after the start of HRT. HRT significantly increased the plasma docosahexaenoic acid and eicosapentaenoic acid concentrations from 134 +/- 5 microg/ml and 69 +/- 4 microg/ml at baseline to 156 +/- 7 microg/ml and 85 +/- 7 microg/ml after 12 months (both p<0.01). However, the control group showed no significant change in their plasma docosahexaenoic acid and eicosapentaenoic acid levels during the study. HRT increased plasma docosahexaenoic acid and eicosapentaenoic acid levels in postmenopausal women. We propose that the increase in docosahexaenoic acid and eicosapentaenoic acid may be partially responsible for the beneficial mechanisms by which HRT induces an antiatherosclerotic effect in postmenopausal women.