Deconstructing the traditional Japanese medicine "Kampo": compounds, metabolites and pharmacological profile of maoto, a remedy for flu-like symptoms.

Pharmacological activities of the traditional Japanese herbal medicine (Kampo) are putatively mediated by complex interactions between multiple herbal compounds and host factors, which are difficult to characterize via the reductive approach of purifying major bioactive compounds and elucidating their mechanisms by conventional pharmacology. Here, we performed comprehensive compound, pharmacological and metabolomic analyses of maoto, a pharmaceutical-grade Kampo prescribed for flu-like symptoms, in normal and polyI:C-injected rats, the latter suffering from acute inflammation via Toll-like receptor 3 activation. In total, 352 chemical composition-determined compounds (CCDs) were detected in maoto extract by mass spectrometric analysis. After maoto treatment, 113 CCDs were newly detected in rat plasma. Of these CCDs, 19 were present in maoto extract, while 94 were presumed to be metabolites generated from maoto compounds or endogenous substances such as phospholipids. At the phenotypic level, maoto ameliorated the polyI:C-induced decrease in locomotor activity and body weight; however, body weight was not affected by individual maoto components in isolation. In accordance with symptom relief, maoto suppressed TNF-α and IL-1ß, increased IL-10, and altered endogenous metabolites related to sympathetic activation and energy expenditure. Furthermore, maoto decreased inflammatory prostaglandins and leukotrienes, and increased anti-inflammatory eicosapentaenoic acid and hydroxyl-eicosapentaenoic acids, suggesting that it has differential effects on eicosanoid metabolic pathways involving cyclooxygenases, lipoxygenases and cytochrome P450s. Collectively, these data indicate that extensive profiling of compounds, metabolites and pharmacological phenotypes is essential for elucidating the mechanisms of herbal medicines, whose vast array of constituents induce a wide range of changes in xenobiotic and endogenous metabolism.

[Development of a statistical metabolic syndrome simulator].

OBJECTIVE: The metabolic syndrome (Mets) is a clustering of cardiovascular disease risk factors: visceral obesity, hyperglycemia, hypertension and dyslipidemia. However, the criteria and definitions of Mets vary among countries, and medical evaluation is not unified as yet. The aim of the present study was to develop a Mets simulator as a tool for health policies, calculating prevalence corresponding to several diagnostic criteria based on checkup results for a group. METHODS: 1) The data for construction of the simulator: To investigate the characteristic of each diagnosis criterion component (abdominal waist circumference, BMI, triglycerides, HDL cholesterol, blood pressure, fasting blood sugar, and HbAlc) actual checkup data were applied to examine for a suitable normal transformation method. Next, variance-covariance matrices were obtained using transformed variables. 2) Construction of the simulator: multivariate normal random values were generated using e mean values input by the user and the variance-covariance matrices calculated from the above process. Next, Mets was diagnosed according to the five diagnostic criteria (NCEP-ATPIII, AHA/NHLBI, IDF, Japan, and Ministry of Health, Labor and Welfare) to obtain the prevalence for each criterion. By repeating the process, average and variance values for prevalence were calculated for each. RESULTS: The Mets simulator was constructed using checkup data in Tokyo and performance assessment and sensitivity analyses were accomplished. Next, two examples referred from the studies in Japan and America, both including missing diagnostic criterion components, were examined using the simulator. Mean and variance values of the prevalence, and missing values, were estimated using the simulator. Change in prevalence with change of values for diagnosis criterion components was calculated. The result clarified a part of the features of the diagnostic criteria such as similarities in those applied in Japan and IDF. CONCLUSION: A simulator corresponding to the five diagnostic criteria of the Mets could be developed by generating multivariate random values, allowing assessment of Mets prevalence. Using the simulator, changes in prevalence according to changes in values of components of the diagnostic criteria were examined. Th simulator may bring useful information for health policies to prevent lifestyle related diseases.