Corrigendum to "Suppression of Dynamical Network Biomarker Signals at the Predisease State (Mibyou) before Metabolic Syndrome in Mice by a Traditional Japanese Medicine (Kampo Formula) Bofutsushosan".
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ABSTRACT:
SUBMITTER: Koizumi K
PROVIDER: S-EPMC8088371 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Due to the increasing incidence of metabolic syndrome, the development of new therapeutic strategies is urgently required. One promising approach is to focus on the predisease state (so-called Mibyou in traditional Japanese medicine) before metabolic syndrome as a preemptive medical target. We recently succeeded in detecting a predisease state before metabolic syndrome using a mathematical theory called the dynamical network biomarker (DNB) theory. The detected predisease state was characterized by 147 DNB genes among a total of 24,217 genes in TSOD (Tsumura-Suzuki Obese Diabetes) mice, a well-accepted model of metabolic syndrome, at 5 weeks of age. The timing of the predisease state was much earlier than the onset of metabolic syndrome in TSOD mice reported to be at approximately 8-12 weeks of age. In the present study, we investigated whether the predisease state in TSOD mice can be inhibited by the oral administration of a Kampo formula, bofutsushosan (BTS), which is usually used to treat obese patients with metabolic syndrome in Japan, from 3 to 7 weeks of age. We found the comprehensive suppression of the early warning signals of the DNB genes by BTS at 5 weeks of age and later. Specifically, the standard deviations of 134 genes among the 147 DNB genes decreased at 5 weeks of age as compared to the nontreatment control group, and 80 of them showed more than 50% reduction. In addition, at 7 weeks of age, the body weight and blood glucose level were significantly lower in the BTS-treated group than in the nontreatment control group. The results of our study suggest a novel mechanism of BTS; it suppressed fluctuations of the DNB genes at the predisease state before metabolic syndrome and thus prevented the subsequent transition to metabolic syndrome. In conclusion, this study demonstrated the preventive and preemptive effects of a Kampo formula on Mibyou before metabolic syndrome for the first time based on scientific evaluation.
| S-EPMC7424500 | biostudies-literature
Project description:Recently, the use of herbal medicines has become popular, and information on drug interactions between herbal medicines and chemical drugs is needed in clinics. In Japan, the number of patients taking Japanese traditional Kampo medicines has been increasing, and the proper drug information about herb-drug interaction is highly demanded. The most established herb-drug interaction is the case of grapefruit juice (GFJ) via the inhibition on CYP3A4 expressed in the small intestine. In the present study, we compared the inhibitory titer on CYP3A4 between the target Kampo products and GFJ used as positive control. We evaluated the inhibitory effects of GFJ and three extracts of Kampo formulas frequently used in gynecological clinics on CYP3A4 in vitro and calculated the related titer of one-time dosage of Kampo formulas to GFJ in order to predict its effect on clinics. Although the extracts of these three Kampo formulas and the most of crude drug components in the formulas exhibited the inhibitory effects on CYP3A4 in some levels, the possibilities of tokishakuyakusan and keishibukuryogan to cause drug interaction can be quite low; however, it is possible that the excessive dosage of kamishoyosan may cause drug interaction with the substrate of CYP3A4 in clinics.
| S-EPMC6188721 | biostudies-literature
Project description:BackgroundObesity-induced liver disease (nonalcoholic fatty liver disease, NAFLD) is now the commonest cause of chronic liver disease in affluent nations. There are presently no proven treatments for NAFLD or its more severe stage, nonalcoholic steatohepatitis (NASH). Bofutsushosan (BTS), a Japanese herbal (Kampo) medicine, long used as an anti-obesity medicine in Japan and other Asian countries, has been shown to reduce body weight and improve insulin resistance (IR) and hepatic steatosis. The precise mechanism of action of BTS, however, remains unclear. To evaluate the ability of BTS to prevent the development of NASH, and determine the mediators and pathways involved.MethodsC57BL/6 mice were injected intra-peritoneally with gold-thioglucose and fed a high-fat diet (HF) or HF diet admixed with either 2 or 5 % BTS for 12 weeks. The effectiveness of BTS in attenuating features of NASH and the mechanisms through which BTS attenuated NASH were then assayed through an assessment of the anthropometric, radiological, biochemical and histological parameters.ResultsBTS attenuated the progression of NASH through induction of adiponectin and its receptors along with an induction of PPAR-α and PPAR-γ, decreased expression of SREBP-1c, increased hepatic fatty acid oxidation and increased hepatic export of triglycerides. BTS moreover, reduced IR through phosphorylation of the protein kinase, Akt.ConclusionsBTS through induction of adiponectin signaling and Akt attenuated development of NASH. Identification of the active entity in BTS should allow development of novel treatments for NASH.
| S-EPMC4048468 | biostudies-literature
Project description:Kampo, an empirically validated system of traditional Sino-Japanese medicine, aims to treat patients holistically. This is in contrast to modern medicine, which focuses in principle on treating the affected parts of the body of the patient. Kampo medicines formulated as combinations of crude drugs are prescribed based on a Kampo-specific diagnosis called Sho (in Japanese), defined as the holistic condition of each patient. Therefore, the medication system is very complex and is not well understood from a modern scientific perspective. Here, we show the informatics framework of Kampo medication by multivariate factor analysis of the elements constituting Kampo medication. First, the variation of Kampo formulas projected by principal component analysis (PCA) indicated that the combination patterns of crude drugs were highly correlated with Sho diagnoses of Deficiency and Excess. In an opposite way, partial least squares projection to latent structures (PLS) regression analysis could also predict Deficiency/Excess only from the composed crude drugs. Secondly, to chemically verify the correlation between Deficiency/Excess and crude drugs, we performed mass spectrometry (MS)-based metabolome analysis of Kampo prescriptions. PCA and PLS regression analysis of the metabolome data also suggested that Deficiency/Excess could be theoretically explained based on the variation in chemical fingerprints of Kampo medicines. Our results show that factor analysis of Kampo concepts and of the metabolomes of Kampo medicines enables interpretation of the complex system of Kampo. This study will theoretically form the basis for establishing traditionally and empirically based medications worldwide, leading to systematically personalized medicine.
| S-EPMC4662717 | biostudies-literature
Project description:PurposeTo determine the potentials of Hochuekkito (HET) treatment for aging infertility.MethodsMice at 36 weeks of age were fed without (control, n = 40) or with low (100 mg/kg/day, n = 24) and high (1000 mg/kg/day, n = 38) doses of HET for 12 weeks. Aging animals at 48 weeks of age were used for in vitro fertilization-embryo transfer (IVF-ET), and their ovaries were subjected to histological and quantitative inflammation analyses.ResultsHET administration decreased transcript levels of ovarian inflammatory markers, interleukin 6 (IL-6), IL-1β, tumor necrosis factor (TNF)-α, and interferon-gamma (IFN-γ) but suppressed ovulation rates and the number of ovulated oocytes in aging mice. Furthermore, HET treatment decreased the rates of oocytes maturation and fertilization and the cumulus-cell expression of TNF-α-induced protein 6 and epidermal growth factor receptor. After IVF-ET, no improvement of declined live offspring rate by aging was achieved by HET administration, although there were no adverse effects on embryo development and implantation as well as gross morphology and bodyweight of pups.ConclusionPresent study indicated HET treatment interfered with ovulation and fertilization in aging mice without affecting ovarian follicle development. No improvement on the age-associated decline of live offspring rate and follicle development was achieved after HET treatment.
| S-EPMC8658873 | biostudies-literature
Project description:Shimotsuto is a traditional Japanese Kampo medicine used to treat gynecological diseases, such as irregular menstruation, in addition to oversensitivity to cold and chilblains. Part of the pharmacological actions of shimotsuto is traditionally considered to be exerted by an improvement effect of the blood and the circulatory system. Multiple ingredients (e.g., catalpol and paeoniflorin) contained in shimotsuto have been reported to have pharmacological activities on the blood and circulatory system, and thus been considered to contribute to the pharmacological actions of shimotsuto. However, it remains unclear whether the ingredients can be absorbed into the body following oral administration of shimotsuto. The aim in the present study was to specify shimotsuto ingredient absorbed into the systemic circulation in rats. Seven candidate active ingredients (catalpol, paeoniflorin, albiflorin, ligustilide, senkyunolide A, butylphthalide, and ferulic acid) in plasma after oral administration of shimotsuto were quantified by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This study also performed nontargeted LC-MS/MS analysis of plasma following administration of constituent crude drugs of shimotsuto to find extensively blood-absorbed ingredients of shimotsuto. Among detected peaks in the nontargeted analysis, two peaks could be identified as bergapten and 8-debenzoylpaeoniflorin, subsequently their concentrations in shimotsuto-treated rat plasma were quantified. These pharmacokinetic studies indicated that catalpol showed the highest plasma concentration following administration of shimotsuto, followed by 8-debenzoylpaeoniflorin. This study suggests that all nine ingredients are absorbed into the blood following oral administration of shimotsuto and possibly contribute to its pharmacological action.
| S-EPMC7902330 | biostudies-literature
Project description:Several basic pharmacokinetic and pharmacological studies were conducted as part of a group of studies to clarify the drug-drug interaction (DDI) between memantine (MEM), a drug used to treat Alzheimer's disease, and yokukansan (YKS), a traditional Japanese Kampo medicine used to treat behavioral and psychological symptoms of dementia. The pharmacokinetic studies showed that there were no statistically significant differences in MEM concentrations in the plasma, brain, and urine between mice treated with MEM alone and with MEM plus YKS. Regarding candidate active ingredients of YKS, there were also no statistically significant differences in concentrations of geissoschizine methyl ether in the plasma and brain, urine, glycyrrhetinic acid in the plasma, and isoliquiritigenin in the urine, in mice treated with YKS alone or with MEM plus YKS. The pharmacological studies showed that isoliquiritigenin, which has an N-methyl-d-aspartic acid (NMDA) receptor antagonistic effect, did not affect the inhibitory effect of MEM on NMDA-induced intracellular Ca2+ influx in primary cultured rat cortical neurons. Moreover, YKS did not affect either the ameliorative effects of MEM on NMDA-induced learning and memory impairment, or the MEM-induced decrease in locomotor activities in mice. These results suggest that there is probably no pharmacokinetic or pharmacological interaction between MEM and YKS in mice, but more detailed studies are needed in the future. Our findings provide important information for future studies, to clarify the DDI more regarding the efficacy and safety of combined use of these drugs in a clinical situation.
| S-EPMC6337661 | biostudies-literature
Project description:BackgroundJapanese Kampo medicine is a traditional medicine with roots in ancient Chinese medicine. Because traditional physicians had been abolished in Japan, the present mainstream of Kampo treatment is that physicians who learned modern Western medicine prescribe Kampo extract products based on Western medical diagnosis. This situation is different from that in other east Asian countries, and the physicians require scientific clinical evidence.MethodsClinical studies were searched from literature databases, clinical trial registry sites, and "Evidence Reports of Kampo Treatment (EKAT)" published by the Japan Society for Oriental Medicine.ResultsAt the approval of Kampo products, scientific clinical evidence was not required because they have a long-period experience as a decoction. However, in the 1990s, Kampo products became a subject for national reevaluation; double-blind and placebo-controlled clinical trials. At the time, a methodological foundation for conducting clinical assessments of Kampo medicines was established. From 2000 onwards, with the evidence-based medicine era, the field of Kampo medicine also saw many randomized controlled trials, and their evidence was collected and published as EKAT. In the 2010s, post-marketing clinical trials of Kampo products also had to be conducted in this environment due to the need for ethical and scientific assurance. Currently, there are numerous clinical trials of Kampo products being conducted with high-grade trial designs.ConclusionThe situation of Kampo clinical studies reflects the unique history and position of Kampo medical system and Kampo products in Japan.
| S-EPMC8181179 | biostudies-literature
Project description:The establishment of new therapeutic strategies for metabolic syndrome is urgently needed because metabolic syndrome, which is characterized by several disorders, such as hypertension, increases the risk of lifestyle-related diseases. One approach is to focus on the pre-disease state, a state with high susceptibility before the disease onset, which is considered as the best period for preventive treatment. In order to detect the pre-disease state, we recently proposed mathematical theory called the dynamical network biomarker (DNB) theory based on the critical transition paradigm. Here, we investigated time-course gene expression profiles of a mouse model of metabolic syndrome using 64 whole-genome microarrays based on the DNB theory, and showed the detection of a pre-disease state before metabolic syndrome defined by characteristic behavior of 147 DNB genes. The results of our study demonstrating the existence of a notable pre-disease state before metabolic syndrome may help to design novel and effective therapeutic strategies for preventing metabolic syndrome, enabling just-in-time preemptive interventions.
2019-06-24 | GSE112653 | GEO
Project description:The establishment of new therapeutic strategies for metabolic syndrome is urgently needed because metabolic syndrome, which is characterized by several disorders, such as hypertension, increases the risk of lifestyle-related diseases. One approach is to focus on the pre-disease state, a state with high susceptibility before the disease onset, which is considered as the best period for preventive treatment. In order to detect the pre-disease state, we recently proposed mathematical theory called the dynamical network biomarker (DNB) theory based on the critical transition paradigm. Here, we investigated time-course gene expression profiles of a mouse model of metabolic syndrome using 64 whole-genome microarrays based on the DNB theory, and showed the detection of a pre-disease state before metabolic syndrome defined by characteristic behavior of 147 DNB genes. The results of our study demonstrating the existence of a notable pre-disease state before metabolic syndrome may help to design novel and effective therapeutic strategies for preventing metabolic syndrome, enabling just-in-time preemptive interventions.
| S-EPMC6591167 | biostudies-literature