Bofutsushosan, a Japanese herbal (Kampo) medicine, attenuates progression of nonalcoholic steatohepatitis in mice

BACKGROUND: Obesity-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. METHODS: C57BL/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. RESULTS: BTS 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. CONCLUSIONS: BTS 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00535-013-0852-8) contains supplementary material, which is available to authorized users

Beneficial Effects of Rikkunshito, a Japanese Kampo Medicine, on Gastrointestinal Dysfunction and Anorexia in Combination with Western Drug: A Systematic Review

Background. Kampo medicines are traditional herbal medicines which have been approved for medicinal use by the Japanese Ministry of Health and Welfare and are currently being used more and more, often in combination with Western drugs. Thus, the need for investigation of interactions between Kampo medicines and Western drugs is now widely recognized. Aim. To summarize the effects and drug interactions of rikkunshito, a Kampo medicine often prescribed for upper gastrointestinal disorders and anorexia. Methods. Animal and human studies were systematically reviewed to identify published data on rikkunshito. Results describing its effects were abstracted, with an emphasis on drug interactions. Results and Discussion. Rikkunshito ameliorates anorexia induced by anticancer drugs, improves quality of life scores, and can even prolong survival compared with monotherapy. Rikkunshito combined with proton pump inhibitor therapy is shown to be useful in the treatment of PPI-refractory gastroesophageal reflux disease patients and patients with gastrointestinal symptoms after endoscopic submucosal dissection. Rikkunshito reduces antidepressant-induced adverse events and improves quality of life without influencing antidepressant effects. Conclusions. Rikkunshito shows ameliorative effects on adverse reactions induced by various Western drugs and can achieve better results (e.g., anticancer drugs and proton pump inhibitor) without influencing the efficacy and bioavailability of Western drugs

Scaling of Paramecium

Scaling analysis was carried out on the unicellular organism, Paramecium in terms of the cellular geometry and metabolic activity. Confocal microscopy and computer assisted tomography revealed the conventional assumption of the cell body as a prolate spheroid is enough applicable to represent the cell volume. The tomographic volume could be estimated as 0.75 times of the prolate volume. This linearity between tomographic and prolate volume suggests the isometric scaling of the cytopharynx volume to the cell volume. The prolate assumption of the cell body, which has the short axis scaled to the long by the power 0.56, suggests the allometric relation of surface area to the cell volume by the power 0.71. Allometric scaling of energy expenditure of Paramecium was tested based on the result of geometrical scaling using the SMR measured by the extrapolation method established by the previous study (Katsu-Kimura et al, 2009)

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities

Usefulness of a Kampo Medicine on Stress-Induced Delayed Gastric Emptying in Mice

Anxiety and depression often occur with gastrointestinal symptoms. Although the Japanese traditional medicine (Kampo medicine) bukuryoingohangekobokuto (BGH) is approved for treating anxiety, neurotic gastritis, and heartburn, its effect on gastrointestinal motility remains poorly known. This study aimed to examine the effect of BGH on delayed gastric emptying in stress model mice and clarified its action mechanism. Seven-week-old C57BL/6 male mice were acclimated for a week and fasted overnight. Stress hormone, corticotropin-releasing factor (CRF), was intracerebroventricularly injected to mice, and solid nutrient meal (ground chow and distilled water) was orally administered 1 hour after. Gastric contents were collected to evaluate gastric emptying rates by measuring its dry weight. Injection of CRF (0.3 or 1.0 μg/mouse) significantly delayed the 2-hour gastric emptying in mice. BGH (1.0 g/kg), which was administered 30 minutes before the CRF injection, significantly ameliorated the delayed gastric emptying induced by CRF (0.3 μg/mouse). BGH (0.5, 1.0 g/kg) significantly enhanced the 1-hour gastric emptying and slightly increased the 2-hour gastric emptying in mice without CRF injection. In vitro functional assays showed that components of BGH antagonized or inhibited CRF type-2, dopamine D2/D3, neuropeptide Y Y2 receptors, or acetylcholinesterase. In conclusion, the components of BGH may exert synergistic effects on improving gastric emptying via various targets. BGH is considered to be potentially useful for treating gastrointestinal dysmotility with psychological symptoms