Combination Effects of Herbs in a Multi-herbal Formula: Expression of Juzen-taiho-to's Immuno-modulatory Activity on the Intestinal Immune System

Herbal formulas of traditional Japanese (Kampo), Chinese and Korean medicines usually comprise multiple herbs in a single formula. These medicines are expected to show their clinical effects by chemical, pharmacological and pharmaceutical combination effects of multi-herbs. However, little effort has been made so far to scientifically clarify the nature of such combination effects. Interestingly, for example, though a Kampo medicine Juzen-taiho-to (Shi-Quan-Da-Bu-Tang in Chinese) stimulates the immune functions of Peyer's patch cells, none of its single component herbs shows such activity. We thus examined the combination effect of herbs in the Juzen-taiho-to formula for the expression of its immuno-stimulating activity. Juzen-taiho-to, a composite formula of 10 herbs, has been generally considered to comprise two kinds of basic formula, each of which consists of four different herbs in addition to two others. The combinations of herbs based on these two basic formulas were evaluated for their stimulating activities on cytokine production from murine Peyer's patch cells both in vitro and ex vivo. Combined decoction of six among 10 herbs in Juzen-taiho-to is crucial for the expression of its stimulating activity on Peyer's patch cells. 3D-HPLC analysis of the ingredients in the fractions from the combined decoctions indicated that, in addition to quantitative changes of ingredients, alterations occur in their chemical composition by decoction of different herbs. The stimulating activity of Juzen-taiho-to on Peyer's patch cells results from the combination effect of its six essential component herbs. This combination effect is based on physicochemical interactions among the ingredients of the component herbs

A case of myasthenia gravis in which the interval to repeated exacerbation was prolonged by L-carnitine

We report the case of a 62-year-old woman diagnosed with myasthenia gravis. She felt dyspnea and weakness of bilateral upper limbs, followed by left blepharoptosis. Pyridostigmine markedly improved her symptoms. But later, blepharoptosis and head drop worsened and predonisolone was ineffective. Yet, after intravenous immunoglobulin therapy her symptoms markedly improved. However, her head drop worsened at intervals of 25.79 days on average. She was administered L-carnitine, and the interval until exacerbation became longer (40.67 days on average). This case is interesting because L-carnitine therapy has never been reported as therapy for myasthenia gravis

Artificial O2 Carrier with Antioxidant Activities

A covalent core–shell structured protein cluster composed of hemoglobin (Hb) at the center and human serum albumins (HSA) at the periphery, Hb-HSAm, is an artificial O2 carrier that can function as a red blood cell substitute. Here we described the preparation of a novel Hb-HSA3 cluster with antioxidant activities and its O2 complex stable in aqueous H2O2 solution. We used an approach of incorporating a Pt nanoparticle (PtNP) into the exterior HSA unit of the cluster. A citrate reduced PtNP (1.8 nm diameter) was bound tightly within the cleft of free HSA with a binding constant (K) of 1.1×107 M−1, generating a stable HSA-PtNP complex. This platinated protein showed high catalytic activities for dismutations of superoxide radical anions (O2•–) and hydrogen peroxide (H2O2), i.e., superoxide dismutase and catalase activities. Also, Hb-HSA3 captured PtNP into the external albumin unit (K = 1.1×107 M−1), yielding an Hb-HSA3(PtNP) cluster. The association of PtNP caused no alteration of the protein surface net charge and O2 binding affinity. The peripheral HSA-PtNP shell prevents oxidation of the core Hb, which enables the formation of an extremely stable O2 complex, even in H2O2 solution

Hochuekkito, a Kampo (traditional Japanese herbal) Medicine, Enhances Mucosal IgA Antibody Response in Mice Immunized with Antigen-entrapped Biodegradable Microparticles

The effect of oral administration of Hochuekkito (HET; Bu-Zhong-Yi-Qi-Tang in Chinese), a traditional Japanese herbal medicine, on mucosal IgA immune response was investigated. To induce the antigen-specific antibodies in mucosal site, ovalbumin (OVA)-entrapped biodegradable microparticles (OVA-microparticles) were used as an antigen. Mice were orally immunized with OVA-microparticles for 3 successive days with intragastric gavage. From 7 days after the onset of immunization, the mice were boosted twice a week with the same antigen for 2 weeks. HET or water alone was orally administered to the mice via the intragastric route from 7 days before to 27 days after the onset of immunization. Although no significant change in total secretory IgA antibody level was observed in intestinal and nasal washes, OVA-specific IgA titers in intestinal washes were significantly enhanced by oral administration of HET. When lymphocytes from spleen, peripheral blood and Payer's patches were investigated for cytokines production, it was found that the IFN-γ secretion from the lymphocytes was increased by the administration of HET. Microarray analysis of Peyer's patch cells revealed enhanced expression of L-selectin gene. The increase of L-selectin positive cells in B lymphocytes fraction was observed in Peyer's patch cells and peripheral blood mononuclear cells by flow cytometry. These results suggest that the enhanced IFN-γ secretion and increased population of L-selectin positive B lymphocytes by orally administered HET may partly contribute to enhancement of IgA immune response against intestinal antigens, and orally administered HET may strengthen defensive systems against various pathogens and food antigens in intestine

Stabilization of SF₅⁻ with Glyme-Coordinated Alkali Metal Cations

The stabilization of complex fluoroanions derived from weakly acidic parent fluorides is a significant and ongoing challenge. The [SF₅]⁻ anion is recognized as one such case, and only a limited number of [SF₅]⁻ salts are known to be stable at room temperature. In the present study, glyme-coordinated alkali metal cations (K⁺, Rb⁺, and Cs⁺) are employed to stabilize [SF₅]⁻, which provides a simple synthetic route to a [SF₅]⁻ salt. The reactivities of KF and RbF with SF₄ are significantly enhanced by complexation with G4, based on Raman spectroscopic analyses. A new room-temperature stable salt, [Cs(G4)₂][SF₅] (G4 = tetraglyme), was synthesized by stoichiometric reaction of CsF, G4, and SF₄. The vibrational frequencies of [SF₅]⁻ were assigned based on quantum chemical calculations, and the shift of the G4 breathing mode accompanying coordination to metal cations was confirmed by Raman spectroscopy. Single-crystal X-ray diffraction revealed that Cs⁺ is completely isolated from [SF₅]⁻ by two G4 ligands and [SF₅]⁻ is disordered along the crystallographic two-fold axis. Hirshfeld surface analysis reveals that the H···H interaction between two neighboring [Cs(G4)₂]⁺ moieties is more dominant on the Hirshfeld surface than the interaction between the H atom in glyme molecules and the F atom in [SF₅]⁻, providing a CsCl-type structural model where the large and spherical [Cs(G4)₂]⁺ cations contact each other and the [SF₅]⁻ anions occupy interstitial spaces in the crystal lattice. The [SF₅]⁻ anion, combined with [Cs(G4)₂]⁺, exhibits a very limited deoxofluorinating ability toward hydroxyl groups in both neat conditions and THF solutions

Pseudogap Phase Boundary in Overdoped Bi_2Sr_2CaCu_2O_8 Studied by Measuring Out-of-plane Resistivity under the Magnetic Fields

The characteristic pseudogap temperature T* in Bi2Sr2CaCu2O8 system has been systematically evaluated as a function of doping, especially focusing on its overdoped region, by measuring the out-of-plane resistivity under the magnetic fields. Overdoped samples have been prepared by annealing TSFZ-grown Bi2Sr2CaCu2O8 single crystals under the high oxygen pressures (990 kgf/cm2). At a zero field, the out-of-plane resistivity showed a metallic behavior down to Tc (= 62 K), while under the magnetic fields of over 3 T,it showed typical upturn behavior from around 65 K upon decreasing temperature. This result suggests that the pseudogap and superconductivity are different phenomena.Comment: 2 pages, 2 figures. Final version accepted for the Proceedings of the M2S-IX Conference (Tokyo, September 2009

Polysaccharide-Containing Macromolecules in a Kampo (Traditional Japanese Herbal) Medicine, Hochuekkito: Dual Active Ingredients for Modulation of Immune Functions on Intestinal Peyer's Patches and Epithelial cells

A traditional Japanese herbal (Kampo) medicine, Hochuekkito (Bu-Zhong-Yi-Qi-Tang in Chinese, TJ-41) is a well-known Kampo formula, and has been found to enhance antigen-specific antibody response in not only local mucosal immune system in upper respiratory tract, but also systemic immune system through upper respiratory mucosal immune system. Although this immunopharmacological effect has been proposed to express by modulation of intestinal immune system including Peyer's patches and intestinal epithelial cells, active ingredients are not known. TJ-41 directly affected the production of bone marrow cell-proliferative growth factors from murine Peyer's patch immunocompetent cells in vitro. Among low molecular, intermediate size and macromolecular weight fractions prepared from TJ-41, only fraction containing macromolecular weight ingredients showed Peyer's patch-mediated bone marrow cell-proliferation enhancing activity. Anion-exchange chromatography and gel filtration gave 17 subfractions comprising polysaccharides and lignins from the macromolecular weight fraction of TJ-41, and some of the subfractions showed significant enhancing activities having different degrees. Some of the subfractions also expressed stimulating activity on G-CSF-production from colonic epithelial cells, and statistically significant positive correlation was observed among enhancing activities of the subfractions against Peyer's patch immunocompetent cells and epithelial cells. Among the fractions from TJ-41 oral administration of macromolecular weight ingredient fraction to mice succeeded to enhance antigen-specific antibody response in systemic immune system through upper respiratory mucosal immune system, but all the separated fractions failed to enhance the in vivo antibody response in upper respiratory tract

Proteomic Analysis of Anti-inflammatory Effects of a Kampo (Japanese Herbal) Medicine “Shoseiryuto (Xiao-Qing-Long-Tang)” on Airway Inflammation in a Mouse Model

Effects of a Kampo (Japanese herbal) medicine “shoseiryuto (SST, xiao-qing-long-tang in Chinese)”, which has been used for the treatment of allergic bronchial asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally administered at 0.5 g kg−1 day−1 from day 1 to 6 after OVA inhalation, SST reduced the inflammation in lung tissue, the number of eosinophils and the OVA-specific immunoglobulin E (IgE) antibody titer in bronchoalveolar lavage (BAL) fluids at 7 days after the OVA inhalation. SST also reduced the airway hyperreactivity at 6 days after the OVA inhalation. Proteomic analysis with the agarose two-dimensional electrophoresis showed that the expression of spectrin α2 was reduced in the lung tissue of OVA-sensitized mice and SST recovered the expression. Western blot and immunohistochemical analyses of lung tissue also confirmed this result. When prednisolone was orally administered at 3 mg kg−1 day−1 from day 1 to 6 after OVA inhalation, the inflammation in lung tissue, the number of eosinophils in BAL fluids and airway hyperreactivity were reduced in the OVA-sensitized mice. However, prednisolone did not reduce the OVA-specific IgE antibody titer in BAL fluids and did not recover the expression of spectrin α2 in lung tissue. These results suggest that at least a part of action mechanism of SST against OVA-sensitized allergic airway inflammation in a mouse model is different from that of prednisolone