Inhibitory Effect of Bisdemethoxycurcumin on DNCB-Induced Atopic Dermatitis in Mice.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Bisdemethoxycurcumin (BDMC) is an ingredient from the rhizome of the traditional Chinese herbal medicine turmeric. BDMC has been reported to have important pharmacological properties, such as anti-inflammatory, antioxidant, antitumor and antiproliferative activities. However, its effect on atopic dermatitis has not been reported. The purpose of our study was to demonstrate the effectiveness of BDMC on TNF-α/IFNγ-stimulated HaCaT cells and on 2,4-dinitrochlorobenzene (DNCB)-induced AD mice. Our studies showed in vitro that BDMC was able to significantly inhibit the mRNA expression of chemokines and cytokines in TNF-α/IFN-γ-stimulated HaCaT cells and alleviate their inflammatory response. Our studies found in vivo that BDMC was able to significantly improve the symptoms of DNCB-induced AD skin lesions, decrease the number of scratches, ear thickness, and spleen index, improve inflammatory cells and mast cell infiltration and decrease skin thickness. Moreover, it was also able to inhibit the mRNA expression levels of chemokines and inflammatory cytokines and the activation of the MAPK and NF-κB signaling pathways. Thus, the results indicated that BDMC can improve atopic dermatitis in mice and that further clinical studies are warranted on its treatment of AD.

A new ocotillol-type ginsenoside from stems and leaves of Panax quinquefolium L. and its anti-oxidative effect on hydrogen peroxide exposed A549 cells.

A new ocotillol-type ginsenoside, namely 12-one-pseudoginsenoside F11 (12-one-PF11), was isolated from stems and leaves of Panax quinquefolium, whose structure was elucidated 6-O-[α-L-rhamnopyranosyl-(1-2)-ß-D-glucopyranosyl]-dammar-12-one-20S,24R-epoxy-3ß,6α,25-triol. 12-one-PF11 significantly suppressed hydrogen peroxide induced oxidative stress in human lung carcinoma A549 cells. As compared with model group, 12-one-PF11 improved cell viability of A549 cells in a dose-dependent manner, and significantly decreased the generation of malondialdehyde (MDA) and increased production of superoxide dismutase (SOD) and glutathione (GSH) and protein expression levels of nuclear related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in A549 cells.

Berberine suppresses mast cell-mediated allergic responses via regulating FcɛRI-mediated and MAPK signaling.

The anti-allergic effect of berberine was evaluated in cellular and animal models of allergic responses. In this study, the results of the in vitro model of immunoglobulin (Ig) E-mediated mast cell degranulation showed that berberine significantly inhibited the release of ß-hexosaminidase (ß-HEX), histamine, IL-4 and TNF-α in rat basophilic leukemia cells (RBL-2H3 cells). Pretreatment with berberine prevented morphological changes in IgE-stimulated RBL-2H3 cells such as the recovery of an elongated shape. Pretreatment with berberine also suppressed the phosphorylation of antigen-induced Lyn, Syk, and Gab2, thus suppressing the downstream MAPK pathways. In the in vivo model of allergic responses, administration of berberine inhibited passive cutaneous anaphylaxis (PCA) in mice. The above results indicate berberine could suppress mast cell activation and allergic responses.

Anti-inflammatory effect of epigallocatechin gallate in a mouse model of ovalbumin-induced allergic rhinitis.

Currently, a variety of studies have demonstrated that green tea has anti-allergic properties, and the major polyphenolic compound, epigallocatechin gallate (EGCG), plays a significant role. Some research indicates that EGCG reduces the production and expression of allergy-related substances. Therefore, EGCG has a potential effect of reducing allergic rhinitis (AR). In this study, the effect of EGCG on allergic rhinitis in an ovalbumin (OVA)-induced mouse model was investigated. After administration of EGCG, the number of sneezes and the occurrence of nasal rubbing were significantly decreased, the concentrations of immunoglobulin E (IgE) and histamine were suppressed in AR mouse serum, the levels of interleukin (IL)-1ß, IL-4, and IL-6 were reduced in AR mice nasal lavage fluid (NLF), and the nasal mucosa mRNA and protein expression of cyclooxygenase 2 (COX-2), IL-1ß, IL-4, and IL-6 were inhibited. The data indicate that EGCG has a beneficial effect of reducing allergic rhinitis.

Effect of Quercetin in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-Induced Mouse Model of Parkinson's Disease.

In this paper, the protective effect of the bioflavonoid quercetin on behaviors, antioxidases, and neurotransmitters in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-(MPTP-) induced Parkinson's disease (PD) was investigated. Quercetin treatment (50 mg/kg, 100 mg/kg and 200 mg/kg body weight) was orally administered for 14 consecutive days. The results show that quercetin treatment markedly improves the motor balance and coordination of MPTP-treated mice. Significant increases were observed in the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and Na(+), K(+)-ATPase, AchE, the content of dopamine (DA) in the quercetin plus MPTP groups compared to those in the MPTP group. Significant reduction the 4-hydroxy-2-nonenal (4-HNE) immunoreactivity in striatum of brains was observed in the quercetin plus MPTP groups in comparison to the MPTP group. Taken together, we propose that quercetin has shown antiparkinsonian properties in our studies. More work is needed to explore detailed mechanisms of action.

Evaluation of immunological effects of hochu-ekki-to (TJ-41) prophylactic administration in mice.

We evaluated the immunological effects of a Kampo (Chinese) prescription Hochuekki-to (TJ-41) for 32 weeks and 1 week prophylactically in mice, The splenic natural killer cells (NK) of C57BL/6N mice prophylactically treated with TJ-41 for 32 weeks showed little enhanced cytotoxicity against NK-sensitive YAC-1 targets, but mice treated for 1 week showed significantly enhanced cytotoxicity. TJ-41 administration for 32 weeks increased the splenic NK cell population and CD4/CD8 significantly, but TJ-41 for 1 week was not affected. Further, there were no adverse effects of TJ-41 administration for 32 weeks. Whether or not that duration of administration can have the same beneficial effects on humans await further studies.

Effects of Inula Britannica on the production of antibodies and cytokines and on T cell differentiation in C57BL/6 mice immunized by ovalbumin.

In this study, we investigated the effects of Inula Britannica on the production of antibodies against ovalbumin, and the differentiation of T cells, in C57BL/6 mice. The oral administration of Inula Britannica suppressed IL-4 and IL-6 production in lymphocytes collected from an inguinal lymph node in the immunized leg. On the other hand, the intraperitoneal administration of Inula Britannica suppressed IgG1 production, the ratio of IFN-gamma+IL-4-/IFN-gamma-IL-4+ cells and cytokine production of IL-6. It was presumed that the effects of Inula Britannica on the production of antibodies were induced by regulation of the balance of Th1 and Th2. Further, IL-4 and IL-6 production by lymphocytes collected from an inguinal lymph node in the immunized leg were suppressed, and therefore production of antibodies was suppressed.

Preventative effects of the flowers of Inula britannica on autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocin.

We have reported that an aqueous extract from the flowers of Inula britannica L. subsp. japonica Kitam. (IB) prevented immunologically induced experimental hepatitis in mice and suggested that the antihepatitic effect of IB is due to inhibition of IFN-gamma production. We then investigated the effects of IB on diabetes in mice induced by multiple low doses of streptozotocin (MLDSTZ), which is a mouse model for IFN-gamma-dependent autoimmune diabetes. C57BL/KsJ mice (male, 7 weeks) were provided with IB extract (500 mg/ kg/ day) in drinking water ad libitum, starting 7 days before the first STZ injection. Autoimmune diabetes was induced by MLDSTZ (40 mg/kg/day for 5 daily doses, i.p.). The IB treatment significantly suppressed the increase of blood glucose levels. Histological analysis of the pancreas showed that the degree of insulitis and destruction of beta-cells were reduced by IB treatment. The IFN-gamma production from stimulated splenic T lymphocytes was inhibited by the IB treatment. Moreover, the proportion of IFN-gamma-producing cells in the CD4(+) population, which was increased by MLDSTZ, was significantly decreased by the IB treatment. These results suggest that IB has a preventative effect on autoimmune diabetes by regulating cytokine production.

Augmentation of immune cell activity against tumor cells by Rauwolfia radix.

In this study, we investigated the effect of Rauwolfia radix on heat shock protein (HSP) 70 expression and cytotoxicity against tumor cells in activated human T cells. When activated T cells were cultured with Rauwolfia radix for 18 h, HSP70 expression after heat shock was remarkably increased, and cytotoxicity against T98G tumor cells was augmented. Moreover, Rauwolfia radix also enhanced the cytotoxicity of heat shocked activated T cells against Molt-4 and T98G tumor cells. Secretions of interferon-gamma (IFN-gamma) and tumor necrosis alpha (TNF-alpha), due to Concanavalin A (Con A) stimulation, were increased by Rauwolfia radix in activated T cells. To investigate the antitumor effect in vivo, EL-4 tumor-bearing mice were administered with Rauwolfia radix in drinking water. The survival period of the Rauwolfia radix treatment group was significantly prolonged compared with that of the control group. Reserpine, the major active ingredient of Rauwolfia radix, also enhanced the cytotoxicity of activated T cells against Molt-4 and T98G tumor cells, and prolonged the survival period of EL-4 tumor-bearing mice. Taken together, our results suggest that Rauwolfia radix can enhance the activity of immune cells against tumor cells.

Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodium-induced colitis in mice.

The anti-inflammatory effect of three flavonoids from the root of Scutellaria baicalensis (baicalein, baicalin and wogonin) was evaluated in a murine model of acute experimental colitis induced by dextran sulfate sodium (DSS). Baicalein, but not baicalin or wogonin, given orally at 20 mg/kg for ten days, ameliorates all the considered inflammatory symptoms of the induced colitis, such as body weight loss, blood haemoglobin content, rectal bleeding and other histological and biochemical parameters. The effect of baicalein was similar to that of sulfasalazine, the reference drug given at 50 mg/kg.

Protective effects of Polygalae root in experimental TNBS-induced colitis in mice.

In this study, the protective effect of Polygalae root was evaluated in a murine model of experimental colitis by intrarectal injection with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Polygalae root, given orally at 2, 4 g/kg body weight of herbs once a day consecutively for 9 days, could recover the lost body weight and decrease the gross rectal bleeding. Polygalae root also reduced the degree of inflammation and improved significantly the histological changes such as infiltration by polymorphonuclear leukocytes and multiple erosive lesions. Furthermore, the cytokine production of intraepithelial lymphocytes was analyzed. The results showed that IFN-gamma was increased, but IL-4 was decreased in TNBS-induced colitis, when those were compared with the sham controls. But the administration of Polygalae root to TNBS-induced colitis mice showed lower production of IFN-gamma and higher production of IL-4 than the TNBS-induced colitis. These results suggest that the protective effects of Polygalae root against the TNBS colitis may be associated with the regulation of cytokine production of intraepithelial lymphocytes.

The combination therapy of Ephedra herb and Loxoprofen caused gastric lesions in mice.

The combination therapy of a Kampo formula and an analgesic-antipyretic agent is often used for the common cold in Japan. We investigated the effect of such a combination therapy, using the Ephedra herb, which is a common ingredient of Kakkon-to and Mao-to, and Loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID), on fever induced in an experimental model of mice under strong stress. The combination therapy of Ephedra herb and Loxoprofen caused gastric mucosal lesions and loss of body weight. It is considered that this combination therapy should be avoided because of its adverse effects.

Effect of Kampo herbal medicines on murine water metabolism in a microgravity environment.

To determine the possibility of new applications of Oriental medicines, we examined the changes in water metabolism of mice that underwent microgravity and were treated with Kampo medicines. Male ICR mice were used in this experiment. Eight extracts of Kampo herbal medicines were dissolved in water and added to the drinking water administered to mice at 1 g/kg body weight for two days. The microgravity experiment was performed at the Japan Microgravity Center. We used a drop-shaft type microgravity experimental system with a free fall of 490 m. Before the drop, 7 ml of physiological saline was injected intraperitoneally. Under fasting and dehydration, body weights were measured and loss of body weight was calculated as urine. Blood samples were collected 24 hours after the microgravity experiment, and the antidiuretic hormone (ADH) in plasma related to water metabolism was measured by the radioimmunoassay (RIA) method. Heat shock protein in the spleen was measured by the enzyme-linked immunosolvent assay (ELISA) method. In the Hachimi-jio-gan and Hochu-ekki-to groups in microgravity, a decrease of urine was observed, which significantly suppressed the increase of ADH due to microgravity. Hachimi-jio-gan reduced the content of heat shock protein (HSP) 70 in the spleen. It is suggested that Hachimi-jio-gan and Hochu-ekki-to could be used as water metabolism adjustment reagents in a space environment. Furthermore, it is suggested that Hachimi-jio-gan could ease the stresses caused by microgravity. The physiological changes resulting from a microgravity environment are serious problems for space flight. Pre-treatment with Kampo medicines is expected to prevent, ease and treat these problems.