Tie Hong

Effects of Astragali root and Hedysari root on the murine B and T cell differentiation.

It has traditionally been known in Asian countries that the Astragali and Hedysari roots have similar beneficial effects. They have been applied in clinical practice for immunological diseases, we investigated their effects on specific antibody production, B cells and T cells in BALB/c mice immunized with ovalbumin (OVA). Both the Astragali and Hedysari roots reduced the production of IgG2a in the primary response to OVA. Hedysari root reduced the production of IgG2a in the secondary response. Both reduced the production of IgM, suppressed IL-6 production in spleen cells. It was presumed that the suppression of IgG2a production was induced by the suppression of IL-6, which is an antibody production inducer. It was found that the Hedysari root increased the B cells and activated them, and the Astragali root also tended to increase them. In addition, Hedysari root decreased the proportions of IFN-gamma-producing cells in splenic CD4(+) T lymphocytes. It was shown that the Astragali and Hedysari roots could act as a growth factor of B cells by increasing the proportion of the total B cells and activated B cells. In conclusion, both the Astragali and Hedysari roots showed the same actions, but the latter was more effective.

Hepatoprotective effects of Inula britannica on hepatic injury in mice.

Inula britannica, a Kampo medicine, is prepared from the heads of Compositae plants such as Inula britannica L., which has been used clinically as a remedy for nausea, hiccup and excessive sputum. Here it is shown that administration of Inula britannica improves the survival rate of mice with hepatic injury induced by LPS/PA. It is also suggested that administration of Inula britannica significantly reduces the fluctuation in the amount of cytokine in the spleen of mice with hepatic injuries, and that the Th1/Th2 control effect is related to the inhibitory action of Inula britannica against hepatic injury. In vitro testing suggests that Inula britannica suppresses Th1 differentiation and induces Th2 differentiation by inhibiting the production of macrophage IL‐12 and promoting the production of IL‐10, thus showing the immunological effect of hepatic injury inhibition by affecting the balance between Th1 and Th2. Copyright © 2000 John Wiley & Sons, Ltd.

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.

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.

Preventive Effect of Ninjin-to (Ren-Shen-Tang), a Kampo (Japanese Traditional) Formulation, on Spontaneous Autoimmune Diabetes in Non-Obese Diabetic (NOD) Mice

We previously found that ingestion of an extract of Ninjin‐to (NJT; Ren‐Shen‐Tang) suppressed the development of autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocin. To verify this effects on spontaneous autoimmune diabetes, the effects of NJT on NOD mice were investigated in the present study. NJT, provided in drinking water (0.25%, 450 mg/kg/day) from 6 weeks of age, significantly prevented the incidence of spontaneous diabetes in female NOD mice at 30 weeks of age (2/10) compared with that of the controls (7/10), with no effects on body growth or food intake. Even in non‐diabetic mice, the blood glucose levels of the NOD controls gradually increased with age, while such increase in NJT‐treated mice was significantly suppressed by preventing any deficiency of glucose tolerance. NJT also significantly suppressed the progression of insulitis, which causes insulin deficiency and diabetes. It is well known that NOD mice develop insulitis and diabetes because of their Th1‐dominant autoimmune response. IFN‐γ production from splenic T lymphocytes stimulated with anti‐CD3 monoclonal antibodies was increased, whereas IL‐4 production was decreased in NOD controls compared to age‐ and sex‐matched normal ICR mice. NJT‐treatment reduced these deviations of cytokine production in NOD mice. These data all suggest that NJT can prevent spontaneous insulitis and diabetes by the modification of deviated cytokine production in NOD mice.

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.

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.

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.

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.

Differential expression of hsp60 and hsp70 associated with cytotoxicity under microgravity conditions.

It is known that space flight affects T lymphocyte function in both humans and animals, but there have been no papers dealing with the effect of microgravity conditions for a very short time (i.e., only 10 s). In the present study, the effect of very short time microgravity on the cytotoxicity and surface markers of human activated T lymphocytes, in vitro, was investigated using the drop-shaft type of microgravity experiment system. The levels of heat shock protein 60 and 70 (hsp60 and hsp70) were also quantified in cells exposed to these microgravity conditions. The results showed that not only the cytotoxicity but also the hsp60 levels were remarkably reduced under these conditions.