Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats.

AIM: To examine the efficacy of glycyrrhizin preparation (GL-p) in the treatment of a rat model of ulcerative colitis (UC). METHODS: Experimental colitis was induced by oral administration of dextran sodium sulfate. Rats with colitis were intrarectally administered GL-p or saline. The extent of colitis was evaluated based on body weight gain, colon wet weight, and macroscopic damage score. The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis. The effect of GL-p on myeloperoxidase (MPO) activity in the inflamed mucosa and purified enzyme was assayed. RESULTS: GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline. Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant-2, and monocyte chemoattractant protein-1 in the inflamed mucosa. Furthermore, GL-p inhibited the oxidative activity of mucosal and purified MPO. CONCLUSION: GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

[PSK-mediated growth suppression and enhancement of 5-FU/docetaxel-induced cytotoxicity in human esophageal cancer cell lines].

PSK, a protein-bound polysaccharide, is widely used for treating cancer patients as an immunostimulant. However, its direct action on cancer cells is not fully understood. In the present study, we investigated direct effects of PSK alone or in combination with 5-FU, CDDP and docetaxel on tumor growth by using esophageal cancer cell lines, KYSE170 and TE13. Cells were incubated with different concentrations of PSK for 72 hour, and cell viability was determined by WST-8 assay, and cell cycle was analyzed by flow cytometry. As a result, PSK of 100 microg/mL induced growth suppression dose-dependently in the both cell lines, and flow cytometric analysis showed a PSK dose-dependent increase of sub-G1 cells indicating apoptotic cells. In addition, when cells were incubated with different concentrations of 5-FU and docetaxel in the presence of PSK at the dose of 5 microg/mL showing no growth suppression, cytotoxicity induced by 5-FU and docetaxel was significantly enhanced. These results indicate that PSK not only shows tumor growth suppression by apoptosis induction, but also enhances 5-FU and docetaxel-induced cytotoxicity.

Pueraria mirifica phytoestrogens improve dyslipidemia in postmenopausal women probably by activating estrogen receptor subtypes.

Impaired lipid metabolism is an important health problem in postmenopausal women with insufficient estrogens, because dyslipidemia is a risk factor for development of atherosclerosis and the incidence of cardiovascular disease markedly increases after menopause. Pueraria mirifica (PM), a Thai herb, has been noticed as a source of phytoestrogens, estrogen-mimicking plant compounds. However, the clinical effects of PM on lipid metabolism and the underlying molecular mechanisms remain undetermined. Therefore, we examined the effects of PM on serum lipid parameters in a randomized, double-blind, placebo-controlled clinical trial. Nineteen postmenopausal women were randomly assigned to receive oral administration of PM powder or placebo. After 2 months of treatment, the PM group showed a significant increase in serum concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-1 (34% and 40%, respectively), and a significant decrease in low-density lipoprotein (LDL) cholesterol and apo B (17% and 9%, respectively), compared with baseline measurements. Moreover, significant decreases were observed in the ratios of LDL cholesterol to HDL cholesterol (37%) and apo B to apo A-1 (35%). Next, we determined the effects of PM phytoestrogens on the activation of estrogen receptor (ER)-mediated transactivation by transient expression assays of a reporter gene in cultured cells. Among PM phytoestrogens, miroestrol and coumestrol enhanced both ERalpha- and ERbeta-mediated transactivation, whereas other phytoestrogens, including daidzein and genistein, preferentially enhanced ERbeta-mediated transactivation. In conclusion, PM has a beneficial effect on lipid metabolism in postmenopausal women, which may result from the activation of gene transcription through selective binding of phytoestrogens to ERalpha and ERbeta.

Zinc ions suppress mitogen-activated interleukin-2 production in Jurkat cells.

Calcineurin (CN) is thought to play an important role in the immune system by regulating cytokine production, for example, interleukin-2 (IL-2) in T-lymphocytes. We have previously shown that physiological concentrations of Zn2+ inhibit CN activity in vitro [K. Takahashi, E. Akaishi, Y. Abe, R. Ishikawa, S. Tanaka, K. Hosaka, Y. Kubohara, Zinc inhibits calcineurin activity in vitro by competing with nickel, Biochem. Biophys. Res. Commun. 307 (2003) 64-68], in spite of the fact that Zn2+ is an essential element of the CN catalytic domain. In this study, in order to assess whether Zn2+ regulates (suppresses) CN activity in vivo and whether Zn2+ can be used as an anti-inflammatory and/or immunosuppressive drug, we examined the effects of Zn2+ on IL-2 production induced by the mitogen, concanavalin A (ConA), in Jurkat T-cells. Zn2+ at 0.2 mM suppressed ConA-induced IL-2 accumulation in the medium of an in vitro culture of Jurkat cells. Zn2+ at 0.03-0.3 mM dose-dependently suppressed ConA-induced IL-2 mRNA expression in Jurkat cells. Zn2+ also suppressed IL-2 mRNA expression induced by phorbol ester (PMA) and ionomycin. Furthermore, Zn2+ and the immunosuppressant FK506 showed an additive inhibitory effect on ConA-induced IL-2 mRNA expression. These results suggest that exogenously added Zn2+ may disturb (increase) the intracellular Zn2+ concentration and inhibit CN activity, thereby suppressing IL-2 production in Jurkat cells. The present study further indicates that Zn2+ may have therapeutic potential in the treatment of T-cell related inflammation and also that Zn2+ may be utilized as a supplemental drug with FK506.

Metronidazole plus ciprofloxacin therapy for active Crohn's disease.

OBJECTIVE: The aim of this study was to investigate the efficacy of metronidazole plus ciprofloxacin for the treatment of Japanese patients with active Crohn's disease. METHODS AND PATIENTS: Seven patients (counting one patient twice with 2 enrollments at a 5-month interval) with a flare-up of Crohn's disease were enrolled. While continuing the baseline treatment under which the patients relapsed, they received metronidazole 250 mg twice (4 patients) or three times (3 patients) daily plus ciprofloxacin 200 mg three times daily for 4 weeks. The efficacy was evaluated by the changes in the assessment score of IOIBD, the International Organization for the Study of Inflammatory Bowel Disease, and the inflammation markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count. RESULTS: Metronidazole plus ciprofloxacin decreased the CRP in seven patients and the IOIBD score in six patients. Significant differences were detected in these parameters at weeks 2 and 4 compared with baseline. Five of the patients achieved normalization of CRP and a reduction of the IOIBD score to zero or one. Although one patient complained of taste disturbance, no other adverse events occurred and all patients completed the 4 weeks of study medication. CONCLUSION: The addition of metronidazole plus ciprofloxacin could be a useful intervention for the treatment of Japanese patients with active Crohn's disease.