The new water-soluble artemisinin derivative SM905 ameliorates collagen-induced arthritis by suppression of inflammatory and Th17 responses.

BACKGROUND AND PURPOSE: Our previous study showed that SM905, a novel artemisinin derivative, exhibited potent immunosuppressive activity. In this study, we evaluate preventive and therapeutic effect of SM905 on collagen-induced arthritis (CIA) in DBA/1 mice, and investigate its mechanisms both in inflammatory and autoimmune aspects of the disease. EXPERIMENTAL APPROACH: CIA was induced by type II bovine collagen (CII) in DBA/1 mice. SM905 was given orally either before (continuously 1 day before booster immunization) or after disease onset (continuously 14 days after booster immunization). Disease incidence and severity were monitored, mRNA expression of proinflammatory mediators was determined by real-time PCR, purified T cell proliferation was assessed using [(3)H]-thymidine incorporated assay, and T helper (Th) 17/Th1/Th2 type cytokine production was examined by ELISA. KEY RESULTS: Oral treatment with SM905 delayed disease onset, reduced arthritis incidence and severity, and suppressed the enhanced expression of pro-inflammatory cytokines, chemokines and chemokine receptors in draining lymph nodes. The CII-induced T cell proliferation and production of interleukin (IL)-17A by T cells were strikingly inhibited. Correspondingly, the mRNA expression of IL-17A and RORgamma t (a specific transcription factor for Th17) was also reduced. This effect was coupled with a striking reduction of IL-6 production, which has a critical role in Th17 development. In established arthritis, SM905 profoundly inhibited disease progression, reduced IL-17A and RORgamma t mRNA expression, and suppressed pro-inflammatory mediator expression in arthritic joints. CONCLUSIONS AND IMPLICATIONS: SM905 had beneficial effects on CIA by suppressing inflammatory and pathogenic Th17 responses.

Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation.

BACKGROUND AND PURPOSE: Artemisinin and its derivatives exhibit potent immunosuppressive activity. The purpose of the current study was to examine the immunosuppressive activity of artemether directly on T lymphocytes and to explore its potential mode of action. EXPERIMENTAL APPROACH: In vitro, T-cell proliferation was measured using [(3)H]-thymidine incorporation assay in cells stimulated with ConA, alloantigen and anti-CD3 antibody. CFSE-labeled cell division and cell cycle distribution were monitored by flow cytometry. In vivo, the effects of artemether were evaluated in delayed-type hypersensitivity (DTH) and purified T-cell responses to ovalbumin in ovalbumin-immunized mice. The activation of extracellular signal-regulated kinase1/2 (ERK1/2) and Raf1 were assessed by Western blot analysis and the activation of Ras was tested in pull-down assays. KEY RESULTS: We show that, in vitro, artemether suppressed ConA- or alloantigen-induced splenocyte proliferation, influenced production of the cytokines IL-2 and IFN-gamma and inhibited cell cycle progression through the G0/G1 transition. In vivo, administration of artemether attenuated CD4 T-cell-mediated DTH reaction, and suppressed antigen-specific T-cell response in immunized mice. Further experiments showed that, treatment with artemether impaired both antigen- and anti-CD3-induced phosphorylation of ERK. In primary T cells, artemether profoundly inhibited anti-CD3-induced phosphorylation of Raf1 and activation of Ras. CONCLUSIONS AND IMPLICATIONS: This study provided experimental evidence of the immunosuppressive effects of artemether directly on T cells both in vitro and in vivo. Its immunosuppressive mechanism involved inhibition of the activation of the Ras-Raf1-ERK1/2 protein kinase cascade in T cells.

Influence of medicinal herbs decocted with different utensils on colony formation of gastric carcinoma cells.

In order to elucidate the different results obtained in cancer patients with similar condition and symptoms treated by the same medicinal herbs, an investigation of the utensils used for making decoctions was carried out. It was found that the decoction made by means of glassware, enamel and earthenware pots had the best effect of inhibiting the colony formation of human gastric carcinoma cells, the next were the decoctions made by means of unrefined iron pots, stainless steel pots and copper pots, and the worst was that made with aluminium pots. It was also found that there was no difference between the water contained in those utensils and normal saline in the influence on the colony formation of human gastric carcinoma cells. Therefore, it is believed that the difference in effect of the decoctions made by means of different kinds of utensils is not due to the trace dissolution of the utensil materials, but is most likely due to the occurrence of some chemical reactions while making the decoction. That the decoctions made by means of different utensils had different peak values in the absorption spectrum also supports this proposition.