concanavalin-a and artemisinin

Artemisinin (Art) is a sesquiterpene trioxane lactone from Artemisia annua L., which has been shown to affect immune responses. However, the underlying mechanism remains elusive. In this study, we examined the anti-inflammatory and immunomodulatory effects of Art in a mouse model of contact hypersensitivity (CHS), a T-cell-mediated cutaneous inflammatory reaction. The data showed that topical administration of Art could suppress CHS response and Con A-induced T cell proliferation effectively. Further experiments indicated that Art induced the generation of regulatory T cells (Tregs) and impaired the phosphorylation of AKT, associated with the up-regulation of p38 MAPK activation. Moreover, Art also exerted a strikingly inhibitory effect on IL-17 production, and diminished the level of IL-6 paralleled with an enhancement of TGF-β, which effects were coupled with a significant reduction of STAT3 activation. These data reveal that Art could effectively block CHS response in mice by inducing the generation of Tregs and suppressing the development of Th17, indicating the potential of Art to be applied as an effective therapeutic agent for treating immune-related diseases.

Topics: Animals; Anti-Inflammatory Agents; Artemisinins; Concanavalin A; Cytokines; Dermatitis, Contact; Dinitrofluorobenzene; Disease Models, Animal; Female; Immunologic Factors; Irritants; Lymph Nodes; Mice; Mice, Inbred BALB C; Mitogens; Organ Size; Phytotherapy; Spleen; T-Lymphocytes, Regulatory; Th17 Cells

Another series of novel dihydroartemisinin derivatives were synthesized and assessed for their cytotoxicity of lymphocyte, inhibitory activity on mitogen-induced spleen lymphocyte proliferation in vitro. Some of the compounds exhibited inhibitory effects on ConA-induced T cell and LPS-induced B cell proliferation comparable to or more potent than parent artemisinin.

Topics: Artemisinins; B-Lymphocytes; Cell Proliferation; Concanavalin A; Esters; Immunosuppressive Agents; Lipopolysaccharides; Lymphocytes; Propionates; Sesquiterpenes; Spleen

A series of novel dihydroartemisinin derivatives were synthesized and evaluated on their immunosuppressive activity in the search for potential immunosuppressive agents with high efficacy and low toxicity. These compounds were assayed in their cytotoxicity of lymphocyte, inhibition activity on concanavalin A (ConA) induced T cell proliferation and lipopolysaccharide (LPS) induced B cell proliferation. Among them, 11b, 13b, 14d, 15b, 16, and 17 remarkably exhibited lower cytotoxicity and higher inhibition activity on the mitogen-induced T cell and B cell proliferation in comparison with artemisinin, artesunate, and artemether in vitro. More significantly, compound 11b displayed reduced cytotoxicity by over 100-fold compared with cyclosporin A (CsA) and comparable inhibition activity (SI = 848) on ConA-induced T cell proliferation to CsA (SI = 963) and more than 4000 times the inhibitory effect (SI = 28473) on LPS-induced B cell proliferation compared with CsA (SI = 7) in vitro. The in vivo experimental results showed that compound 16 could inhibit 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type hypersensitivity (DTH) reaction and sheep red blood cell (SRBC) induced antibody production, respectively. The structure and activity relationships (SAR) of these compounds were also discussed.

Topics: Animals; Antibody Formation; Artemisinins; B-Lymphocytes; Cell Proliferation; Concanavalin A; Dinitrofluorobenzene; Erythrocytes; Esters; Fatty Acids; Female; Hypersensitivity, Delayed; Immunosuppressive Agents; In Vitro Techniques; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Mitogens; Sesquiterpenes; Sheep; Structure-Activity Relationship; T-Lymphocytes

Artemisinin and its derivatives, dihydroartemisinin and sodium artesunate, enhanced DNA synthesis of mouse spleen cells that had been activated with alloantigens or T cell mitogen Con A, but not B cell mitogen LPS, both in vitro and ex vivo. In vivo experiments showed that DTH response and antibody response against sheep erythrocytes were augmented in sodium artesunate-treated animals. In addition, sodium artesunate, a representative of these compounds, increased IL-2 production from mouse splenocytes stimulated with Con A. Because of the long-term T cell function deficiency in mice after bone marrow transplantation, the effect of sodium artesunate on the immune reconstitution was assessed. The results demonstrated that 10 mg/kg sodium artesunate significantly accelerated the immune reconstitution in mice after syngeneic bone marrow transplantation. These data suggested that artemisinin and its derivatives appeared to promote T cell function selectively, and these compounds had a potential application for the recovery of immune function.

Topics: Adjuvants, Immunologic; Analysis of Variance; Animals; Antimalarials; Artemisinins; Artesunate; B-Lymphocytes; Bone Marrow Transplantation; Concanavalin A; DNA; Dose-Response Relationship, Immunologic; Female; Hypersensitivity, Delayed; Immunity, Cellular; Interleukin-2; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Sesquiterpenes; Spleen; T-Lymphocytes