concanavalin-a and genipin

We investigated the modulation of innate and adaptive immune cell activation by Eucommia ulmoides Oliver extract (EUE) and its ingredient genipin. As an innate immunity indicator, the phagocytic activity of macrophages was determined by measuring engulfed, fluorescently labeled Escherichia coli. As a surrogate marker for the respective activation of cellular and humoral adaptive immunity, concanavalin A (Con A) and lipopolysaccharide (LPS) induction of primary splenocyte proliferation was assayed in in vitro and ex vivo systems. EUE and genipin suppressed the proliferation of primary splenic lymphocytes induced by Con A or LPS, but not macrophage phagocytosis. Oral administration of EUE and genipin to mice decreased splenic lymphocyte proliferation induced by Con A or LPS. These results revealed that E. ulmoides and genipin suppressed cellular and humoral adaptive immunity, and they suggest that E. ulmoides and genipin are promising candidates for immunosuppressive drugs that target diseases that involve excessive activation of adaptive immunity.

Topics: Adaptive Immunity; Administration, Oral; Animals; Cell Proliferation; Concanavalin A; Eucommiaceae; Immunosuppressive Agents; Iridoids; Lipopolysaccharides; Lymphocytes; Macrophages; Male; Mice, Inbred BALB C; Phagocytosis; Plant Extracts; Spleen

Glucose-responsive systems are significant for self-regulated insulin delivery. The aim of this study was to assess the potential of genipin-crosslinked concanavalin A/GEA-chitosan microgels as a glucose-responsive insulin delivery system. A chitosan derivative (GEA-chitosan) was designed in this study as the polymer ligand of concanavalin A (Con A), which not only exhibits a strong affinity to Con A, but also could be directly crosslinked with Con A by genipin, thus avoiding the modification of Con A during an immobilization process. Glucose responsive microgels were fabricated by the reversed-phase emulsion crosslinking method. The in vitro release of insulin indicated that the insulin release was influenced by glucose concentrations, and a desired pulsatile release behavior was detected in response to stepwise glucose challenges for more than eight cycles. The release data were fitted well to an exponential model, without any significant influence of the surface effect. The released insulin was proved to remain active without destruction of the tertiary structure. The analysis of L929 cells viability suggested that these microgels possessed no in vitro cytotoxicity. The obtained genipin crosslinked Con A/GEA-chitosan microgels might be a potential candidate for self-regulated insulin delivery.

Topics: Animals; Cell Line; Cell Survival; Chitosan; Concanavalin A; Cross-Linking Reagents; Drug Delivery Systems; Fibroblasts; Gels; Glucose; Insulin; Iridoids; Mice

The traditional Japanese (kampo) medicine inchinkoto (ICKT) is used in Eastern Asia as a choleretic and hepatoprotective agent. Previously, we reported that ICKT ameliorates murine concanavalin A (con A)-induced hepatitis via suppression of interferon (IFN)-gamma and interleukin (IL)-12 production. In the present study, we investigated the active ingredients of ICKT.. ICKT and extracts of its component herbs were fractionated, and their effects on liver injury and cytokine production in vivo (biochemical markers of liver injury and cytokine levels in serum) and in vitro (cytokine and nitrite production in the cultures of splenocytes and peritoneal macrophages).. Decoctions of component herbs, Artemisiae Capillari Spica (Artemisia capillaris Thunberg: 'Inchinko' in Japanese), Gardeniae Fructus (Gardenia jasminoides Ellis: 'Sanshishi') and Rhei Rhizoma (Rheum palmatum Linné: 'Daio') were administered orally. Inchinko and Sanshishi decreased serum transaminases and IFN-gamma concentrations. Examination of fractions of component herbs suggested that capillarisin, a component of Inchinko, has potent hepatoprotective activity in vivo. In in vitro studies, capillarisin and genipin, an intestinal metabolite of geniposide that is contained in Sanshishi, were examined. IFN-gamma production was significantly suppressed by capillarisin and genipin in con A-stimulated splenocyte culture. Genipin also suppressed IL-1beta, IL-6, and IL-12p70 synthesis. Capillarisin and genipin decreased nitrite release from IFN-gamma-stimulated macrophages.. These results suggested that both Inchinko and Sanshishi may contribute to the protective effects of ICKT against con A hepatitis. Capillarisin was found to be potently hepatoprotective, and genipin may also contribute, especially via modulation of cytokine production.

Topics: Animals; Artemisia; Chemical and Drug Induced Liver Injury; Chromones; Concanavalin A; Cytokines; Disease Models, Animal; Gardenia; Hepatitis; Interferon-gamma; Iridoid Glycosides; Iridoids; Liver; Macrophages; Magnoliopsida; Male; Medicine, Kampo; Mice; Mice, Inbred BALB C; Nitrites; Phytotherapy; Plant Extracts; Rheum; Transaminases