G1-4A, an immunomodulatory polysaccharide from Tinospora cordifolia, modulates macrophage responses and protects mice against lipopolysaccharide induced endotoxic shock

Pro-inflammatory cytokines are known to be the mediators of endotoxic shock and several immunomodulatory herbs can modulate the expression of these cytokines. Therefore we have investigated the possibility of using an arabinogalactan polysaccharide, Gl-4A, from the stem of Tinospora cordifolia, for protection against endotoxin induced sepsis. There was 100% protection against lipopolysaccharide (LPS) induced mortality in mice pretreated with Gl-4A. To elucidate the mechanism of action, its effect on macrophages, the primary source of these pro-inflammatory molecules was evaluated. G l-4A was shown to bind to the murine macrophages leading to their activation and reciprocally inhibited binding of LPS to macrophages. Following treatment with Gl-4A, there was a small increase in serum TNF-alpha and IL-l beta levels. However, challenge with LPS elicited significantly reduced levels of TNF-a in G l-4A pretreated mice as compared to the controls while the level of soluble TNFR was enhanced. An increase in serum IL-l beta, IL-6, IFN-gamma levels and decrease in that of IL-10 was observed following challenge with LPS in mice pretreated with Gl-4A as compared to the controls. In addition, Gl-4A also modulated the release of nitric oxide by murine macrophages. Similar phenomenon was observed in a human monocytic cell line, U937. Thus Gl-4A appeared to induce tolerance against endotoxic shock by modulation of cytokines and nitric oxide. (c) 2007 Elsevier B.V. All rights reserved.