Iron modulatory property of a polysaccharide from Indian medicinal plant Ocimum sanctum.

Despite being an essential element for normal functioning of cells and organisms, iron, in excess, can induce oxidative stress by generating reactive oxygen species. A water-soluble, non-toxic iron chelator can reduce the iron-induced oxidative stress in the body as well as help in extricating excess iron. Herein, we report an Ocimum sanctum-derived antioxidant polysaccharide (OSP) that inhibits the deleterious effect of iron. Ocimum sanctum is a widely acknowledged medicinal plant contributing toward several biological benefits. Besides showing good hydroxyl radical scavenging activity, OSP could bind to ferric and ferrous ions to prevent their participation in redox reactions as revealed from modified 2-deoxyribose assays, carried out under various conditions. It also acted as an iron modulator to prevent site-specific damage and was effective in protecting mouse fibroblast L929 cells against iron induced death.

Molecular events in the activation of B cells and macrophages by a non-microbial TLR4 agonist, G1-4A from Tinospora cordifolia.

G1-4A, a polysaccharide from an Indian medicinal plant Tinospora cordifolia, was recently shown to protect mice against septic shock by modulating the proinflammatory cytokines. G1-4A also activated B cells polyclonally. The present report describes in detail the molecular events associated with G1-4A-induced immunomodulation in vitro and in vivo. G1-4A treatment led to an increase in the CD69 expression in lymphocytes. G1-4A-induced proliferation of B cells was completely inhibited by PI3K inhibitor Ly294002, mTOR inhibitor rapamycin and NF-kappaB inhibitor plumbagin. Akt, ERK and JNK were activated by G1-4A which finally resulted in the activation of IKK, degradation of IkappaB-alpha and translocation of NF-kappaB to the nucleus. Administration of G1-4A to mice led to splenomegaly and an increase in the numbers of T cells, B cells and macrophages. This increase in spleen cellularity was due to in vivo proliferation of lymphocytes and upregulation of anti-apoptotic genes. Anti-TLR4-MD2 complex antibody inhibited G1-4A-induced B cell proliferation and degradation of IkappaB-alpha suggesting that TLR-4 was a receptor for G1-4A on B cells. Activation of RAW 264.7 macrophages by G1-4A was found to be dependent on ERK and NF-kappaB-mediated signals. The phagocytosis index in peritoneal exudate cells (PEC) isolated from G1-4A treated mice was significantly higher as compared to that in PEC from control mice. G1-4A administration also increased the number of CD11b(+) cells in the PEC without an increase in the total number of PEC. Thus the present understanding of the molecular mechanism of action of G1-4A, a novel non-microbial TLR4 agonist, will pave the way for its application as an immunomodulator and adjuvant.

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, G1-4A, 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 G1-4A. To elucidate the mechanism of action, its effect on macrophages, the primary source of these pro-inflammatory molecules was evaluated. G1-4A was shown to bind to the murine macrophages leading to their activation and reciprocally inhibited binding of LPS to macrophages. Following treatment with G1-4A, there was a small increase in serum TNF-alpha and IL-1beta levels. However, challenge with LPS elicited significantly reduced levels of TNF-alpha in G1-4A pretreated mice as compared to the controls while the level of soluble TNFR was enhanced. An increase in serum IL-1beta, IL-6, IFN-gamma levels and decrease in that of IL-10 was observed following challenge with LPS in mice pretreated with G1-4A as compared to the controls. In addition, G1-4A also modulated the release of nitric oxide by murine macrophages. Similar phenomenon was observed in a human monocytic cell line, U937. Thus G1-4A appeared to induce tolerance against endotoxic shock by modulation of cytokines and nitric oxide.

Structural confirmation of decussatin, a Swertia decussata xanthone.

Reinvestigation of the plant, Swertia decussata resulted in the isolation of four antioxidant xanthones, which were characterized as 1-hydroxy-3,7,8-trimethoxy, 1,8-dihydroxy-3,7-dimethoxy, 1,7-dihydroxy-3,8-dimethoxy and 1,7,8-trihydroxy-3-methoxyxanthones. The structural ambiguity of the first compound was settled by ASIS-NMR and 2D NOESY spectroscopy.

Antioxidant and radioprotective properties of an Ocimum sanctum polysaccharide.

The antioxidant activity of two polysaccharides isolated from the Indian medicinal plants, Ocimum sanctum and Tinospora malabarica, was studied. Only the O. sanctum polysaccharide (OSP) showed significant activity. OSP could prevent oxidative damage to liposomal lipids and plasmid DNA induced by various oxidants such as iron, AAPH and gamma-radiation, besides scavenging important ROS such as the superoxide radical and hydrogen peroxide and inhibiting xanthine oxidase. In addition, OSP could prevent gamma-radiation-mediated cell deaths in mouse splenocytes.

Antioxidant activities of Swertia decussata xanthones.

The lipid peroxidation inhibitory activities of four hydroxyxanthones, isolated from the whole plant Swertia decussata, were evaluated for the first time. The most promising antioxidant among the xanthones, 1,7,8-trihydroxy-3-methoxyxanthone (swertianine, 4) was also tested for its scavenging potential against DPPH and superoxide radicals. The data clearly revealed good antioxidant activity of the xanthones, especially 4 which also showed strong protection against y-ray induced pBR322 DNA damage. A comparison of the radioprotecting activities of the monomethylated tetrahydroxyxanthone 4 with that of its congener, 1,3,7-trihydroxy-8-methoxyxanthone (5) revealed that the radioprotecting activity was not affected by the position of methylation.

Radioprotective property of polysaccharide in Tinospora cordifolia.

Radioprotective activity of a polysaccharide preparation from the Indian medicinal plant. Tinospora cordifolia Miers has been established using Saccharomyces cerevisiae X2180 strain as the in vivo test model. The entire activity could be attributed to the radical scavenging capacity of the preparation, as it did not enhance the expression of the protective enzymes, catalase and superoxide dismutase in the yeast cells.

Antioxidant properties of a Tinospora cordifolia polysaccharide against iron-mediated lipid damage and gamma-ray induced protein damage.

The antioxidant activity of an arabinogalactan polysaccharide (TSP) isolated from Tinospora cordifolia, an Indian medicinal plant, was studied. The polysaccharide showed good protection against iron-mediated lipid peroxidation of rat brain homogenate as revealed by the thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide (LOOH) assays. TSP also provided significant protection to protein against gamma-ray induced damage. The protective action can possibly be explained by its very high reactivity towards DPPH, superoxide radicals and the most damaging of radicals, the hydroxyl radical.

Protective activities of some phenolic 1,3-diketones against lipid peroxidation: possible involvement of the 1,3-diketone moiety.

The protective activities of four ginger-derived phenolic 1,3-diketones (1-4) and curcumin (5) against lipid peroxidation was studied by using different biologically relevant model systems and pulse radiolysis. The extraordinary activity of 5 vis-à-vis 1-4 against Fe(2+)-mediated peroxidation may be attributed to the additional phenolic hydroxy group in the former, which lends it better iron-chelating and radical-scavenging properties. In iron-independent peroxidation, however, the ginger constituent [6]-dehydrogingerdione (1) showed activity comparable to that of 5; this indicates its higher affinity for the lipid peroxide radical (LOO(.)), due to its higher hydrophobicity. A very high rate constant for the reaction between 1 and Cl(3)COO(.), measured by pulse radiolysis, not only confirmed this, but also established the superior antioxidant efficacy of 1 in comparison to vitamins E and C. This was also evident from the results obtained from a liposomal peroxidation study with 1 and vitamin C. This study also established a synergistic effect of the latter on the antioxidant activity of 1. HPLC analysis of the products of the reaction between 1 and Cl(3)COO(.) revealed the formation of higher concentrations of ferulic acid (7), along with vanillin (6). The presence of ascorbate affected the generation of 7 more than it did that of 6. On this basis, a mechanism for the antioxidant action of 1 has been proposed, which suggests the contribution of the phenolic group as well as the active methylene group of the 1,3-diketones.