Role of JAK in the Induction of iNOS in Macrophages using Pharmacological Inhibitors

Inducible nitric oxide synthase (iNOS) is induced in different cell types by cytokines and lipopolysaccharide (LPS). Cytokine signal transduction is believed to be mediated primarily through the JAK/STAT pathway. We, therefore, examined the effects of JAKs (Janus Kinase) in the induction of iNOS in macrophages using pharmacological inhibitors by using cell culture, Griess assay, protein assay, and western blotting techniques and also to compare the responses of JAK1and JAK2 inhibitor at different concentrations. The result of this study concludes that JAK inhibitors, i.e., JAK 1 and AG-490 down-regulates multiple signaling pathways such as STAT1-activation, iNOS gene expression and NO production in LPS treated macrophages. JAK2 proved to be an active ingredient and has shown anti-inflammatory effects. Activated JAK2 regulates the phosphorylation of JAK through the activation of PI3K thus plays a pivotal role in LPS-induced iNOS expression.

Chemomodulatory action of Brassica compestris (var sarason) on hepatic carcinogen metabolizing enzymes, antioxidant profiles and lipid peroxidation.

The effect of two different doses (400 and 800 mg/kg body wt/day for 15 days) of a 95% ethanolic extract of the seeds of Brassica compestris (var sarason) was examined on carcinogen metabolizing phase-I and phase-II enzymes,antioxidant enzymes and glutathione content and lipid peroxidation in the liver of Swiss albino mice. Positive control mice were treated with butylated hydroxyanisole (BHA). Significant elevation in the levels of cytochrome p450 (p<0,.05), cytochrome b5 (p < 0.05) glutathione s-transferase (p<0.01), DT-diaphorase (p<0.05), superoxide dismutase (p<0.01), catalase (p < 0.001) and reduced glutathione (p<0.001) was noted in the group treated with 800 mg/kg body wt. of Brassica extract in comparison with the negative control group. Brassica compestris acted as a bifunctional inducer since it induced both phase - I and phase - H enzyme systems. Since phase-I and phase-II enzymes are considered to be reliable markers for evaluating the chemoprevention efficacy of particular test materials,these findings are suggestive of potential chemopreventive roles for Brassica seed extract.

Modulatory influence of Brassica compestris Linn var sarson on phase-II carcinogen metabolizing enzymes and glutathione levels in mice.

The present study reports the modulatory influence of 95% ethanolic extract from the seeds of B. compestris on the activity of phase-II enzymes such as glutathione S-transferase (GST), DT-diaphorase (DTD) and reduced glutathione (GSH) level in the skin, lung, kidney and forestomach of the mouse. Oral treatment with the seed extract at 800 mg/kg body wt. for 15 days significantly elevated GST in lung and forestomach and DT-diaphorase in forestomach and skin and GSH level in lung, kidney forestomach and skin. The lower dose 400 mg/kg body wt was effective only in inducing GST and DT-diaphorase activity in forestomach and reduced glutathione level in lung. The findings suggest that B. compestris seed extract may block or suppress the events associated with chemical carcinogenesis at least in part, by inducing metabolic detoxification of the carcinogen.