The current study was designed to evaluate the renoprotective effect of hydro-alcoholic extract of Caralluma fimbriata (CFE) against high-fat diet-induced oxidative stress in Wistar rats. Male Wistar rats were randomly divided into five groups: control (C), control treated with CFE (C + CFE), high-fat diet fed (HFD), high-fat diet fed treated with CFE (HFD + CFE), and high-fat diet fed treated with metformin (HFD + metformin). CFE was orally administered (200 mg/kg body weight) to Groups C + CFE and HFD + CFE rats for 90 days. Renal functional markers such as, urea, uric acid, and creatinine levels in plasma were quantified during the experimental period. At the end of the experimental period, activities of transaminases and oxidative stress markers, i.e., reduced glutathione (GSH), lipid peroxidation, protein oxidation, and activities of antioxidant enzymes were assayed in renal tissue. Coadministration of CFE along with HF-diet in Group HFD + CFE prevented the rise in the levels of plasma urea, uric acid, and creatinine, and elevated activities of renal transaminases with decreased protein content of Group HFD (p < 0.05). Establishment of oxidative stress in Group HFD, as evident from elevated lipid peroxidation, protein oxidation levels with depleted levels of GSH, and decreased activities of GSH dependent and independent antioxidant enzymes, was prevented in Groups HFD + CFE and HFD + metformin rats. Further, there were no deviations in the studied parameters but there was improved antioxidant status of Group C + CFE from Group C which revealed the nontoxic nature of CFE even under chronic treatment. Thus, CFE treatment effectively alleviated the HF-diet induced renal damage. Hence, this plant could be used as an adjuvant therapy for the prevention and/or management of HF-diet induced renal damage.

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SummaryNuclear factor (NF)-kB is a transcription factor implicated in the pathogenesis of autoimmune disorders such as rheumatoid arthritis (RA). Here we have examined the effect of intra-articular administration of the IKK inhibitor, NEMO-binding domain peptide (NBD), on the severity of collageninduced arthritis (CIA). NBD peptides were injected intra-articularly into the knee joints of DBA/1J mice after the onset of disease. Collagen-injected mice given a scrambled peptide served as controls. Arthritis severity was determined by visual examination of paws. Intra-articular NBD injection reduced the arthritis score and ameliorated morphological signs of bone destruction compared to the controls. Serum levels of type-II collagenspecific immunoglobulin (Ig)G2a antibodies were lower in NBD-treated mice versus the control mice, whereas the levels of type-II collagen-specific IgG1 antibodies were increased by NBD treatment. NBD treatment diminished the proinflammatory cytokines interleukin (IL)-17 and interferon (IFN)-g in serum, but increased the regulatory cytokine IL-10. NBD-treated CIA mice exhibited significantly higher percentages and numbers of forkhead box protein 3 (FoxP3 +) CD4 + CD25 + regulatory T cells than controls. Immunofluorescence analysis of NBD-treated mice revealed that FoxP3 and Ym1, a marker of alternatively activated macrophages, were juxtaposed to each other within draining inguinal lymph nodes. Intra-articular administration of NBD peptide is effective as an experimental therapy in a murine model of RA. Nevertheless, the intra-articular treatment modality is still associated with systemic effects on the immune system.

SummarySystemic lupus erythematosus (SLE) is a polygenic autoimmune disease characterized by the production of anti-nuclear autoantibodies that lead to subsequent end organ damage. Previous array-based studies in patients with SLE have shown that high immunoglobulin (Ig)G anti-nuclear autoantibody reactivity was associated with severe renal lupus, whereas IgM polyreactivity was associated with less severe disease. To ascertain how different murine lupus strains recapitulate these different autoantibody profiles seen in patients, serum from New Zealand black (NZB)/NZ white (W) F1, Murphy Roths large (MRL)/lpr, NZ mixed (M)2410 and BXSB strains were compared using a comprehensive array-based screen. The array results were verified using enzyme-linked immunosorbent assays (ELISAs). Serum from MRL/lpr mice exhibited high levels of IgG anti-nuclear antibodies as well as anti-glomerular antibodies and variable levels of antibodies to myosin, Matrigel and thyroglobulin. Elevated anti-nuclear IgG antibodies were associated with severe nephritis in this strain. In contrast, NZM2410 mice exhibited lower IgG autoantibody levels with less severe nephritis but a significantly higher polyreactive IgM autoantibody profile. ELISA analysis confirmed these results. The NZB/NZW F1 and BXSB strains exhibited an intermediate serological profile. Hence, just as in patients with SLE, whereas strong IgG reactivity to nuclear antigens is associated with severe renal disease, a polyreactive IgM seroprofile is also less ominous in murine lupus.