Combinatorial therapeutic effect of resveratrol and piperine on murine model of systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is a chronic multi-system inflammatory disease associated with autoantibody formation. Clinical management of lupus is associated with multiple adverse events. Resveratrol is a phytoalexin with several pharmacological properties. This study aimed to evaluate the combinatorial effect of resveratrol (25mg/kg and 50mg/kg) and its bio-enhancer piperine (1/10th dose of resveratrol) on pristane-induced SLE murine model. Mice were injected with 0.5ml of pristane and after 2months they were orally dosed with resveratrol combinations for 4months. Determined by indirect immunofluorescence, resveratrol was unable to abrogate autoantibody formation. The increased IFN-α, IL-6 and TNF-α was mitigated by low dose of resveratrol and piperine (RP-1). None of the doses regulated the increase in nitric oxide. Lipogranulomas associated with injected pristane were not observed after RP-1 and high dose of resveratrol (Res-2) treatment. Lupus mice witnessed IgG and IgM immune complexes by direct immunofluorescence assay and associated histopathological observations in kidneys, liver, lung, spleen and skin. None of the treatment regimens were able to regulate the manifestations observed in spleen and skin. RP-1 and Res-2 proved beneficial in kidney, liver and lungs and were able to ameliorate lupus associated manifestations. Renal manifestations (proteinuria and decreased creatinine in urine) were successfully mitigated by RP-1 and Res-2 and high dose combination of resveratrol and piperine. Oxidative stress (reactive oxygen species by flowcytometry and catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione and lipid peroxidation by biochemical analysis) was evident by pristane injection. These were regulated by different doses of resveratrol alone and in combination with piperine. Hence, resveratrol when used in combination with piperine successfully reduces some measures of morbidity with little or no effect on mortality associated with lupus.