piperine and pristane

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 (25 mg/kg and 50 mg/kg) and its bio-enhancer piperine (1/10th dose of resveratrol) on pristane-induced SLE murine model. Mice were injected with 0.5 ml of pristane and after 2 months they were orally dosed with resveratrol combinations for 4 months. 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.

Topics: Alkaloids; Animals; Autoantibodies; Benzodioxoles; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Lupus Erythematosus, Systemic; Mice; Mice, Inbred BALB C; Piperidines; Polyunsaturated Alkamides; Resveratrol; Terpenes; Treatment Outcome

Systemic lupus erythematosus is a multisystem autoimmune disease. Apart from usual treatments, approximately 50% of lupus patients use complementary medicine. Resveratrol is a phytoalexin with various pharmacological properties. We hypothesised that prophylactic treatment with resveratrol may abrogate manifestations in pristane-induced murine model of lupus-like disease and piperine; a bio-enhancer of resveratrol may enhance these properties. The prophylactic effect of resveratrol (25 mg/kg body weight: P-Res) alone and in combination with piperine (2.5 mg/kg body weight: P-RP) were assessed. P-Res and P-RP were equally efficient in mitigating oxidative stress (enzyme activity of catalase, superoxide dismutase, glutathione peroxidase and level of reduced glutathione, lipid peroxidation, and reactive oxygen species). Inflammation is associated with an increase in inflammatory cytokines. IL-6 was decreased by 71.60% with P-Res, and TNF-α was reduced by 59.70% with P-Res and 62.66% with P-RP (p < 0.05). Prevention of renal pathologies was evident by reduction in creatinine level by P-RP (p < 0.05) and abrogation of proteinuria (P-Res and P-RP). P-RP was efficient in restoring histopathology of liver and lungs and decreased immune complexes in lungs. P-Res proved more beneficial by extenuating lipogranulomas, histopathological manifestations in kidney, liver, and lungs, and eliminating immune complexes in liver and lungs. None of the treatments could regulate auto-antibody formation. Resveratrol decreases the susceptibility of developing pathogenesis in murine model of lupus-like disease. The results also conclude that addressing the bioavailability of resveratrol using it in combination with piperine does not prove more efficacious in preventing lupus-associated pathologies than resveratrol alone.

Topics: Alkaloids; Animals; Antioxidants; Benzodioxoles; Cytokines; Disease Models, Animal; Female; Inflammation; Kidney; Lipid Peroxidation; Liver; Lung; Lupus Erythematosus, Systemic; Mice; Mice, Inbred BALB C; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Resveratrol; Terpenes