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 (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.

中文翻译：

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白藜芦醇和胡椒碱对系统性红斑狼疮小鼠模型的联合治疗作用。

摘要

系统性红斑狼疮（SLE）是与自身抗体形成相关的慢性多系统炎性疾病。狼疮的临床管理与多种不良事件有关。白藜芦醇是一种具有多种药理特性的植物抗毒素。这项研究旨在评估白藜芦醇（25 mg / kg和50 mg / kg）及其生物增强胡椒碱（白藜芦醇的1/10剂量）对on烷诱导的SLE小鼠模型的组合作用。给小鼠注射0.5ml的rist烷，并在2个月后口服给予白藜芦醇组合4个月。通过间接免疫荧光测定，白藜芦醇不能消除自身抗体的形成。低剂量白藜芦醇和胡椒碱（RP-1）可减轻IFN-α，IL-6和TNF-α的升高。没有一个剂量能调节一氧化氮的增加。RP-1和高剂量白藜芦醇（Res-2）治疗后未观察到与注射的rist烷相关的脂肪肉芽肿。狼疮小鼠通过直接免疫荧光测定法以及在肾脏，肝脏，肺脏，脾脏和皮肤中的相关组织病理学观察结果见证了IgG和IgM免疫复合物。没有一种治疗方案能够调节在脾脏和皮肤中观察到的表现。RP-1和Res-2被证明对肾脏，肝脏和肺部有益，并且能够改善狼疮的相关表现。RP-1和Res-2以及高剂量的白藜芦醇和胡椒碱可成功缓解肾脏表现（蛋白尿和尿中肌酐降低）。氧化应激（通过流式细胞仪和过氧化氢酶，超氧化物歧化酶，谷胱甘肽过氧化物酶，rist烷注射液可明显减少谷胱甘肽和脂质过氧化作用（通过生化分析）。这些可以通过单独或与胡椒碱联合使用的不同剂量白藜芦醇来调节。因此，白藜芦醇与胡椒碱联合使用可成功降低发病率，对狼疮相关死亡率几乎没有影响。