Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain; Instituto de Biomedicina de Sevilla, IBiS (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), Seville, Spain.
Department of Normal and Pathological Cytology and Histology, Faculty of Medicine, Universidad de Sevilla, 41012 Seville, Spain.
Food Res Int. 2023 Jan;163:112140. doi: 10.1016/j.foodres.2022.112140. Epub 2022 Nov 20.
Systemic lupus erythematosus (SLE) is a multiorgan disorder with a deregulated immune-inflammatory response. Nutritional therapy has been considered a promising approach to SLE management. Oleocanthal (OLE), the main extra virgin olive oil (EVOO)-derived secoiridoid, has shown to regulate the immune-inflammatory response in various disease contexts; however, its possible beneficial effects on SLE remain unclear. This study sought to evaluate the effects of OLE enriched diet on renal damage and aortic endothelial dysfunction in murine pristane-induced SLE, focusing on the action mechanisms and signaling pathways involved. BALB/c mice were injected with pristane and fed with OLE supplemented diet (0.01 % (w/w)) for six months. Levels of cytokines were measured by ELISA in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and splenocytes. Presence of immunoglobulin G (IgG) and IgM immune complexes were examined by immunofluorescence and immunohistochemistry. Thoracic aortas were used to evaluate endothelial dysfunction. Western blotting was employed to detect signaling pathways and oxidative-inflammatory-related mediators. Dietary OLE supplementation reduced Th1/Th17 pro-inflammatory cytokines production and alleviated renal damage by decreasing immunoglobulin complexes deposition, and inflammation-mediating enzymes expression. The mechanisms underlying these protective effects could be related to the regulation of nuclear factor erythroid 2-related factor 2/Haem oxygenase 1 (Nrf-2/HO-1), mitogen-activated protein kinases (MAPKs), signal transducer and transcription activator of transcription (STAT-3), inflammasome and, nuclear factor kappa B (NF-κB) signaling pathways. Also, dietary OLE improved aortic endothelial dysfunction and vascular reactivity, normalizing endothelial nitric oxide synthase (eNOS) uncoupling, and NADPH oxidase-1 (NOX-1) overexpression. This study shows the immunomodulatory effects of OLE in an in vivo model of SLE by improving renal damage and regulating aortic endothelial dysfunction. These preliminary results provide OLE as a new therapeutic strategy in SLE management.
系统性红斑狼疮（SLE）是一种多器官疾病，具有免疫炎症反应失调。营养疗法被认为是 SLE 管理的一种有前途的方法。橄榄苦苷（OLE）是特级初榨橄榄油（EVOO）衍生的主要次高利马豆素，已显示在各种疾病情况下调节免疫炎症反应；然而，其对 SLE 的可能有益影响尚不清楚。本研究旨在评估富含 OLE 的饮食对鼠类诱导性 SLE 肾损伤和主动脉内皮功能障碍的影响，重点关注相关作用机制和信号通路。BALB/c 小鼠注射了 pristane，并以富含 OLE 的饮食（0.01%（w/w））喂养六个月。通过酶联免疫吸附试验（ELISA）测量脂多糖（LPS）刺激的腹腔巨噬细胞和脾细胞中的细胞因子水平。通过免疫荧光和免疫组织化学检查免疫球蛋白 G（IgG）和 IgM 免疫复合物的存在。使用胸主动脉评估内皮功能障碍。采用 Western blot 检测信号通路和氧化炎症相关介质。饮食 OLE 补充减少了 Th1/Th17 促炎细胞因子的产生，并通过减少免疫球蛋白复合物沉积和炎症介导酶的表达减轻了肾损伤。这些保护作用的机制可能与核因子红细胞 2 相关因子 2/血红素加氧酶 1（Nrf-2/HO-1）、丝裂原激活蛋白激酶（MAPKs）、信号转导和转录激活因子 3（STAT-3）、炎性小体和核因子 kappa B（NF-κB）信号通路的调节有关。此外，饮食 OLE 改善了主动脉内皮功能障碍和血管反应性，使内皮型一氧化氮合酶（eNOS）解偶联和 NADPH 氧化酶-1（NOX-1）过表达正常化。本研究通过改善肾损伤和调节主动脉内皮功能障碍，在 SLE 体内模型中显示了 OLE 的免疫调节作用。这些初步结果为 OLE 在 SLE 管理中的治疗策略提供了新的依据。
