Ligstroside aglycon 是一种特级初榨橄榄油 secoiridoid，通过调节 LPS 刺激的小鼠腹腔巨噬细胞中的 MAPK、JAK/STAT、NF-κB、Nrf2/HO-1 和 NLRP3 炎性体信号通路来预防炎症,Food & Function

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Ligstroside aglycon 是一种特级初榨橄榄油 secoiridoid，通过调节 LPS 刺激的小鼠腹腔巨噬细胞中的 MAPK、JAK/STAT、NF-κB、Nrf2/HO-1 和 NLRP3 炎性体信号通路来预防炎症
Food & Function ( IF 5.1 ) Pub Date : 2022-09-16 , DOI: 10.1039/d2fo00351a
María Luisa Castejón ₁ , Tatiana Montoya ₁ , Juan Ortega-Vidal ₂ , Joaquín Altarejos ₂ , Catalina Alarcón-de-la-Lastra ₁

Affiliation

Ligstroside aglycon (LA) 是特级初榨橄榄油 (EVOO) 中的主要多酚之一；然而，它几乎没有被调查。本研究的目的是评估 LA 对脂多糖 (LPS) 刺激的小鼠腹腔巨噬细胞的免疫调节和抗炎作用，以及所涉及的潜在信号通路。在存在或不存在 LPS (5 μg ml ^-1) 18 小时。使用磺基罗丹明 B (SRB) 测定法测定细胞活力。分别通过 Griess 法和酶联免疫吸附试验 (ELISA) 分析一氧化氮 (NO) 和促炎细胞因子的产生。通过蛋白质印迹分析评估促炎标志物和信号通路的蛋白质表达。LA 通过减少氧化应激标志物（如 NO 产生、诱导型一氧化氮合酶 (iNOS) 和 NADPH 氧化酶-1 (NOX-1) 蛋白表达）显示出显着的抗氧化和抗炎作用。此外，LA 能够降低促炎细胞因子水平并调节环加氧酶 2 (COX-2) 和微粒体前列腺素 E 合酶 1 (mPGEs-1) 蛋白的过度表达。这些保护作用背后的机制可能通过以下方式相关核因子（红细胞衍生 2）样 (Nrf2)/血红素加氧酶 1 (HO-1) 的激活和核因子 kappa-B (NF-κB)、丝裂原活化蛋白激酶 (MAPKs) 和 Janus 激酶的抑制/信号转导和转录激活 (JAK2/STAT3) 信号通路。此外，LA 抑制了核苷酸结合 (NOD) 样受体 (NLRP3) 炎性体的非经典和经典激活。我们得出结论，LA 在 LPS 刺激的小鼠腹腔巨噬细胞中显示出显着的抗氧化和抗炎活性。然而，有必要进行进一步的体内研究，以进一步研究这种有趣的化合物的生物活性，这种化合物可能是治疗免疫炎症性疾病的有希望的天然药物。

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Ligstroside aglycon, an extra virgin olive oil secoiridoid, prevents inflammation by regulation of MAPKs, JAK/STAT, NF-κB, Nrf2/HO-1, and NLRP3 inflammasome signaling pathways in LPS-stimulated murine peritoneal macrophages

Ligstroside aglycon (LA) is one of the main polyphenols in extra virgin olive oil (EVOO); nevertheless, it is scarcely investigated. The aim of this study was to evaluate the immunomodulatory and anti-inflammatory effects of LA on lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages, as well as the potential signaling pathways involved. Isolated macrophages were treated with LA (50, 25, and 12.5 μM) in the presence or absence of LPS (5 μg ml⁻¹) for 18 h. Cell viability was determined using the sulforhodamine B (SRB) assay. Nitric oxide (NO) and pro-inflammatory cytokine production was analyzed by the Griess method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression of pro-inflammatory markers and signaling pathways were evaluated by western blot analysis. LA showed significant antioxidant and anti-inflammatory effects through decreasing oxidative stress markers such as NO production, inducible nitric oxide synthase (iNOS) and NADPH oxidase-1 (NOX-1) protein expression. Besides, LA was able to reduce pro-inflammatory cytokine levels and modulate cyclo-oxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGEs-1) protein overexpression. The mechanisms underlying these protective effects could be related via activation of nuclear factor (erythroid-derived 2)-like (Nrf2)/heme oxygenase 1 (HO-1) and inhibition of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinases (MAPKs), and Janus kinase/signal transducer and activation of transcription (JAK2/STAT3) signaling pathways. In addition, LA inhibited non-canonical and canonical activation of a nucleotide-binding (NOD)-like receptor (NLRP3) inflammasome. We conclude that LA showed significant antioxidant and anti-inflammatory activities in LPS-stimulated murine peritoneal macrophages. However, further in vivo studies are warranted to further investigate the bioactivity of this interesting compound that might be a promising natural agent for the treatment of immune-inflammatory diseases.

更新日期：2022-09-16

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