Apigenin-7-O-β-D-glucuronide (AG), an active flavonoid derivative isolated from the agricultural residue of Juglans sigillata fruit husks, possesses multiple pharmacological activities, including anti-oxidant, anti-complement, and aldose reductase inhibitory activities. To date, no report has identified the anti-inflammatory mechanisms of AG. This study was therefore designed to characterize the molecular mechanisms of AG on lipopolysaccharide (LPS)-induced inflammatory cytokines in RAW 264.7 cells and on endotoxin-induced shock in mice. AG suppressed the release of nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumour necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner without affecting cell viability. Additionally, AG suppressed LPS-induced mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α. AG treatment decreased the translocation of c-Jun into the nucleus, and decreased activator protein-1 (AP-1)-mediated luciferase activity through the inhibition of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) phosphorylation. Consistent with the in vitro observations, AG protected mice from LPS-induced endotoxin shock by inhibiting proinflammatory cytokine production. Taken together, these results suggest that AG may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion.

中文翻译：

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芹菜素-7 - O - β - d-葡糖醛酸苷通过使RAW 264.7巨噬细胞中的AP-1和MAPK信号通路失活而抑制LPS诱导的炎症，并保护小鼠免受内毒素休克

芹菜素-7 - O - β - D-葡糖醛酸苷（AG）是一种从胡桃木果壳的农业残留物中分离得到的活性类黄酮衍生物，具有多种药理活性，包括抗氧化剂，抗补体和醛糖还原酶抑制活性。迄今为止，尚未有报道鉴定AG的抗炎机制。因此，本研究旨在表征AG对脂多糖（LPS）诱导的RAW 264.7细胞中炎症细胞因子以及小鼠内毒素诱导的休克的分子机制。AG抑制一氧化氮（NO），前列腺素E ₂（PGE ₂）和LPS刺激的RAW 264.7巨噬细胞中的肿瘤坏死因子-α（TNF-α）呈剂量依赖性，而不会影响细胞生存力。此外，AG抑制LPS诱导的诱导型一氧化氮合酶（iNOS），环氧合酶2（COX-2）和TNF-α的mRNA表达。AG处理可通过抑制p38促分裂原活化蛋白激酶（MAPK）和细胞外信号调节激酶（ERK）来降低c-Jun向核内的转运，并降低激活蛋白1（AP-1）介导的萤光素酶活性。 ）磷酸化。与体外一致观察发现，AG通过抑制促炎细胞因子的产生，保护小鼠免受LPS诱导的内毒素休克。综上所述，这些结果表明AG可以用作抗炎剂的来源以及健康促进的饮食补充。