Department of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, Korea.
Molecules. 2022 Mar 21;27(6):2019. doi: 10.3390/molecules27062019.
Lipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models. This study aimed to investigate the renoprotective effect of hispidulin on LPS-induced AKI. Male C57BL/6 mice were administered LPS (10 mg/kg) with or without hispidulin (50 mg/kg). Hispidulin administration attenuated renal dysfunction, histological alterations, and the upregulation of neutrophil gelatinase-associated lipocalin. This flavonoid also reduced cytokine production and Toll-like receptor 4 expression, inhibited nuclear factor-κB and mitogen-activated protein kinase cascades, and alleviated immune cell infiltration. The oxidation of lipids and DNA was also inhibited by hispidulin administration. This antioxidant effect of hispidulin was associated with the downregulation of NADPH oxidase 4, the activation of catalase and superoxide dismutase activities, and the restoration of glutathione levels. Moreover, hispidulin administration attenuated tubular cell apoptosis by inhibiting caspase-3 pathway. These data suggest that hispidulin ameliorates endotoxin-induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death.
脂多糖 (LPS) 是一种内毒素，在脓毒症急性肾损伤 (AKI) 中起着至关重要的作用。蛇床子素是一种具有多种生物学活性的天然黄酮类化合物。最近的研究表明，蛇床子素给药可减轻动物模型中的各种炎症性疾病。本研究旨在探讨蛇床子素对 LPS 诱导的 AKI 的肾保护作用。雄性 C57BL/6 小鼠给予 LPS（10mg/kg），并用或不用蛇床子素（50mg/kg）处理。蛇床子素给药可减轻肾功能障碍、组织学改变以及中性粒细胞明胶酶相关脂质运载蛋白的上调。这种黄酮类化合物还可减少细胞因子的产生和 Toll 样受体 4 的表达，抑制核因子-κB 和丝裂原激活蛋白激酶级联反应，并减轻免疫细胞浸润。蛇床子素给药还抑制脂质和 DNA 的氧化。蛇床子素的这种抗氧化作用与 NADPH 氧化酶 4 的下调、过氧化氢酶和超氧化物歧化酶活性的激活以及谷胱甘肽水平的恢复有关。此外，蛇床子素给药通过抑制半胱天冬酶-3 途径减轻肾小管细胞凋亡。这些数据表明，蛇床子素通过抑制炎症、氧化应激和肾小管细胞死亡来改善内毒素引起的肾损伤。
