Polygonum cuspidatum Sieb. et Zucc. Extracts improve sepsis-associated acute kidney injury by inhibiting NF-?B-mediated inflammation and pyroptosis
Polygonum cuspidatum Sieb. et Zucc. Extracts improve sepsis-associated acute kidney injury by inhibiting NF-?B-mediated inflammation and pyroptosis
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DOI：
10.1016/j.jep.2023.117101
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发表时间：
2023-09-07
影响因子：
5.4
通讯作者：
Xiao，Han
中科院分区：
文献类型：
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作者：
Yang，Yuan;Xu，Jia;Xiao，Han
虎杖的民族药理学研究。调查。虎杖蓼（Polygonum cuspidatum）是蓼科多年生草本植物，可生产具有生物功能的芪和醌类。干燥的根茎和根。传统的东方医学已经用于改善炎症性疾病，糖尿病，痛风，癌症和其他疾病。本研究旨在探讨黄芪多糖的保护作用。虎柏提取物（PCE）对脓毒症相关急性肾损伤（SA-AKI）的影响及其潜在机制。材料与方法应用网络药理学方法初步预测PCE改善SA-AKI的可能机制。采用冷冻干燥法制备PCE干粉。通过腹腔注射脂多糖（LPS）建立小鼠SA-AKI模型。采用病理和生化方法研究PCE对SA-AKIin的保护作用。制备lps刺激的HK-2细胞进行体外评价。qPCR和免疫印迹分析证实了其机制。结果网络药理学结果表明，大黄素（Emo）和多聚丹素（PD）是黄芪的潜在活性成分。cuspidatumameliorating SA-AKI。实验结果表明，PCE可改善SA-AKI小鼠的肾功能指标（肌酐、尿素氮和尿蛋白）。机制上，PCE在体内通过灭活核因子κB （NF-κB）信号通路，减轻氧化应激，调节焦热相关蛋白的表达水平，抑制炎症细胞因子的产生。在Emo或PD存在下，lps刺激的HK-2细胞也观察到类似的结果。结论PCE及PCE中的活性成分Emo和PD通过抑制氧化应激、炎症和焦亡来改善SA-AKI。
Ethnopharmacological relevancePolygonum cuspidatumSieb. et Zucc. (Polygonum cuspidatum) is a herbaceous perennial plant in the Polygonaceae family that produces biofunctional stilbenes and quinones. The dried rhizome and root ofP. cuspidatumin traditional oriental medicine have been used for ameliorating inflammatory illnesses, diabetes, gout, cancer, and other ailments.Aim of the studyThis work aimed to investigate the protective effects ofP. cuspidatumextracts (PCE) on sepsis-associated acute kidney injury (SA-AKI) and its underlying mechanism.Materials and methodsThe potential mechanisms by which PCE improved SA-AKI were preliminarily predicted by network pharmacology. The dry powders of PCE were obtained using the freeze-drying method. A mouse model of SA-AKI was established by intraperitoneal injection of lipopolysaccharide (LPS). The protective effects of PCE on SA-AKIin vivowere studied using pathological and biochemical methods. LPS-stimulated HK-2 cells were prepared forin vitroevaluation. The qPCR and immunoblotting assays were performed to confirm the mechanism involved.ResultsThe network pharmacology results indicate that emodin (Emo) and polydatin (PD) are potential active components ofP. cuspidatumameliorating SA-AKI. The experimental results showed that PCE improved renal function indices (creatinine, urea nitrogen, and urinary protein) in SA-AKI mice. Mechanistically, PCE mitigated oxidative stress, regulated the expression levels of pyroptosis-related proteins, and repressed the production of inflammatory cytokines by inactivating nuclear factor-kappa B (NF-κB) signalingin vivo. Similar results were observed in LPS-stimulated HK-2 cells in the presence of Emo or PD.ConclusionsOur results demonstrated that PCE and active ingredients (Emo and PD) in PCE ameliorated SA-AKI by suppressing oxidative stress, inflammation, and pyroptosis.