诸多测评研究表明，闪血双面锄(Polygonum cuspidatum Sieb. et Zucc.) 是一种多年生草本植物，属于蓼科，可以产生生物功能性的类脊酚和醌类物质。中医传统上常用该植物的干燥根和根茎来治疗炎症性疾病、糖尿病、痛风、癌症等疾病。本研究旨在探究闪血双面锄提取物(P. cuspidatum extracts, PCE) 对与脓毒症相关的急性肾损伤(sepsis-associated acute kidney injury, SA-AKI) 的保护作用及其潜在机制。通过网络药理学，初步预测了 PCE 改善 SA-AKI 的潜在机制。利用冷冻干燥法获得 PCE 的干粉。通过腹腔注射脂多糖(lipopolysaccharide, LPS) 建立 SA-AKI 小鼠模型，并利用病理学和生化学方法研究 PCE 在体内对 SA-AKI 的保护作用。利用 LPS 刺激 HK-2 细胞进行体外评估，并进行了 qPCR 和免疫印迹等实验验证涉及的机制。网络药理学结果表明，大黄素(emodin, Emo) 和虫草素(polydatin, PD) 是闪血双面锄改善 SA-AKI 的潜在活性成分。实验结果表明，PCE 可以改善 SA-AKI 小鼠的肾功能指标（肌酐、尿素氮和尿蛋白）。从机制上看，PCE 在体内通过减轻氧化应激、调节炎症性肽酶源性蛋白的表达水平以及通过失活核因子 κB (nuclear factor-kappa B, NF-κB) 信号通路来抑制炎性因子的产生，起到抑制作用。在 LPS 刺激 HK-2 细胞时加入 Emo 或 PD，也观察到了类似的结果。我们的研究结果表明，PCE 以及 PCE 中的活性成分 Emo 和 PD 可以通过抑制氧化应激、炎症反应和炎症性疾病，改善 SA-AKI。版权所有 © 2023. 由 Elsevier B.V. 发表。

Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) is an herbaceous perennial plant in the Polygonaceae family that produces biofunctional stilbenes and quinones. The dried rhizome and root of P. cuspidatum in traditional oriental medicine have been used for ameliorating inflammatory illnesses, diabetes, gout, cancer, and other ailments.This work aimed to investigate the protective effects of P. cuspidatum extracts (PCE) on sepsis-associated acute kidney injury (SA-AKI) and its underlying mechanism.The 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-AKI in vivo were studied using pathological and biochemical methods. LPS-stimulated HK-2 cells were prepared for in vitro evaluation. The qPCR and immunoblotting assays were performed to confirm the mechanism involved.The network pharmacology results indicate that emodin (Emo) and polydatin (PD) are potential active components of P. cuspidatum ameliorating 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) signaling in vivo. Similar results were observed in LPS-stimulated HK-2 cells in the presence of Emo or PD.Our results demonstrated that PCE and active ingredients (Emo and PD) in PCE ameliorated SA-AKI by suppressing oxidative stress, inflammation, and pyroptosis.Copyright © 2023. Published by Elsevier B.V.