Ouabain Octahydrate

Ouabain Octahydrate is a Na⁺/K⁺-ATPase inhibitor that can be used to study congestive heart failure^[1]. Ouabain Octahydrate can be used to induce cardiac dysfunction or hypertension models in animal models^[2]. Ouabain Octahydrate can exert anti-cancer activity by downregulating intracellular signal transducer and activator of transcription 3 (STAT3)^[3].

In vitro, Ouabain Octahydrate (3nM) treatment of autosomal dominant polycystic kidney disease (ADPKD) cells for 24h reduced the expression of epithelial cell marker E-cadherin in ADPKD cells, and increased the expression of mesenchymal cell markers N-cadherin, α-smooth muscle actin (αSMA), type I collagen, and tight junction proteins occludin and claudin-1^[4]. Ouabain Octahydrate (25, 50, 100nM) treated Burkitt lymphoma Raji cells for 48h inhibited cell proliferation in a dose-dependent manner, significantly reduced cell viability, and induced cell autophagy^[5].

In vivo, Ouabain Octahydrate (3mg/kg) was intraperitoneally injected into LPS-pretreated WT, IL-1β^−/−, NLRP3^−/−, Casp1^−/− mice, which significantly reduced left ventricular systolic function in WT mice, increased plasma CPK levels and cardiac IL-1β protein levels, induced macrophage infiltration and myocardial damage, but these effects were significantly attenuated in IL-1β^⁻/⁻, NLRP3^⁻/⁻, and Casp1^⁻/⁻ mice^[6].

References:
[1] Harich O O, Gavriliuc O I, Ordodi V L, et al. In Vitro Study of the Multimodal Effect of Na+/K+ ATPase Blocker Ouabain on the Tumor Microenvironment and Malignant Cells[J]. Biomedicines, 2023, 11(8): 2205.
[2] Ferrari P, Ferrandi M, Valentini G, et al. Targeting Ouabain-and Adducin-dependent mechanisms of hypertension and cardiovascular remodeling as a novel pharmacological approach[J]. Medical Hypotheses, 2007, 68(6): 1307-1314.
[3] Du J, Jiang L, Chen F, et al. Cardiac glycoside ouabain exerts anticancer activity via downregulation of STAT3[J]. Frontiers in oncology, 2021, 11: 684316.
[4] Venugopal J, McDermott J, Sanchez G, et al. Ouabain promotes partial epithelial to mesenchymal transition (EMT) changes in human autosomal dominant polycystic kidney disease (ADPKD) cells[J]. Experimental cell research, 2017, 355(2): 142-152.
[5] Meng L, Wen Y, Zhou M, et al. Ouabain induces apoptosis and autophagy in Burkitt’s lymphoma Raji cells[J]. Biomedicine & Pharmacotherapy, 2016, 84: 1841-1848.
[6] Kobayashi M, Usui-Kawanishi F, Karasawa T, et al. The cardiac glycoside ouabain activates NLRP3 inflammasomes and promotes cardiac inflammation and dysfunction[J]. PloS one, 2017, 12(5): e0176676.

Ouabain Octahydrate是一种Na⁺/K⁺-ATPase抑制剂，能够用于研究充血性心力衰竭^[1]。Ouabain Octahydrate在动物模型中，能够被用来诱导心脏功能异常或高血压模型^[2]。Ouabain Octahydrate能够通过下调细胞内信号转导及转录激活蛋白3（STAT3）发挥抗癌活性^[3]。

在体外，Ouabain Octahydrate（3nM）处理常染色体显性遗传性多囊肾病（ADPKD）细胞24h，降低了ADPKD细胞上皮细胞标志物E-钙粘蛋白的表达，增加了间质细胞标志物N-钙粘蛋白、α平滑肌肌动蛋白（αSMA）、I型胶原以及紧密连接蛋白闭合蛋白（occludin）和紧密连接蛋白-1（claudin-1）的表达^[4]。Ouabain Octahydrate（25, 50, 100nM）处理伯基特淋巴瘤Raji细胞48h，以剂量依赖性方式抑制了细胞增殖，显著降低了细胞活力，诱导了细胞自噬^[5]。

在体内，Ouabain Octahydrate（3mg/kg）通过腹腔注射治疗LPS预处理的WT, IL-1β^−/−, NLRP3^−/−, Casp1^−/−的小鼠，显著降低了WT小鼠左心室收缩功能，升高了血浆CPK水平和心脏IL-1β蛋白水平，诱导了巨噬细胞浸润及心肌损伤，然而这些效应在IL-1β⁻/⁻、NLRP3⁻/⁻和Casp1⁻/⁻小鼠中显著减弱^[6]。