Aloe‐emodin inhibits hypertension‐induced inter‐endothelial junction dysfunction through endothelial ROS‐TXNIP‐Nlrp3 inflammasome axle

Abstract

Recent studies have revealed that Aloe‐emodin, a natural compound from the root and rhizome of Rheum palmatum L., exhibits significant pharmacological activities. However, the pharmacological relevance of the compound, particularly for cardiovascular disease, remains largely unknown. Here, we hypothesized that Aloe‐emodin could improve endothelial injury by inhibiting the activation of Nlrp3 inflammasome, and ultimately prevent cardiovascular disease. In vitro, our findings demonstrated that Aloe‐emodin inhibits AngII‐induced Nlrp3 inflammasome formation and activation in Microvascular Endothelial Cells (MECs), as shown by fluorescence confocal microscopy and Western blot. At the same time, the data shown that Aloe‐emodin exerts anti‐oxidation and ROS scavenged effects. Interestingly, thioredoxin‐interacting protein (TXNIP) protein and high mobility group box 1 (HMGB1) markedly decreased with Aloe‐emodin treatment. We also demonstrated that the decreased expression of the tight junction proteins ZO‐1/ZO‐2, which are related to endothelial permeability after stimulation by AngII in endothelial cells. Aloe‐emodin could recover the gap junction protein and decrease monolayer cell permeability in endothelial cells. Similarly, we used confocal microscopy to study the formation and activation of NOD‐like receptor family pyrin domain containing‐3 (Nlrp3) inflammasomes and expression of tight junction proteins in coronary arteries of AngII/DOCA‐treated mice. We found that Aloe‐emodin inhibited the formation and activation of Nlrp3 inflammasome, and also could restore the expression of the endothelial connective protein ZO1/2 and the release of HMGB1. Together with these changes, we revealed a new protection mechanism of Aloe‐emodin that inhibits Nlrp3 inflammasome activation and decreases subsequent caspase‐1 activation, triggering the release of HMGB1 by reducing ROS generation. Our findings indicate that Aloe‐emodin exhibits immense potential and specific therapeutic value in hypertension‐related cardiovascular disease and the development of innovative drugs.Support or Funding InformationThe National Key Research and Development Program of China (No. 2017YFC1700400); the project supported by National Natural Science Foundation of China (No. 81603587); Guangdong Natural Science Funds for Distinguished Young Scholar (No. 2018B030306027); Science and Technology Development Plan of Guangdong Province (No. 2017A020211016)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.