AUTHOR=Li Wei , He Weiming , Xia Ping , Sun Wei , Shi Ming , Zhou Yao , Zhu Weiwei , Zhang Lu , Liu Buhui , Zhu Jingjing , Zhu Yiye , Zhou Enchao , Sun Minjie , Gao Kun 

TITLE=Total Extracts of Abelmoschus manihot L. Attenuates Adriamycin-Induced Renal Tubule Injury via Suppression of ROS-ERK1/2-Mediated NLRP3 Inflammasome Activation

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00567

DOI=10.3389/fphar.2019.00567

ISSN=1663-9812

ABSTRACT=<p><italic>Abelmoschus manihot</italic> (L.) Medik. (Malvaceae) is a herb used in traditional Chinese medicine to treat some kidney diseases. To date, the detailed mechanisms by which <italic>A. manihot</italic> improves some kinds of renal disease are not fully understood. In this study, we established Adriamycin-induced NRK-52E cells, the normal rat kidney epithelial cell line, injury, and Sprague-Dawley rats with Adriamycin-induced nephropathy to evaluate the role and mechanisms of total extracts of <italic>A. manihot</italic> flower (TEA) both <italic>in vitro</italic> and <italic>in vivo</italic>. We found that TEA ameliorated Adriamycin-induced cellular morphological changes, cell viability, and apoptosis through the suppression of protein oxidation and ERK1/2 signaling. However, this anti-oxidative stress role of TEA was independent of ROS inhibition. Adriamycin activated ERK1/2 signaling followed by activation of NLRP3 inflammasomes. TEA suppressed NLRP3 inflammasomes via inhibition of ERK1/2 signal transduction; decreased proteinuria and attenuated renal tubule lesions; and inhibited the expression of NLRP3 in tubules in rats with Adriamycin nephropathy. Collectively, TEA protects renal tubular cells against Adriamycin-induced tubule injury via inhibition of ROS-ERK1/2-NLRP3 inflammasomes.</p>