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

Abstract

Abelmoschus manihot (L.) Medik. (Malvaceae) is a herb used in traditional Chinese medicine to treat some kidney diseases. To date, the detailed mechanisms by which A. manihot 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 A. manihot flower (TEA) both in vitro and in vivo . 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.

Huangkui Capsule Ameliorates Renal Fibrosis in a Unilateral Ureteral Obstruction Mouse Model Through TRPC6 Dependent Signaling Pathways

“…We demonstrated that HKC suppressed both smad2/3 expression and phosphorylated protein of p38, JNK1/2, and ERK1/2 suggesting that HKC was capable of suppressing both canonic and non-canonic TGF-b signaling pathways. This is consistent with the report that HKC attenuates renal inflammation and glomerular injury through inhibition of ROS-MAPK signaling pathway (Tu et al, 2013;Mao et al, 2015;Li et al, 2019).…”

“…HKC decreases albuminuria, attenuates early glomerular pathology and renal tubular epithelial-mesenchymal transition in the diabetic nephropathy animal model (Mao et al, 2015;Ge et al, 2016;Kim et al, 2018;Wu et al, 2018;Han et al, 2019). Similarly, in an adriamycin-induced renal injury murine model, HKC attenuates kidney inflammation and glomerular injury, likely through inhibition of reactive oxygen species (ROS)-mitogen-activated protein kinase (MAPK) signaling pathway (Tu et al, 2013;Mao et al, 2015;Li et al, 2019).…”

Traditional Uses, Chemical Constituents, Biological Properties, Clinical Settings, and Toxicities of Abelmoschus manihot L.: A Comprehensive Review

“…Similarly, the results of an in vivo study proved that TEA at a dose of 1.5 g/kg (i.g.) significantly reduced proteinuria and low serum albumin levels, alleviated lesions of the renal tubules, and inhibited the expression of ROS, ERK 1/2 , and NLRP3 inflammasome proteins in the renal tubules of rats with doxorubicin-induced nephropathy in comparison with a doxorubicin model group ( Li et al., 2019 ), which indicates that TEA protects renal tubular cells against doxorubicin-induced injury by suppressing the ROS-ERK 1/2 -NLRP3 inflammasome signaling pathway both in vitro and in vivo .…”

“…The total extract of A. manihot flowers (TEA) at a concentration of 100 μg/mL reduced doxorubicin-induced changes in cellular histology, decreases in cell viability, and apoptosis in NRK-52E cells by suppressing protein oxidation and the p38 and ERK 1/2 signaling pathways in vitro ( Li et al., 2019 ). Similarly, the results of an in vivo study proved that TEA at a dose of 1.5 g/kg (i.g.)…”

Data Mining‐Based Analysis of Chinese Medicinal Herb Formulae in Chronic Kidney Disease Treatment

“…Notably, it has long been used to treat kidney disease [6]. e effectiveness and safety of TCM have progressed considerably over several decades, especially in the case of some herbs and herbal compounds prescribed for CKD treatment [7][8][9][10].…”