Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Ruscogenin protects against cisplatin-induced apoptosis, inflammation, and oxidative stress of renal tubular epithelial cells`

Yean Yu¹, Baohong Feng¹, Li Yan², Zhimin Bi¹, Geli Zhu¹, Fen Jiang³

¹Department of Nephrology; ²Department of Respiratory, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan City, Hubei Province 430060; ³Department of Nephrology, The first Affiliated Hospital of the University of South China, Hengyang City, Hunan Province 421000, China.

For correspondence:- Fen Jiang Email: jiangfen202102@163.com Tel:+867348578702

Accepted: 27 May 2021 Published: 30 June 2021

Citation: Yu Y, Feng B, Yan L, Bi Z, Zhu G, Jiang F. Ruscogenin protects against cisplatin-induced apoptosis, inflammation, and oxidative stress of renal tubular epithelial cells`. Trop J Pharm Res 2021; 20(6):1159-1164 doi: 10.4314/tjpr.v20i6.9

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To determine the potential effect of ruscogenin in cisplatin-induced nephrotoxicity.

Methods: Rat renal tubular epithelial cells (NRK-52E) were treated with 50 μM cisplatin to establish an in vitro cell model of nephrotoxicity. Cytotoxicity was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry, and western blot. Different concentrations of ruscogenin (2.5, 5, and 10 μM) were incubated with cisplatin-treated NRK-52E cells. Alterations in the nod-like receptor family, the pyrin domain-containing protein (NLRP3) inflammasome, toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB), and nuclear factor erythropoietin-2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) components were determined using western blot. Flow cytometry was also used to investigate the levels of reactive oxygen species (ROS).

Results: Ruscogenin significantly increased cell viability (p < 0.01) and suppressed apoptosis of NRK-52E cells (p < 0.01), attenuating cisplatin-induced cytotoxicity. The NLRP3 inflammasome was activated in cisplatin-treated NRK-52E cells with enhanced NLRP3, interleukin 1 beta, and cleaved caspase-1; however, ruscogenin significantly decreased the expression of NLRP3 inflammasome components (p < 0.01). Ruscogenin attenuated cisplatin-induced expression of TLR4, myeloid differentiation primary response 88, and NF-κB. Further, cisplatin induction enhanced ROS formation, with increased malondialdehyde and decreased glutathione reductase and catalase levels. Ruscogenin attenuated cisplatin-induced ROS accumulation in NRK-52E cells through up-regulation of Nrf2 and HO-1.

Conclusion: Ruscogenin protects against cisplatin-induced apoptosis, inflammation, and oxidative stress in renal tubular epithelial cells via suppression of TLR4/NF-κB activation and promotion of Nrf2/HO-1 activation. Therefore, ruscogenin provides a potential therapeutic strategy for mitigating cisplatin-induced nephrotoxicity.

Keywords: Ruscogenin, Cisplatin, Apoptosis, Inflammation, Oxidative stress, Renal tubular epithelial cells, TLR4/NF-κB, Nrf2/HO-1