Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating infl ammation and SIRT6/TNF-α signaling

Yuqi Gao; Kezheng Peng; Yida Wang; Yannan Guo; Chenye Zeng; Rui Hua; Qingfei Liu; Xue Li; Ying Qiu; Zhao Wang

doi:10.1016/j.fshw.2023.03.043

Food Science and Human Wellness 2023, 12(6): 2232-2241 https://doi.org/10.1016/j.fshw.2023.03.043

Research Article |

Open Access | Issue | Published: 04 April 2023

Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating infl ammation and SIRT6/TNF-α signaling

Show Author's Information Hide Author's Information Yuqi Gao^{^a^,¹}, Kezheng Peng^{^a^,¹}, Yida Wang^{^a}, Yannan Guo^{^a}, Chenye Zeng^{^a}, Rui Hua^{^a}, Qingfei Liu^{^a}, Xue Li^{^b}, Ying Qiu^{^b}, Zhao Wang^{^a}(

)

The Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China

School of Medicine, Tsinghua University, Beijing 100084, China

¹ These authors contributed equally to this work

Peer review under responsibility of KeAi Communications Co., Ltd.

Keywords:

Cisplatin, TNF-α, SIRT6, Ellagic acid, Nephrotoxicity

Cite this article:

Gao Y, Peng K, Wang Y, et al. Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating infl ammation and SIRT6/TNF-α signaling. Food Science and Human Wellness, 2023, 12(6): 2232-2241. https://doi.org/10.1016/j.fshw.2023.03.043

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Abstract

Despite cisplatin has been widely used in the treatment of various cancers, the noteworthy nephrotoxicity greatly constrained its clinical value. For this reason, finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant. Our previous study found that histone deacetylase sirtuin 6 (SIRT6) could be an ideal target for the treatment of cisplatin-induced acute kidney injury. In this study, we explored the protective effects of ellagic acid, a natural polyphenol compound that activates SIRT6, on cisplatin-induced nephrotoxicity. Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells. Moreover, ellagic acid ameliorated renal dysfunction, apoptosis and fibrosis induced by cisplatin in mice. Furthermore, ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin (IL)-1β and IL-6 expression both in vitro and in vivo. Mechanistically, ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor (TNF)-α expression. And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis, indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation. Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury, and support ellagic acid as a potential adjunctive therapy for future cancer treatment.

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Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating infl ammation and SIRT6/TNF-α signaling

Show Author's information Hide Author's Information Yuqi Gao^{^a^,¹}, Kezheng Peng^{^a^,¹}, Yida Wang^{^a}, Yannan Guo^{^a}, Chenye Zeng^{^a}, Rui Hua^{^a}, Qingfei Liu^{^a}, Xue Li^{^b}, Ying Qiu^{^b}, Zhao Wang^{^a}(

)

The Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China

School of Medicine, Tsinghua University, Beijing 100084, China

¹ These authors contributed equally to this work

Peer review under responsibility of KeAi Communications Co., Ltd.

Abstract

Keywords: Cisplatin, TNF-α, SIRT6, Ellagic acid, Nephrotoxicity

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Publication history

Received: 31 May 2022

Revised: 14 June 2022

Accepted: 08 August 2022

Published: 04 April 2023

Issue date: November 2023

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Acknowledgements

This work was financially supported by grants from the National Natural Science Foundation of China (82170873, 81871095), the National Key R&D Program of China (2018YFC2000304), the Tsinghua Precision Medicine Foundation (10001020132), and the Tsinghua University Spring Breeze Fund (20211080005). We thank Jingjing Wang at Cell Biology Facility, Center of Biomedical Analysis, Tsinghua University for the technical support.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).