Notoginsenoside Fc ameliorates renal tubular injury and mitochondrial damage in acetaminophen-induced acute kidney injury partly by regulating SIRT3/SOD2 pathway

Miaomiao Wei; Yuancheng Gao; Dongsheng Cheng; Haiying Zhang; Wei Zhang; Yilan Shen; Qunwei Huang; Xiaoning An; Bing Wang; Zhonghai Yu; Niansong Wang; Hongbo Chen; Youhua Xu; Dingkun Gui

doi:10.3389/fmed.2022.1055252

Notoginsenoside Fc ameliorates renal tubular injury and mitochondrial damage in acetaminophen-induced acute kidney injury partly by regulating SIRT3/SOD2 pathway

Front Med (Lausanne). 2023 Jan 6:9:1055252. doi: 10.3389/fmed.2022.1055252. eCollection 2022.

Authors

Miaomiao Wei^{1

2}, Yuancheng Gao³, Dongsheng Cheng², Haiying Zhang², Wei Zhang⁴, Yilan Shen², Qunwei Huang², Xiaoning An², Bing Wang⁵, Zhonghai Yu⁵, Niansong Wang², Hongbo Chen⁶, Youhua Xu⁷, Dingkun Gui^{2

8}

Affiliations

¹ College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
² Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ The Third Affiliated Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
⁴ Department of Nephrology, Shanghai Yangpu Hospital of Traditional Chinese Medicine, Shanghai, China.
⁵ Department of Traditional Chinese Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China.
⁷ Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, China.
⁸ Department of Central Laboratory, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Introduction: Mitochondria dysfunction is one of the primary causes of tubular injury in acute kidney injury (AKI). Notoginsenoside Fc (Fc), a new saponin isolated from Panax notoginseng, exhibited numerous pharmacological actions. However, the beneficial effects of Fc on renal tubular impairment and mitochondrial dysfunction in AKI have not been fully studied.

Methods: In this study, we established acetaminophen (APAP)-induced AKI model in mice to examine the therapeutic impacts of Fc on AKI.

Results: Our results showed that Fc could decrease the levels of the serum creatinine (Scr), blood urea nitrogen (BUN) and Cystatin C in mice with AKI. Fc also ameliorated renal histopathology, renal tubular cells apoptosis and restored expression of apoptosis-related proteins such as Bax, Bcl-2 and caspase3 (C-caspase3). Additionally, Fc increased the protein expression of SIRT3 and SOD2 in kidneys from mice with AKI. In vitro studies further showed Fc reduced the apoptosis of HK-2 cells exposure to APAP, attenuated the loss of mitochondrial membrane potential and decreased the formation of mitochondrial superoxide. Fc also partly restored the protein expression of Bax, Bcl-2, C-Caspase3, SIRT3, and SOD2 in HK-2 cells exposure to APAP.

Conclusion: In summary, Fc might reduce renal tubular injury and mitochondrial dysfunction in AKI partly through the regulation of SIRT3/SOD2 pathway.

Keywords: SIRT3/SOD2; acetaminophen; acute kidney injury; mitochondria dysfunction; notoginsenoside Fc.

Grants and funding

This study was supported by the National Key R&D Program of China (2019YFE0110500), Science and Technology Development Fund of Macau (File No. 0055/2019/AMJ), and Science and Technology Commission of Shanghai Municipality (14DZ2260200 and 20DZ2271600, the project of Shanghai Key Laboratory of Kidney and Blood Purification). This work was also supported by the National Natural Science Foundation of China (82074175 and 81673919) and the Interdisciplinary Program of Shanghai Jiao Tong University (Grant Number YG2019QNB14).