Rhaponticum carthamoides improved energy metabolism and oxidative stress through the SIRT6/Nrf2 pathway to ameliorate myocardial injury

Zihan Zheng; Yushan Xian; Zhen Jin; Feng Yao; YiZhen Liu; Ying Deng; Bo Wang; Danli Chen; Jianjun Yang; Lingxuan Ren; Rong Lin

doi:10.1016/j.phymed.2022.154197

Rhaponticum carthamoides improved energy metabolism and oxidative stress through the SIRT6/Nrf2 pathway to ameliorate myocardial injury

Phytomedicine. 2022 Oct:105:154197. doi: 10.1016/j.phymed.2022.154197. Epub 2022 May 22.

Authors

Zihan Zheng¹, Yushan Xian², Zhen Jin¹, Feng Yao¹, YiZhen Liu¹, Ying Deng¹, Bo Wang¹, Danli Chen¹, Jianjun Yang¹, Lingxuan Ren¹, Rong Lin³

Affiliations

¹ Department of Pharmacology, Xi'an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, PR China.
² Department of Pharmacology, Xi'an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, PR China; Department of Pharmacy, Xi'an NO.3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, Shaanxi 710018, PR China.
³ Department of Pharmacology, Xi'an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, PR China. Electronic address: linrong@xjtu.edu.cn.

PMID: 35917770
DOI: 10.1016/j.phymed.2022.154197

Abstract

Background: Rhaponticum carthamoides (Willd.) Iljin (Rha) is a member of the family Compositae that is widely used in folk medicine as a dietary supplement to treat cardiovascular diseases (CVDs), such as senile cardiac insufficiency, and to restore myocardial function after surgery. Sirtuin 6 (SIRT6), an NAD⁺-dependent class III histone deacetylase, plays a considerable role in the administration of CVDs. However, the specific effects and mechanism of Rha on myocardial injury remain unknown.

Purpose: This study aimed to explore the therapeutic potential of Rha against myocardial injury as well as its underlying mechanisms in vivo and in vitro.

Methods: A myocardial ischaemia model was established in male SD rats by subcutaneously injecting ISO. The rats were gavaged with Rha (40, 80, 160 mg/kg) or Rho (6 ml/kg) for 14 successive days and then injected subcutaneously with ISO or saline solution on the 13th and 14th days. The positive effects of Rha against myocardial injury in rats were evaluated by ECG assessment, BP measurements, H&E staining, and myocardial enzyme detection. Biochemical indicators of energy metabolism and oxidative stress, such as NAD⁺/NADH, ATP, and MDA, were analysed by assay kits to assess the effects of Rha. The protein and mRNA expression levels of SIRT6 and Nrf2 in the myocardium were determined by western blotting and real-time PCR.

Results: Our results showed that Rha ameliorated myocardial ischaemia and inhibited energy metabolism disorders (NAD⁺/NADH ratio, ATP, and LD) and oxidative stress (SOD, ROS, etc.) in rat myocardial tissue and H9c2 cells. In addition, Rha upregulated SIRT6 and Nrf2 expression in myocardial injury. Mechanistic studies then found that SIRT6 knockdown reduced the expression of Nrf2 as well as the effects of Rha on the levels of ATP, LD, and ROS, whereas activation of Nrf2 improved the effects of Rha in cells. In summary, Rha might exert its cardioprotective effects via the SIRT6-mediated Nrf2 signaling pathway.

Conclusion: The results suggest that Rha regulates energy metabolism and oxidative stress through the SIRT6/Nrf2 signaling pathway to play a protective role in myocardial injury.

Keywords: Myocardial injury; Nicotinamide adenine dinucleotide; Rhaponticum carthamoides; Sirtuin 6.

MeSH terms

Adenosine Triphosphate
Animals
Energy Metabolism
Leuzea*
Male
Myocardial Ischemia*
NAD
NF-E2-Related Factor 2
Oxidative Stress
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Sirtuins*

Substances

Adenosine Triphosphate
NAD
NF-E2-Related Factor 2
Reactive Oxygen Species
Sirtuins