<em>Lycium barbarum</em> polysaccharides attenuate cardiovascular oxidative stress injury by enhancing the Keap1/Nrf2 signaling pathway in exhaustive exercise rats

Hu,Xiaohui; Mu,Le; Zhu,Lingqin; Chang,Xiaoyu; Nie,Lihong; Wang,Li; Li,Guanghua

doi:10.3892/mmr.2021.12282

Lycium barbarum polysaccharides attenuate cardiovascular oxidative stress injury by enhancing the Keap1/Nrf2 signaling pathway in exhaustive exercise rats

Authors:
- Xiaohui Hu
- Le Mu
- Lingqin Zhu
- Xiaoyu Chang
- Lihong Nie
- Li Wang
- Guanghua Li
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Affiliations: School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, School of Public Health and Management, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of General Practice, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
Published online on: July 11, 2021 https://doi.org/10.3892/mmr.2021.12282
Article Number: 643

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Abstract

Moderate exercise is beneficial to physical and mental health. When the amount of exercise and exercise intensity exceeds a certain limit and reaches the state of exhaustion, oxidative stress levels in the body increase, which can lead to oxidative stress‑associated damage. Lycium barbarum polysaccharide (LBP) is one of the primary active ingredients extracted from wolfberry. Following exhausting exercise in rats, LBP supplements decrease damage to the myocardium and blood vessels, indicating that LBP exerts a protective effect on the cardiovascular system. The Kelch‑like ECH‑associated protein 1 (Keap1)/NF‑E2‑related factor 2 (Nrf2) anti‑oxidative stress signaling pathway improves total oxidizing ability; anti‑apoptosis and other aspects serve a vital role. In the present study, LBP intervention was performed in vivo and in vitro to observe its effect on the Keap1/Nrf2 pathway and oxidative stress‑associated indicators in order to clarify its protective mechanism. For the in vivo experiments, 60 male Sprague‑Dawley rats were randomly divided into normal control and aerobic, exhaustive and exhaustive exercise + LBP (200 mg/kg/day) groups. For the in vitro experiments, a rat thoracic aortic endothelial cell (RTAEC) oxidative stress model was established using angiotensin II (AngII) and divided into blank control, LBP (3,200 µg/ml), AngII (1x10^‑4 mol/l) and AngII + LBP groups. For in vitro experiments, small interfering (si)RNA (50 nmol) was used to transfect RTAEC and induce gene silencing of Nrf2. ELISA, hematoxylin and eosin staining, TUNEL, immunofluorescence, western blotting, immunohistochemistry and reverse transcription‑quantitative PCR were used to evaluate and verify the effect of LBP on oxidative stress indicators and the expression of Keap1/Nrf2 antioxidative stress signaling pathway. The in vivo experiments showed that LBP decreased the expression of serum malondialdehyde (MDA) and AngII, as well as apoptosis of blood vessels and cardiomyocytes and expression of TNF‑α in rats following exhaustive exercise. Meanwhile, LBP enhanced expression of the Keap1/Nrf2 signaling pathway and downstream associated protein glutamyl‑cysteine synthetase catalytic subunit (GCLC), quinone oxidoreductase 1 (NQO1) and glutamate‑cysteine ligase modified subunit (GCLM) in the thoracic aorta and myocardium of rats following exhaustive exercise. In RTAEC in vitro, LBP decreased the expression of MDA and TNF‑α in the supernatant, promoted the nuclear translocation of Nrf2 and increased expression levels of GCLC, NQO1 and GCLM. Following siNrf2 transfection into endothelial cells, the anti‑inflammatory and antioxidant stress effects of LBP were decreased. LBP was found to enhance the expression of the Keap1/Nrf2 antioxidant stress signaling pathway in endothelial cells, decreasing oxidative stress and the inflammatory response. Moreover, LBP improved the antioxidant stress ability of endothelial cells and alleviated injury of myocardial vascular tissue, thereby protecting the cardiovascular system.

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