Vitexin protects against high glucose-induced endothelial cell apoptosis and oxidative stress via Wnt/β-catenin and Nrf2 signalling pathway

Abstract

 

Vitexin, a polyphenolic flavonoid, has been reported to be traditionally applied in the treatment of diabetes, cancer and cardiovascular diseases.

Objective

The aim of this study was to investigate the anti-apoptosis and anti-oxidation effect and the potential mechanism of vitexin on high glucose-induced HUVECs.

Materials and methods

A high dose of glucose was added to HUVECs to establish an in vitro model. The cell viability was detected by CCK8 and flow cytometry assays. 2,7-dichlorodihydrofluorescein diacetate, colorimetry, and enzyme-linked immunosorbent assay were performed to detect oxidative stress. Besides, top flash and western blotting were employed to evaluate the effect of vitexin on Wnt/β-catenin. Furthermore, a Wnt/β-catenin inhibitor (KYA1797K) was used to confirm whether Wnt/β-catenin is involved in the protection of vitexin. At the same time, RT-PCR and western blot were performed to determine the effect of vitexin on Nrf2, while immunofluorescence assays were employed for the assessment of Nrf2 localisation. Then, in order to validate that Nrf2 plays an important role in the anti-oxidant effect of vitexin, methods were utilised to silence Nrf2 gene.

Results

Herein, vitexin inhibited the proliferation and apoptosis of HG-mediated HUVECs. Mechanically, vitexin disrupted Wnt/β-catenin signalling pathway, thus resulting in the decrease of apoptosis in HG-induced HUVECs. A Wnt/β-catenin inhibitor (KYA1797K), was used for reverse verification. In the meantime, vitexin administration decreased reactive oxygen species (ROS) production and malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in HG-induced HUVECs. Further investigations have revealed vitexin activated Nrf2 in HUVEC under high glucose, which was involved in its anti-oxidant effects.

Conclusion

Our investigation demonstrated that vitexin protected HUVECs from high glucose-induced injury via up-regulation of Wnt/β-catenin and Nrf2 signalling pathway. These results suggested that vitexin might serve as a potential drug for atherosclerosis and cardiovascular complications of diabetes.

Keywords:

• Endothelial cell apoptosis
• oxidative stress
• diabetic vascular disease
• vitexin

Author contributions

Yue Chen and Hao Lu substantially contributed to the general idea and design of the study. Sheng Zhang, Shenyi Jin, Shunxiao Zhang, Yuan-Yuan Li, Hua Wang took part in the study. Sheng Zhang and Shenyi Jin completed the data analysis and the manuscript. All authors have read, consented and approved the manuscript.

Acknowledgements

The authors would like to thank all of the colleagues who contributed to this study.

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by Shanghai Municipal Health and Family Planning Commission Scientific Research Project (20204Y0356).