Neferine improves oxidative stress and apoptosis in benign prostate hyperplasia via Nrf2-ARE pathway

Redox Rep. 2021 Dec;26(1):1-9. doi: 10.1080/13510002.2021.1871814.

Abstract

Background: Progression of Benign Prostate hyperplasia (BPH) is vulnerable to oxidative stress (OS) and prostatic enlargement among the aging males through apoptosis deregulation. Our present study aimed to investigate the effect of neferine (NF) in the regulation of oxidative stress and apoptosis in human BPH-1 cells.

Methods: BPH epithelial cell line BPH-1 was treated with NF for 24 and 48 h. To measure oxidative stress (OS) we investigated MDA, SOD, and GST expression along with Nrf2 and its downstream gene and protein expression. Cell proliferation and apoptosis regulation was assayed with respective methods.

Results: Investigation revealed NF remarkably activate Nrf2 and its downstream proteins HO-1 and NQO1 at 48 h more substantially. Nrf2/Keap1 relative gene and protein expression indicated that NF might trigger Nrf2 upregulation by decreasing Keap1 expression. Both NF concentrations (3 µM and 9 µM) were able to deplete ROS and lipid peroxidation, concurrently, up-regulated SOD and GST. NF reduced cell proliferation significantly along with the regulation of apoptotic proteins Bax, Bcl2, Cyt-C, Caspase 9, and Caspase 3 at the same time (48 h).

Conclusion: This study is the first to manifest that NF may potentially regulate BPH by counterbalancing between OS and apoptosis through the activation of Nrf2-ARE pathway.

Keywords: BPH; Bax; Bcl-2; Keap1; Neferine; Nrf2; apoptosis; oxidative stress.

MeSH terms

  • Apoptosis
  • Benzylisoquinolines
  • Humans
  • Hyperplasia
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Male
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress
  • Prostate
  • Prostatic Hyperplasia* / drug therapy
  • Prostatic Hyperplasia* / genetics

Substances

  • Benzylisoquinolines
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • neferine

Grants and funding

This study was supported by National Nature Science Foundation of China (Grand No. 81973277).