Procyanidin B2 alleviates oxidative stress-induced nucleus pulposus cells apoptosis through upregulating Nrf2 via PI3K-Akt pathway

J Orthop Res. 2023 Jul;41(7):1555-1564. doi: 10.1002/jor.25492. Epub 2022 Dec 10.

Abstract

Oxidative stress can lead to nucleus pulposus cell (NPC) apoptosis, which is considered to be one of the main contributors to intervertebral disc degeneration (IVDD). Procyanidin B2 is a natural antioxidant that protects against oxidative stress. However, whether procyanidin B2 protects NPCs from oxidative stress remains unknown. In this study, we demonstrated that procyanidin B2 could reduce tert-butyl hydroperoxide-induced reactive oxygen species in rat NPCs and attenuate rat NPC apoptosis. Further experiments revealed that procyanidin B2 upregulated the expression of both nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylation of protein kinase B (Akt). We then used silencing of Nrf2 and LY294002 to silence Nrf2 expression and block the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited. Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment.

Keywords: Nrf2; apoptosis; nucleus pulposus cells; oxidative stress; procyanidin B2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Intervertebral Disc Degeneration* / drug therapy
  • Intervertebral Disc Degeneration* / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • NF-E2-Related Factor 2 / therapeutic use
  • Nucleus Pulposus* / metabolism
  • Oxidative Stress
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphatidylinositol 3-Kinase / therapeutic use
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt / physiology
  • Rats

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinase
  • Phosphatidylinositol 3-Kinases
  • procyanidin B2
  • NF-E2-Related Factor 2