Salvianolic acid B inhibits the development of diabetic peripheral neuropathy by suppressing autophagy and apoptosis

J Pharm Pharmacol. 2019 Mar;71(3):417-428. doi: 10.1111/jphp.13044. Epub 2018 Dec 7.

Abstract

Objectives: The aim of this study was to evaluate the neuroprotective effects of SalB on high glucose (HG)-induced excessive autophagy and apoptosis in vitro.

Methods: The proliferation and apoptosis of RSC96 cells were determined using the MTT assay and flow cytometry, respectively. Western blot analysis was performed to examine the expression of autophagy and apoptosis-related proteins. RT-PCR and flow cytometry were manipulated to examine the level of Bcl-2. The signals of autophagy markers were detected using immunofluorescence methods.

Key findings: We found that HG significantly reduced RSC96 cell's proliferation and induced apoptosis. What's more, HG increased the level of autophagy and apoptosis-related proteins. However, these effects were reversed by SalB. In addition, we also found that 3-MA decreased the expression of LC3A/B and Beclin1, while the JNK inhibitor SP600125 reduced the levels of phosphorylated JNK, LC3A/B and Beclin1.

Conclusions: High glucose not only induced apoptosis but also caused autophagic cell death by activating the JNK pathway. These effects prevented by SalB in an opposite manner.

Keywords: Salvianolic acid B; apoptosis; autophagy; diabetic peripheral neuropathy; high glucose.

MeSH terms

  • Animals
  • Anthracenes / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Beclin-1 / metabolism
  • Benzofurans / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / prevention & control*
  • Glucose / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / prevention & control*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Signal Transduction / drug effects

Substances

  • Anthracenes
  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Benzofurans
  • Proto-Oncogene Proteins c-bcl-2
  • pyrazolanthrone
  • salvianolic acid B
  • Glucose