Conessine Interferes with Oxidative Stress-Induced C2C12 Myoblast Cell Death through Inhibition of Autophagic Flux

PLoS One. 2016 Jun 3;11(6):e0157096. doi: 10.1371/journal.pone.0157096. eCollection 2016.


Conessine, a steroidal alkaloid isolated from Holarrhena floribunda, has anti-malarial activity and interacts with the histamine H3 receptor. However, the cellular effects of conessine are poorly understood. Accordingly, we evaluated the involvement of conessine in the regulation of autophagy. We searched natural compounds that modulate autophagy, and conessine was identified as an inhibitor of autophagic flux. Conessine treatment induced the formation of autophagosomes, and p62, an autophagic adapter, accumulated in the autophagosomes. Reactive oxygen species such as hydrogen peroxide (H2O2) result in muscle cell death by inducing excessive autophagic flux. Treatment with conessine inhibited H2O2-induced autophagic flux in C2C12 myoblast cells and also interfered with cell death. Our results indicate that conessine has the potential effect to inhibit muscle cell death by interfering with autophagic flux.

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Autophagosomes / drug effects
  • Autophagy / drug effects*
  • Blotting, Western
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Fluorescent Antibody Technique
  • HEK293 Cells
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • MCF-7 Cells
  • Mice
  • Microscopy, Confocal
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species


  • Alkaloids
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • conessine

Grant support

This study was supported by a grant from the Leading Space Core Technology Development Program through the NRF funded by the Ministry of Science, ICT & Future Planning (2013M1A3A3A02042433) ( The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.