Berberine enhances the AMPK activation and autophagy and mitigates high glucose-induced apoptosis of mouse podocytes

Eur J Pharmacol. 2017 Jan 5;794:106-114. doi: 10.1016/j.ejphar.2016.11.037. Epub 2016 Nov 22.


High glucose concentration can induce injury of podocytes and berberine has a potent activity against diabetic nephropathy. However, whether and how berberine can inhibit high glucose-mediated injury of podocytes have not been clarified. This study tested the effect of berberine on high glucose-mediated apoptosis and the AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) activation and autophagy in podocytes. The results indicated that berberine significantly mitigated high glucose-decreased cell viability, and nephrin and podocin expression as well as apoptosis in mouse podocytes. Berberine significantly increased the AMPK activation and mitigated high glucose and/or the AMPK inhibitor, compound C-mediated mTOR activation and apoptosis in podocytes. Berberine significantly enhanced the AMPK activation and protected from high glucose-induced apoptosis in the AMPK-silencing podocytes. Furthermore, berberine significantly increased the high glucose-elevated Unc-51-like autophagy-activating kinase 1 (ULK1) S317/S555 phosphorylation, Beclin-1 expression, the ratios of LC3II to LC3I expression and the numbers of autophagosomes, but reduced ULK1 S757 phosphorylation in podocytes. In addition, berberine significantly attenuated compound C-mediated inhibition of autophagy in podocytes. The protective effect of berberine on high glucose-induced podocyte apoptosis was significantly mitigated by pre-treatment with 3-methyladenine or bafilomycin A1. Collectively, berberine enhanced autophagy and protected from high glucose-induced injury in podocytes by promoting the AMPK activation. Our findings may provide new insights into the molecular mechanisms underlying the anti-diabetic nephropathy effect of berberine and may aid in design of new therapies for intervention of diabetic nephropathy.

Keywords: AMPK; Autophagy; Berberine; High glucose; Podocyte.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Berberine / pharmacology*
  • Cell Survival / drug effects
  • Cytoprotection / drug effects*
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Glucose / pharmacology*
  • Mice
  • Phosphorylation / drug effects
  • Podocytes / cytology*
  • Podocytes / drug effects*
  • Podocytes / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism


  • Berberine
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Glucose