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Atorvastatin-induced intracerebral hemorrhage is inhibited by berberine in zebrafish

Xin-Yan Liu1, Bo Chen1, Rui Zhang1

  • 1Key Laboratory of Biotechnology of Antibiotics, the National Health Commission (NHC), Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Journal of Applied Toxicology : JAT
|April 19, 2024
PubMed

Insights

Berberine (BBR) protects against atorvastatin-induced brain hemorrhage in zebrafish by maintaining vascular integrity. It reduces inflammation and injury by reversing abnormal protein phosphorylation in vascular endothelial cells.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cardiovascular Research

Background:

  • Intracerebral hemorrhage (ICH) has a high fatality rate with limited treatment options.
  • Statins like atorvastatin (ATV) are widely used for hyperlipidemia but can rarely cause ICH.
  • Berberine (BBR) is investigated for potential therapeutic benefits.

Purpose of the Study:

  • To investigate the protective effects of berberine (BBR) against atorvastatin (ATV)-induced intracerebral hemorrhage (ICH).
  • To elucidate the underlying mechanisms of BBR's action in mitigating ATV-associated brain hemorrhage.

Main Methods:

  • An ICH model was established in zebrafish using ATV (2 μM).
  • The effects of BBR (10, 50, 100 μM) on vascular integrity were assessed using hemocyte staining and transgenic zebrafish.
  • Mechanisms involving VE-cadherin, occludin, phosphorylation, and autophagy were examined using co-immunoprecipitation (co-IP).

Main Results:

  • ATV induced ICH, increased brain inflammation, and caused locomotion deficits in zebrafish.
  • ATV disrupted vascular integrity by promoting abnormal phosphorylation and mislocalization of VE-cadherin and occludin in vascular endothelial cells (VECs).
  • BBR treatment reversed these effects, reduced inflammation and injury, and preserved vascular integrity.

Conclusions:

  • Berberine (BBR) demonstrates a protective effect against atorvastatin (ATV)-induced intracerebral hemorrhage (ICH).
  • BBR mitigates ATV-induced vascular damage by promoting the autophagic degradation of phosphorylated VE-cadherin and occludin.
  • These findings highlight BBR's potential in maintaining vascular integrity and managing adverse effects of ATV.

Keywords:
VE‐cadherinatorvastatinautophagyberberineintracerebral hemorrhageoccludinvascular integrity

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