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Updated: Jan 18, 2026

Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction
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Muscone Reduces OGD/R-Induced Hyperpermeability of the Brain Endothelial Barrier by Activating the PKA/RHOA/MLC

Ziteng Yang1, Yuanqi Zuo2, Guangyun Wang2

  • 1Department of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.

Current Neurovascular Research
|June 2, 2025
PubMed
Abstract

Insights

Muscone protects the brain endothelial barrier by reducing cell death and improving tight junction integrity. This Traditional Chinese Medicine component activates the PKA/RHOA/MLC pathway, offering a potential mechanism for treating ischemic stroke.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • The brain endothelial barrier, crucial for brain function, is compromised in ischemic stroke.
  • Muscone, a key component of musk, is used in Traditional Chinese Medicine for stroke treatment, but its mechanism is unclear.
  • This study investigates muscone's protective effects on brain microvascular endothelial cells (BMECs) against oxygen-glucose deprivation/reperfusion (OGD/R) injury.

Purpose of the Study:

  • To explore the protective effect of muscone on OGD/R-induced endothelial barrier disruption.
  • To determine the underlying molecular mechanism of muscone's action.

Main Methods:

  • BMEC damage and apoptosis assessed via MTT, LDH assays, western blot, and Hoechst staining.
  • Tight junction protein expression and localization evaluated using western blot, immunofluorescence, and phalloidin staining.
  • Barrier integrity measured by TEER and sodium fluorescein permeability; pathway activation verified by molecular docking, DARTS, and CETSA.

Main Results:

  • Muscone reduced OGD/R-induced BMEC apoptosis and tight junction protein degradation.
  • Muscone restored endothelial barrier integrity by promoting ZO-1 membrane expression and increasing TEER.
  • Mechanistic studies revealed muscone activates the PKA/RHOA/MLC pathway, crucial for maintaining endothelial barrier function.

Conclusions:

  • Muscone inhibits BMEC apoptosis and improves endothelial barrier function, presenting a potential therapeutic mechanism for ischemic stroke.
  • Activation of the PKA/RHOA/MLC pathway by muscone is key to reducing hyperpermeability in the brain endothelial barrier.
Keywords:
BMECMusconePKA/RHOA/MLC pathwayTJ proteins.actin cytoskeletonapoptosisendothelial barrierischemic stroke

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