The neuroprotective effect of dl-3-n-butylphthalide on the brain with experimental intracerebral hemorrhage

Eur J Pharmacol. 2023 Nov 15:959:176105. doi: 10.1016/j.ejphar.2023.176105. Epub 2023 Oct 4.

Abstract

Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, nevertheless specific treatments with conclusive clinical benefit in improving outcomes of ICH remain lacking. The present study applied dl-3-n-butylphthalide (NBP), a compound approved for the treatment of ischemic stroke and rarely studied in ICH, to an experimental animal model of ICH, aiming to evaluate the therapeutic effects of NBP on ICH and the potential mechanisms. The results showed that rats receiving NBP administration exhibited a structural and functional restoration of brain after ICH mainly manifested as alleviation of neuronal apoptosis, suppression of neuroinflammation and oxidative stress, neurovascular remodeling, and eventually improvement of neurological deficits. In addition, several protein targets of NBP were revealed, which mainly play molecular functions of ribonucleoside triphosphate phosphatase activity, pyrophosphatase activity, hydrolase activity and GTPase activity, and participate in the biological process of brain development by regulating the formation of cellular components such as spindles, polymeric cytoskeletal fibers, microtubules and synapses, through mediating pathways such as VEGF signaling pathway, Fc epsilon RI signaling pathway, ECM-receptor interaction, Fc gamma R-mediated phagocytosis, peroxisome and so on, guiding the mechanism exploration of NBP therapy to some extent. Taken together, the study added some new evidence to the application of NBP in ICH treatment.

Keywords: Cerebral restoration; Dl-3-n-butylphthalide; Intracerebral hemorrhage.

MeSH terms

  • Animals
  • Brain
  • Cerebral Hemorrhage / drug therapy
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Rats
  • Stroke* / drug therapy

Substances

  • Neuroprotective Agents
  • 3-n-butylphthalide