Neuroprotective effect of Umbelliferone against Cerebral ischemia/Reperfusion induced neurological deficits: in-vivo and in-silico studies

Abstract

Inflammatory pathway is the significant marker of neuro-inflammation and plays a significant role in the expansion of cerebral ischemia/reperfusion injury. Umbelliferone (UF), 7-hydroxy coumarin, has been already proved for its anti-inflammatory and anti-oxidative effects against ischemic brain injury in the rodent model, but its underlying pharmacological mechanism for neuro-protection remain unclear. In this study, we try to explore the neuro-protective effect of umbelliferone against ischemia/Reperfusion induced neurological deficits in rats and explore the underlying mechanism. Inserting thread into the middle cerebral artery was used to induce the ischemic stroke model. The rats were treated with the umbelliferone (5, 10 and 20 mg/kg) for 14 days prior to the ischemic stroke. At the end of the experimental study, brain infarction volume, neurological score, brain edema, pro-inflammatory cytokines, inflammatory mediator were estimated in the region of brain and serum. The mRNA expression of Toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88), Fas and FasL were also estimated at the end of the study. Dose dependently treatment of umbelliferone down-regulated the neurological score, brain infarction, inflammatory mediator (TNF-α, IL-1β, IL-6, COX-2, NF-kB and PGE₂) in the serum and brain tissue as compared to I/R induced control group rats. Umbelliferone also reduced the expression of TRL4, MyD88, Fas and FasL as compared to I/R control group rats. Umbelliferone also decreased the level of nuclear factor kappa B (NF-kB) compared to MACO control group rats. Collectively, the obtained result showed that the umbelliferone protected the brain against the ischemic injury in the rats through the inhibition of inflammatory pathway.

Communicated by Ramaswamy H. Sarma

Keywords:

• Umbelliferone
• ischemia reperfusion injury
• Inflammation
• nuclear factor kappa B
• Toll-like receptor-4
• myeloid differentiation factor 88

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The project was supported by grants from National Administration of Traditional Chinese Medicine (K2019BZ07). Jiangsu Province Administration of Traditional Chinese Medicine (ZX2016A2); 333 high level talents training project in Jiangsu(BRA2016507). National Administration of traditional Chinese medicine evidence-based capacity building project, Project No.: 2019xzzx-nb007.