Urolithin B Attenuates Cerebral Ischemia-reperfusion Injury by Modulating Nrf2-regulated Anti-oxidation in Rats

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Ischemia-reperfusion (IR) causes irreversible brain injury (IRI), with no current effective treatments.
• Oxidative stress is a key factor in IRI initiation and progression.
• Urolithin B (UB), an ellagitannin metabolite, shows antioxidant properties but its mechanism in IRI is unknown.

Purpose of the Study:

• To investigate the neuroprotective effects of Urolithin B (UB) against cerebral ischemia-reperfusion injury (IRI).
• To elucidate the underlying mechanisms of UB's action, focusing on oxidative stress and the Nrf2/HO-1 pathway.

Main Methods:

• Assessed neurological deficit scores and cerebral infarction (TTC, Nissl staining) in an IRI model.
• Evaluated neuronal apoptosis (TUNEL assay, Caspase-3) and oxidative stress markers (MDA, SOD, iNOS, 8-OHdG).
• Investigated the role of the Nrf2/HO-1 pathway using an Nrf2 inhibitor (ATRA).

Main Results:

• UB administration significantly reduced neurological impairment and cerebral infarction.
• UB inhibited neuronal apoptosis and decreased oxidative stress markers.
• UB activated the Nrf2/HO-1 signaling pathway, confirmed by reduced neuroprotection with ATRA.

Conclusions:

• Urolithin B effectively mitigates cerebral ischemia-reperfusion injury.
• UB exerts its neuroprotective effects by inhibiting oxidative stress via activation of the Nrf2/HO-1 pathway.
• UB shows promise as a therapeutic agent for treating cerebral IRI.