Usnic acid improves memory impairment after cerebral ischemia/reperfusion injuries by anti-neuroinflammatory, anti-oxidant, and anti-apoptotic properties

Document Type : Original Article


1 Department of Biology, Faculty of Science, Ilam University, Ilam, Iran

2 Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

3 Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

4 Department of Biology, Faculty of Science, Razi University of Kermanshah, Kermanshah, Iran

5 Rayan Center for Neuroscience and Behavior, Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

6 School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran


Objective(s): Cerebral ischemia/reperfusion causes complex pathological mechanisms that lead to brain tissue damage. Usnic acid is a lichen secondary metabolite that has many different biological properties including anti-inflammatory and anti-oxidant activities. Therefore, the objective of the current study was to investigate the neuroprotective effects of usnic acid on apoptotic cell death, neuroinflammation, anti-oxidant enzyme activities, and oxidative stress levels after transient cerebral ischemia/reperfusion.
Materials and Methods: Forty-two male Wistar rats were randomly assigned to three groups (sham, ischemia/reperfusion, and ischemia/reperfusion+usnic acid). Ischemia was induced by 20 min occlusion of common carotid arteries. Injection of usnic acid (25 mg/kg, intraperitoneally) and saline was done at the beginning of reperfusion time. Morris water maze was applied to assess spatial memory. The protein expression amount was measured using immunohistochemical and immunofluorescence staining. Spectrophotometric assay was performed to determine the levels of anti-oxidant enzymes.
Results: Usnic acid significantly reduced caspase-3, glial fibrillary acidic protein-
positive and ionized calcium-binding adaptor molecule 1-positive cells (P<0.001) and enhanced spatial memory disorders (P<0.05) due to brain ischemia. In addition, treatment with usnic acid improves effects in the antioxidant system following cerebral ischemia (P<0.05).
Conclusion: Our findings indicate that usnic acid has neuroprotective properties, which possibly is applicable as a promising candidate for cerebral injuries caused by ischemia.


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