The Potential Effects of 2,3,4-Trihydroxybenzophenone on the Transient Cerebral Ischemic Stroke in Male Mice

Abstract

Acute ischemic stroke is a cerebrovascular disease associated with high mortality and severe aftereffects which is caused by the blockage of cerebral blood vessels by a thrombus or embolus. Treatments for this condition are extremely limited. Herein, we aimed to explore the potential of 2,3,4-trihydroxybenzophenone (THB), a drug that suppresses oxidative stress and neuroinflammation, to promote functional recovery through neurite outgrowth, and to identify its protective effects in a mouse model of ischemic stroke. To determine the effects of THB on neurite outgrowth, neurite-bearing cells and neurite lengths were measured in Neuro2a cells. 1,1-Diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays were further performed to determine the antioxidant activity of THB, while lipopolysaccharide-activated BV2 cells were used to determine the anti-inflammatory effects of THB. Transient middle cerebral artery occlusion (tMCAO) was further performed in a mouse model to determine the effects of THB on ischemic stroke. THB increased neurite outgrowth in mouse neuroblastoma cell lines and exhibits antioxidant and anti-neuroinflammatory properties. In addition, THB reduced infarct volume in a concentration- dependent manner in the tMCAO model, leading to an increase in survival rate. Moreover, THB significantly suppressed microglial activation in the cortex and striatum. These results suggest that THB has potential for treating transient cerebral ischemic stroke.