Abstract 294: Therapeutic Effects Of Ginseng Gintonin In A Mouse Model Of Focal Ischemic Stroke Via Inhibition Of Lysophosphatidic Acid Receptors

Abstract

Background & Objective: Gintonin is a ginseng-derived lysophosphatidic acid receptor (LPAR) ligand. Previous studies showed beneficial roles of gintonin in mouse models of neurogenerative diseases such as Alzheimer disease and Parkinson disease. We aimed to investigate if gintonin has neurovascular protective effects in a mouse model of focal ischemic stroke. Method: C57BL/6N mice were treated orally with saline (n=50) or gintonin 150 (n=65) or 300 (n=20) mg/kg once daily for 1 week. Among the 150 mg/kg group animals, 15 randomly selected mice were pretreated with intraperitoneal administration of an LPAR antagonist (Ki16425, 30 mg/kg) before the oral treatment. Then, all mice underwent common carotid artery occlusion (CCAO)-related hemispheric ischemia after inducing cerebral autoregulatory dysfunction (CAD). We compared post-ischemic survival rates (Log-rank test) and final infarct volumes (Studen’s t-test) at 1 week. Results: Gintonin 150mg/kg (vs. saline) increased the 1-week survival rate (35/50 [70%] vs. 23/50 [46%], p=0.011) and reduced the infarct size (92.20±14.53mm 3 vs. 138.70±16mm 3 , p=0.038). Gintonin 300mg/kg tended to increase the survival rate (12/20 [60%], p=0.11 vs. saline) and did not significantly reduce the infarct size (40±36 mm 3 , p=0.97). Pretreatment with the LPA receptor antagonist abolished the gintonin 150mg/kg-mediated improvement in post-stroke survival (6/15 [40%], p=0.61 vs. saline) and the reduction of infarct size (197.81±31.97mm 3 , p=0.88 vs. saline). Conclusion: This study suggests that gintonin could improve post-stroke survival and reduce infarct volume through LPAR inhibition in mice.