Asian Journal
Of Traditional Medicines

Abstract: To investigate the effects of 4-methyl-2-{[4-(toluene-4-sulfonyl)-thiomorpholine-3-carbonyl]-amino}-pentanoic acid isopropyl ester (HD5-6) against cerebral ischemia in rodents, the models with global and focal ischemia were induced by bilateral common carotid artery occlusion plus hypotension (BCAOH) and permanent cerebral artery occlusion (p-MCAO) in mice (n = 10 – 12 per group in BCAOH; n = 8 per group in p-MCAO) and rats (n = 10 - 11 in each group). HD5-6 prolonged lifetime and improved neurological function. Neurological deficits score in HD5-6 (30 mg/kg) decreased significantly. Malonaldehyde (MDA) in HD5-6-treated mice with ischemia considerably dropped. The infarction volume of the HD5-6-treated rats with MCAO-induced ischemia decreased significantly in the high dose group (P < 0.05, i.g. and P < 0.01, i.v.). Immunohistochemistry showed that Brain derived neurotrophic factor (BDNF) in the ipsilateral hemisphere increased and Vascular endothelial growth factor (VEGF) decreased with HD5-6 treatment. HD5-6 has protective effects against experimental cerebral ischemia in rodents and the action mechanism may involve anti-oxidation and neurogenesis.

Key words: HD5-6, global ischemia, focal ischemia, MDA, BDNF, VEGF