Investigation of Linarinic acid and one of its derivatives against cerebral ischemia in mice

The study aims to investigate the effects of (-)-Linarinic acid (LA) and one of its derivatives (LA_d) on brain injury induced by ischemia. Malonaldehyde (MDA) is determined as an index for lipid peroxidation both in vitro and vivo. Mice were pre-treated with LA and LA_d for 3 d. Thereafter, they were induced to have incomplete cerebral ischemia with both bilateral carotid artery occlusion and hypotension (BCAOH). In the first part of the in vivo experiment, mice were divided into four groups: sham (control), ischemia, ischemia + LA (200 mg/kg, i.g.) and ischemia + LA_d (200 mg/kg, i.g.). In the second part, the dose-response of LA_d was investigated at 100, 200 and 400 mg/kg i.g., respectively. A modified neurological severity score was developed for evaluating behavioral deficits of the mice with ischemia. Brains of the mice were excised in order to determinate MDA after ischemia for 6 h. Survival time, survival rate, neurological injury score and MDA level in brains were observed. Results were: 1) The data in vitro showed that both LA and LA_d could inhibit the generation of MDA. IC₅₀ values obtained by Probit analysis were 2.9 mM for LA_d and 4.88 mM for LA; 2) BCAOH could significantly shorten the survival span, reduce the survival rate and cause neurological deficits, which were associated with high level of lipid hydroperoxide production in cerebral tissues; 3) LA_d decreased lipid peroxidation and improved the neurological outcome more than LA. It is concluded that LA_d offers a better neuroprotection than LA against brain damage caused by cerebral ischemia.