Neuroprotective effect of Longshengzhi capsule following permanent middle cerebral artery occlusion in rats

Abstract

Objective: Longshengzhi capsule (LSZC) is an optimized preparation based on the traditional Chinese Medicine formula Buyanghuanwu Decoction (BYHWD), and is approved by the China Food and Drug Administration for treating stroke-induced disability and vascular diseases. Herein, we examined the pharmacodynamics, anti-apoptotic and anti-oxidant actions, and potential mechanisms of action of LSZC following stroke in rats. Methods: Permanent middle cerebral artery occlusion (MCAO) was used as an ischemic stroke model. LSZC was administered intragastrically. We examined the survival rate, bodyweight, and neurological deficits in stroke rats. Brain infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Brain pathology was examined using hematoxylin and eosin staining, Nissl staining, and TdT-mediated dUTP Nick-End Labeling staining. Malondialdehyde, catalase, superoxide dismutase, and glutathione levels were examined by commercial kits. Expression of Nrf2, heme oxygenase-1, Bax, Bcl-2, cleaved caspase-3, and caspase-3 proteins in brain tissue was measured by Western blot. Results: LSZC markedly improved the survival rate and bodyweight, and reduced infarct volume and neurological deficit scores, in MCAO stroke rats. LSZC also significantly attenuated oxidative stress, as indicated by decreased expression of malondialdehyde, and upregulation of Nrf2, heme oxygenase-1, catalase, superoxide dismutase, and glutathione. Moreover, LSZC significantly decreased apoptosis, including a decrease in Bax and cleaved caspase-3 expression, and an increase in Bcl-2, as well as a reduction in numbers of apoptotic neurons. Conclusion: LSZC treatment is neuroprotective against ischemic stroke, potentially via reducing oxidative stress and apoptosis. The Nrf2 and apoptotic signaling pathways may play important roles in the antioxidant and anti-apoptotic actions of LSZC. Keywords: Longshengzhi capsule, Middle cerebral artery occlusion, Oxidative stress, Apoptosis, Cerebral protective