Ligustilide prevents cognitive impairment and attenuates neurotoxicity in D-galactose induced aging mice brain.

Ligustilide (LIG) is a principal active ingredient of traditional Chinese medicine, Radix Angelica sinensis, which has versatile pharmacological activities including neuroprotection. Previous studies have demonstrated that LIG has beneficial effects on cognition deficits associated with cerebral damage or neurodegenerative disorders. In present study, we investigated the neuroprotective effect of LIG on cognitive impairment and neurotoxicity in the brain of aging mouse induced by d-galactose (d-gal). The aging model mice were induced by subcutaneous (S.C.) injection of d-gal once daily for 8 weeks and LIG (80 mg/kg) was simultaneously administered orally. The Morris water maze (MWM) test was used to assess the spatial learning and memory abilities. The activity of Na(+)-K(+)-ATPase and the content of lipid peroxidation product malondialdehyde (MDA) in brain were examined. The levels of glial fibrillary acidic protein (GFAP), growth-associated protein GAP-43, and cleaved caspase-3 in brain were also determined by immunohistochemistry. The MWM test showed that LIG administration markedly improved behavioral performance of d-gal treated mice. This action could be partly explained by the results that LIG reduced the level of MDA as well as increased the activity of Na(+)-K(+)-ATPase in the brain of d-gal induced aging mice. Moreover, LIG significantly raised the expression of GAP-43 and reduced cleaved caspase-3 and GFAP levels in the brain of d-gal treated mice. These results demonstrated that LIG improves d-gal-induced cognitive dysfunction and brain toxicity, which suggests that LIG may be developed as a new medicine for the treatment of aged-related conditions.

Ligustilide alleviates brain damage and improves cognitive function in rats of chronic cerebral hypoperfusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustilide (LIG), a main lipophilic component of Danggui (Chinese Angelica root, Radix Angelica sinensis) which is a popular used herb to treat menstrual disorders in traditional chinese medicine, has been reported to possess some neuroprotective effects on permanent focal ischemia and transient forebrain ischemia. AIM OF THE STUDY: Based on previous work, we intended to investigate the protective effects of LIG on parietal cortex and hippocampus of rats in chronic cerebral hypoperfusion model. MATERIALS AND METHODS: Chronic cerebral hypoperfusion was induced by permanent, bilateral common carotid artery's occlusion (2VO). The rats were treated with LIG (80mg/kg, by oral) from the eighth day after surgery for seven consecutive days. Their spatial learning and memory abilities were assessed using the Morris water maze. After six days for maze test, rats were sacrificed. Coronal sections in cortex and hippocampus were stained with cresyl violet or labeled with NeuN (Neuronal Nuclei), MAP-2 (Microtubule-Associated Protein-2), Caspase-3 and GFAP (Glial Fibrillary Acidic Protein) antibodies. RESULTS: LIG treatment for seven days decreased escape latency and swimming distance of 2VO rats from the third day in maze tests, and increased percent time in the target quadrant. LIG prevented neuronal loss, dendrites damage and neuronal apoptosis in both parietal cortex and hippocampus of 2VO rats; and it also inhibited astrocytic activation and proliferation stimulated by hypoperfusion. CONCLUSIONS: These results demonstrate that LIG show obvious neuroprotective potential for treating chronic cerebral hypoperfusion injury, which may be attributed to its anti-apoptosis of neuron and anti-proliferation of astrocyte both in cortex and in hippocampus of 2VO rats. We suggest that LIG can be developed as an effective drugs for the prevention of vascular dementia (VD).