Neuroprotective effects of bacopaside I in ischemic brain injury
Article type: Research Article
Authors: Liu, Xiaojun | Yue, Rongcai | Zhang, Jigang | Shan, Lei | Wang, Rui | Zhang, Weidong;
Affiliations: School of Pharmacy, Second Military Medical University, Shanghai, PR China | Shanghai Key Laboratory of New Drug Design, Department of Pharmaceutical Science, School of Pharmacy, East China University of Science and Technology, Shanghai, PR China | School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China
Note: [] Corresponding author: Weidong Zhang, Rui Wang and Lei Shan, School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, PR China. Tel./Fax: +86 21 81871244; E-mail: wdzhangy@hotmail.com (Weidong Zhang); Tel./Fax: +86 21 64250823; E-mail: ruiwang@ecust.edu.cn (Rui Wang); Tel./Fax: +86 21 81871246; E-mail: shanleish@yahoo.com.cn (Lei Shan).
Note: [] Corresponding author: Weidong Zhang, Rui Wang and Lei Shan, School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, PR China. Tel./Fax: +86 21 81871244; E-mail: wdzhangy@hotmail.com (Weidong Zhang); Tel./Fax: +86 21 64250823; E-mail: ruiwang@ecust.edu.cn (Rui Wang); Tel./Fax: +86 21 81871246; E-mail: shanleish@yahoo.com.cn (Lei Shan).
Note: [] Corresponding author: Weidong Zhang, Rui Wang and Lei Shan, School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, PR China. Tel./Fax: +86 21 81871244; E-mail: wdzhangy@hotmail.com (Weidong Zhang); Tel./Fax: +86 21 64250823; E-mail: ruiwang@ecust.edu.cn (Rui Wang); Tel./Fax: +86 21 81871246; E-mail: shanleish@yahoo.com.cn (Lei Shan).
Abstract: Purpose: Bacopa monnieri (L.) WETTST. is extensively used in traditional Indian medicine as a nerve tonic. The neuropharmacological properties of bacopaside I, an important component from B. monnieri, have not been studied so far. The present study investigated the effects and possible mechanisms of bacopaside I in a rat model of transient focal ischemia induced by middle cerebral artery occlusion (MCAO). Methods: Adult male Sprague-Dawley rats were divided into five groups: sham-operated group, ischemia group, and three bacopaside I-treated groups (3, 10 and 30 mg/kg) respectively. Bacopaside I or vehicle (0.5% CMC-Na) was administered orally once a day for 6 days. On the third day, the rats were subjected to 2 h right MCAO via the intraluminal filament technique and 70 h reperfusion. Assessment of behavioral deficits both at 22 and 70 h, and measurement of cerebral infarct volume, edema, cerebral energy metabolism, relative enzyme activities, malondialdehyde (MDA) content, nitric oxide (NO) level, and antioxidant enzyme activities at 70 h, performed after MCAO reperfusion. Results: Bacopaside I (10 and 30 mg/kg) treatment produced significant reduction in neurological deficits at 22 and 70 h, and significantly reduced cerebral infarct volume and edema at 70 h, when compared with the ischemia group. Animal, that were orally treated with bacopaside I (3, 10 and 30 mg/kg) showed increased the brain ATP content, energy charge (EC), total adenine nucleotides (TAN), nitric oxide (NO) level, Na+K+ATPase and Ca2+Mg2+ATPase activity. Bacopaside I (3, 10 and 30 mg/kg) treatment also improved antioxidant enzyme activities including brain superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), in varying degrees, compared with the ischemia group. In addition, three doses of bacopaside I (3, 10 and 30 mg/kg) markedly inhibited the increase in MDA content of the brain. Conclusions: These findings indicated that bacopaside I possess a neuroprotective effect against injury caused by cerebral ischemia. The protective mechanism might be related to improving cerebral energy metabolism and increasing antioxidant levels.
Keywords: Bacopaside I, stroke, ischemic injury, reactive oxygen radicals, energy metabolism
DOI: 10.3233/RNN-120228
Journal: Restorative Neurology and Neuroscience, vol. 31, no. 2, pp. 109-123, 2013