1. Neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides on cerebral ischemic injury in rats
- Author
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Zhou, Zi-Yi, Tang, Yu-Ping, Xiang, Jun, Wua, Pin, Jin, Hui-Ming, Wang, Zhong, Mori, Masao, and Cai, Ding-Fang
- Subjects
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GANODERMA lucidum , *CEREBRAL ischemia , *BRAIN injury prevention , *APOPTOSIS , *LABORATORY rats , *PREVENTION , *THERAPEUTICS , *ALTERNATIVE medicine , *ANALYSIS of variance , *ANIMAL experimentation , *BIOLOGICAL assay , *BIOLOGICAL models , *BIOPHYSICS , *COMPUTER software , *FLOW cytometry , *HISTOLOGICAL techniques , *RESEARCH methodology , *MICROSCOPY , *EDIBLE mushrooms , *NEURONS , *ORAL drug administration , *RATS , *RESEARCH funding , *STATISTICS , *T-test (Statistics) , *WESTERN immunoblotting , *PLANT extracts , *DATA analysis - Abstract
Aim of the study: To investigate the neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides (GLPS) on cerebral ischemic injury in rats, and to explore the involved mechanisms. Materials and methods: Two models [middle cerebral artery occlusion (MCAO) in Sprague–Dawley (SD) rats and oxygen and glucose deprivation (OGD) in primary cultured rat cortical neurons] were employed to mimic ischemia–reperfusion (I/R) damage, in vivo and in vitro, respectively. Cerebral infarct area was measured by tetrazolium staining, and neurological functional deficits were assessed at 24h after I/R. Neuronal apoptosis was studied by Nissl staining and DNA fragmentation assay. Neuronal injury was assessed by morphological examination using phase-contrast microscopy and quantified by measuring the amount of lactate dehydrogenase (LDH) leakage, cell viability was measured by sodium 3′-1- (phenylaminocarbonyl)-3, 4-tetrazolium-bis (4-methoxy-6-nitro) benzene sulfonic acid (XTT) reduction. Neuronal apoptosis was determined by flow cytometry, and electron microscopy was used to study morphological changes of neurons. Caspase-3, -8 and -9 activation and Bcl-2, Bax protein expression were determined by western blot analysis. Results: Oral administration of GLPS (100, 200 and 400mg/kg) significantly reduced cerebral infarct area, attenuated neurological functional deficits, and reduced neuronal apoptosis in ischemic cortex. In OGD model, GLSP (0.1, 1 and 10μg/ml) effectively reduced neuronal cell death and relieved cell injury. Moreover, GLPS decreased the percentage of apoptotic neurons, relieved neuronal morphological damage, suppressed overexpression of active caspases-3, -8 and -9 and Bax, and inhibited the reduction of Bcl-2 expression. Conclusions: Our findings indicate that GLPS protects against cerebral ischemic injury by inhibiting apoptosis by downregulating caspase-3 activation and modulating the Bcl-2/Bax ratio. [Copyright &y& Elsevier]
- Published
- 2010
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