title: Neuroprotective effect of Danshensu derivatives as anti-ischaemia agents on SH-SY5Y cells and rat brain.
abstract: Novel Danshensu derivatives (3-8) were designed and synthesized to improve bioactivity based on the strategy of 'medicinal chemical hybridization'. Our previous studies indicated that these compounds exhibited noticeable cardioprotective activities. Here, we investigate whether these novel Danshensu derivatives exert neuroprotective activities. An in vitro study revealed that these compounds could increase cell viability and reduce LDH (lactate dehydrogenase) leakage. Moreover, Danshensu-cysteine derivative compounds 6 and 8 could significantly inhibit lipid peroxidation of cell membrane and regulate the expression of apoptosis-related protein (Bcl-2, Bax and caspase 3). An in vivo study demonstrated that treatment with compound 6 at 30 mg/kg markedly decreased the infarct volume of MCAO (middle cerebral artery occlusion) insulted rat brain. Furthermore, treatment with compound 6 showed the antioxidant capacity by increasing the activity of SOD (superoxide dismutase) and GPx (glutathione peroxidase) and decreasing the level of MDA (malondialdehyde) and the ROS (reactive oxygen species) production significantly. These results suggested that these novel conjugates exert significant neuroprotective effects as anti-ischaemia agents and those with high potential merit further investigation.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, People's Republic of China.
authors.forename: Sunisa
authors.initials: S
authors.lastname: Seetapun
authors.forename: Jia
authors.initials: J
authors.lastname: Yaoling
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005978:Glutathione; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D007773:Lactates; D018696:Neuroprotective Agents; C035055:3,4-dihydroxyphenyllactic acid; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione