Sánchez-Reus M I, Gómez del Rio M A, Iglesias I, Elorza M, Slowing K, Benedí J
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.
Neuropharmacology. 2007 Feb;52(2):606-16. doi: 10.1016/j.neuropharm.2006.09.003. Epub 2006 Oct 27.
Since oxidative stress is implicated in the pathophysiology of dementia and depression, this study was designed to investigate the pro-oxidant activity of rotenone, the protective role of standardized extract of Hypericum perforatum (SHP), as well as the mRNA levels of antioxidant enzymes, in brain homogenates of rats following exposure to rotenone and SHP extract. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions to serve as a positive control. The animals received pretreatment with SHP (4 mg/kg) or quercetin liposomes (25 and 100 mg/kg) 60 min before of rotenone injection (2 mg/kg). All treatments were given intraperitoneally in a volume of 0.5 ml/kg body weight, for 45 days. Rotenone treatment increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and levels of malondialdehyde (MDA). The content of reduced glutathione (GSH) was decreased due to chronic rotenone treatment. Rotenone significantly induced the gene expression of CuZnSOD, MnSOD; CAT and GPx in brain. In contrast, SHP extract exerted an antioxidant action which was related with a decreased of MnSOD activity and mRNA levels of some antioxidant enzymes evaluated. Liposomal quercetin treatment resulted in a significant preservation of the activities of antioxidant enzymes and a decreased in the mRNA levels of these antioxidant enzymes. One possible mechanism of action of SHP extract may be related to quercetin in protecting neurons from oxidative damage. Therefore standardized extract of H. perforatum could be a better alternative for depressed elderly patients with degenerative disorder exhibiting elevated oxidative stress status.
由于氧化应激与痴呆和抑郁症的病理生理学有关，本研究旨在调查鱼藤酮的促氧化活性、贯叶连翘标准化提取物（SHP）的保护作用以及暴露于鱼藤酮和SHP提取物后的大鼠脑匀浆中抗氧化酶的mRNA水平。在相同实验条件下测试了脂质体中的槲皮素这一活性成分作为阳性对照。在注射鱼藤酮（2mg/kg）前60分钟，动物接受SHP（4mg/kg）或槲皮素脂质体（25和100mg/kg）预处理。所有处理均以0.5ml/kg体重的体积腹腔注射，持续45天。鱼藤酮处理增加了超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）的活性以及丙二醛（MDA）的水平。由于长期鱼藤酮处理，还原型谷胱甘肽（GSH）的含量降低。鱼藤酮显著诱导了脑中铜锌超氧化物歧化酶（CuZnSOD）、锰超氧化物歧化酶（MnSOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的基因表达。相比之下，SHP提取物发挥了抗氧化作用，这与所评估的一些抗氧化酶的MnSOD活性和mRNA水平降低有关。脂质体槲皮素处理导致抗氧化酶活性显著保留，且这些抗氧化酶的mRNA水平降低。SHP提取物的一种可能作用机制可能与槲皮素保护神经元免受氧化损伤有关。因此，贯叶连翘标准化提取物可能是患有退行性疾病且氧化应激状态升高的老年抑郁症患者的更好选择。
