Liu Mei, Jiang Qiu-Hong, Hao Ji-Li, Zhou Lan-Lan
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei, People's Republic of China.
Anat Rec (Hoboken). 2009 Mar;292(3):412-22. doi: 10.1002/ar.20864.
Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic. We investigated the protective effect of TFA against poststroke depression (PSD) injury in mice and its action mechanism. A mouse model of PSD was induced by middle cerebral artery occlusion (MACO) 30 min/reperfusion, followed by isolation feeding and chronic unpredictable mild stress for 2 weeks. Treatment groups received TFA at three different doses (160, 80, and 40 mg/kg, p.o.) or fluoxetine (Flu, 2.5 mg/kg, p.o.) daily for 24 days. Change in behavior, brain tissue malondialdehyde (MDA) levels, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. The expression of brain-derived neurotrophic factor (BDNF) was detected by immunohistochemistry, and mRNA expression of BDNF and cAMP response element-binding protein (CREB) analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Treatment with TFA (160, 80, and 40 mg/kg) significantly ameliorated mice escape-directed behavioral impairment induced by PSD, markedly reduced MDA levels, and increased the activity of SOD, GSH-Px close to normal levels. TFA administration also attenuated PSD-induced neuronal death/losses, upregulated expression of BDNF both at mRNA and protein levels, as well as CREB mRNA levels. TFA had a protective effect against PSD injury in mice. Cardioprotection involves the inhibition of lipid peroxidation and upregulation of BDNF-CREB levels in the hippocampus, which may also be important mechanism of its antidepressants. This potential protection makes TFA a promising therapeutic agent for the PSD.
黄蜀葵花总黄酮（TFA）是从传统中药黄蜀葵中分离出的主要活性成分。我们研究了TFA对小鼠脑卒中后抑郁（PSD）损伤的保护作用及其作用机制。通过大脑中动脉闭塞（MACO）30分钟/再灌注诱导PSD小鼠模型，随后进行单独饲养和慢性不可预测轻度应激2周。治疗组连续24天每天接受三种不同剂量（160、80和40mg/kg，口服）的TFA或氟西汀（Flu，2.5mg/kg，口服）。测量行为变化、脑组织丙二醛（MDA）水平以及超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性。通过免疫组织化学检测脑源性神经营养因子（BDNF）的表达，并通过逆转录-聚合酶链反应（RT-PCR）分析BDNF和环磷酸腺苷反应元件结合蛋白（CREB）的mRNA表达。用TFA（160、80和40mg/kg）治疗可显著改善PSD诱导的小鼠逃避定向行为障碍，显著降低MDA水平，并使SOD、GSH-Px的活性增加至接近正常水平。给予TFA还可减轻PSD诱导的神经元死亡/损失，上调BDNF在mRNA和蛋白质水平的表达以及CREB mRNA水平。TFA对小鼠PSD损伤具有保护作用。心脏保护作用涉及抑制脂质过氧化和上调海马中BDNF-CREB水平，这也可能是其抗抑郁作用的重要机制。这种潜在的保护作用使TFA成为治疗PSD的有前景的治疗药物。
