Protective effect of total flavones of Abelmoschus manihot L. Medic against poststroke depression injury in mice and its action mechanism.
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.
Liu
Mei
M
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei, People's Republic of China.
Jiang
Qiu-Hong
QH
Hao
Ji-Li
JL
Zhou
Lan-Lan
LL
D028483:Abelmoschus / Q000737:chemistry*; D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D047309:Flavones / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced / Q000150:complications; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008517:Phytotherapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000209:etiology / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; D047309:Flavones; D012333:RNA, Messenger; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase