Osthole improves chronic cerebral hypoperfusion induced cognitive deficits and neuronal damage in hippocampus.
This study is to investigate the effects of osthole on cognitive impairment and neuronal degeneration in hippocampus induced by chronic cerebral hypoperfusion in rats, as well as the potential mechanism. Permanent occlusion of bilateral common carotid arteries (2VO) induced severe cognitive deficits tested by the water maze task, along with oxidative stress and neuronal loss in hippocampus. Oral administration of osthole for 3 weeks markedly attenuated cognitive deficits and neuronal damage. Biochemical experiments revealed that osthole decreased the production of malondialdehyde (MDA) and significantly increased the activities of Glutathione Peroxidase (GPx) and Catalase. Western blot analyses indicated that osthole prevented the downregulation of bcl-2 expression and upregulation of bax expression, which resulted in decreasing bax/bcl-2 ratio in hippocampus of 2VO rats. Additionally, osthole effectively alleviated the activation of caspase-3 induced by permanent occlusion of bilateral common carotid arteries. The observed results in present study suggest that osthole exhibits therapeutic potential for vascular dementia, which is most likely related, at least in part, to its antioxidation and anti-apoptotic actions.
Ji
Hai-Jie
HJ
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Hu
Jin-Feng
JF
Wang
Yong-Hui
YH
Chen
Xiao-Yu
XY
Zhou
Ran
R
Chen
Nai-Hong
NH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D017536:Carotid Artery, Common / Q000601:surgery; D002374:Catalase / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003374:Coumarins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008026:Ligation; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D003374:Coumarins; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C046627:osthol