title: Curcumin induces ABCA1 expression and apolipoprotein A-I-mediated cholesterol transmembrane in the chronic cerebral hypoperfusion aging rats.
abstract: Cerebral hypoperfusion or aging often results in the disturbances of cholesterol and lipoprotein, which have been well depicted as a common pathological status contributing to neurodegenerative diseases such as vascular dementia (VaD) and Alzheimer's dementia (AD). The pathway of the liver X receptor-β (LXR-β)/retinoic X receptor-α (RXR-α)/ABCA1 plays a vital role in lipoprotein metabolism. Curcumin, a kind of phenolic compound, has been widely used. It has been reported that curcumin can reduce the levels of cholesterol in serum, but the underlying mechanisms are poorly understood. In this study, we evaluated the effects of curcumin on the cholesterol level in brain, vascular cognitive impairment and explored whether the mechanisms for those effects are through activating LXR-β/RXR-α and ABCA1 expression and apoA-I. With a Morris water test, we found that curcumin treatment could attenuate cognitive impairment. With HE and Nissl staining, we found that curcumin could significantly ameliorate the abnormal changes of pyramidal neurons. Meanwhile, the expression of LXR-β, RXR-α, ABCA1 and apoA-I mRNA and protein were increased in a dose-dependent manner after curcumin treatment. Interestingly, both serum HDL cholesterol and total cholesterol levels were statistically higher in the curcumin treatment group than those other groups. We conclude that curcumin has the ability to activate permissive LXR-β/RXR-α signaling and thereby modulate ABCA1 and apoA-I-mediated cholesterol transmembrane transportation, which is a new preventive and therapeutic strategy for cerevascular diseases.
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing 400016, China , Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China , Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Tian
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.forename: Linhui
authors.initials: L
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics* / Q000502:physiology; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D002908:Chronic Disease; D003072:Cognition Disorders / Q000188:drug therapy; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D015140:Dementia, Vascular / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000502:physiology; D008517:Phytotherapy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D002784:Cholesterol; D008076:Cholesterol, HDL; D003474:Curcumin; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D047490:Retinoid X Receptor alpha; C577834:Abca1 protein, rat