title: β-asarone and levodopa co-administration increase striatal dopamine level in 6-hydroxydopamine induced rats by modulating P-glycoprotein and tight junction proteins at the blood-brain barrier and promoting levodopa into the brain.
abstract: Levodopa (L-dopa) is widely considered as one of the most effective drug constituents in the treatment of Parkinson's disease (PD), but the blood-brain barrier (BBB) permeability of L-dopa is <5%, which causes low efficacy. Neuroprotective effects of β-asarone on 6-hydroxydopamine (6-OHDA)-induced PD rats were demonstrated by our previous studies. Co-administration of β-asarone and L-dopa has not been explored until being investigated on PD rats in this study. PD rats were divided into four groups: untreated, L-dopa-treated, β-asarone-treated and co-administered-treated groups. All of the treatments were administered to the rats twice per day for 30 days. The L-dopa, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), S100β and neuron-specific enolase (NSE) levels were subsequently determined. The P-glycoprotein (P-gp), zonula occludens-1 (ZO-1), claudin-5, occludin and actin expression was also assessed in cortex. Changes in BBB ultrastructure were observed using transmission electron microscopy. Our results showed that the co-administered treatment increased levels of L-dopa, DA, DOPAC and HVA in striatum, and S100β in plasma, but down-regulated NSE, P-gp, ZO-1, occludin, actin and claudin-5 in cortex. Crevices were observed between capillary endothelial cells at intercellular tight junction of the striatum in co-administered-treated group, while the endothelial cells in untreated group were tightly jointing each other. In addition, the correlations of L-dopa or DA and P-gp or tight junction proteins respectively were significantly negative in co-administered- and β-asarone-treated groups. These findings suggest that co-administered treatment may enhance the L-dopa BBB permeability and attenuate brain injury, which may be beneficial to PD treatment.
authors.affiliation: Hainan Medical University, Haikou, China.|The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Minzhen
authors.initials: M
authors.lastname: Deng
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: He
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Shiyao
authors.initials: S
authors.lastname: Lu
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Ruanxin
authors.initials: R
authors.lastname: Ma
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Fang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004359:Drug Therapy, Combination; D007980:Levodopa / Q000008:administration & dosage / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D051381:Rats; D062725:Tight Junction Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000081248:Allylbenzene Derivatives; D000840:Anisoles; D062725:Tight Junction Proteins; C012195:asarone; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine
keywords: P-glycoprotein; actin; claudin-5; occluding; zonula occludens-1; β-asarone