title: Functional activation of monoamine transporters by luteolin and apigenin isolated from the fruit of Perilla frutescens (L.) Britt.
abstract: Monoamine transporters playing major roles in regulating normal and abnormal synaptic activity are associated with various neuropsychological disorders. In spite of the discovery of a series of structurally different monoamine transporter antagonists for the therapy approach, no practical pharmaceutical can act as a transporter activator. Here, we isolated luteolin and apigenin from the fruit of Perilla frutescens (L.) Britt by using an activity-guided extraction technique, and proved that the two compounds possess actions of enhancing monoamine uptake either upon monoamine-transporter transgenic Chinese hamster ovary (CHO) cells or upon wild dopaminergic cell lines, with higher specificity for dopamine (DA) uptake than for norepinephrine (NE)- and serotonin (5HT)-uptake, as well as with more potency and greater efficacy for luteolin than for apigenin. Further, in the transgenic cells, the principal NE/DA uptake activation by luteolin was significantly prevented by respective transporter inhibitor, and the transmitter-uptake-enhancing action was independent of its ligands, which is in support of the compounds as monoamine transporter activators. Furthermore, luteolin evoked a marked disinhibition of cocaine-targeted effect in CHO cells overexpressing dopamine transporter. Thus, luteolin and apigenin function as monoamine transporter activators, which would improve several hypermonoaminergic neuropsychological disorders, especially cocaine dependence, through up-regulating monoamine transporter activity.
authors.affiliation: Cell Star Bio-Technologies Co., Limited, Shanghai, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Qin
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Chu
authors.forename: Li-He
authors.initials: LH
authors.lastname: Guo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D047310:Apigenin / Q000302:isolation & purification / Q000494:pharmacology*; D016466:CHO Cells; D002460:Cell Line; D003042:Cocaine / Q000819:agonists; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006224:Cricetinae; D003412:Cricetulus; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000819:agonists; D047311:Luteolin / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D031344:Perilla frutescens / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D050493:Vesicular Monoamine Transport Proteins / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018765:Dopamine Uptake Inhibitors; D010936:Plant Extracts; D050493:Vesicular Monoamine Transport Proteins; D012701:Serotonin; D047310:Apigenin; D003042:Cocaine; D047311:Luteolin; D004298:Dopamine; D009638:Norepinephrine