title: Yokukansan, a Traditional Japanese Medicine, Enhances the L-DOPA-Induced Rotational Response in 6-Hydroxydopamine-Lesioned Rats: Possible Inhibition of COMT.
abstract: The aim of the present study was to investigate the effects of the traditional Japanese medicine yokukansan (YKS) on the function of dopamine (DA) in the rat nigrostriatal system. Unilateral 6-hydroxydopamine lesions were produced in the rat nigrostriatal system. Despite a marked loss in the striatal immunoreactivity of tyrosine hydroxylase on the lesion side, striatal serotonin (5-HT) immunoreactivity was not affected. Treatment using L-3,4-dihydroxyphenylalanine (L-DOPA) in conjunction with benserazide for 15 d induced abnormal involuntary movements (AIMs) such as locomotive (rotational response), axial, forelimb, and orolingual movements in the lesioned rats. The L-DOPA-induced locomotive and axial, but not forelimb and orolingual, AIMs were significantly increased and prolonged by the pre-administration of YKS. We next investigated the effects of YKS on the production of DA from L-DOPA in 5-HT synthetic RIN 14B cells. RIN 14B cells produced DA and its metabolite, 3-methoxytyramine (3-MT), following L-DOPA treatment. YKS significantly augmented DA production and inhibited its metabolism to 3-MT in a manner similar to the catechol-O-methyltransferase (COMT) inhibitor entacapone. YKS and some alkaloids (corynoxeine: CX, geissoschizine methyl ether: GM) in Uncaria hook, a constituent herb of YKS, also inhibited COMT activity, indicating that the augmenting effect of YKS on L-DOPA-induced DA production in 5-HT synthetic cells was due to the inhibition of COMT by CX and GM. Our results suggest that YKS facilitates the DA supplemental effect of L-DOPA, and that COMT inhibition by CX and GM contributes, at least in part, to the effects of YKS.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishida
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ebihara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabuchi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Imamura
authors.forename: Kyoji
authors.initials: K
authors.lastname: Sekiguchi
authors.forename: Kazushige
authors.initials: K
authors.lastname: Mizoguchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
authors.forename: Go
authors.initials: G
authors.lastname: Koganemaru
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Abe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
mesh_terms: D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002460:Cell Line; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008518:Medicine, East Asian Traditional; D009570:Nitriles / Q000494:pharmacology; D016627:Oxidopamine / Q000633:toxicity*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002396:Catechols; D004365:Drugs, Chinese Herbal; D006834:Hydrazines; D009570:Nitriles; C524644:Yi-Gan San; D007980:Levodopa; C071192:entacapone; D001545:Benserazide; D016627:Oxidopamine; D010293:Pargyline; C004297:3-hydroxybenzylhydrazine; C001746:3-methoxytyramine; D004298:Dopamine