Huang Liping, Deng Minzhen, Zhang Sheng, Fang Yongqi, Li Ling
The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Clin Exp Pharmacol Physiol. 2014 Sep;41(9):685-90. doi: 10.1111/1440-1681.12270.
The aim of the present study was to investigate the effect of coadministration of β-asarone and levodopa (l-dopa) on increasing dopamine (DA) in the striatum of healthy rats. Rats were randomly divided into four groups: (i) a normal group, administered normal saline; (ii) a Madopar group, administered 75 mg/kg Madopar (l-dopa : benserazide, 4 : 1); (iii) an l-dopa group, administered 60 mg/kg l-dopa; and (iv) a group coadministered 15 mg/kg β-asarone and 60 mg/kg l-dopa. All drugs (or normal saline) were administered intragastrically twice a day for 7 days. Then, plasma and striatum concentrations of DA, l-dopa, 5-hydroxytryptamine (5-HT), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAO-B) were determined. In the group coadministered β-asarone and l-dopa, there was a decline in plasma and striatal concentrations of l-dopa; however, DA and DOPAC concentrations increased in the striatum and plasma and plasma HVA concentrations increased, whereas there was no significant change in striatal levels. Concentrations of 5-HT in the striatum and plasma were similar in the coadministered and Madopar-treated groups. In addition, plasma and striatal COMT levels decreased after coadministration of β-asarone and l-dopa, whereas there were no significant differences in MAO-B concentrations among groups. Furthermore, coadministration of β-asarone and l-dopa increased plasma TH concentrations. Altogether, β-asarone affects the conversion of l-dopa to DA by modulating COMT activity and DA metabolism. The mechanism of coadministration is different from that of Madopar in Parkinson's disease (PD) treatment. Thus, the coadministration of β-asarone and l-dopa may be beneficial in the treatment of PD.
本研究的目的是探讨β-细辛醚与左旋多巴（L-多巴）联合给药对增加健康大鼠纹状体中多巴胺（DA）的影响。大鼠被随机分为四组：（i）正常组，给予生理盐水；（ii）美多芭组，给予75mg/kg美多芭（L-多巴：苄丝肼，4：1）；（iii）L-多巴组，给予60mg/kg L-多巴；（iv）联合给予15mg/kgβ-细辛醚和60mg/kg L-多巴的组。所有药物（或生理盐水）每天经胃内给药两次，共7天。然后，测定血浆和纹状体中DA、L-多巴、5-羟色胺（5-HT）、高香草酸（HVA）、3,4-二羟基苯乙酸（DOPAC）、酪氨酸羟化酶（TH）、儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶B（MAO-B）的浓度。在联合给予β-细辛醚和L-多巴的组中，血浆和纹状体中L-多巴的浓度下降；然而，纹状体和血浆中DA和DOPAC的浓度增加，血浆HVA浓度增加，而纹状体水平无显著变化。联合给药组和接受美多芭治疗组的纹状体和血浆中5-HT的浓度相似。此外，联合给予β-细辛醚和L-多巴后，血浆和纹状体中的COMT水平下降，而各组间MAO-B浓度无显著差异。此外，联合给予β-细辛醚和L-多巴可提高血浆TH浓度。总之，β-细辛醚通过调节COMT活性和DA代谢影响L-多巴向DA的转化。联合给药的机制与帕金森病（PD）治疗中美多芭的机制不同。因此，β-细辛醚与L-多巴联合给药可能对PD治疗有益。
