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。