Lingnan Normal University, Zhanjiang 524048, PR China; Hainan Medical University, Haikou 571199, PR China; Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510120, PR China; The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
Biomed Pharmacother. 2017 Oct;94:666-678. doi: 10.1016/j.biopha.2017.07.125. Epub 2017 Aug 5.
Levodopa (L-dopa) is the key component in Parkinson's disease (PD) treatment. Recently, we demonstrated that β-asarone improves the motor behavior of rats with unilateral striatal 6-hydroxydopamine lesion. Striatal level of dopamine (DA) and L-dopa increased after β-asarone and L-dopa co-administered treatment in healthy rat. Since its effects and mechanisms on PD rats are still unclear, we investigated whether coadministration could help treat PD rats. Here, PD rats were randomly divided into seven groups (n=10/group): an untreated group, a Madopar-treated group, a L-dopa-treated group, a β-asarone-treated group, and groups receiving low, medium or high doses of β-asarone respectively plus the same dose of L-dopa. The sham-operated group rats were injected with saline. Treatments were administered to the rats twice per day continuously for 30days. The behavioral tests were assessed. Neurotransmitters, dopa decarboxylase (DDC), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT), monoamine oxidase B (MAO-B) and dopamine transporter (DAT) levels were detected. The pathological characteristics of liver and kidney and ultrastructure of dopaminergic neurons were observed. The behavior of PD rats improved significantly after co-administered treatment compared with the untreated group. In addition, our results also showed that co-administered treatment increased L-dopa, DA, DOPAC, HVA and 5-HT levels, enhanced the MAO-B, COMT, TH and DAT levels, reduced creatinine level, decreased the amount of lysosome and mitochondria and showed no liver and kidney toxicity. These findings suggest that co-administered treatment could elevate striatal levels of L-dopa and DA and improve the behavioral abilities in PD rats by regulating the DDC, TH, MAO-B, COMT and DAT levels.
左旋多巴(L-dopa)是治疗帕金森病(PD)的关键组成部分。最近,我们证明β-细辛脑可改善单侧纹状体 6-羟多巴胺损伤大鼠的运动行为。在健康大鼠中,β-细辛脑与左旋多巴共同给药治疗后,纹状体多巴胺(DA)和左旋多巴水平升高。由于其对 PD 大鼠的作用和机制仍不清楚,我们研究了共同给药是否有助于治疗 PD 大鼠。在这里,PD 大鼠被随机分为七组(n=10/组):未治疗组、美多芭治疗组、左旋多巴治疗组、β-细辛脑治疗组以及分别接受低、中、高剂量β-细辛脑加相同剂量左旋多巴的组。假手术组大鼠注射生理盐水。治疗每天两次连续进行 30 天。评估行为测试。检测神经递质、多巴脱羧酶(DDC)、酪氨酸羟化酶(TH)、儿茶酚-O-甲基转移酶(COMT)、单胺氧化酶 B(MAO-B)和多巴胺转运体(DAT)水平。观察肝肾的病理特征和多巴胺能神经元的超微结构。与未治疗组相比,共同给药治疗后 PD 大鼠的行为明显改善。此外,我们的结果还表明,共同给药治疗可增加左旋多巴、DA、DOPAC、HVA 和 5-HT 水平,增强 MAO-B、COMT、TH 和 DAT 水平,降低肌酐水平,减少溶酶体和线粒体的数量,且无肝肾毒性。这些发现表明,共同给药治疗可通过调节 DDC、TH、MAO-B、COMT 和 DAT 水平,提高 PD 大鼠纹状体的左旋多巴和 DA 水平,并改善其行为能力。