Effects of puerarin on gait disturbance in a 6-hydroxydopamine mouse model of Parkinson's disease.

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pharmacological Reports Pub Date : 2024-10-28 DOI:10.1007/s43440-024-00673-7

Na-Hyun Kim, Yukiori Goto, Young-A Lee

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引用次数: 0

Abstract

Background: Parkinson's disease (PD) is a neurodegenerative disorder caused by dopamine (DA) neuronal dysfunction. Although DA agonists and N-methyl-D-aspartate receptor (NMDAR) antagonists are used to treat PD, chronic use causes severe side effects. Puerarin (PUE) is a natural bioactive compound that affects the DA system; however, its effect on PD-associated motor functions is unknown. Therefore, we investigated whether PUE treatment in a 6-hydroxydopamine (6-OHDA) PD mouse model affects motor dysfunction.

Methods: Adult male ICR mice received unilateral 6-OHDA microinfusion into the right medial forebrain bundle. After a 2-week recovery period, PUE (20 or 50 mg/kg) or the vehicle (saline, VEH) was administered intraperitoneally once daily for 21 days. Motor dysfunction was assessed using the locomotion, gait cycle, and rotation tests. Local field potentials (LFPs) were measured in the substantia nigra compacta (SNc), striatum (STR), subthalamic nucleus (STN), and primary motor cortex.

Results: 6-OHDA-lesioned PD mice showed increased gait cycle disturbance and unidirectional rotation. PUE treatment ameliorated the gait cycle disturbance, but not unidirectional rotation of PD mice. These effects differed with DA agonist treatment (which improved PD symptoms) and NMDAR antagonist treatment (which aggravated PD symptoms). Moreover, locomotion was increased only in NMDAR antagonist treatment. PUE treatment induced no changes in the attenuated LFP of the beta wave in the STR and STN, and SNc-STN delta-wave coherence was shown in PD animals.

Conclusions: This study suggests that PUE is a beneficial co-therapeutic agent for alleviating gait cycle disturbance in PD symptoms.

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葛根素对 6-羟基多巴胺帕金森病小鼠模型步态障碍的影响

背景：帕金森病（PD）是一种由多巴胺（DA）神经元功能障碍引起的神经退行性疾病。虽然DA激动剂和N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂可用于治疗帕金森病，但长期使用会产生严重的副作用。葛根素（PUE）是一种天然生物活性化合物，可影响 DA 系统，但其对与帕金森病相关的运动功能的影响尚不清楚。因此，我们研究了在6-羟基多巴胺（6-OHDA）PD小鼠模型中使用葛根素是否会影响运动功能障碍：方法：成年雄性 ICR 小鼠右侧内侧前脑束接受单侧 6-OHDA 显微灌注。经过 2 周的恢复期后，腹腔注射 PUE（20 或 50 mg/kg）或载体（生理盐水，VEH），每天一次，连续 21 天。运动功能障碍通过运动、步态循环和旋转测试进行评估。在黑质（SNc）、纹状体（STR）、丘脑下核（STN）和初级运动皮层测量局部场电位（LFPs）：结果：6-OHDA缺失型帕金森病小鼠的步态周期紊乱和单向旋转增加。PUE治疗可改善步态周期紊乱，但不能改善PD小鼠的单向旋转。这些效果与DA激动剂治疗（改善帕金森病症状）和NMDAR拮抗剂治疗（加重帕金森病症状）不同。此外，只有在 NMDAR 拮抗剂治疗中运动才会增加。PUE治疗没有引起STR和STN中β波LFP衰减的变化，PD动物的SNc-STNδ波相干性也显示出来：本研究表明，PUE 是一种有益的联合治疗药物，可缓解帕金森病症状中的步态周期紊乱。

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来源期刊

Pharmacological Reports 医学-药学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures. Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology. Studies of plant extracts are not suitable for Pharmacological Reports.