Zhao Jie, Kumar Manish, Sharma Jeevan, Yuan Zhihai
Department of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China.
Department of Pharmacology, Swift School of Pharmacy, Rajpura (Patiala), Punjab, India.
Neural Regen Res. 2021 Oct;16(10):2030-2040. doi: 10.4103/1673-5374.308102.
An antagonistic communication exists between adenosinergic and dopaminergic signaling in the basal ganglia, which suggests that the suppression of adenosine A receptors-cyclic adenosine monophosphate pathway may be able to restore the disrupted dopamine transmission that results in motor symptoms in Parkinson's disease (PD). Arbutin is a natural glycoside that possesses antioxidant, anti-inflammatory, and neuroprotective properties. The purpose of this study was to investigate whether arbutin could ameliorate the symptoms of PD and to examine the underlying mechanism. In this study, Swiss albino mouse models of PD were established by the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 4 successive days, with the concurrent intraperitoneal administration of arbutin (50 and 100 mg/kg) for 7 days. The results showed that arbutin significantly reduced lipid peroxidation, total nitrite levels, and inflammation in the substantia nigra and striatum of PD mouse models. In addition, arbutin decreased the activity of endogenous antioxidants, reduced the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and γ-aminobutyric acid, and minimized neurodegeneration in the striatum. Arbutin also reduced the abnormal performance of PD mouse models in the open field test, bar test, pole test, and rotarod test. The therapeutic efficacy of arbutin was similar to that of madopar. The intraperitoneal injection of the AR agonist CGS21680 (0.5 mg/kg) attenuated the therapeutic effects of arbutin, whereas the intraperitoneal injection of forskolin (3 mg/kg) enhanced arbutin-mediated improvements. These findings suggest that arbutin can improve the performance of PD mouse models by inhibiting the function of the AR and enhancing the effects of cyclic adenosine monophosphate. This study was approved by the Institutional Animal Ethics Committee (1616/PO/Re/S/12/CPCSEA) on November 17, 2019 (approval No. IAEC/2019/010).
基底神经节中腺苷能信号与多巴胺能信号之间存在拮抗作用，这表明抑制腺苷A受体 - 环磷酸腺苷途径可能能够恢复帕金森病（PD）中导致运动症状的多巴胺传递紊乱。熊果苷是一种天然糖苷，具有抗氧化、抗炎和神经保护特性。本研究的目的是调查熊果苷是否能改善PD症状并探究其潜在机制。在本研究中，通过连续4天腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶建立PD瑞士白化小鼠模型，同时腹腔注射熊果苷（50和100 mg/kg）7天。结果表明，熊果苷显著降低了PD小鼠模型黑质和纹状体中的脂质过氧化、总亚硝酸盐水平和炎症。此外，熊果苷降低了内源性抗氧化剂的活性，降低了多巴胺、3,4-二羟基苯乙酸、高香草酸和γ-氨基丁酸的水平，并使纹状体中的神经退行性变最小化。熊果苷还降低了PD小鼠模型在旷场试验、棒试验、杆试验和转棒试验中的异常表现。熊果苷的治疗效果与美多芭相似。腹腔注射AR激动剂CGS21680（0.5 mg/kg）减弱了熊果苷的治疗效果，而腹腔注射福斯高林（3 mg/kg）增强了熊果苷介导的改善作用。这些发现表明，熊果苷可以通过抑制AR功能和增强环磷酸腺苷的作用来改善PD小鼠模型的表现。本研究于2019年11月17日获得机构动物伦理委员会（1616/PO/Re/S/12/CPCSEA）批准（批准号IAEC/2019/010）。
