Parkinson’s disease (PD) is a neurodegenerative disorder of dopaminergic, noradrenergic, and serotonergic systems, in which dopamine, noradrenaline, and serotonin levels are depleted and lead to the development of motor and non-motor symptoms such as tremor, bradykinesia, weight changes, fatigue, depression, and visual hallucinations. Therapeutic strategies place much focus on dopamine replacement and the inhibition of dopamine metabolism. The present study was based on the known abilities of chalcones to act as molecular scaffolds that selectively inhibit MAO-B with the added advantage of binding reversibly. Recently, we synthesized a series of 26 chalcone compounds, amongst which (2E)-1-(2H-1,3-benzodioxol-5-yl)-3-(4-fluorophenyl)prop-2-en-1-one (O10) and (2E)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(4-fluorophenyl)prop-2-en-1-one (O23) most inhibited MAO-B. Hence, the present study was performed to explore the molecular mechanisms responsible for the neuroprotective effect of O10 and O23 at varying doses such as 10, 20, and 30 mg/kg each in a haloperidol-induced murine model of PD. Both compounds were effective (though O23 was the more effective) at ameliorating extrapyramidal and non-motor symptoms in the model and improved locomotory and exploratory behaviors, reduced oxidative stress markers, and enhanced antioxidant marker and neurotransmitter levels. Furthermore, histopathological studies showed O10 and O23 both reduced neurofibrillary tangles and plaques to almost normal control levels.

帕金森病 (PD) 是一种多巴胺能、去甲肾上腺素能和 5-羟色胺能系统的神经退行性疾病，其中多巴胺、去甲肾上腺素和 5-羟色胺水平被耗尽并导致运动和非运动症状的发展，例如震颤、运动迟缓、体重变化、疲劳、抑郁和幻视。治疗策略非常关注多巴胺替代和多巴胺代谢的抑制。本研究基于查尔酮作为分子支架的已知能力，该分子支架选择性地抑制 MAO-B，并具有可逆结合的额外优势。最近，我们合成了一系列 26 种查尔酮化合物，其中 (2 E )-1-(2 H -1,3-benzodioxol-5-yl)-3-(4-fluorophenyl)prop-2-en-1-一（O10) 和 (2 E )-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(4-fluorophenyl)prop-2-en-1-one ( O23 ) 最能抑制 MAO- B. 因此，本研究旨在探索在氟哌啶醇诱导的 PD 小鼠模型中，不同剂量（例如 10、20 和 30 mg/kg）的O10和O23的神经保护作用的分子机制。两种化合物都有效（尽管O23更有效）改善模型中的锥体外系和非运动症状，改善运动和探索行为，减少氧化应激标志物，提高抗氧化标志物和神经递质水平。此外，组织病理学研究显示O10和O23两者都将神经原纤维缠结和斑块减少到几乎正常的控制水平。