Department of Pharmacology and Toxicology, KLE College of Pharmacy, KLE Academy of Higher Education and Research, Belagavi, Karnataka, 590010, India.
ICMR-National Institute of Traditional Medicine, Belagavi, India.
Metab Brain Dis. 2022 Feb;37(2):411-426. doi: 10.1007/s11011-021-00878-2. Epub 2022 Jan 13.
Parkinsonism is a neurodegenerative disease, mainly imbalance in dopamine and acetylcholine neurotransimitter in mid brain, which manifestation of dysfunctions of extrapyramidal like akinesia, tremor, rigidity and catalepsy etc., even cognitive and memory loss. The current study is framed to evaluate the effect of Vitex negundo (VNL) leaf extract in Haloperidol induced PD in rats. In vitro studies of antioxidant capacity were checked via DPPH and NO assays and identified its Acetylcholinesterase (AChE) inhibitory activity. Secondly the In vivo study of anti-PD activity in Haloperidol induced in rats were evaluated by Rotarod, morris water maze (MWM), cooks pole climb (CPC), actophotometer, novel object recognition (NOR), and T-maze were utilized to assess extrapyramidal, cognitive and memory function. Thirdly, changes in biomarker level viz. (AChE), butyrylcholinesterase. (BChE) in hippocampus and cortex, reduced glutathione (GSH), malondialdehyde (MDA), total protein (TP), superoxide dismutase (SOD), catalase (CAT), and dopamine level in the whole brain were measured. Finally, histopathology of hippocampus and cortex was examined at 40x magnification to access restoring integrity and maintaining the architecture of neuronal cell in the treatment group compared to control group and L-DOPA as a standard treatment group. V. negundo showed potent antioxidant potency on scavenging of DPPH (IC 84.81 μg/ml) and NO (IC 133.20 μg/ml) and possess AChE inhibitory potency (IC 114.35 μg/ml) by in vitro studies. The Rotarod, MWM, CPC, Actophotometer, NOR, T-maze demonstrated that Haloperidol group administration declines performance time, ELT, TL and decreases locomotion, cognitive and memory respectively. The treatment of VNL 100, 200, and 400 mg/kg p.o. significantly (p < 0.05 to p < 0.0001) reversed. Whole brain AChE, BChE, and MDA level were significantly raised and GSH, TP, SOD, CAT and Dopamine were significantly declined in Haloperidol treated group rats, especially V. negundo 400 mg/kg p.o. highly significantly ameliorate the Haloperidol group altered pathological changes through the restoration of the cholinergic function, enhancing the antioxidant defense and by increasing the dopaminergic function. The current study provides validation of V. negundo for its anti-PD activity and could be a valuable source for the treatment of PD in future.
帕金森病是一种神经退行性疾病，主要是中脑中多巴胺和乙酰胆碱神经递质的失衡，表现为锥体外系功能障碍，如运动迟缓、震颤、僵硬和强直等，甚至认知和记忆丧失。本研究旨在评估牡荆叶提取物（VNL）对大鼠氟哌啶醇诱导的帕金森病的影响。通过 DPPH 和 NO 测定法对其进行体外抗氧化能力研究，并确定其乙酰胆碱酯酶（AChE）抑制活性。其次，通过旋转棒、莫里斯水迷宫（MWM）、库克杆攀爬（CPC）、活动光度计、新物体识别（NOR）和 T 迷宫评估氟哌啶醇诱导的大鼠抗帕金森病的体内活性，以评估锥体外系、认知和记忆功能。第三，测量海马体和皮质中生物标志物水平（AChE）、丁酰胆碱酯酶（BChE）、还原型谷胱甘肽（GSH）、丙二醛（MDA）、总蛋白（TP）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和大脑中多巴胺水平。最后，在 40x 放大倍数下检查海马体和皮质的组织病理学，以评估与对照组和 L-DOPA 作为标准治疗组相比，治疗组神经元细胞结构的完整性和维持情况。V.negundo 在清除 DPPH（IC 84.81μg/ml）和 NO（IC 133.20μg/ml）方面表现出强大的抗氧化能力，并且通过体外研究具有 AChE 抑制能力（IC 114.35μg/ml）。旋转棒、MWM、CPC、活动光度计、NOR、T 迷宫表明，氟哌啶醇组给药后运动时间、ELT、TL 下降，运动、认知和记忆分别下降。VNL 100、200 和 400mg/kg po 治疗显著（p<0.05 至 p<0.0001）逆转。氟哌啶醇治疗组大鼠全脑 AChE、BChE 和 MDA 水平显著升高，GSH、TP、SOD、CAT 和多巴胺水平显著降低，特别是 V.negundo 400mg/kg po 高度显著改善了氟哌啶醇组改变的病理变化，通过恢复胆碱能功能、增强抗氧化防御和增加多巴胺能功能。本研究为牡荆叶的抗帕金森病活性提供了验证，并可能成为未来治疗帕金森病的有价值来源。
