Lawal Bilqis Abiola, Ayipo Yusuf Oloruntoyin, Adekunle Abisola Oyindamola, Amali Mohammed Otuofu, Badeggi Umar Muhammad, Alananzeh Waleed A, Mordi Mohd Nizam
Department of Pharmacognosy and Drug Development, University of Ilorin, P.M.B., 1515, Ilorin, Nigeria.
Centre for Drug Research, Universiti Sains Malaysia, USM, 11800, Pulauz, Pinang, Malaysia; Department of Chemistry and Industrial Chemistry, Kwara State University, P. M. B., 1530, Malete, Ilorin, Nigeria.
J Ethnopharmacol. 2023 Jan 10;300:115753. doi: 10.1016/j.jep.2022.115753. Epub 2022 Sep 24.
Parkinson's disease (PD) is a prominent health challenge characterized by complex aetiology and limited therapeutic breakthroughs. Datura metel (DM) is a medicinal plant containing active phytoconstituents with neuropharmacological potentials. In traditional medicine, it exerts anticholinergic, anti-inflammatory and antioxidant effects, and protection from organophosphate poisoning inclusively involved in the pharmacotherapy of PD. Its other PD-related medicinal potency includes treatment of motor sickness and bradycardia. However, the exact mechanisms of anti-PD effects of its phytoconstituents remain underexplored.
In this study, methanolic extract of DM was evaluated for anti-PD behavioural effects in vivo haloperidol-induced cataleptic mice. The GC-MS-identified phytochemicals were studied for one-drug-multi-target inhibitory mechanisms against some key targets for PD treatment, alpha-synuclein (ASN) and dopa decarboxylase (DDC) using molecular docking.
and discussion: Chronic administration of 50, 100 and 200 mg/kg of DM extract improved the 14-s latency time induced by haloperidol to 54, 54 and 57 s respectively, whereas levodopa (30 mg/kg) produced 47 s in rotarod tests. Similarly, the descending times for haloperidol-induced cataleptic mice were significantly reduced from 110 s to 17.7, 17.7 and 12.5 s by the respective chronic doses of DM extract, whereas levodopa-administered mice spent 17.5 s descending the same 30 cm pole. The interesting motor coordination enhancements are suggestively due to synergistic inhibition of ASN and DCC by the phytoconstituents of DM, especially, atropine and scopolamine. From the docking analysis, the two phytochemicals interacted more potently with the active therapeutic sites of the dual targets than levodopa and carbidopa.
Methanolic extract of DM contains active phytochemicals for multi-target-directed antiparkinsonian mechanisms amenable for further studies.
帕金森病（PD）是一项重大的健康挑战，其病因复杂，治疗突破有限。洋金花（DM）是一种药用植物，含有具有神经药理学潜力的活性植物成分。在传统医学中，它具有抗胆碱能、抗炎和抗氧化作用，并且对有机磷中毒有保护作用，这些作用均包含在帕金森病的药物治疗中。其其他与帕金森病相关的药用功效包括治疗晕动病和心动过缓。然而，其植物成分的抗帕金森病作用的确切机制仍未得到充分研究。
在本研究中，评估了洋金花的甲醇提取物对氟哌啶醇诱导的僵住症小鼠的抗帕金森病行为效应。使用分子对接技术，研究了气相色谱-质谱（GC-MS）鉴定出的植物化学物质对帕金森病治疗的一些关键靶点，即α-突触核蛋白（ASN）和多巴脱羧酶（DDC）的单药多靶点抑制机制。
在转棒试验中，慢性给予50、100和200mg/kg的洋金花提取物分别将氟哌啶醇诱导的14秒潜伏期时间改善至54、54和57秒，而左旋多巴（30mg/kg）产生的潜伏期为47秒。同样，在各自的慢性剂量下，洋金花提取物使氟哌啶醇诱导的僵住症小鼠的下降时间从110秒显著减少至17.7、17.7和12.5秒，而给予左旋多巴的小鼠下降相同的30厘米杆花费17.5秒。有趣的运动协调增强作用提示是由于洋金花的植物成分，特别是阿托品和东莨菪碱对ASN和DDC的协同抑制作用。从对接分析来看，这两种植物化学物质与双靶点的活性治疗位点的相互作用比左旋多巴和卡比多巴更强。
洋金花的甲醇提取物含有活性植物化学物质，具有多靶点抗帕金森病机制，适合进一步研究。
Zotero 插件