Evaluation of the Neurobehavioural Toxicity Potential of Aqueous Ethanol Extracts of Leaf/Seed of Datura metel, Mucuna pruriens, and Tapinanthus globiferus Growing on Azadirachta indica Host Tree in Mice

None Umarudeen A. M., None Khan F., None Tahir Y., None Modibbo M. R.
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Abstract

Aqueous ethanol extracts of Mucuna pruriens seed (AEMPS), Datura metel leaf (AEDML) and seed (AEDMS), and Tapinanthus globiferus (AETGL) Growing on Azadirachta indica host tree are being evaluated for their anxiolytic, antidepressant, anti-parkinsonian, and addictive activities in other studies. The aim of this study was to investigate the liability or otherwise of extracts of the selected medicinal plants for some benzodiazepines-related neurobehavioural toxicities in mice. Actophotometry was used for the evaluation of the locomotory activity related to central nervous system depressant (cns) effect, diazepam-induced sleep potentiation for hypnotic liability, rodent beam (rod)-walking assay for balance and motor co-ordination, and novel object recognition test (NORT) for cognitive deficit evaluation. The results indicate, compared to negative control (distilled water) treatment mean values of 4.69±0.95 % locomotory activity reduction, 430.71±16.80 sec. sleep onset and 168.43±10.56 min. duration, 5.00±0.00 balance/motor co-ordination performance, and 54.41±1.99 novel object recognition, treatments with high oral doses of AETGL and AEMPS (1500 mg/kg each) did not significantly negatively impact these behavioural indices but even enhanced novel object recognition. High oral doses of AEDML and AEDMS (750 mg/kg each), and tramadol (133 mg/kg) caused significant (p<0.05) 42.24±2.64, 27.73±2.17, and 36.74±4.44, mean % locomotory activity reductions, 196.86±10.12, 193.88±15.39, and 189.14±18.31 second mean sleep onsets and 319.71±18.85, 309.57±20.27, and 356.00±26.01 minute mean sleep durations, 1.67±0.42, 1.30±0.40, 1.833±0.48 mean balance/motor co-ordination performances, and 40.49±5.45, 31.33±5.23, 19.37±3.96 mean novel object recognitions, respectively. Diazepam (2 mg/kg) treatment caused 33.71±2.19 mean % locomotory activity reduction, 1.33±0.49 mean balance/motor co-ordination performance, and 29.91±2.81 mean novel object recognitions. Additionally, most mouse groups exposed to tramadol, AEDML, and AEDMS extracts displayed unusual (hallucination-like, predator-like) fearful trepidations when in proximity with the novel objects. These findings indicate AETGL and AEMPS extracts may be devoid of neurobehavioural toxicities but tramadol, diazepam, AEDML and AEDMS extracts may be liable to significant sedative, hypnotic, myo-relaxant, and anti-cognitive effects. These findings justify the traditional uses of Tapinanthus species and Mucuna pruriens extracts for the treatment of memory deficits and related neurological disorders. They also justify the morbid and fatal toxicity risks associated with the use of Datura metel extracts, tramadol, and the benzodiazepines.
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印楝树寄主树上生长的曼陀罗、麻豆和金针花叶/种子水乙醇提取物对小鼠神经行为毒性的评价
麻瓜种子(AEMPS),曼陀罗叶(AEDML)和种子(AEDMS),以及印楝树上生长的Tapinanthus globiferus (AETGL)的水乙醇提取物在其他研究中被评价其抗焦虑、抗抑郁、抗帕金森和成瘾活性。本研究的目的是调查所选药用植物提取物对某些苯二氮卓类药物相关小鼠神经行为毒性的责任或其他方面。采用视光法评价与中枢神经系统抑制剂(cns)作用相关的运动活动,采用地西泮诱发睡眠增强法评价催眠倾向,采用鼠梁(杆)行走法评价平衡和运动协调,采用新物体识别试验评价认知缺陷。结果表明,与阴性对照(蒸馏水)处理相比,运动活动减少4.69±0.95%,睡眠开始时间为430.71±16.80秒,持续时间为168.43±10.56分钟,平衡/运动协调能力为5.00±0.00,新物体识别能力为54.41±1.99,高剂量口服AETGL和AEMPS(各1500 mg/kg)处理对这些行为指标没有显著负面影响,甚至增强了新物体识别能力。高剂量口服AEDML和AEDMS(各750 mg/kg)和曲马多(133 mg/kg)显著(p<0.05)导致运动活动减少42.24±2.64、27.73±2.17和36.74±4.44,平均睡眠时间为196.86±10.12、193.88±15.39和189.14±18.31秒,平均睡眠时间为319.71±18.85、309.57±20.27和356.00±26.01分钟,平均平衡/运动协调能力为1.67±0.42、1.30±0.40、1.833±0.48分钟,平均新物体识别能力为40.49±5.45、31.33±5.23、19.37±3.96分钟。分别。地西泮(2 mg/kg)治疗导致运动活动平均减少33.71±2.19 %,平衡/运动协调平均减少1.33±0.49 %,新物体识别平均减少29.91±2.81 %。此外,大多数暴露于曲马多、AEDML和AEDMS提取物的小鼠组在接近新物体时表现出不寻常的(幻觉样的,捕食者样的)恐惧。这些发现表明,AETGL和AEMPS提取物可能没有神经行为毒性,但曲马多、地西泮、AEDML和AEDMS提取物可能具有显著的镇静、催眠、肌松弛和抗认知作用。这些发现证明了Tapinanthus和Mucuna pruriens提取物用于治疗记忆缺陷和相关神经系统疾病的传统用途。它们还证明了与曼陀罗提取物、曲马多和苯二氮卓类药物的使用相关的病态和致命毒性风险。
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