Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.
Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, PAMO University of Medical Sciences, Port Harcourt, Nigeria.
Drug Metab Pers Ther. 2020 Oct 15;35(4):dmpt-2020-0119. doi: 10.1515/dmpt-2020-0119.
Diosmin (DSM), commonly isolated from various plants, is a citrus nutrient that has been shown to increase intracellular antioxidant capacity and assuage symptoms associated with neurological disorders. Deficiency in the antioxidant system has been implicated in the pathogenesis of schizophrenia. The use of antioxidants as neuroprotectants to suppress schizophrenia pathology is increasingly being sought. Hence, this study investigated the effects of DSM on schizophrenia-like behavior and the underlying changes in biomarkers of oxidative stress and acetylcholinesterase (AChE) activity in mice.
The acute antipsychotic effect of DSM (25, 50, and 100 mg/kg, intraperitoneally [i.p.]), haloperidol (1 mg/kg, i.p.), and risperidone (RIS) (0.5 mg/kg, i.p.) was investigated on stereotyped behaviors induced by apomorphine (2 mg/kg, i.p.) and ketamine (10 mg/kg, i.p.). The effect of DSM on ketamine-induced hyperlocomotion, immobility enhancement, and its woodblock cataleptogenic potential was evaluated. Also, the subacute antipsychotic potential of DSM was assessed following intraperitoneal injection of DSM (25-100 mg/kg, i.p.) alone and in combination with ketamine (20 mg/kg, i.p.) for 10 days. The behaviors of the animals were assessed in the open-field, Y-maze, and forced swim tests. Brains of the animals were afterward processed for spectrophotometric assay of oxidative stress and AChE contents.
DSM (25, 50, and 100 mg/kg) attenuated apormorphine-induced stereotypy and devoid of cataleptogenic effect. DSM and RIS reversed acute and subacute ketamine-induced schizophrenia-like behaviors. Disomin alone increased cognitive function and reduced despair-like phenotype. Furthermore, DSM increased superoxide dismutase and glutathione and decreased malondialdehyde and AChE levels in naïve and ketamine schizophrenic mice.
DSM prevents schizophrenia-like behavior, attenuates oxidative stress, and AChE activity in naïve and ketamine schizophrenic mice.
地奥司明（DSM）是一种从各种植物中分离出来的柑橘营养素，已被证明可以增加细胞内抗氧化能力，并缓解与神经紊乱相关的症状。抗氧化系统的缺乏与精神分裂症的发病机制有关。因此，越来越多的人寻求使用抗氧化剂作为神经保护剂来抑制精神分裂症的病理。因此，本研究调查了 DSM 对类似精神分裂症行为的影响，以及在小鼠中氧化应激和乙酰胆碱酯酶（AChE）活性的生物标志物变化。
通过腹腔内注射阿扑吗啡（2mg/kg）和氯胺酮（10mg/kg）诱导刻板行为，研究 DSM（25、50 和 100mg/kg）、氟哌啶醇（1mg/kg）和利培酮（RIS）（0.5mg/kg）的急性抗精神病作用。评估 DSM 对氯胺酮诱导的过度活跃、不动增强及其木方块镇静作用的影响。此外，还评估了 DSM 在腹腔注射 DSM（25-100mg/kg）单独和与氯胺酮（20mg/kg）联合 10 天后的亚急性抗精神病潜力。通过在旷场、Y 迷宫和强迫游泳试验中评估动物的行为。之后，对动物的大脑进行分光光度法测定氧化应激和 AChE 含量。
DSM（25、50 和 100mg/kg）可减轻阿扑吗啡诱导的刻板行为，且无镇静作用。DSM 和 RIS 逆转了急性和亚急性氯胺酮诱导的精神分裂症样行为。DSM 单独使用可提高认知功能并降低绝望样表型。此外，DSM 增加了超氧化物歧化酶和谷胱甘肽，降低了未处理和氯胺酮精神分裂症小鼠的丙二醛和 AChE 水平。
DSM 可预防类似精神分裂症的行为，减轻未处理和氯胺酮精神分裂症小鼠的氧化应激和 AChE 活性。
