Department of Pharmacology and Therapeutics, Neuropharmacology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Department of Pharmacology and Therapeutics, Neuropharmacology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
J Ethnopharmacol. 2023 Jan 30;301:115767. doi: 10.1016/j.jep.2022.115767. Epub 2022 Oct 4.
Persistent ketamine insults to the central nervous system block NMDA receptors and disrupt putative neurotransmission, oxido-nitrosative, and inflammatory pathways, resulting in schizophrenia-like symptoms in animals. Previously, the ethnomedicinal benefits of Carpolobia lutea against insomnia, migraine headache, and insanity has been documented, but the mechanisms of action remain incomplete.
Presently, we explored the neuro-therapeutic role of Carpolobia lutea ethanol extract (C. lutea) in ketamine-induced schizophrenia-like symptoms in mice.
Sixty-four male Swiss (22 ± 2 g) mice were randomly assigned into eight groups (n = 8/group) and exposed to a reversal ketamine model of schizophrenia. For 14 days, either distilled water (10 mL/kg; p.o.) or ketamine (20 mg/kg; i.p.) was administered, following possible reversal treatments with C. lutea (100, 200, 400, and 800 mg/kg; p.o.), haloperidol (1 mg/kg, p.o.), or clozapine (5 mg/kg; p.o.) beginning on days 8-14. During the experiment, a battery of behavioral characterizations defining schizophrenia-like symptoms were obtained using ANY-maze software, followed by neurochemical, oxido-inflammatory and histological assessments in the mice brains.
A 7-day reversal treatment with C. lutea reversed predictors of positive, negative and cognitive symptoms of schizophrenia. C. lutea also mitigated ketamine-induced neurochemical derangements as evidenced by modulations of dopamine, glutamate, norepinephrine and serotonin neurotransmission. Also, the increased acetylcholinesterase activity, malondialdehyde nitrite, interleukin-6 and tumor necrosis-factor-α concentrations were reversed by C. lutea accompanied with elevated levels of catalase, superoxide dismutase and reduced glutathione. Furthermore, C. lutea reversed ketamine-induced neuronal alterations in the prefrontal cortex, hippocampus and cerebellum sections of the brain.
These findings suggest that C. lutea reverses the cardinal symptoms of ketamine-induced schizophrenia in a dose-dependent fashion by modulating the oxido-inflammatory and neurotransmitter-related mechanisms.
持续的氯胺酮对中枢神经系统的损伤会阻断 NMDA 受体，并破坏潜在的神经传递、氧化应激、炎症途径，导致动物出现类似精神分裂症的症状。此前，已经记录了 Carpolobia lutea 治疗失眠、偏头痛和精神错乱的民族医学益处，但作用机制仍不完整。
目前，我们探讨了 Carpolobia lutea 乙醇提取物（C. lutea）在氯胺酮诱导的小鼠精神分裂症样症状中的神经治疗作用。
64 只雄性瑞士（22±2g）小鼠被随机分为 8 组（每组 8 只），并接受氯胺酮致精神分裂症逆转模型的处理。14 天内，每日分别给予蒸馏水（10mL/kg；灌胃）或氯胺酮（20mg/kg；腹腔注射），并在第 8-14 天开始可能的逆转治疗，给予 C. lutea（100、200、400 和 800mg/kg；灌胃）、氟哌啶醇（1mg/kg，灌胃）或氯氮平（5mg/kg；灌胃）。在实验过程中，使用 ANY-maze 软件获得一系列定义精神分裂症样症状的行为特征描述，然后对小鼠大脑进行神经化学、氧化炎症和组织学评估。
为期 7 天的 C. lutea 逆转治疗可逆转精神分裂症阳性、阴性和认知症状的预测指标。C. lutea 还减轻了氯胺酮引起的神经化学紊乱，表现为多巴胺、谷氨酸、去甲肾上腺素和 5-羟色胺神经递质传递的调节。此外，乙酰胆碱酯酶活性、丙二醛亚硝酸盐、白细胞介素-6 和肿瘤坏死因子-α浓度的增加也被 C. lutea 逆转，同时伴随过氧化氢酶、超氧化物歧化酶和还原型谷胱甘肽水平的升高。此外，C. lutea 逆转了氯胺酮诱导的大脑前额叶皮质、海马和小脑部分的神经元改变。
这些发现表明，C. lutea 通过调节氧化应激和神经递质相关机制，以剂量依赖的方式逆转氯胺酮诱导的精神分裂症的主要症状。
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