Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, Cagliari, Italy.
Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, Cagliari, Italy.
Biomed Pharmacother. 2023 May;161:114475. doi: 10.1016/j.biopha.2023.114475. Epub 2023 Mar 9.
Withania somnifera (WS) is utilized in Ayurvedic medicine owing to its central and peripheral beneficial properties. Several studies have accrued indicating that the recreational amphetamine-related drug (+/-)- 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) targets the nigrostriatal dopaminergic system in mice, inducing neurodegeneration and gliosis, causing acute hyperthermia and cognitive impairment. This study aimed to investigate the effect of a standardized extract of W. somnifera (WSE) on MDMA-induced neurotoxicity, neuroinflammation, memory impairment and hyperthermia. Mice received a 3-day pretreatment with vehicle or WSE. Thereafter, vehicle- and WSE-pretreated mice were randomly divided into four groups: saline, WSE, MDMA alone, WSE plus MDMA. Body temperature was recorded throughout treatment, and memory performance was assessed by a novel object recognition (NOR) task at the end of treatment. Thereafter, immunohistochemistry was performed to evaluate in the substantia nigra pars compacta (SNc) and striatum the levels of tyrosine hydroxylase (TH), as marker of dopaminergic degeneration, and of glial fibrillary acidic protein (GFAP) and TMEM119, as markers of astrogliosis or microgliosis, respectively. MDMA-treated mice showed a decrease in TH-positive neurons and fibers in the SNc and striatum respectively, an increase in gliosis and body temperature, and a decrease in NOR performance, irrespective of vehicle or WSE pretreatment. Acute WSE plus MDMA counteracted the modifications in TH-positive cells in SNc, GFAP-positive cells in striatum, TMEM in both areas and NOR performance, as compared to MDMA alone, while no differences were observed as compared to saline. Results indicate that WSE acutely administered in combination with MDMA, but not as pretreatment, protects mice against the noxious central effects of MDMA.
睡茄（Withania somnifera）由于其中枢和外周的有益特性，被用于阿育吠陀医学。有几项研究表明，娱乐性安非他命相关药物（+/-）-3,4-亚甲二氧基甲基苯丙胺（MDMA；摇头丸）在小鼠中靶向黑质纹状体多巴胺能系统，诱导神经退行性变和神经胶质增生，导致急性体温过高和认知障碍。本研究旨在研究标准化睡茄提取物（WSE）对 MDMA 诱导的神经毒性、神经炎症、记忆障碍和体温过高的影响。小鼠接受了 3 天的 vehicle 或 WSE 预处理。此后，将 vehicle 和 WSE 预处理的小鼠随机分为四组：盐水、WSE、单独的 MDMA、WSE 加 MDMA。在整个治疗过程中记录体温，在治疗结束时通过新物体识别（NOR）任务评估记忆性能。此后，通过免疫组织化学评估纹状体和黑质致密部（SNc）中酪氨酸羟化酶（TH）的水平，作为多巴胺能变性的标志物，以及神经胶质纤维酸性蛋白（GFAP）和 TMEM119 的水平，分别作为星形胶质细胞或小胶质细胞增生的标志物。与单独的 MDMA 处理相比，MDMA 处理的小鼠分别显示 SNc 和纹状体中的 TH 阳性神经元和纤维减少、神经胶质增生和体温升高以及 NOR 性能下降，无论是否进行 vehicle 或 WSE 预处理。与单独的 MDMA 相比，急性 WSE 加 MDMA 可逆转 SNc 中 TH 阳性细胞、纹状体中 GFAP 阳性细胞、两个区域中的 TMEM119 和 NOR 性能的变化，而与盐水相比则没有差异。结果表明，WSE 急性联合 MDMA 给药，而不是预处理，可保护小鼠免受 MDMA 的中枢毒性影响。
