{"title":"淫羊藿苷通过GSK-3β和酪氨酸羟化酶调控机制减轻氟哌啶醇诱导的帕金森病大鼠多巴胺能神经损失","authors":"Hend A. Sabry , Mai M. Zahra","doi":"10.1016/j.jchemneu.2023.102385","DOIUrl":null,"url":null,"abstract":"<div><p><span><span><span>Parkinson’s Disease (PD) is an age-dependent, incessant, dynamic neurodegenerative illness. In animal models<span><span>, the administration of the dopaminergic </span>D2 antagonist </span></span>Haloperidol<span> (HP) affects the nigrostriatal pathway<span><span><span>, inducing catalepsy, a state of immobility like PD, </span>bradykinesia<span>, and akinesia. The present study investigated the neural effects of </span></span>Icariin (ICA), a </span></span></span>flavonoid derived from </span><em>Herba Epimedii</em><span><span>, against HP-induced PD in rats compared to a standard drug levodopa (L-DOPA). Twenty-four adult male rats were divided into 4 groups: the control group treated with vehicle, the 2nd group treated with HP intraperitoneally, the 3rd group treated with the same dose of HP+L-DOPA orally, and the 4th one, treated with the same dose of HP+ICA orally. All the groups were treated for fourteen consecutive days. Two days before the last dose, locomotor activity was assessed in open field and rotarod tasks. At the end of the experiment, the malondialdehyde, </span>nitric oxide<span><span> (NO), iron, glycogen synthase kinase-3beta (GSK-3β), and tyrosine hydroxylase (TH) contents, glutathione S-transferase, </span>catalase<span>, superoxide dismutase<span>, activities were estimated in the midbrain. Also, cortex and midbrain monoamine<span> contents (norepinephrine, dopamine, and serotonin) were determined. Moreover, the midbrain histopathology<span><span> was detected in all treated groups. The results suggested that the neuroleptic effect of HP was completely improved by ICA. This improvement occurred by decreasing the neurotoxicity via lowering midbrain </span>lipid peroxidation, NO, GSK-3β contents, increasing antioxidant biomarkers, TH, and recovering the treated groups' cortex and midbrain monoamines contents. In conclusion, this study suggests that ICA is a suitable treatment for Parkinson's induced by HP.</span></span></span></span></span></span></p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"136 ","pages":"Article 102385"},"PeriodicalIF":2.7000,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Icariin attenuates dopaminergic neural loss in haloperidol-induced Parkinsonism in rats via GSK-3β and tyrosine hydroxylase regulation mechanism\",\"authors\":\"Hend A. Sabry , Mai M. Zahra\",\"doi\":\"10.1016/j.jchemneu.2023.102385\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span><span>Parkinson’s Disease (PD) is an age-dependent, incessant, dynamic neurodegenerative illness. In animal models<span><span>, the administration of the dopaminergic </span>D2 antagonist </span></span>Haloperidol<span> (HP) affects the nigrostriatal pathway<span><span><span>, inducing catalepsy, a state of immobility like PD, </span>bradykinesia<span>, and akinesia. The present study investigated the neural effects of </span></span>Icariin (ICA), a </span></span></span>flavonoid derived from </span><em>Herba Epimedii</em><span><span>, against HP-induced PD in rats compared to a standard drug levodopa (L-DOPA). Twenty-four adult male rats were divided into 4 groups: the control group treated with vehicle, the 2nd group treated with HP intraperitoneally, the 3rd group treated with the same dose of HP+L-DOPA orally, and the 4th one, treated with the same dose of HP+ICA orally. All the groups were treated for fourteen consecutive days. Two days before the last dose, locomotor activity was assessed in open field and rotarod tasks. At the end of the experiment, the malondialdehyde, </span>nitric oxide<span><span> (NO), iron, glycogen synthase kinase-3beta (GSK-3β), and tyrosine hydroxylase (TH) contents, glutathione S-transferase, </span>catalase<span>, superoxide dismutase<span>, activities were estimated in the midbrain. Also, cortex and midbrain monoamine<span> contents (norepinephrine, dopamine, and serotonin) were determined. Moreover, the midbrain histopathology<span><span> was detected in all treated groups. The results suggested that the neuroleptic effect of HP was completely improved by ICA. This improvement occurred by decreasing the neurotoxicity via lowering midbrain </span>lipid peroxidation, NO, GSK-3β contents, increasing antioxidant biomarkers, TH, and recovering the treated groups' cortex and midbrain monoamines contents. In conclusion, this study suggests that ICA is a suitable treatment for Parkinson's induced by HP.</span></span></span></span></span></span></p></div>\",\"PeriodicalId\":15324,\"journal\":{\"name\":\"Journal of chemical neuroanatomy\",\"volume\":\"136 \",\"pages\":\"Article 102385\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-12-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of chemical neuroanatomy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0891061823001552\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of chemical neuroanatomy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891061823001552","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
帕金森病(Parkinson's Disease,PD)是一种与年龄有关的、持续的、动态的神经退行性疾病。在动物模型中,服用多巴胺能 D2 拮抗剂氟哌啶醇(Haloperidol,HP)会影响黑质神经通路,诱发催眠、类似帕金森病的静止状态、运动迟缓和运动障碍。与标准药物左旋多巴(L-DOPA)相比,本研究探讨了淫羊藿中提取的黄酮类化合物淫羊藿苷对HP诱导的帕金森氏症大鼠神经系统的影响。24只成年雄性大鼠被分为4组:对照组用药物治疗,第2组腹腔注射HP,第3组口服相同剂量的HP+L-DOPA,第4组口服相同剂量的HP+ICA。所有组均连续治疗14天。在最后一次给药的前两天,在开阔地和旋转任务中对运动活动进行评估。实验结束时,对中脑的丙二醛、一氧化氮(NO)、铁、糖原合酶激酶-3β(GSK-3β)、酪氨酸羟化酶(TH)含量、谷胱甘肽 S-转移酶、过氧化氢酶、超氧化物歧化酶活性进行了评估。此外,还测定了皮层和中脑单胺(去甲肾上腺素、多巴胺和血清素)的含量。此外,还对所有治疗组的中脑组织病理学进行了检测。结果表明,ICA 完全改善了 HP 的神经抑制作用。这种改善是通过降低中脑脂质过氧化反应、NO、GSK-3β 含量,增加抗氧化生物标志物、TH,以及恢复治疗组的大脑皮层和中脑单胺含量来实现的。总之,本研究表明,ICA 是治疗 HP 诱发的帕金森病的一种合适方法。
Icariin attenuates dopaminergic neural loss in haloperidol-induced Parkinsonism in rats via GSK-3β and tyrosine hydroxylase regulation mechanism
Parkinson’s Disease (PD) is an age-dependent, incessant, dynamic neurodegenerative illness. In animal models, the administration of the dopaminergic D2 antagonist Haloperidol (HP) affects the nigrostriatal pathway, inducing catalepsy, a state of immobility like PD, bradykinesia, and akinesia. The present study investigated the neural effects of Icariin (ICA), a flavonoid derived from Herba Epimedii, against HP-induced PD in rats compared to a standard drug levodopa (L-DOPA). Twenty-four adult male rats were divided into 4 groups: the control group treated with vehicle, the 2nd group treated with HP intraperitoneally, the 3rd group treated with the same dose of HP+L-DOPA orally, and the 4th one, treated with the same dose of HP+ICA orally. All the groups were treated for fourteen consecutive days. Two days before the last dose, locomotor activity was assessed in open field and rotarod tasks. At the end of the experiment, the malondialdehyde, nitric oxide (NO), iron, glycogen synthase kinase-3beta (GSK-3β), and tyrosine hydroxylase (TH) contents, glutathione S-transferase, catalase, superoxide dismutase, activities were estimated in the midbrain. Also, cortex and midbrain monoamine contents (norepinephrine, dopamine, and serotonin) were determined. Moreover, the midbrain histopathology was detected in all treated groups. The results suggested that the neuroleptic effect of HP was completely improved by ICA. This improvement occurred by decreasing the neurotoxicity via lowering midbrain lipid peroxidation, NO, GSK-3β contents, increasing antioxidant biomarkers, TH, and recovering the treated groups' cortex and midbrain monoamines contents. In conclusion, this study suggests that ICA is a suitable treatment for Parkinson's induced by HP.
期刊介绍:
The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches.
Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples.
The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.