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丹皮酚是徐长卿的活性成分,可通过调节 MK-801 处理的小鼠的 PI3K-Akt-GSK3β-NF-κB 信号通路改善精神分裂样行为。

Paeonol, the active component of Cynanchum paniculatum, ameliorated schizophrenia-like behaviors by regulating the PI3K-Akt-GSK3β-NF-κB signalling pathway in MK-801-treated mice.

机构信息

Agriculture and Life Science Research Institute, Kangwon National University, Chuncheon, 24341, Republic of Korea.

Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, 02447, Republic of Korea.

出版信息

J Ethnopharmacol. 2023 Oct 5;314:116627. doi: 10.1016/j.jep.2023.116627. Epub 2023 May 9.

DOI:10.1016/j.jep.2023.116627
PMID:37164258
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Cynanchum paniculatum (Bunge) Kitag. ex H. Hara (Asclepiadaceae) have been traditionally used in East Asia as analgesic or antiviral agents. Interestingly, some Chinese and Korean traditional medicinal books reported that the use of C. paniculatum in the treatment of psychotic symptoms, such as hallucinations and delusions.

AIM OF THE STUDY

In this study, we aimed to investigate whether C. paniculatum could improve sensorimotor gating disruption in mice with MK-801-induced schizophrenia-like behaviors. We also aimed to identify the active component of C. paniculatum that could potentially serve as a treatment for schizophrenia and found that paeonol, the major constituent compound of C. paniculatum, showed potential as a treatment for schizophrenia.

MATERIALS AND METHODS

To assess the effect of paeonol on mice with MK-801-induced schizophrenia-like behaviors, we carried out a series of behavioral tests related with symptoms of schizophrenia. In addition, we utilized Western blotting and ELISA techniques to investigate the antipsychotic actions of paeonol.

RESULT

C. paniculatum extract (100 or 300 mg/kg) and paenol (10 or 30 mg/kg) significantly reversed MK-801-induced prepulse deficits in acoustic startle response test. In addition, paeonol (10 or 30 mg/kg) attenuated social novelty preference and novel object recognition memory on MK-801-induced schizophrenia-like behaviour in mice. Furthermore, the phosphorylation levels of PI3K, Akt, GSK3β and NF-κB, as well as related pro-inflammatory cytokine, such as IL-1β and TNF-α, were significantly reversed by the administration of paeonol (10 or 30 mg/kg) in the prefrontal cortex of MK-801-treated mice.

CONCLUSIONS

Collectively, these data show that paeonol can potentially be used as an agent for treating sensorimotor gating deficits, negative symptoms, and cognitive deficits, such as those observed in schizophrenia with few adverse effects.

摘要

民族药理学相关性

徐长卿(Bunge)Kitag。 ex H. Hara(夹竹桃科)在东亚传统上被用作镇痛药或抗病毒药。有趣的是,一些中国和韩国的传统医学书籍报告说,使用徐长卿治疗精神病症状,如幻觉和妄想。

研究目的

在这项研究中,我们旨在研究徐长卿是否可以改善 MK-801 诱导的类精神分裂症样行为小鼠的感觉运动门控障碍。我们还旨在确定徐长卿的活性成分,该成分可能作为精神分裂症的治疗方法,并发现丹皮酚,徐长卿的主要成分化合物,显示出作为精神分裂症治疗的潜力。

材料和方法

为了评估丹皮酚对 MK-801 诱导的类精神分裂症样行为小鼠的影响,我们进行了一系列与精神分裂症症状相关的行为测试。此外,我们利用 Western blotting 和 ELISA 技术研究丹皮酚的抗精神病作用。

结果

徐长卿提取物(100 或 300mg/kg)和丹皮酚(10 或 30mg/kg)显著逆转了听觉惊跳反应试验中 MK-801 诱导的前脉冲缺陷。此外,丹皮酚(10 或 30mg/kg)减轻了 MK-801 诱导的精神分裂症样行为小鼠的社会新颖性偏好和新颖性物体识别记忆。此外,在 MK-801 处理的小鼠的前额叶皮层中,丹皮酚(10 或 30mg/kg)给药显著逆转了 PI3K、Akt、GSK3β 和 NF-κB 的磷酸化水平以及相关的促炎细胞因子,如 IL-1β 和 TNF-α。

结论

总之,这些数据表明丹皮酚可能可作为治疗感觉运动门控缺陷、阴性症状和认知缺陷的药物,如精神分裂症中观察到的那样,副作用很少。

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