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刺芒柄花素对与帕金森病相关的慢性不可预测应激(CUS)的保护作用。

Protective effect of formononetin in chronic unpredictable stress (CUS) linked to parkinson disease.

作者信息

Pingale Tanvi Dayanand, Gupta Girdhari Lal

机构信息

Department of Pharmacology, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM'S NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, 400 056, Maharashtra, India.

Department of Pharmacology, School of Pharmacy & Technology Management, SVKM'S NMIMS, Shirpur Campus, Shirpur-425 405, Mumbai, Maharashtra, India.

出版信息

J Neural Transm (Vienna). 2025 May 16. doi: 10.1007/s00702-025-02939-7.

Abstract

Formononetin [FMN] belongs to the member of class 7-hydroxyisoflavones possesses anti-oxidant and anti-inflammatory activity. However, its efficacy in chronic unpredictable stress (CUS) associated with Parkinson disease (PD) is not evaluated. In a current study the effect of FMN on CUS associated with PD was screened to examine efficacy using different behavioral, biochemical and immuno-histochemical evaluation. During the study, CUS associated with PD was induced in mice by administering rotenone followed by exposure to different mild stressors. Animals showing CUS linked to PD were included in the study and treated daily with FMN (5, 10 & 20 mg/kg) by intraperitoneal route. After the treatment, animals evaluated for behavioral, biochemical parameters and immunohistochemistry analysis. Treatment with FMN was effective in alleviating core symptoms of chronic stress linked to PD and improved cognitive function, gait abnormality and impairment in co-ordination of CUS + ROT model. FMN showed dose dependent reduction in IL- 1β, TNF- α, IL- 6 concentration. FMN increasing the levels of dopamine, norepinephrine and serotonin. Immunohistochemical study revealed that the expression of α-synuclein reduced which helps to improve CUS linked to Parkinson's. Furthermore, expression of BDNF and BCL-2 found to be improved after FMN treatment and helps in elevation of dopamine levels thereby surviving neuronal system. Study findings revealed that formononetin is effective in the treatment of chronic unpredictable stress linked to Parkinson's, however further clinical investigation is required to evaluate its effect in human.

摘要

大豆苷元[FMN]属于7-羟基异黄酮类成员,具有抗氧化和抗炎活性。然而,其在与帕金森病(PD)相关的慢性不可预测应激(CUS)中的功效尚未得到评估。在当前的一项研究中,对FMN在与PD相关的CUS中的作用进行了筛选,以通过不同的行为、生化和免疫组织化学评估来检验其功效。在研究过程中,通过给予鱼藤酮,然后使其暴露于不同的轻度应激源,在小鼠中诱导与PD相关的CUS。表现出与PD相关的CUS的动物被纳入研究,并通过腹腔注射途径每天用FMN(5、10和20mg/kg)进行治疗。治疗后,对动物进行行为、生化参数和免疫组织化学分析。FMN治疗有效地减轻了与PD相关的慢性应激的核心症状,并改善了CUS+ROT模型的认知功能、步态异常和协调障碍。FMN显示出IL-1β、TNF-α、IL-6浓度呈剂量依赖性降低。FMN增加了多巴胺、去甲肾上腺素和血清素的水平。免疫组织化学研究表明,α-突触核蛋白的表达降低,这有助于改善与帕金森病相关的CUS。此外,发现FMN治疗后BDNF和BCL-2的表达有所改善,并有助于提高多巴胺水平,从而使神经元系统存活。研究结果表明,大豆苷元在治疗与帕金森病相关的慢性不可预测应激方面是有效的,然而,需要进一步的临床研究来评估其在人类中的作用。

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