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红花标准化总黄酮提取物对鱼藤酮诱导的帕金森病大鼠模型的预防作用。

Preventive effects of a standardized flavonoid extract of safflower in rotenone-induced Parkinson's disease rat model.

机构信息

School of Mental Health, Bengbu Medical College, Bengbu, 233030, China.

State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.

出版信息

Neuropharmacology. 2022 Oct 1;217:109209. doi: 10.1016/j.neuropharm.2022.109209. Epub 2022 Aug 5.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder that occurs after Alzheimer's disease. Rotenone is a neurotoxin commonly used in creating PD models. Safflower (Carthamus tinctorius L.) contains some flavonoids that are effective against neurodegenerative diseases, and it has long been used in the treatment of cerebrovascular diseases in China. In this study, we investigated the preventive effect of safflower standardized flavonoid extract (SAFE) on a rotenone-induced PD rat model. The results showed that SAFE (17.5, 35, or 70 mg kg·day) treatment modified the progressive loss in body weight, alleviated behavioral deficits, and promoted survival, especially in the middle-dose SAFE (35 mg kg·day) group. SAFE treatment significantly modifies the progressive decrease in the level of DA and its metabolites, DOPAC and HVA, 5-HT and its metabolite 5-HIAA in the St, and levels of TH-positive DA-ergic neurons in the SNpc. SAFE also inhibited the decrease in TH and DA levels and increase in Ach content in the St. SAFE (35 mg kg·day) group treatment modifying the rotenone-induced downregulation of JAK2, STAT3, and ɑ7-nAChR, and also modifying the increase in ACh in the hippocampus. SAFE preventive treatment can also partially inhibit changes in the ECS parameters associated with PD. The marker components of SAFE such as Kaempferol 3-O-rutinoside or anhydrosafflor yellow B can bind with TH, JAK2, STAT3, and ɑ7-nAChR based on molecular docking analyses. Current studies have shown that SAFE is a potential candidate for the prevention of PD.

摘要

帕金森病(PD)是继阿尔茨海默病之后发生的一种进行性神经退行性疾病。鱼藤酮是一种常用于创建 PD 模型的神经毒素。红花(Carthamus tinctorius L.)含有一些对神经退行性疾病有效的类黄酮,在中国长期用于治疗脑血管疾病。在这项研究中,我们研究了红花标准化黄酮提取物(SAFE)对鱼藤酮诱导的 PD 大鼠模型的预防作用。结果表明,SAFE(17.5、35 或 70 mg kg·day)治疗可改善体重的进行性下降,减轻行为缺陷,并促进生存,特别是在中剂量 SAFE(35 mg kg·day)组。SAFE 处理显著改变了 DA 及其代谢物 DOPAC 和 HVA、5-HT 及其代谢物 5-HIAA 在纹状体中的水平以及 SNpc 中 TH 阳性 DA 能神经元的水平的进行性下降。SAFE 还抑制了纹状体中 TH 和 DA 水平的降低以及 Ach 含量的增加。SAFE(35 mg kg·day)组治疗可调节鱼藤酮诱导的 JAK2、STAT3 和 ɑ7-nAChR 下调,并调节海马中 Ach 的增加。SAFE 预防性治疗还可以部分抑制与 PD 相关的 ECS 参数的变化。SAFE 的标记成分,如山奈酚 3-O-芸香糖苷或脱水红花黄色 B,可根据分子对接分析与 TH、JAK2、STAT3 和 ɑ7-nAChR 结合。目前的研究表明,SAFE 是预防 PD 的潜在候选药物。

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