Guangzhou University of Chinese Medicine, Guangzhou, China.
Guangzhou University of Chinese Medicine, Guangzhou, China; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
Behav Brain Res. 2024 May 8;465:114966. doi: 10.1016/j.bbr.2024.114966. Epub 2024 Mar 20.
It is unclear whether β-asarone has a good antidepressant effect and what is the main mechanism in Depression in Parkinson's disease (DPD) model rats.
In this study, DPD model rats were screened from 6-OHDA induced rats by sucrose preference test (SPT) and forced swimming test (FST). DPD model rats were divided into eight groups: model group, pramipexole group, β-asarone low-dose group (β-asarone 7.5 group), β-asarone medium-dose group (β-asarone 15 group), β-asarone high-dose group (β-asarone 30 group), 3-MA group, rapamycin group, and PI3K inhibitor group. 28 days after the end of treatment, open field test (OFT), SPT and FST were conducted in rats. The level of α-synuclein (α-syn) in the striatum was determined by enzyme-linked immunosorbent assay (ELISA). The expression of Beclin-1, p62 in the striatum was determined by western blot. The expression of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, Beclin-1, and p62 in the hippocampus was determined by western blot. The spine density of neurons in the hippocampus was detected by golgi staining.
The results showed that 4-week oral administration of β-asarone improve the motor and depressive symptoms of DPD model rats, and decrease the content of α-syn in the striatum. β-asarone inhibited the expression of autophagy in the striatum of DPD model rats. Furthermore, β-asarone decreased the levels of Beclin-1 protein, increased the expression of p62, p-PI3K, p-AKT, and p-mTOR, and improved the density of neuron dendritic spine in the hippocampus.
We concluded that β-asarone might improve the behavior of DPD model rats by activating the PI3K/Akt/mTOR pathway, inhibiting autophagy and protecting neuron.
β-细辛脑是否对帕金森病伴发抑郁（DPD）模型大鼠具有良好的抗抑郁作用及其主要作用机制尚不明确。
本研究采用蔗糖偏好试验（SPT）和强迫游泳试验（FST）从 6-羟基多巴胺（6-OHDA）诱导的大鼠中筛选 DPD 模型大鼠。将 DPD 模型大鼠分为模型组、普拉克索组、β-细辛脑低剂量组（β-细辛脑 7.5mg/kg 组）、β-细辛脑中剂量组（β-细辛脑 15mg/kg 组）、β-细辛脑高剂量组（β-细辛脑 30mg/kg 组）、3-甲基腺嘌呤（3-MA）组、雷帕霉素组、PI3K 抑制剂组。治疗结束 28d 后，进行大鼠旷场实验（OFT）、SPT 和 FST。酶联免疫吸附试验（ELISA）检测纹状体中α-突触核蛋白（α-syn）的水平。Western blot 检测纹状体中 Beclin-1、p62 的表达。Western blot 检测海马组织中 PI3K、p-PI3K、Akt、p-Akt、mTOR、p-mTOR、Beclin-1、p62 的表达。高尔基染色检测海马神经元树突棘密度。
结果显示，4 周口服β-细辛脑可改善 DPD 模型大鼠的运动和抑郁症状，降低纹状体中α-syn 的含量。β-细辛脑抑制 DPD 模型大鼠纹状体中的自噬表达。此外，β-细辛脑降低 Beclin-1 蛋白水平，增加 p62、p-PI3K、p-AKT 和 p-mTOR 的表达，改善海马神经元树突棘密度。
我们的结论是，β-细辛脑可能通过激活 PI3K/Akt/mTOR 通路、抑制自噬和保护神经元来改善 DPD 模型大鼠的行为。
