State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong, Guangzhou, China.
Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
Front Immunol. 2024 Aug 2;15:1410784. doi: 10.3389/fimmu.2024.1410784. eCollection 2024.
PaBing-II Formula (PB-II) is a traditional Chinese medicine for treating Parkinson's disease (PD). However, owing to the complexity of PB-II and the difficulty in obtaining human dopaminergic neurons (DAn), the mechanism of action of PB-II in PD treatment remains unclear. The aim of this study was to investigate the mechanisms underlying the therapeutic benefits of PB-II in patients with PD.
hiPSCs derived DAn were treated with HO to construct the DAn oxidative damage model. SwissTargetPrediction was employed to predict the potential targets of the main compounds in serum after PB-II treatment. Metascape was used to analyze the pathways. Sprague-Dawley rats were used to construct the 6-hydroxydopamine (6-OHDA)-induced PD model, and the duration of administration was four weeks. RNA sequencing was used for Transcriptome analysis to find the signal pathways related to neuronal damage. The associated inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). We identified PB-II as an Nrf2 activator using antioxidant-responsive element luciferase assay in MDA-MB-231 cells.
experiments showed that the treatment of PB-II-treated serum increased the percentage of TH cells, decreased inflammation and the apoptosis, reduced cellular reactive oxygen species, and upregulated the expression of Nrf2 and its downstream genes. Pathway analysis of the RNA-seq data of samples before and after the treatment with PB-II-treated serum identified neuron-associated pathways. experiments demonstrated that PB-II treatment of PD rat model could activate the Nrf2 signaling pathway, protect the midbrain DAn, and improve the symptoms in PD rats.
PB-II significantly protects DAn from inflammation and oxidative stress via Nrf2 pathway activation. These findings elucidate the roles of PB-II in PD treatment and demonstrate the application of hiPSC-derived DAn in research of Chinese medicine.
帕金森病（PD）的中药方剂帕宾-Ⅱ号（PB-Ⅱ）。然而，由于 PB-Ⅱ 的复杂性和获得人多巴胺能神经元（DAn）的困难，其在 PD 治疗中的作用机制仍不清楚。本研究旨在探讨 PB-Ⅱ治疗 PD 的潜在机制。
利用 HO 处理 hiPSC 衍生的 DAn 构建 DAn 氧化损伤模型。采用 SwissTargetPrediction 预测 PB-Ⅱ 治疗后血清中主要化合物的潜在靶点。采用 Metascape 分析通路。构建 6-羟多巴胺（6-OHDA）诱导的 PD 大鼠模型，给药时间为 4 周。使用 RNA 测序进行转录组分析，寻找与神经元损伤相关的信号通路。通过酶联免疫吸附试验（ELISA）检测相关炎症因子。采用 MDA-MB-231 细胞抗氧化反应元件荧光素酶检测法鉴定 PB-Ⅱ 作为 Nrf2 激活剂。
实验表明，PB-Ⅱ 处理的血清可增加 TH 细胞的百分比，减少炎症和凋亡，减少细胞内活性氧，上调 Nrf2 及其下游基因的表达。对 PB-Ⅱ 处理前后血清样本的 RNA-seq 数据进行通路分析，确定了与神经元相关的通路。实验表明，PB-Ⅱ 治疗 PD 大鼠模型可激活 Nrf2 信号通路，保护中脑 DAn，改善 PD 大鼠的症状。
PB-Ⅱ 通过激活 Nrf2 通路显著保护 DAn 免受炎症和氧化应激的影响。这些发现阐明了 PB-Ⅱ 在 PD 治疗中的作用，并证明了 hiPSC 衍生的 DAn 在中药研究中的应用。
