Zhang Shuai, Shao Si-Yuan, Song Xiu-Yun, Xia Cong-Yuan, Yang Ya-Nan, Zhang Pei-Cheng, Chen Nai-Hong
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Neurotoxicology. 2016 Jan;52:72-83. doi: 10.1016/j.neuro.2015.09.009. Epub 2015 Sep 25.
The present study investigated the neuroprotective effects of Forsythia suspense extract in a rotenone-induced neurotoxic model. FS8, one of the herbal extracts, markedly protected PC12 cells against rotenone toxicity and was selected for the in vivo study. Gavage administration of FS8 (50 and 200mg/kg, but not 10mg/kg) for 25 days significantly improved the behavior function, decreased the loss of dopaminergic neurons in substantia nigra (SN), and maintained the level of dopamine in striatum after unilateral infusion of rotenone in SN. Wherein, the protective effects of FS8 at the dose of 200mg/kg were better than selegiline. Further study indicated the excellent antioxidant activity of FS8 on the 5th and 21st days after intranigral injection of rotenone. Moreover, FS8 could inhibit microglia activity and accumulation in SN, and obviously decreased the expression of pro-inflammatory molecules (IL-6, TNF-α, iNOS and COX-2), which indicated the anti-inflammatory effects of FS8. In the PI3K/Akt/NF-κB and MAPK pathways, FS8 significantly down-regulated the protein expression of p-PI3K, p-Akt, p-IκB, p-P65, cleaved Caspase 8, p-p38 and p-JNK but not p-mTOR, cleaved Caspase 3 and p-ERK. Therefore, FS8 protected dopamine neurons against rotenone toxicity via antioxidant and anti-inflammatory effects, which suggested the promising application of FS8 in the prevention and treatment of Parkinson disease.
本研究在鱼藤酮诱导的神经毒性模型中研究了连翘提取物的神经保护作用。FS8是其中一种草药提取物，能显著保护PC12细胞免受鱼藤酮毒性作用，并被选用于体内研究。在黑质单侧注射鱼藤酮后，连续25天灌胃给予FS8（50和200mg/kg，但不是10mg/kg）可显著改善行为功能，减少黑质中多巴胺能神经元的损失，并维持纹状体中多巴胺的水平。其中，200mg/kg剂量的FS8的保护作用优于司来吉兰。进一步研究表明，在黑质注射鱼藤酮后的第5天和第21天，FS8具有出色的抗氧化活性。此外，FS8可抑制黑质中微胶质细胞的活性和聚集，并明显降低促炎分子（IL-6、TNF-α、iNOS和COX-2）的表达，这表明FS8具有抗炎作用。在PI3K/Akt/NF-κB和MAPK信号通路中，FS8显著下调p-PI3K、p-Akt、p-IκB、p-P65、裂解的Caspase 8、p-p38和p-JNK的蛋白表达，但不影响p-mTOR、裂解的Caspase 3和p-ERK的表达。因此，FS8通过抗氧化和抗炎作用保护多巴胺能神经元免受鱼藤酮毒性，这表明FS8在帕金森病的预防和治疗中具有广阔的应用前景。
