远志皂苷元通过触发PINK1/Parkin介导的线粒体自噬缓解Aβ1-42诱导的神经元损伤

Abstract

Ethnopharmacological relevance Senegenin (SEN), an active compound extracted from the traditional Chinese herb Polygala tenuifolia Willd. (a species in the genus Polygala , family Polygalaceae ), could nourish neurons and resist neuronal damage in mouse models of Alzheimer's disease (AD). Amyloid-β (Aβ) depositions in neuronal cells may cause pathological changes such as oxidative stress which one return could cause severe damage to mitochondria in AD patients or animal models. Mitophagy is an important mechanism to selectively remove damaged mitochondria. In neurons, this process is mainly mediated by PTEN-induced putative kinase 1 (PINK1)/Parkin pathway. Previous studies have shown that SEN could reduce mitochondrial damage and inhibit apoptosis in neurons. Therefore, this study speculated that SEN might activate mitophagy to clear damaged mitochondria, thereby mitigating Aβ-induced cell damage in neuronal cells. Aim of the study This study aimed to determine the effects of SEN on Aβ-induced cell damage, and further to explore whether SEN could induce mitophagy. Moreover, the regulatory role of mitophagy in the neuroptrotective effect of SEN would be elucidated. Materials and methods This study established an in vitro cell damage model using Aβ 1-42 to treat mouse hippocampal neuron HT22 cells. The effects of SEN on cell damage were determined by MTT assay and lactate dehydrogenase (LDH) release assay. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by Cytation™5  cell imaging microplate detection system. The apoptotic rate was analyzed by flow cytometry. The effects of SEN on mitophagy were detected by transmission electron microscope, immunofluorescence and immunoblotting . Results Firstly, HT22 cells were treated with 30 μM Aβ 1-42 for 24 h to establish the damage model. It was found that 30 μM Aβ 1-42 caused neuronal damages as evidenced by reduced cell viability, increased LDH release and ROS, collapse