Liensinine and neferine exert neuroprotective effects via the autophagy pathway in transgenic Caenorhabditis elegans

Liensinine and neferine are the main bisbenzylisoquinoline alkaloids obtained from the seeds of Nelumbo nucifera , which commonly used as edible food and traditional medicine in Asia. It was reported that liensinine and neferine could inhibit the activities of acetylcholinesterase and cross the blood-brain barriers, maybe promising candidates to treat Alzheimer’s disease. Here we employed the APPswe transfected SH-SY5Y neural cells and transgenic Caenorhabditis elegans to investigate the neuroprotective effects and underlying mechanism of liensinine and neferine. Finally, we found that liensinine and neferine could significantly improve the viability and reduce ROS levels in APPswe cells, inhibit β-amyloid and tau-induced toxicity, and enhance stress resistance in nematodes. Moreover, liensinine and neferine had obviously neuroprotective effects by assaying chemotaxis, 5-hydroxytryptamine sensitivity and the integrity of injured neurons in nematodes. Preliminary mechanism studies revealed that liensinine and neferine could upregulate the expression of autophagy related genes ( lgg-1 , unc-51 , pha-4 , atg-9 and ced-9 ) and reduce the accumulation of β-amyloid induced autophagosomes, which suggested autophagy pathway played a key role in neuroprotective effects of these two alkaloids. Altogether, our findings provided a certain working foundation for the use of liensinine and neferine to treat Alzheimer’s disease based on neuroprotective effects.