Neuro-protection of swertisin against impairment induced by Aβ25-35 by acting on COX-2 to up-regulate 2-AG and suppressing neuroinflammation

Abstract

Ziziphi Spinosae Semen (Suan Zao Ren) is a traditional Chinese medicine with the functions of nourishing the heart and liver, calming the mind, and stopping sweating. Swertisin, one of the main active ingredients in Ziziphi Spinosae Semen, has a wide range of pharmacological effects such as anti-inflammation, anti-oxidation, and enhancement of learning and memory. Based on the Aβ cascade and the neuroinflammatory theory, combined with the anti-inflammatory neuroprotective effect of endocannabinoid 2-AG, this work integrated modern biochemical technology methods such as liquid chromatography-mass spectrometry, Western blot, and electrophysiological technique to explore the neuroprotective effects and potential mechanism of swertisin on the Alzheimer’s disease (AD) model induced by Aβ_25-35. The results showed that swertisin relieved impairment of learning and memory caused by Aβ_25-35 on hippocampus slice by decreasing COX-2 expression and inhibiting COX-2 activity to up-regulate the endogenous 2-AG, and suppressing neuroinflammation and neuronal apoptosis via CB1R-dependent NF-κB pathway. It was further discovered that swertisin protected the primary hippocampal neurons, reduced over-expression of COX-2, and relieved the neuroinflammatory against Aβ_25-35 through the CB1R-dependent NF-κB signaling pathway. Finally, it was confirmed that swertisin alleviated BV-2 cell apoptosis induced by Aβ_25-35. These results help us understand the mechanism of swertisin against AD and promote the development of related drugs and healthy products.