Natural therapeutic agents for neurodegenerative diseases from the shells of Xanthoceras sorbifolium

Abstract Neuroinflammation is linked to neurodegenerative diseases, manifested by the microglial-released over-production of nitric oxide (NO). However, so far there is no effective strategy regarding curing or preventing neurodegenerative diseases. Triterpene saponins from Xanthoceras sorbifolium were proved to be capable of eliciting a protective effect in neurodegenerative diseases. Thus, a systematic chemical study on the 70% ethanol extract of X. sorbifolium was conducted, leading to the identification of 22 compounds, including four previously undescribed triterpenes saponins and 14 known ones, along with four alkaloids. Their structures were elucidated by physicochemical and spectral methods. The in vivo anti-AD effects of 1-18 were predicted with a field-based 3D-QSAR model and anti-neuroinflammatory activities were assayed in BV-2 cells by assessing LPS-induced NO production and examine levels of iNOS, TNF-α, IL-1β, and IL-6 to support the predicted results. As a result, compounds 14, 16, 19, and 20 could have therapeutic potentials for neurodegenerative diseases due to their potent anti-neuroinflammatory activities.