Bioactive Terpenoids and Steroids from Astragalus complanatus Seeds underlie Its Potent Neuroprotective Efficacy In Vitro and In Vivo

Abstract

An investigation of the seeds of Astragalus complanatus (SAC), a homologous food-medicine plant in China, yielded 29 compounds, including four new terpenoids, astranoids A–D (1, 2, 6, 23), and one new stigmastane steroid, astrasteroid (12). Structural elucidation was achieved using NMR, HRESIMS, quantum-chemical ECD, and NMR computations, and X-ray crystallography. Astranoid A (1) features a novel 5/6/6/6/5 pentacyclic skeleton with cis-fused A/B rings. All isolates were evaluated for nitric oxide inhibition in LPS-stimulated BV-2 cells. 7-oxo-β-sitosterol (11) demonstrated potent antineuroinflammatory activity with an IC50 of 6.09 ± 0.49 μM. This compound suppressed proinflammatory cytokines, NF-κB translocation, and iNOS/COX-2 expression, activated Nrf2/HO-1 in HT22 cells, and protected neurons from Aβ-induced inflammatory injury. In APP/PS1 mice, compound 11 dose-dependently improved cognitive function, reduced Aβ plaques, and attenuated glial inflammation, supporting its promising neuroprotective potential.