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

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.