Neuroprotective triterpenoids from Astragalus membranaceus stems and leaves: Anti-inflammatory and anti-apoptotic mechanisms for memory improvement via in vivo and in vitro models.

Astragalus membranaceus is a versatile plant resource that can be used for both medicinal and food purposes. The stems and leaves of A.membranaceus (AMSL), which are by-products generated during the processing of its medicinal roots, are commonly reused as a feed additive for animals. Given the rising prevalence of memory impairment, particularly in aging populations and neurodegenerative diseases like Alzheimer's, identifying novel therapeutic agents to alleviate cognitive deficits is of critical importance. This study aimed to explore the therapeutic effects and mechanisms of AMSL in alleviating memory impairment, as well as to identify its active ingredients responsible for such effects. Using a mouse model of memory deficits induced by D-gal combined with AlCl₃, it was demonstrated that AMSL significantly alleviated memory impairment. Meanwhile, through a combination of multiple chromatographic techniques along with LC-MS and NMR spectroscopy, ten new triterpenoids (1-10) coupled with six analogues (11-16) were isolated, purified, and identified from AMSL. Notably, compounds 1 and 12 were found to attenuate inflammatory responses-evidenced by reduction in pro-inflammatory cytokines IL-6, IL-1β, and TNF-α and to inhibit apoptotic pathways, as reflected by downregulated expression of Caspase-3, Bax, and Cytochrome C in PC12 cells induced by Aβ. These findings provide valuable insights into the potential applications of AMSL in neuroprotective interventions and highlight its potential as a therapeutic agent for memory-related disorders.