Anti-neuroinflammatory phenylpropanoids and phenolics from Astragalus membranaceus var. mongholicus

Astragalus membranaceus is used in traditional Chinese medicine for neuroinflammation-related conditions like ischemic stroke and Alzheimer's disease. A phytochemical investigation of its roots led to the isolation of three previously undescribed compounds, astragalusmonol A (1), astragalusmonosides A and B (2-3), along with seventeen known compounds (4-20). Their structures were confirmed by HRESIMS, NMR, IR, UV, electronic circular dichroism (ECD) calculations, X-ray crystallography, and chemical hydrolysis. All isolates were evaluated for anti-neuroinflammatory activity in lipopolysaccharide (LPS)-induced BV2 microglia. Fifteen of them exhibited significant activity, with compounds 12, 6, and 1 showing particularly potent effects (IC₅₀ values of 3.74, 9.71, and 26.47 μM, respectively). The most active compound, 12, also significantly attenuated thrombus formation in a zebrafish cerebral thrombosis model. This study not only enriches the chemical diversity of Astragalus membranaceus but also highlights the active compounds, notably compound 12, as promising candidates for targeting neuroinflammatory disorders.