New Schinortriterpenoids Including an Unprecedented 7/5/5/5 Carbon Skeleton with Antineuroinflammatory Activity from Leaves of Schisandra chinensis

Schisandra chinensis leaves are a nutrient-rich edible resource with important medicinal properties that have been extensively utilized in traditional Chinese folk medicine. Herein, we report the isolation of nine previously unknown highly oxygenated schinortriterpenoids (SNTs) (1-9) and 12 known SNTs (10-21) from S. chinensis leaves. Their chemical structures were determined using spectroscopic data analysis, with their corresponding absolute configurations measured using X-ray crystallographic analysis, ECD calculations, and DP4+ technologies. Notably, schinensilactone G (1) is the first reported SNT with a 7/5/5/5-fused carbon skeleton. Furthermore, we used a lipopolysaccharide (LPS)-induced BV-2 cell line as an in vitro inflammatory model to measure the antineuroinflammatory activity of all separated compounds. Compounds 1, 2, 9, 13, 15, 20, and 21 showed suppressive activities against LPS-induced nitric oxide secretion in BV-2 microglial cells. Furthermore, compounds 9 and 15 inhibited inflammation in BV-2 cells via the MyD88/NF-κB/NLRP3 signaling pathway, providing neuroprotection by reducing cell activation.