Oligosaccharide esters from Polygala paniculata with their NO inhibitory activity

Polygala paniculata L. has been reported to exhibit diverse therapeutic effects, including neuroprotective, gastroprotective, antinociceptive, antidepressant, vasorelaxant, and hypotensive effects, as well as traditional uses in treating stomachache, rheumatic pain, rhinitis, and chronic bronchitis. Using multiple chromatographic techniques, 10 oligosaccharide esters were isolated from the whole plants of P. paniculata, comprising seven new compounds, polypanicoses A-G (1-7), one new natural product, 3'-O-benzoylsucrose (8), and two known ones, senegose F (9) and tenuifoliside A (10). Their structures were elucidated through comprehensive spectroscopic methods, including NMR and HRESI mass spectra. Compounds 1-6, 8, and 9 inhibited nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with IC₅₀ values ranging from 44.6 ± 1.0 to 99.6 ± 8.3 μM. Molecular docking simulations suggested that 1 and 4 inhibit NO overproduction by binding to the active site of iNOS, thereby modulates the protein's activity. Both 1 and 4 further attenuated iNOS expression, suggesting that their NO inhibitory activity is associated with down-regulation of iNOS expression.