Nitric oxide inhibitory phenolic constituents isolated from the roots and rhizomes of Notopterygium incisum

Abstract

Fourteen phenolic constituents, notopheninetols A−E (1–5), notoflavinols A and B (6 and 7), and (2R)-5,4′-dihydroxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl]flavanone (8a), along with 12 known analogues (8b and 9–19) were isolated from the roots and rhizomes of Notopterygium incisum. Compounds 1–4 and 6–8 were seven pairs of enantiomers, and they were separated by chiral HPLC to obtain the optically pure compounds. The structures of the new compounds were elucidated based on detailed analyses of 1D and 2D NMR and HRESIMS data, and the absolute configurations were determined by quantum chemical calculations of the electronic circular dichroism (ECD) spectra, comparison of the experimental ECD data with those reported, and chemical methods. Compounds 1 and 2 possessed a 1-benzyl-2-methyl-indane skeleton, which was unprecedented in natural source. All of the isolated compounds were evaluated for their nitric oxide (NO) inhibitory effects on RAW264.7 cells induced by LPS, and compounds 6a/6b, 7a, 8a/8b, and the hydrogenated products 6′a and 7′a showed moderate inhibitory activities with IC50 values in the range of 6.2–20.6 μM. Moreover, the interactions of these bioactive compounds with inducible nitric oxide synthase (iNOS) were explored by employing molecular docking simulation.