Suspensaditerpenes A–Q, anti-inflammatory labdane and nor-labdane diterpenoids from the seeds of Forsythia suspensa

Abstract

Phytochemical investigation of the seeds of Forsythia suspensa resulted in the isolation and characterization of 17 undescribed labdane and nor-labdane diterpenoids, named suspensaditerpenes A−Q (1−17), along with 13 known ones (18−30). Their structures were elucidated by a combination of NMR, HR-MS, and X-ray diffraction analyses. Structurally, 5, 10, and 13 are labdane diterpenoids featuring a lactone ring at the side chain, marking their first description in F. suspensa. Compounds 4, 14, 15, and 25 are 14,15-dinor-diterpenoids, among which 14 and 15 have a rare 6/6/5 ring skeleton. Furthermore, all known compounds were isolated from F. suspensa for the first time. The in vitro anti-inflammatory activities assay showed that 5, 8, 13, and 14 significantly inhibited the LPS-induced NO production at 20 μM in LPS-induced RAW264.7 cells, while the remaining 24 compounds demonstrated slight NO inhibitory activity. Further studies showed that 5 suppressed the LPS-induced expression of iNOS, p-p65, and NLRP3 proteins as well as NF-κB nuclear translocation in RAW264.7 cells.