Labdane and norlabdane diterpenoids from Amomum sericeum rhizomes and their potential anti-inflammatory activities

Phytochemical investigation of the rhizomes of Amomum sericeum led to the isolation and identification of twenty-seven labdane and norlabdane diterpenoids, including two unprecedented rearranged dinorditerpenoids (1 and 2), two novel norditerpenoids (3 and 4), seven undescribed labdane and norlabdane diterpenoids (5-11), along with sixteen known analogs (12-27). Their structures were established by comprehensive analysis of spectroscopic data, single crystal X-ray diffraction, Rh₂(OCOCF₃)₄-induced electronic circular dichroism (ECD), and quantum chemistry calculations. Compounds 1 and 2 represented two unique labdane dinorditerpenoid skeletons, with a 6/6/5 tricyclic system and a 6/9 bicyclic system, respectively. Compounds 3 and 4 were the first labdane norditerpenoids featuring a furan ring (in 3) and an α,β-unsaturated γ-butyrolactone unit (in 4) attached to C-9 of the decalin core. In the anti-inflammatory activity assay, compounds 7, 8, and 19 showed significant inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells. Further research indicated that 7, 8, and 19 could downregulate inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression, inhibit intracellular reactive oxygen species (ROS) generation, and activate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. These findings revealed that 7, 8, and 19 may be important potential components of Amomum sericeum for developing anti-inflammatory agents.