Diverse anti-inflammatory lindenane sesquiterpenoid hetero- or homo-dimers from Chloranthus holostegius var. shimianensis.

Twenty-seven dimeric lindenane sesquiterpenoid (LS) derivatives, including thirteen new hetero- or homo-dimers (1-13), were discovered from rare Chloranthaceae plant Chloranthus holostegius var. shimianensis. Their structures were elucidated by a combination of HRMS, spectroscopic analysis, single-crystal X-ray diffraction and CD exciton chirality method. Fortunoids D-G (1-4) and chlorfortunones C-F (5-8) are rare hetero-dimers of lindenane with eudesmane or acrane sesquiterpenoid through classical [4 + 2] cycloaddition respectively, and 9-13 are homo-LS dimers with low oxidation at C4'/13'/15'. Anti-inflammatory potential of these new isolates was evaluated by screening the IL-1β inhibition in THP-1 cells. Compounds 2-4 exhibited moderate anti-inflammatory effect (IC50 ≈ 10 μM) at non-cytotoxic concentrations (cell viability >80 %), and subsequent investigation on 2 demonstrated that it inhibited IL-1β production by inhibiting NLRP3 inflammasome activation but not the assembly. Based on the structural features of these LS dimers, the abundance of hetero-LS dimers and the low oxidation level at C4'/13'/15' of homo-LS dimers might be the chemotaxonomic characteristics distinguished from other Chloranthus species.