Hyperelatolides A-D, Antineuroinflammatory Constituents with Unusual Carbon Skeletons from .

Four new δ- and γ-lactone derivatives, hyperelatolides A-D (-, respectively), were discovered from the aerial portions of R. Keller. Their structures were elucidated by analysis of NMR spectra, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and X-ray crystallographic data. Hyperelatolides A () and B () represent the first examples of δ-lactone derivatives characterized by a ()-(5,5-dimethyl-2-(2-oxopropyl)cyclohexylidene)methyl moiety and a benzoyloxy group attached to the β- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C () and D () are unprecedented γ-lactone derivatives featuring substituents similar to those of and . All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones and exhibited considerable antineuroinflammatory activity, with IC values of 5.74 ± 0.27 and 7.35 ± 0.26 μM, respectively. Moreover, the mechanistic study revealed that lactone significantly suppressed nuclear factor kappa B signaling and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-induced cells, which may contribute to its antineuroinflammatory activity.