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

Four new δ- and γ-lactone derivatives, hyperelatolides A-D (1-4, respectively), were discovered from the aerial portions of Hypericum elatoides 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 (1) and B (2) represent the first examples of δ-lactone derivatives characterized by a (Z)-(5,5-dimethyl-2-(2-oxopropyl)cyclohexylidene)methyl moiety and a benzoyloxy group attached to the ß- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C (3) and D (4) are unprecedented γ-lactone derivatives featuring substituents similar to those of 1 and 2. All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones 1 and 2 exhibited considerable antineuroinflammatory activity, with IC50 values of 5.74 ± 0.27 and 7.35 ± 0.26 µM, respectively. Moreover, the mechanistic study revealed that lactone 1 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.

Phytoecdysteroids from Dianthus superbus L.: Structures and anti-neuroinflammatory evaluation.

Six undescribed C27-phytoecdysteroid derivatives, named superecdysones A-F, and ten known analogs were extracted from the whole plant of Dianthus superbus L. Their structures were identified by extensive spectroscopy, mass spectrometric methods, chemical transformations, chiral HPLC analysis, and the single-crystal X-ray diffraction analysis. Superecdysones A and B possess a tetrahydrofuran ring in the side chain and superecdysones C-E are rare phytoecdysones containing a (R)-lactic acid moiety, whereas superecdysone F is an uncommon B-ring-modified ecdysone. Notably, based on the variable temperature (from 333 K to 253 K) NMR experiments of superecdysone C, the missing carbon signals were visible at 253 K and assigned. The neuroinflammatory bioassay of all compounds were evaluated, and 22-acetyl-2-deoxyecdysone, 2-deoxy-20-hydroxyecdysone, 20-hydroxyecdysone, ecdysterone-22-O-benzoate, 20-hydroxyecdysone-20,22-O-R-ethylidene, and acetonide derivative 20-hydroxyecdysterone-20, 22-acetonide significantly suppressed the LPS-induced nitric oxide generation in microglia cells (BV-2), with IC50 values ranging from 6.9 to 23.0 µM. Structure-activity relationships were also discussed. Molecular docking simulations of the active compounds confirmed the possible mechanism of action against neuroinflammations. Furthermore, none compounds showed cytotoxicity against HepG2 and MCF-7. It is the first report about the occurrence and anti-neuroinflammatory activity of the phytoecdysteroids in the genus Dianthus. Our findings demonstrated that ecdysteroids may be used as potential anti-inflammatory drugs.