Eleutherlenes A-D, Diverse Types of Naphthalene Derivatives with Anti-inflammatory Activity from Eleutherine bulbosa

Eleutherlene A (1), an unprecedented carbon skeleton featuring an aryl-fused 6-methyl-2,7-dioxabicyclo[3.2.1]octane unit, and eleutherlene B (2), a naphthoquinone derivative with interesting ring fusion of an alpha,beta-unsaturated gamma-lactam and a tetrahydropyran moiety, along with two novel naphthoquinone alkaloids, eleutherlenes C (3) and D (4), were isolated from Eleutherine bulbosa and identified. Their structures were elucidated by spectroscopic analyses along with computer-assisted structure elucidation, including ACD/Structure Elucidator and computational calculations and X-ray crystal diffraction. A plausible biosynthetic route for 1 and 2 was proposed. Compound 1 showed significant anti-inflammatory activity with respect to the inhibition of pro-inflammatory mediators NO, IL-1 beta, iNOS, and COX-2. Mechanistically, compound 1 inhibited the inflammatory response by suppressing NF-kappa B/MAPK and activating the Nrf2/Keap1 signaling pathway in LPS-induced RAW 264.7 cells.