New Polyhydroxysteroids Derivatives from Starfish Asterias amurensis Induce Embryotoxicity in Marine Medaka.

In recent years, multiple population outbreaks of the Northern Pacific starfish (Asterias amurensis) have been documented off the coast of Qingdao. Starfish use chemosensation to regulate their life history and interactions with the environment, with their secondary metabolites serving as deterrents and dispersal agents against predators. While the eggs of marine fish are passive and susceptible, we hypothesized that the secondary metabolites of A. amurensis may cause embryotoxicity and exhibit a more insidious chemical function. In this study, we identified the secondary metabolites of A. amurensis collected from the Yellow Sea of China. Five new polyhydroxysteroid derivatives, (22Z)-26-O-β-D-xylopyranosyl-24-nor-5α-cholestane-22(23)-ene-3β,6α,7α,15α,26-pentaol (1), (24S)-O-β-D-xylopyranosyl-5α-cholestane-3β,6α,7α,15α,24-pentaol (2), (22E,24S)-24-O-[4-O-sulfo-β-D-xylopyranosyl]-5α-cholest-9(11)-ene-3β,6α,7α,15β,24-pentol (3), (24S)-methylene-28-O-sulfo-5α-cholestane-3β,6α,15α,24-tetraol (4), and 6α-O-sulfo-5α-cholestane-3β,5-diol (5), together with two known steroids, (24S)-24-methyl-5α-cholestane-3β,6α,15β,24,24'-pentaol (6) and (20E)-3β,6α-dihydroxy-5α-cholesta-9(11),20(22)-dien-23-one (7) were identified from the n-butanol extract. NMR and HRESI-MS were employed for structure elucidations. The embryotoxicity and teratogenicity of the isolated compounds were assessed using embryos of marine medaka (Oryzias melastigma). Compound 5 induced significantly higher mortality rates than other compounds, causing up to 70% mortality at 96 hpf, with a 96 h-LC of 60.51 µM.