We have screened microbial culture filtrates for nitrogen monoxide (NO) production inhibitors using mouse macrophage cell line RAW264.7. As a result, paxilline, 21-isopentenylpaxilline and a novel analog of paxilline have been isolated from the culture filtrate of fungus Eupenicillium shearii. The novel analog possesses an additional dihydropyran ring, and was named as pyrapaxilline. This compound inhibited the NO production with lower toxicity than paxilline.
Lysenin is a pore-forming toxin derived from coelomic fluid of the earthworm Eisenia foetida. The model of lysenin-induced hemolysis includes the specific binding of lysenin to sphingomyelin, oligomerization of the pore proteins, and pore formation. Although the mechanism of lysenin-induced hemolysis is unique, its precise mechanism of action and its inhibitors are poorly understood. In the present study, we screened for inhibitors of lysenin-induced hemolysis by using an optimized screening system and found a methanolic extract of Dalbergia latifolia leaves to be a potential candidate. After isolation and identification, all-E-lutein was identified as the hemolysis inhibitor with an effective dose of 0.025-2.5 ng/mL without any toxicity. The inhibition by all-E-lutein is likely to occur during the receptor binding and/or pore-forming protein oligomerization.
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