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- W4200260878 abstract "Current anti-inflammatory strategies suppress pro-inflammatory lipid mediator biosynthesis but do not engage their pro-resolving counterparts that relieve chronic inflammation [1]. Systematic exploration of our Vietnamese medical plant library led to the discovery of a biflavonoid from Dracaena cambodiana, which alleviates inflammation by inducing a lipid mediator class switch from leukotrienes to specialized pro-resolving mediators (SPM) [2]. We elucidated the absolute configuration of the active isomer and identified 5-lipoxygenase as major target. Molecular docking studies suggest that the compound binds to an allosteric cavity at the interface of the catalytic and regulatory 5-lipxoygenase domain. Inhibition of microsomal prostaglandin E2 synthase-1 and other enzymes within lipid mediator biosynthesis was only evident at substantially higher concentrations. Leukotriene production is effectively reduced across human primary innate immune cells (neutrophils, macrophages), in blood and during peritonitis in mice. SPM formation, on the other hand, selectively increases in macrophages of the M2 subtype, is elevated in vivo and associated with diminished immune cell infiltration. Together, starting from Vietnamese plants, we identified a biflavonoid that reprograms the lipid mediator profile of innate immune cells towards resolution." @default.
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- W4200260878 date "2021-12-01" @default.
- W4200260878 modified "2023-10-18" @default.
- W4200260878 title "Switching from inflammation to resolution: what can we learn from medicinal plants?" @default.
- W4200260878 doi "https://doi.org/10.1055/s-0041-1736757" @default.
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