ent-Pimarane Diterpenoid Dimers from Sigesbeckia glabrescens with Potent Anti-inflammatory Activitie

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Chromatographic purification of Sigesbeckia glabrescens extracts led to three undescribed ent-pimarane diterpenoid dimers,named glabreside A—C (1-3).Their structures were confirmed by comprehensive spectroscopic analyses,and the structures of compound 1 and 3 were confirmed by X-ray crystallography.The results of anti-inflammatory activity assay showed that glabreside C (3) exhibited the most potent inhibition activity on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV2 microglia compared with the other two compounds.Glabreside C also increased the protein expression level of heme oxygenase-1 (HO-1),and sup-pressed inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) in LPS-stimulated BV2 cells.Mechanistically,glabreside C exerts its anti-inflammatory effect by inhibiting AKT/MAPKs signaling pathway.These findings indicate the vital role of ent-pimarane diterpenoid dimers in explaining the anti-inflammatory activity of S.glabrescens and provide important evidence for further devel-opment and utilization of Sigesbeckiae Herba.These results also suggest that glabreside C is a potential lead compound for an-ti-inflammatory drugs.
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