Anti-inflammatory oxazole-, nitro- and hexahydropyrrolo[2,1-b]oxazole-containing abietane diterpenoid alkaloids from Salvia miltiorrhiza.

Abstract

Nine undescibed abietane diterpenoid alkaloids (DAs), salviamines G‒H (1-2), isosalviamines G‒J (3-6), and miltiorramines A‒C (7-9) were isolated from the roots of Salvia miltiorrhiza. Their chemical structures including absolute configurations were elucidated by extensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS), combined with the calculated ECD method and single-crystal X-ray diffraction analysis. Among them, compounds 1-6 are unusual 20-nor- or 19,20-bisnor-abietane DAs with an oxazole ring. Compounds 7-8 are the first examples of DAs with a nitro group isolated from plant sources. Notably, compound 9 possesses a rare hexahydropyrrolo[2,1-b]oxazole unit that is fused in the ring B of the abietane skeleton. Bioactivity assay indicated that compound 3 showed significant anti-inflammatory activity by decreasing the gene expressions of IL-1β, IL-6, and TNF-α in LPS-induced RAW264.7 cells in a dose-dependent manner.