Anti-infammatory scalemic chromanoids and chromenoids from Rhododendron dauricum

Four pairs of undescribed chromane and chromene meroterpenoid scalemic mixtures (1a/1b-4a/4b), together with three pairs of known chromane meroterpenoid ones (5a/5b-7a/7b) were isolated from the twigs and leaves of Rhododendron dauricum L. Among them, 1a/1b-3a/3b and 5a/5b-7a/7b were the chromane ones derived from an intramolecular [2 + 2] cyclic addition of their respective chromene precursors, forming a 6/6/6/4 and 6/6/5/4 ring fused scaffold. The absolute configurations of the chiral center at C-15 of 2a/2b were determined by Snatzke's method, and comparing the experimental and calculated electronic circular dichroism (ECD) data. The inhibitory effects of the isolated compounds were tested against lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 macrophage cells to evaluate their anti-inflammatory activity. Compounds 4a, 4b and 6a displayed inhibitory effects on nitric oxide (NO) production, and compound 4b exhibited the obvious anti-inflammatory activity, with an IC50 value of 6.91 +/- 0.97 mu M, by downregulating nuclear factor kappa B (NF-kappa B) and reducing the expression of inducible nitric oxide synthase (iNOS) in LPS-induced RAW264.7 cells. These results intimated that 4b could be used as a leading compound to develop anti-inflammatory drugs and is worthy of further investigated.

Automated summary

Four pairs of undescribed scalemic mixtures of chromane and chromene meroterpenoids (1a/1b-4a/4b) were isolated from Rhododendron dauricum L. The compounds demonstrated anti-inflammatory activity by inhibiting nitric oxide production in LPS-induced macrophage cells. Compound 4b exhibited significant anti-inflammatory activity and could be explored as a potential lead compound for the development of anti-inflammatory drugs.