Phytochemical investigation of Himatanthus sucuuba bark leading to the identification of novel and anti-inflammatory compounds
Himatanthus sucuuba (Spruce ex Müll. Arg.) Woodson (Apocynaceae) is used in the Amazonian region for the treatment of inflammatory diseases . The bark of this medicinal plant was phytochemically investigated guided by an LPS/TNF stimulated assay measuring E-selectin and IL-8. Out of bioactive fractions 11 constituents were isolated and identified by MS and 1D and 2D NMR experiments as iridoids (plumericin, plumieridin, allamandicin, and the new natural product (2'R,3R,4R,4aS,7aR)-methyl 3-hydroxy-4'-((S)-1-hydroxyethyl)-5'-oxo-3,4,4a,7a-tetrahydro-1H,5'H-spiro[cyclopenta[c]pyran-7,2'-furan]-4-carboxylate), flavonoids (biochanin A, dihydrobiochanin A, dalbergioidin, naringenin, ferreirin, and dihydrocajanin), and the lignan pinoresinol. Except for plumericin and pinoresinol this is the first time these compounds are reported to be isolated from Himatanthus sucuuba. The structure of the new iridoid was determined using X-ray crystallography. Interestingly, NMR experiments showed the presence of two compounds indicating stereochemical conversion.
The isolated constituents were analyzed for their anti-inflammatory activity. They showed only moderate or no effects with the exception of plumericin which exhibited dose-dependent inhibitory activity on LPS or TNF induced expression of IL-8 and E-selectin in the low µM range.
In conclusion, several known components were isolated from Himatanthus sucuuba for the first time together with one new natural product. Plumericin revealed as the most active compound in this general anti-inflammatory assay. The elucidation of the molecular mechanism of action is currently under evaluation.
Acknowledgement: This work was granted by the Austrian Science Fund (S10703).
References: 1. Amaral ACF et al. (2007) Pharmacogn Rev 1: 305–313.