Piper tectoniifolium Kunth: A New Natural Source of the Bioactive Neolignan (-)-Grandisin

The Piper species are a recognized botanical source of a broad structural diversity of lignans and its derivatives. For the first time, Piper tectoniifolium Kunth is presented as a promising natural source of the bioactive (-)-grandisin. Phytochemical analyses of extracts from its leaves, branches and inflorescences showed the presence of the target compound in large amounts, with leaf extracts found to contain up to 52.78% in its composition. A new HPLC-DAD-UV method was developed and validated to be selective for the identification of (-)-grandisin being sensitive, linear, precise, exact, robust and with a recovery above 90%. The absolute configuration of the molecule was determined by X-ray diffraction. Despite the identification of several enantiomers in plant extracts, the major isolated substance was characterized to be the (-)-grandisin enantiomer. In vascular reactivity tests, it was shown that the grandisin purified from botanical extracts presented an endothelium-dependent vasorelaxant effect with an IC50 of 9.8 +/- 1.22 mu M and around 80% relaxation at 30 mu M. These results suggest that P. tectoniifolium has the potential to serve as a renewable source of grandisin on a large scale and the potential to serve as template for development of new drugs for vascular diseases with emphasis on disorders related to endothelial disfunction.

Automated summary

Piper species, especially Piper tectoniifolium Kunth, are potential natural sources of the bioactive compound (-)-grandisin. A new method for identifying (-)-grandisin was developed, and the molecule was found to have a vasorelaxant effect. These findings suggest that P. tectoniifolium has the potential to be a renewable source of grandisin and a template for the development of new drugs.