Insight into medicinal chemistry behind traditional Chinese medicines: polybenzyls in Gastrodia elata

Thirteen undescribed minor polybenzyl constituents included derivatives of six tetrabenzyls (gastrotetrabenzins A-F, 1-6), five pentabenzyls (gastropentabenzins A-E, 7-11), and two hexabenzyls (gastrohexabenzins A and B, 12 and 13), along with a known pentabenzyl (14), were isolated from an aqueous extract of Gastrodia elata Blume rhizomes (tian ma). Meanwhile, 4-10 and 12-14 as well as fourteen undescribed polybenzyls (15-28) and one known analogue (29) were isolated and structurally characterized from a refluxed water solution of p-hydroxybenzyl alcohol. Subsequent UPLC-HRESIMS analysis of the extracts of commercial tian ma and fresh G. elata rhizomes proved that the polybenzyls from the aqueous extract are producible by the traditional application methods of processing and decocting. Bioassays showed that the polybenzyls were much more active than the main constituents p-hydroxybenzyl alcohol and gastrodin of tian ma. These results provide experimental evidences to explain why tian ma is processed and decocted in traditional Chinese medicine (TCM), unravelling structural modification and active optimization behind the TCM application methods.