Neuroprotective Xanthones and Their Biosynthesis in Shoot Cultures of Hoppea fastigiata (Griseb.) C.B. Clarke

Abstract

Hoppea fastigiata (Griseb.) C.B. Clarke, an annual medicinal herb belonging to Gentianaceae, is mostly found in South-Asian countries. The genus possesses a unique class of compounds called xanthones, which are known for their potential against Alzheimer's and Parkinson's diseases. Three major xanthones were isolated and structurally confirmed as 1,5,7-trihydroxy-3-methoxyxanthone, 1,5-dihydroxy-3,7-dimethoxyxanthone, and 1,3,5-trihydroxy-8-methoxyxanthone from the in vitro shoot cultures which showed potential inhibitions against acetylcholinesterase, monoamine oxidase A, and monoamine oxidase B enzymes. Upon treatment with different elicitors, yeast extract (YE) was found to be most effective which led to a 20-fold increase of 1,3,5-trihydroxy-8-methoxy xanthone. YE treatment caused a rapid burst of reactive oxygen species (ROS) and the subsequent increase in xanthone contents. Phenylalanine ammonia lyase activity remained suppressed and 4-coumarate: CoA ligase activity remained unaffected after elicitation. However, shikimate dehydrogenase and shikimate kinase activities increased after elicitation. This suggested phenylalanine-independent biosynthesis of xanthones. Subsequent treatment of shoots cultures with different inhibitors of superoxide radicals (O 2À), hydrogen peroxide (H 2 O 2) generation, and calcium channel was found to suppress accumulation of xanthones. Thus, calcium mediated generation of H 2 O 2 followed by the activation of shikimate pathway enzymes is the key early step of xanthone biosynthesis in H. fastigiata.