Comparative Metabolome and Transcriptome analyses Reveal Mechanisms for Differences in Ginsenoside Profiles of Herbal Medicines Derived from Panax Species

Panax ginseng ( P. ginseng , Pg), P. quinquefolium (Pq), and P. notoginseng (Pn) are valuable medicinal plants, and their roots and rhizomes are commonly used as herbal medicines worldwide. While all three herbs contain abundant ginsenosides as major bioactive compounds, their clinical applications differ remarkably. To elucidate the chemical differences in ginsenosides among these three Panax species, we conducted a targeted secondary metabolomic analysis by determining the contents of 40 ginsenosides in 147 batches of herbal samples by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). To further elucidate the biosynthetic mechanisms underlying these differences, we conducted a comparative transcriptome analysis to identify key differential biosynthetic genes. The results revealed that Pn had higher levels of ginsenosides than Pg and Pq, probably due to the high expression of upstream genes in the triterpenoid biosynthetic pathway. The ratio of protopanaxadiol- to protopanaxatriol-type ginsenosides (PPD/PPT) followed the order Pn (0.69) < Pg (1.11) < Pq (2.19), which was consistent with the expression levels of CYP716A53, an enzyme that catalyzes the 6-hydroxylation of PPD to produce PPT. Moreover, the ginsenoside Rg1/Re ratio followed the order of Pq (0.13) < Pg (0.97) < Pn (5.96), which may be related to the expression levels and catalytic efficiency of the rhamnosyltransferases that catalyze the 2′- O -rhamnosylation of ginsenoside Rg1 to generate Re. This work demonstrates the potential of the combination of metabolome and transcriptome analyses to elucidate the mechanisms underlying the chemical differences of phylogenetically related herbal medicines