Mass spectrometry-based ginsenoside profiling: Recent applications, limitations, and perspectives

Abstract

Ginseng, the roots of Panax species, is an important medicinal herb used as a tonic. As ginsenosides are key bioactive components of ginseng, holistic chemical profiling of them has provided many insights into understanding ginseng. Mass spectrometry has been a major methodology for profiling, which has been applied to realize numerous goals in ginseng research, such as the discrimination of different species, geographical origins, and ages, and the monitoring of processing and biotransformation. This review summarizes the various applications of ginsenoside profiling in ginseng research over the last three decades that have contributed to expanding our understanding of ginseng. However, we also note that most of the studies overlooked a crucial factor that influences the levels of ginsenosides: genetic variation. To highlight the effects of genetic variation on the chemical contents, we present our results of untargeted and targeted ginsenoside profiling of different genotypes cultivated under identical conditions, in addition to data regarding genome-level genetic diversity. Additionally, we analyze the other limitations of previous studies, such as imperfect variable control, deficient metadata, and lack of additional effort to validate causation. We conclude that the values of ginsenoside profiling studies can be enhanced by overcoming such limitations, as well as by integrating with other -omics techniques.

Keywords: Chemical profiling; Genetic variation; Ginseng; Ginsenoside; Mass spectrometry.

Graphical abstract

Fig. 1

Structures of the four major types of ginsenosides. The major sites of glycosylation of each type of aglycone are represented as R, and representative ginsenosides for each type are indicated with their sugar moieties.

Fig. 2

Phylogenetic analysis of 119 ginseng accessions, utilizing 249,885 single nucleotide polymorphisms identified via genotyping-by-sequencing.

Fig. 3

Untargeted LC-MS/MS analysis reveals the relative contents of 71 putative ginsenosides in the roots and berries of 60 P. ginseng accessions. Due to the different mass spectral intensities of the ions, the values were normalized to yield Z-scores. The blanks mean each compound was not detected. The putative annotations of ginsenosides G1–G71 are summarized in Table 1.

Fig. 4

Targeted LC-MS/MS analysis reveals the variety in the contents of 13 ginsenosides in the roots of 87 P. ginseng accessions. (A) The multiple reaction monitoring chromatogram of the reference standard mixture. (B–D) Absolute contents of the analyzed ginsenosides in the samples.