Advances in the chemistry, pharmacological diversity, and metabolism of 20(R)-ginseng saponins

Abstract

Ginseng has been used as a popular herbal medicine in East Asia for at least two millennia. However, 20(R)-ginseng saponins, one class of important rare ginsenosides, are rare in natural products. 20(R)-ginseng saponins are generally prepared by chemical epimerization and microbial transformation from 20(S)-isomers. The C20 configuration of 20(R)-ginseng saponins are usually determined by ¹³C NMR and X-ray single-crystal diffraction. 20(R)-ginseng saponins have antitumor, antioxidative, antifatigue, neuroprotective, and osteoclastogenesis inhibitory effects, among others. Owing to the chemical structure and pharmacological and stereoselective properties, 20(R)-ginseng saponins have attracted a great deal of attention in recent years. In this study, the discovery, identification, chemical epimerization, microbial transformation, pharmacological activities, and metabolism of 20(R)-ginseng saponins are summarized.

Keywords: 20(R)-ginseng saponin; Epimerization; Identification; Metabolism; Pharmacological activity.

Fig. 1

The structures of 20(R)-ginseng saponins. (A) Protopanaxadiol (PPD)- and protopanaxatriol (PPT)-type saponins; (B) Panaxadiol (PD)-type, panaxatriol (PT)-type, and modified saponins; (C) Modified PPD- and PPT-type saponins; (D) Ocotillol-type and modified saponins.

Fig. 2

The oak ridge thermal ellipsoid plot (ORTEP) figures of 3, 7, 34, 35, 39, and 40, showing the atom-labeling scheme. Displacement ellipsoids are drawn at the 30% probability level, and H atoms are shown as spheres of arbitrary radii.

Fig. 3

Epimerization of 20(S)-ginseng saponins to 20(R)-isomers in acid. The dehydration reaction produced a carbocation intermediate at C-20 of 20(S)-ginseng saponins. Upon rehydration, an oxonium ion was generated, resulting in the conversion of the configuration at C-20 and the creation of 20(R)-ginseng saponins.