Chemical diversity of ginseng saponins from Panax ginseng

Abstract

Ginseng, a perennial plant belonging to the genus Panax of the Araliaceae family, is well known for its medicinal properties that help alleviate pathological symptoms, promote health, and prevent potential diseases. Among the active ingredients of ginseng are saponins, most of which are glycosides of triterpenoid aglycones. So far, numerous saponins have been reported as components of Panax ginseng, also known as Korean ginseng. Herein, we summarize available information about 112 saponins related to P. ginseng; >80 of them are isolated from raw or processed ginseng, and the others are acid/base hydrolysates, semisynthetic saponins, or metabolites.

Keywords: Araliaceae; Panax ginseng; dammarane; ginsenoside; triterpene.

Fig. 1

Biosynthetic pathways of ginseng saponins. 2,3-Oxidosqualene may be cyclized into three different compounds, two of which are dammarenediol-II and β-amyrin, the precursor of dammarane-type saponins and oleanane-type saponins, respectively.

Fig. 2

Structures of ginseng saponins. A. Structures of ginseng saponins whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); B. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-24-hydroperoxydammar-25-ene/3β,6α,12β,20-tetrahydroxy-24-hydroperoxydammar-25-ene; (b) 3β,12β,20,24-tetrahydroxydammar-25-ene/3β,6α,12β,20,24-pentahydroxydammar-25-ene; (c) 3β,6α,12β,20-tetrahydroxydammar-24-one-25-ene; C. Structures of ginseng saponins whose genin is (a) (E)-3β,12β,20-trihydroxy-25-hydroperoxydammar-23-ene/(E)-3β,6α,12β,20-tetrahydroxy-25-hydroperoxydammar-23-ene; (b) (E)-3β,6α,12β,20,25-pentahydroxydammar-23-ene; (c) 3β,6α,12β,26-tetrahydroxydammar-24-ene/3β,6α,12β,27-tetrahydroxydammar-24-ene; D. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-25,26,27-trinordammar-24-al/3β,12β,20,23-tetrahydroxy-25,26,27-trinordammar-24-al; (b) 3β,6α,12β,20-tetrahydroxy-24,24-dimethoxy-25,26,27-trinordammarane; E. Structures of ginseng saponins whose genin is 3β,12β,20,25-tetrahydroxydammarane/3β,6α,12β,20,25-pentahydroxydammarane; F. Structures of ginseng saponins whose genin is (a) (E)-3β,12β-dihydroxydammar-20(22),24-diene/(E)-3β,6α,12β-trihydroxydammar-20(22),24-diene; (b) (Z)-3β,12β-dihydroxydammar-20(22),24-diene; (c) 3β,12β-dihydroxydammar-20(21),24-diene/3β,6α,12β-trihydroxydammar-20(21),24-diene; G. Structures of ginseng saponins whose genin is (a) 3β,12β-dihydroxy-20,25-epoxydammarane (panaxadiol)/3β,6α,12β-trihydroxy-20,25-epoxydammarane (panaxatriol); (b) 3β,6α,20-trihydroxy-12,23-epoxydammar-24-ene; (3) 6α,25-dihydroxy-20,24-epoxydammar-3,12-dione; H. Structure of a ginseng saponin whose genin is (a) 3β,6α,12β,24-tetrahydroxydammar-20(22),25-diene; (b) 3β,7β,12β,20-tetrahydroxydammar-5,24-diene; (c) 3β,6α,20-trihydroxydammar-12-one-24-ene; (d) oleanolic acid; I. Structures of ginseng saponins whose genin is (a) 3β,6α,12β-trihydroxy-24-hydroperoxydammar-20(22),25-diene; (b) 3β,6α,12β-trihydroxy-23-hydroperoxydammar-20(21),24-diene; (c) 3β,6α,12β-trihydroxy-22,23,24,25,26,27-hexanordammar-20-one; (d) (E)-3β,12β,25-trihydroxydammar-20(22)-ene; J. Structures of synthesized saponins whose genin is (a) 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); (b) 3β,12β,25-trihydroxy-20,24-epoxydammarane/3β,6α,12β,25-tetrahydroxy-20,24-epoxydammarane; (c) 3β,12β-dihydroxydammarane; K. Structures of ginseng saponin metabolites whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol).

Fig. 2

Structures of ginseng saponins. A. Structures of ginseng saponins whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); B. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-24-hydroperoxydammar-25-ene/3β,6α,12β,20-tetrahydroxy-24-hydroperoxydammar-25-ene; (b) 3β,12β,20,24-tetrahydroxydammar-25-ene/3β,6α,12β,20,24-pentahydroxydammar-25-ene; (c) 3β,6α,12β,20-tetrahydroxydammar-24-one-25-ene; C. Structures of ginseng saponins whose genin is (a) (E)-3β,12β,20-trihydroxy-25-hydroperoxydammar-23-ene/(E)-3β,6α,12β,20-tetrahydroxy-25-hydroperoxydammar-23-ene; (b) (E)-3β,6α,12β,20,25-pentahydroxydammar-23-ene; (c) 3β,6α,12β,26-tetrahydroxydammar-24-ene/3β,6α,12β,27-tetrahydroxydammar-24-ene; D. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-25,26,27-trinordammar-24-al/3β,12β,20,23-tetrahydroxy-25,26,27-trinordammar-24-al; (b) 3β,6α,12β,20-tetrahydroxy-24,24-dimethoxy-25,26,27-trinordammarane; E. Structures of ginseng saponins whose genin is 3β,12β,20,25-tetrahydroxydammarane/3β,6α,12β,20,25-pentahydroxydammarane; F. Structures of ginseng saponins whose genin is (a) (E)-3β,12β-dihydroxydammar-20(22),24-diene/(E)-3β,6α,12β-trihydroxydammar-20(22),24-diene; (b) (Z)-3β,12β-dihydroxydammar-20(22),24-diene; (c) 3β,12β-dihydroxydammar-20(21),24-diene/3β,6α,12β-trihydroxydammar-20(21),24-diene; G. Structures of ginseng saponins whose genin is (a) 3β,12β-dihydroxy-20,25-epoxydammarane (panaxadiol)/3β,6α,12β-trihydroxy-20,25-epoxydammarane (panaxatriol); (b) 3β,6α,20-trihydroxy-12,23-epoxydammar-24-ene; (3) 6α,25-dihydroxy-20,24-epoxydammar-3,12-dione; H. Structure of a ginseng saponin whose genin is (a) 3β,6α,12β,24-tetrahydroxydammar-20(22),25-diene; (b) 3β,7β,12β,20-tetrahydroxydammar-5,24-diene; (c) 3β,6α,20-trihydroxydammar-12-one-24-ene; (d) oleanolic acid; I. Structures of ginseng saponins whose genin is (a) 3β,6α,12β-trihydroxy-24-hydroperoxydammar-20(22),25-diene; (b) 3β,6α,12β-trihydroxy-23-hydroperoxydammar-20(21),24-diene; (c) 3β,6α,12β-trihydroxy-22,23,24,25,26,27-hexanordammar-20-one; (d) (E)-3β,12β,25-trihydroxydammar-20(22)-ene; J. Structures of synthesized saponins whose genin is (a) 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); (b) 3β,12β,25-trihydroxy-20,24-epoxydammarane/3β,6α,12β,25-tetrahydroxy-20,24-epoxydammarane; (c) 3β,12β-dihydroxydammarane; K. Structures of ginseng saponin metabolites whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol).

Fig. 2

Structures of ginseng saponins. A. Structures of ginseng saponins whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); B. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-24-hydroperoxydammar-25-ene/3β,6α,12β,20-tetrahydroxy-24-hydroperoxydammar-25-ene; (b) 3β,12β,20,24-tetrahydroxydammar-25-ene/3β,6α,12β,20,24-pentahydroxydammar-25-ene; (c) 3β,6α,12β,20-tetrahydroxydammar-24-one-25-ene; C. Structures of ginseng saponins whose genin is (a) (E)-3β,12β,20-trihydroxy-25-hydroperoxydammar-23-ene/(E)-3β,6α,12β,20-tetrahydroxy-25-hydroperoxydammar-23-ene; (b) (E)-3β,6α,12β,20,25-pentahydroxydammar-23-ene; (c) 3β,6α,12β,26-tetrahydroxydammar-24-ene/3β,6α,12β,27-tetrahydroxydammar-24-ene; D. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-25,26,27-trinordammar-24-al/3β,12β,20,23-tetrahydroxy-25,26,27-trinordammar-24-al; (b) 3β,6α,12β,20-tetrahydroxy-24,24-dimethoxy-25,26,27-trinordammarane; E. Structures of ginseng saponins whose genin is 3β,12β,20,25-tetrahydroxydammarane/3β,6α,12β,20,25-pentahydroxydammarane; F. Structures of ginseng saponins whose genin is (a) (E)-3β,12β-dihydroxydammar-20(22),24-diene/(E)-3β,6α,12β-trihydroxydammar-20(22),24-diene; (b) (Z)-3β,12β-dihydroxydammar-20(22),24-diene; (c) 3β,12β-dihydroxydammar-20(21),24-diene/3β,6α,12β-trihydroxydammar-20(21),24-diene; G. Structures of ginseng saponins whose genin is (a) 3β,12β-dihydroxy-20,25-epoxydammarane (panaxadiol)/3β,6α,12β-trihydroxy-20,25-epoxydammarane (panaxatriol); (b) 3β,6α,20-trihydroxy-12,23-epoxydammar-24-ene; (3) 6α,25-dihydroxy-20,24-epoxydammar-3,12-dione; H. Structure of a ginseng saponin whose genin is (a) 3β,6α,12β,24-tetrahydroxydammar-20(22),25-diene; (b) 3β,7β,12β,20-tetrahydroxydammar-5,24-diene; (c) 3β,6α,20-trihydroxydammar-12-one-24-ene; (d) oleanolic acid; I. Structures of ginseng saponins whose genin is (a) 3β,6α,12β-trihydroxy-24-hydroperoxydammar-20(22),25-diene; (b) 3β,6α,12β-trihydroxy-23-hydroperoxydammar-20(21),24-diene; (c) 3β,6α,12β-trihydroxy-22,23,24,25,26,27-hexanordammar-20-one; (d) (E)-3β,12β,25-trihydroxydammar-20(22)-ene; J. Structures of synthesized saponins whose genin is (a) 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); (b) 3β,12β,25-trihydroxy-20,24-epoxydammarane/3β,6α,12β,25-tetrahydroxy-20,24-epoxydammarane; (c) 3β,12β-dihydroxydammarane; K. Structures of ginseng saponin metabolites whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol).

Fig. 2

Structures of ginseng saponins. A. Structures of ginseng saponins whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); B. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-24-hydroperoxydammar-25-ene/3β,6α,12β,20-tetrahydroxy-24-hydroperoxydammar-25-ene; (b) 3β,12β,20,24-tetrahydroxydammar-25-ene/3β,6α,12β,20,24-pentahydroxydammar-25-ene; (c) 3β,6α,12β,20-tetrahydroxydammar-24-one-25-ene; C. Structures of ginseng saponins whose genin is (a) (E)-3β,12β,20-trihydroxy-25-hydroperoxydammar-23-ene/(E)-3β,6α,12β,20-tetrahydroxy-25-hydroperoxydammar-23-ene; (b) (E)-3β,6α,12β,20,25-pentahydroxydammar-23-ene; (c) 3β,6α,12β,26-tetrahydroxydammar-24-ene/3β,6α,12β,27-tetrahydroxydammar-24-ene; D. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-25,26,27-trinordammar-24-al/3β,12β,20,23-tetrahydroxy-25,26,27-trinordammar-24-al; (b) 3β,6α,12β,20-tetrahydroxy-24,24-dimethoxy-25,26,27-trinordammarane; E. Structures of ginseng saponins whose genin is 3β,12β,20,25-tetrahydroxydammarane/3β,6α,12β,20,25-pentahydroxydammarane; F. Structures of ginseng saponins whose genin is (a) (E)-3β,12β-dihydroxydammar-20(22),24-diene/(E)-3β,6α,12β-trihydroxydammar-20(22),24-diene; (b) (Z)-3β,12β-dihydroxydammar-20(22),24-diene; (c) 3β,12β-dihydroxydammar-20(21),24-diene/3β,6α,12β-trihydroxydammar-20(21),24-diene; G. Structures of ginseng saponins whose genin is (a) 3β,12β-dihydroxy-20,25-epoxydammarane (panaxadiol)/3β,6α,12β-trihydroxy-20,25-epoxydammarane (panaxatriol); (b) 3β,6α,20-trihydroxy-12,23-epoxydammar-24-ene; (3) 6α,25-dihydroxy-20,24-epoxydammar-3,12-dione; H. Structure of a ginseng saponin whose genin is (a) 3β,6α,12β,24-tetrahydroxydammar-20(22),25-diene; (b) 3β,7β,12β,20-tetrahydroxydammar-5,24-diene; (c) 3β,6α,20-trihydroxydammar-12-one-24-ene; (d) oleanolic acid; I. Structures of ginseng saponins whose genin is (a) 3β,6α,12β-trihydroxy-24-hydroperoxydammar-20(22),25-diene; (b) 3β,6α,12β-trihydroxy-23-hydroperoxydammar-20(21),24-diene; (c) 3β,6α,12β-trihydroxy-22,23,24,25,26,27-hexanordammar-20-one; (d) (E)-3β,12β,25-trihydroxydammar-20(22)-ene; J. Structures of synthesized saponins whose genin is (a) 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); (b) 3β,12β,25-trihydroxy-20,24-epoxydammarane/3β,6α,12β,25-tetrahydroxy-20,24-epoxydammarane; (c) 3β,12β-dihydroxydammarane; K. Structures of ginseng saponin metabolites whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol).

Fig. 2

Structures of ginseng saponins. A. Structures of ginseng saponins whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); B. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-24-hydroperoxydammar-25-ene/3β,6α,12β,20-tetrahydroxy-24-hydroperoxydammar-25-ene; (b) 3β,12β,20,24-tetrahydroxydammar-25-ene/3β,6α,12β,20,24-pentahydroxydammar-25-ene; (c) 3β,6α,12β,20-tetrahydroxydammar-24-one-25-ene; C. Structures of ginseng saponins whose genin is (a) (E)-3β,12β,20-trihydroxy-25-hydroperoxydammar-23-ene/(E)-3β,6α,12β,20-tetrahydroxy-25-hydroperoxydammar-23-ene; (b) (E)-3β,6α,12β,20,25-pentahydroxydammar-23-ene; (c) 3β,6α,12β,26-tetrahydroxydammar-24-ene/3β,6α,12β,27-tetrahydroxydammar-24-ene; D. Structures of ginseng saponins whose genin is (a) 3β,12β,20-trihydroxy-25,26,27-trinordammar-24-al/3β,12β,20,23-tetrahydroxy-25,26,27-trinordammar-24-al; (b) 3β,6α,12β,20-tetrahydroxy-24,24-dimethoxy-25,26,27-trinordammarane; E. Structures of ginseng saponins whose genin is 3β,12β,20,25-tetrahydroxydammarane/3β,6α,12β,20,25-pentahydroxydammarane; F. Structures of ginseng saponins whose genin is (a) (E)-3β,12β-dihydroxydammar-20(22),24-diene/(E)-3β,6α,12β-trihydroxydammar-20(22),24-diene; (b) (Z)-3β,12β-dihydroxydammar-20(22),24-diene; (c) 3β,12β-dihydroxydammar-20(21),24-diene/3β,6α,12β-trihydroxydammar-20(21),24-diene; G. Structures of ginseng saponins whose genin is (a) 3β,12β-dihydroxy-20,25-epoxydammarane (panaxadiol)/3β,6α,12β-trihydroxy-20,25-epoxydammarane (panaxatriol); (b) 3β,6α,20-trihydroxy-12,23-epoxydammar-24-ene; (3) 6α,25-dihydroxy-20,24-epoxydammar-3,12-dione; H. Structure of a ginseng saponin whose genin is (a) 3β,6α,12β,24-tetrahydroxydammar-20(22),25-diene; (b) 3β,7β,12β,20-tetrahydroxydammar-5,24-diene; (c) 3β,6α,20-trihydroxydammar-12-one-24-ene; (d) oleanolic acid; I. Structures of ginseng saponins whose genin is (a) 3β,6α,12β-trihydroxy-24-hydroperoxydammar-20(22),25-diene; (b) 3β,6α,12β-trihydroxy-23-hydroperoxydammar-20(21),24-diene; (c) 3β,6α,12β-trihydroxy-22,23,24,25,26,27-hexanordammar-20-one; (d) (E)-3β,12β,25-trihydroxydammar-20(22)-ene; J. Structures of synthesized saponins whose genin is (a) 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol); (b) 3β,12β,25-trihydroxy-20,24-epoxydammarane/3β,6α,12β,25-tetrahydroxy-20,24-epoxydammarane; (c) 3β,12β-dihydroxydammarane; K. Structures of ginseng saponin metabolites whose genin is 3β,12β,20-trihydroxydammar-24-ene (protopanaxadiol)/3β,6α,12β,20-tetrahydroxydammar-24-ene (protopanaxatriol).

Fig. 3

Probable pathways of the formation of artifactual saponins owing to heating. Deglycosylation and dehydration may occur at C-20 when a PPD- or PPT-type ginsenoside is steamed or heat-processed. The resultant double bond is formed either between C-20 and C-21 or between C-20 and C-22, leading to positional and geometric isomerism. PPD, protopanaxadiol; PPT, protopanaxatriol.

Fig. 4

Suggested metabolic pathways of PPD- and PPT-type ginsenosides. PPD-type ginsenosides tend to be deglycosylated at C-3, and M1 (compound K) may result. PPT-type ginsenosides are deglycosylated at C-6 and/or C-20. PPD, protopanaxadiol; PPT, protopanaxatriol.