Elsevier

Biochemical Pharmacology

Volume 58, Issue 11, 1 December 1999, Pages 1685-1693
Biochemical Pharmacology

Original Articles
Ginseng pharmacology: Multiple constituents and multiple actions

https://doi.org/10.1016/S0006-2952(99)00212-9Get rights and content

Abstract

Ginseng is a highly valued herb in the Far East and has gained popularity in the West during the last decade. There is extensive literature on the beneficial effects of ginseng and its constituents. The major active components of ginseng are ginsenosides, a diverse group of steroidal saponins, which demonstrate the ability to target a myriad of tissues, producing an array of pharmacological responses. However, many mechanisms of ginsenoside activity still remain unknown. Since ginsenosides and other constituents of ginseng produce effects that are different from one another, and a single ginsenoside initiates multiple actions in the same tissue, the overall pharmacology of ginseng is complex. The ability of ginsenosides to independently target multireceptor systems at the plasma membrane, as well as to activate intracellular steroid receptors, may explain some pharmacological effects. This commentary aims to review selected effects of ginseng and ginsenosides and describe their possible modes of action. Structural variability of ginsenosides, structural and functional relationship to steroids, and potential targets of action are discussed.

Section snippets

Pharmacological effects

Most pharmacological actions of ginseng are attributed to ginsenosides [2]. More than twenty ginsenosides have been isolated [3], and novel structures continue to be reported, particularly from Panax quinquefolius and Panax japonicus[5]. Figure 1 illustrates the structures of some ginsenosides. Since cardiovascular effects of ginseng have been well documented 3, 6, they will not be discussed here.

Why are there so many diverse effects?

Ginseng contains over twenty ginsenosides, and single ginsenosides have been shown to produce multiple effects in the same tissue 8, 47. In addition, non-ginsenoside constituents of ginseng also exert pharmacological effects. Thus, it is not surprising that the overall activity of the herb is complex.

What are the underlying mechanisms of action?

Ginsenosides are amphiphilic in nature [48], and have the ability to intercalate into the plasma membrane. This leads to changes in membrane fluidity, and thus affects membrane function, eliciting a cellular response. There is evidence to suggest that ginsenosides interact directly with specific membrane proteins. Moreover, like steroid hormones, they are lipid-soluble signaling molecules, which can traverse the plasma membrane and initiate genomic effects. Figure 2 illustrates possible sites

Summary and future work

This commentary discusses ginsenoside effects that may be initiated at the cell membrane, as well as via intracellular protein binding. Consequently, ginsenosides may follow a dual model of action.

One pathway of ginsenoside activity involves binding to membrane receptors that trigger changes in electrolyte transport systems, and activation of signaling pathways. In this regard, differences in lipophilicity between the ginsenosides and the cholesterol content of membrane domains may be

Acknowledgements

This work was supported, in part, by the Tang Family Foundation, and the Clinical Practice Enhancement & Anesthesia Research Foundation.

References (80)

  • H.S. Kim et al.

    Inhibition by ginseng total saponin of the development of morphine reverse tolerance and dopamine receptor supersensitivity in mice

    Gen Pharmacol

    (1995)
  • C. Wakabayashi et al.

    An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells

    Biochem Biophys Res Commun

    (1998)
  • Y.S. Kim et al.

    Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells into granulocytesModulation of protein kinase C isoforms during differentiation by ginsenoside Rh2

    Int J Biochem Cell Biol

    (1998)
  • S.W. Cho et al.

    Ginsenosides activate DNA polymerase from bovine placenta

    Life Sci

    (1995)
  • S. Odashima et al.

    Induction of phenotypic reverse transformation by ginsenosides in cultured Morris hepatoma cells

    Eur J Cancer

    (1979)
  • B. Kenarova et al.

    Immunomodulating activity of ginsenoside Rg1 from Panax ginseng

    Jpn J Pharmacol

    (1990)
  • Y.J. Lee et al.

    Ginsenoside-Rg1, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor

    Mol Cell Endocrinol

    (1997)
  • E. Chung et al.

    Ginsenoside-Rg1 down-regulates glucocorticoid receptor and displays synergistic effects with cAMP

    Steroids

    (1998)
  • K. Kudo et al.

    Properties of ginseng saponin inhibition of catecholamine secretion in bovine adrenal chromaffin cells

    Eur J Pharmacol

    (1998)
  • C.N. Wang et al.

    Activation of human platelet phospholipases C and A2 by various oxygenated triterpenes

    Eur J Pharmacol

    (1994)
  • D.W. Brann et al.

    Emerging diversities in the mechanism of action of steroid hormones

    J Steroid Biochem Mol Biol

    (1995)
  • J.S. Mogil et al.

    Ginsenoside Rf, a trace component of ginseng root, produces antinociception in mice

    Brain Res

    (1998)
  • C.J. Sherr

    G1 phase progressionCycling on cue

    Cell

    (1994)
  • R. Zidovetzki et al.

    The mechanism of activation of protein kinase CA biophysical perspective

    Biochim Biophys Acta

    (1992)
  • I.J. McEwan et al.

    The glucocorticoid receptor functions at multiple steps during transcription initiation by RNA polymerase II

    J Biol Chem

    (1994)
  • F.C. Lee

    Facts about Ginseng, the Elixir of Life

    (1992)
  • K.C. Huang

    The Pharmacology of Chinese Herbs

    (1999)
  • C.S. Yuan et al.

    Gut and brain effects of American ginseng root on brainstem neuronal activities in rats

    Am J Chin Med

    (1998)
  • M. Yoshikawa et al.

    Bioactive saponins and glycosides. XI. Structures of new dammarane-type triterpene oligoglycosides, quinquenosides I, II, III, IV, and V, from American Ginseng, the roots of Panax quinquefolium L

    Chem Pharm Bull (Tokyo)

    (1998)
  • X. Chen

    Cardiovascular protection by ginsenosides and their nitric oxide releasing action

    Clin Exp Pharmacol Physiol

    (1996)
  • D. Tsang et al.

    Ginseng saponinsInfluence on neurotransmitter uptake in rat brain synaptosomes

    Planta Med

    (1985)
  • C.G. Benishin et al.

    Effects of ginsenoside Rb1 on central cholinergic metabolism

    Pharmacology

    (1991)
  • Y. Yamaguchi et al.

    Effects of oral and intraventricular administration of ginsenoside Rg1 on the performance impaired by scopolamine in rats

    Biomed Res

    (1996)
  • E.K. Perry

    The cholinergic hypothesis—ten years on

    Br Med Bull

    (1986)
  • Y. Takemoto et al.

    Potentiation of nerve growth factor-mediated nerve fiber production in organ cultures of chicken embryonic ganglia by ginseng saponinsStructure-activity relationship

    Chem Pharm Bull (Tokyo)

    (1984)
  • T.C. Wen et al.

    Ginseng root prevents learning disability and neuronal loss in gerbils with 5-minute forebrain ischemia

    Acta Neuropathol

    (1996)
  • J.Q. Li et al.

    Effects of age and ginsenoside Rg1 on membrane fluidity of cortical cells in rats

    Acta Pharm Sin

    (1997)
  • X.Y. Jiang et al.

    Mechanism of action of ginsenoside Rb1 in decreasing intracellular Ca2+

    Acta Pharm Sin

    (1996)
  • L. Min et al.

    Effects of ginsenoside Rb1 and Rg1 on synaptosomal free calcium level, ATPase, and calmodulin in rat hippocampus

    Chin Med J (Engl)

    (1995)
  • S.Y. Nah et al.

    A trace component of ginseng that inhibits Ca2+ channels through a pertussis toxin-sensitive G protein

    Proc Natl Acad Sci USA

    (1995)
  • Cited by (0)

    View full text