Pharmacology of ginsenosides: a literature review

The therapeutic potential of ginseng has been studied extensively, and ginsenosides, the active components of ginseng, are shown to be involved in modulating multiple physiological activities. This article will review the structure, systemic transformation and bioavailability of ginsenosides before illustration on how these molecules exert their functions via interactions with steroidal receptors. The multiple biological actions make ginsenosides as important resources for developing new modalities. Yet, low bioavailability of ginsenoside is one of the major hurdles needs to be overcome to advance its use in clinical settings.

[1]  R. Kasai,et al.  Further Studies on Dammarane-Saponins of Ginseng Roots , 1984 .

[2]  Junxia Xie,et al.  Ginsenoside Rg1 protects against 6‐OHDA‐induced neurotoxicity in neuroblastoma SK‐N‐SH cells via IGF‐I receptor and estrogen receptor pathways , 2009, Journal of neurochemistry.

[3]  Xiumei Gao,et al.  A Comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials , 2008, Phytotherapy research : PTR.

[4]  Dong-Hyun Kim,et al.  Transformation of ginsenosides Rb2 and Rc from Panax ginseng by food microorganisms. , 2005, Biological & pharmaceutical bulletin.

[5]  F. Vermeylen,et al.  Effects of population, age, and cultivation methods on ginsenoside content of wild American ginseng (Panax quinquefolium). , 2005, Journal of agricultural and food chemistry.

[6]  D. Kitts,et al.  Structure-function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line. , 2002, Archives of biochemistry and biophysics.

[7]  H. Kwon,et al.  KG-135, enriched with selected ginsenosides, inhibits the proliferation of human prostate cancer cells in culture and inhibits xenograft growth in athymic mice. , 2010, Cancer letters.

[8]  T. Miyase,et al.  Studies on absorption, distribution, excretion and metabolism of ginseng saponins. V. The decomposition products of ginsenoside Rb2 in the large intestine of rats. , 1990, Chemical & pharmaceutical bulletin.

[9]  Zhe Zhou,et al.  Ginsenoside Rg1 protects rat cardiomyocyte from hypoxia/reoxygenation oxidative injury via antioxidant and intracellular calcium homeostasis , 2009, Journal of cellular biochemistry.

[10]  A. Gray,et al.  Antimicrobial activity of pentacyclic triterpenes isolated from African Combretaceae. , 2003, Phytochemistry.

[11]  M. Elliott.  Properties and applications of pyrethroids. , 1976, Environmental health perspectives.

[12]  S. Benetton,et al.  In vitro effect of standardized ginseng extracts and individual ginsenosides on the catalytic activity of human CYP1A1, CYP1A2, and CYP1B1. , 2002, Drug metabolism and disposition: the biological fate of chemicals.

[13]  Eunah Chung,et al.  Ginsenoside-Rg1, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor , 1997, Molecular and Cellular Endocrinology.

[14]  R. Kasai,et al.  Saponins of red ginseng. , 1983 .

[15]  J. H. Park,et al.  Liquid chromatographic determination of less polar ginsenosides in processed ginseng. , 2001, Journal of chromatography. A.

[16]  M. Bernards,et al.  THE ALLELOPATHIC POTENTIAL OF GINSENOSIDES , 2006 .

[17]  Y. Shoyama,et al.  Formation of monoclonal antibody against a major ginseng component, ginsenoside Rg1 and its characterization. Monoclonal antibody for a ginseng saponin , 2000, Cytotechnology.

[18]  J. Menke.  Herbal remedies. , 1997, South Dakota journal of medicine.

[19]  D. Kitts,et al.  Characterizing the mechanism for ginsenoside-induced cytotoxicity in cultured leukemia (THP-1) cells. , 2007, Canadian Journal of Physiology and Pharmacology.

[20]  T. Vanden Hoek,et al.  Antioxidant effects of ginsenoside Re in cardiomyocytes. , 2006, European journal of pharmacology.

[21]  Y. Takino,et al.  [Studies on the pharmacodynamics of ginsenoside-Rg1, -Rb1 and -Rb2 in rats]. , 1994, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[22]  Q. Ping,et al.  Enhancement by adrenaline of ginsenoside Rg1 transport in Caco-2 cells and oral absorption in rats. , 2009, The Journal of pharmacy and pharmacology.

[23]  Xiao-jie Gong,et al.  Isolation, synthesis and structures of cytotoxic ginsenoside derivatives. , 2007, Molecules.

[24]  M. Choo,et al.  Metabolism of ginsenoside R(c) by human intestinal bacteria and its related antiallergic activity. , 2002, Biological & pharmaceutical bulletin.

[25]  Y. Takino,et al.  Studies on the absorption, distribution, excretion and metabolism of ginseng saponins. II. The absorption, distribution and excretion of ginsenoside Rg1 in the rat. , 1983, Chemical & pharmaceutical bulletin.

[26]  Q. Ping,et al.  Active absorption of ginsenoside Rg1 in vitro and in vivo: the role of sodium‐dependent glucose co‐transporter 1 , 2009, The Journal of pharmacy and pharmacology.

[27]  Zimei Wu,et al.  Protective effects of ginsenoside Rb3 on oxygen and glucose deprivation-induced ischemic injury in PC12 cells , 2010, Acta Pharmacologica Sinica.

[28]  S. Benetton,et al.  IN VITRO EFFECT OF STANDARDIZED GINSENG EXTRACTS AND INDIVIDUAL GINSENOSIDES ON THE CATALYTIC ACTIVITY OF HUMAN CYP 1 A 1 , CYP 1 A 2 , AND CYP 1 B 1 , 2002 .

[29]  S. Raja,et al.  Antifeedant activity of some pentacyclic triterpene acids and their fatty acid ester analogues. , 2003, Journal of agricultural and food chemistry.

[30]  Y. Takino,et al.  Studies on the absorption, distribution, excretion and metabolism of ginseng saponins. III. The absorption, distribution and excretion of ginsenoside Rb1 in the rat. , 1983, Chemical & pharmaceutical bulletin.

[31]  J. Sung,et al.  Main ginseng saponin metabolites formed by intestinal bacteria. , 1996, Planta medica.

[32]  Kevin Spelman,et al.  Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators. , 2006, Alternative medicine review : a journal of clinical therapeutic.

[33]  Inderjit,et al.  Allelochemicals: biological control of plant pathogens and diseases , 2006 .

[34]  K. Leung,et al.  Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells , 2009, British journal of pharmacology.

[35]  Man Yang,et al.  Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction , 2009, Chinese journal of integrative medicine.

[36]  Jeong-Hill Park,et al.  Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng , 1996, Archives of pharmacal research.

[37]  O. Tanaka,et al.  STUDIES ON THE CONSTITUENTS OF JAPANESE AND CHINESE CRUDE DRUGS. XI. PANAXADIOL, A SAPOGENIN OF GINSENG ROOTS. , 1963, Chemical & pharmaceutical bulletin.

[38]  O. Tanaka,et al.  Panax ginseng: Relation between Age of Plant and Content of Ginsenosides. , 1984, Planta medica.

[39]  L. W. Cheung,et al.  Ginsenoside Rb1 inhibits tube‐like structure formation of endothelial cells by regulating pigment epithelium‐derived factor through the oestrogen β receptor , 2007, British journal of pharmacology.

[40]  P. Xiao,et al.  Recent advances on ginseng research in China. , 1992, Journal of ethnopharmacology.

[41]  S. Shibata,et al.  Studies on the Constituents of Japanese and Chinese Crude Drugs. VIII. Paeoniflorin, A Glucoside of Chinese Paeony Root. (1). , 1963 .

[42]  Hyeonseok Ko,et al.  Anti-tumor activity of the ginsenoside Rk1 in human hepatocellular carcinoma cells through inhibition of telomerase activity and induction of apoptosis. , 2008, Biological & pharmaceutical bulletin.

[43]  Y. Shoyama,et al.  Formation of monoclonal antibody against a major ginseng component, ginsenoside Rb1 and its characterization , 2004, Cytotechnology.

[44]  H H Fong,et al.  Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. , 2001, Journal of agricultural and food chemistry.

[45]  D. Crosby,et al.  Naturally Occurring Insecticides , 1972 .

[46]  C. Benishin,et al.  Neurotrophic and Neuroprotective Actions of Ginsenosides Rb1 and Rg1 , 2001, Planta medica.

[47]  O. Tanaka,et al.  Studies on the Saponins of Ginseng. I. Structures of Ginsenoside-Ro, -Rb1, -Rb2, -Rc and -Rd , 1974 .

[48]  Shin-Il Kim,et al.  Ginsenoside Rf2, a new dammarane glycoside from Korean red ginseng (Panax ginseng) , 1998, Archives of pharmacal research.

[49]  D. G. Lee,et al.  In vitro candidacidal action of Korean red ginseng saponins against Candida albicans. , 2008, Biological & pharmaceutical bulletin.

[50]  K. Leung,et al.  Non‐genomic effects of ginsenoside‐Re in endothelial cells via glucocorticoid receptor , 2007, FEBS letters.

[51]  N. D. Kim,et al.  Steaming of ginseng at high temperature enhances biological activity. , 2000, Journal of natural products.

[52]  P. Mellon,et al.  Estrogenic activity of herbs commonly used as remedies for menopausal symptoms , 2002, Menopause.

[53]  Structure–activity analysis on ecdysteroids: A structural and quantum chemical approach based on two biological systems , 2006 .

[54]  O. Tanaka,et al.  STUDIES ON SAPONINS AND SAPOGENINS OF GINSENG. THE STRUCTURE OF PANAXATRIOL. , 1965, Tetrahedron letters.

[55]  Q. Ping,et al.  Active absorption of ginsenoside Rg1 in vitro and in vivo: the role of sodium‐dependent glucose co‐transporter 1 , 2009 .

[56]  Y. Lee,et al.  Ginsenoside-Rg5 suppresses cyclin E-dependent protein kinase activity via up-regulating p21Cip/WAF1 and down-regulating cyclin E in SK-HEP-1 cells. , 1997, Anticancer research.

[57]  R. Creelman,et al.  BIOSYNTHESIS AND ACTION OF JASMONATES IN PLANTS. , 1997, Annual review of plant physiology and plant molecular biology.

[58]  Eunhye Kim,et al.  Selective toxicity of ginsenoside Rg3 on multidrug resistant cells by membrane fluidity modulation , 2008, Archives of pharmacal research.

[59]  T. Miyase,et al.  Studies on absorption, distribution, excretion and metabolism of ginseng saponins. VI. The decomposition products of ginsenoside Rb2 in the stomach of rats. , 1990, Chemical & pharmaceutical bulletin.

[60]  F. Fang,et al.  Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress. , 2003, European journal of pharmacology.

[61]  Yuen-Kit Cheng,et al.  Signaling pathway of ginsenoside‐Rg1 leading to nitric oxide production in endothelial cells , 2006, FEBS letters.

[62]  Toshiyuki Harada,et al.  Evaluation of hydrogen bonds of ecdysteroids in the ligand-receptor interactions using a protein modeling system. , 2009, Bioorganic & medicinal chemistry.

[63]  Xiao-ling Fang,et al.  Difference in oral absorption of ginsenoside Rg1 between in vitro and in vivo models , 2006, Acta Pharmacologica Sinica.

[64]  K. Leung,et al.  Ginsenoside-Rg1 Induces Vascular Endothelial Growth Factor Expression through the Glucocorticoid Receptor-related Phosphatidylinositol 3-Kinase/Akt and β-Catenin/T-cell Factor-dependent Pathway in Human Endothelial Cells* , 2006, Journal of Biological Chemistry.

[65]  J. Hendel,et al.  Influence of root age on the concentration of ginsenosides of American ginseng (Panax quinquefolium) , 1996 .

[66]  S. Pyo,et al.  Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3). , 2003, Biochemical pharmacology.

[67]  Youngjoo Lee,et al.  A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[68]  Jeong-Hill Park,et al.  Ginsenoside Rg5, a genuine dammarane glycoside from Korean red ginseng , 1996 .

[69]  S. Xu,et al.  Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. , 2000, Life sciences.

[70]  Hitoshi Kaneko,et al.  Proof of the mysterious efficacy of ginseng: basic and clinical trials: clinical effects of medical ginseng, korean red ginseng: specifically, its anti-stress action for prevention of disease. , 2004, Journal of pharmacological sciences.

[71]  M. Yoshikawa,et al.  Saponins of plants of Panax species collected in Central Nepal, and their chemotaxonomical significance. III. , 1986, Chemical & pharmaceutical bulletin.

[72]  B. Baum,et al.  Phytochemistry of wild populations of Panax quinquefolius L. (North American ginseng). , 2003, Journal of agricultural and food chemistry.

[73]  S. Nah,et al.  Effects of ginsenoside Rg2 on the 5-HT3A receptor-mediated ion current in Xenopus oocytes. , 2003, Molecules and cells.

[74]  S. Nah,et al.  Effects of ginsenosides, active components of ginseng, on nicotinic acetylcholine receptors expressed in Xenopus oocytes. , 2002, European journal of pharmacology.

[75]  D. Sohn,et al.  A dammarane glycoside from Korean red ginseng , 1997 .

[76]  Ying Xin,et al.  Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer. , 2007, Chinese medical journal.

[77]  Dong-Hyun Kim,et al.  Transformation of ginseng saponins to ginsenoside rh2 by acids and human intestinal bacteria and biological activities of their transformants , 2004, Archives of pharmacal research.

[78]  Ling Yang,et al.  Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[79]  B. McEwen,et al.  Ginsenoside Rb1 regulates ChAT, NGF and trkA mRNA expression in the rat brain. , 1997, Brain research. Molecular brain research.

[80]  R. J. Aerts,et al.  Feeding Deterrence and Toxicity of Neem Triterpenoids , 1997, Journal of Chemical Ecology.

[81]  Y. Surh,et al.  KG‐135 Inhibits COX‐2 Expression by Blocking the Activation of JNK and AP‐1 in Phorbol Ester–Stimulated Human Breast Epithelial Cells , 2007, Annals of the New York Academy of Sciences.

[82]  M. McIntosh,et al.  Ginsenoside content and variation among and within American ginseng (Panax quinquefolius L.) populations. , 2006, Phytochemistry.

[83]  Xiao-ling Fang,et al.  Oral Absorption of Ginsenoside Rb1 using in vitro and in vivo Models , 2006, Planta medica.

[84]  Junxia Xie,et al.  Ginsenoside Rg1 protects against 6-OHDA-induced toxicity in MES23.5 cells via Akt and ERK signaling pathways. , 2010, Journal of ethnopharmacology.

[85]  Z. Z. Lu,et al.  EVALUATION OF CONSISTENCY OF STANDARDIZED ASIAN GINSENG PRODUCTS IN THE GINSENG EVALUATION PROGRAM , 2001 .

[86]  Jianqing Gao,et al.  Evaluation of intestinal absorption of ginsenoside Rg1 incorporated in microemulison using parallel artificial membrane permeability assay. , 2009, Biological & pharmaceutical bulletin.

[87]  M. Bonfill,et al.  Elicitation of different Panax ginseng transformed root phenotypes for an improved ginsenoside production , 2003 .

[88]  Y. Shoyama,et al.  Detection and quantification of ginsenoside Re in ginseng samples by a chromatographic immunostaining method using monoclonal antibody against ginsenoside Re. , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[89]  Seikwan Oh,et al.  Ginsenoside Rc and Rg1 Differentially Modulate NMDA Receptor Subunit mRNA Levels after Intracerebroventricular Infusion in Rats , 2000, Neurochemical Research.

[90]  Y. Ye,et al.  Ginsenoside Rd from Panax notoginseng Is Cytotoxic towards HeLa Cancer Cells and Induces Apoptosis , 2006, Chemistry & biodiversity.

[91]  Yeong Shik Kim,et al.  Generation and characterization of monoclonal antibody to ginsenoside rg3. , 2009, Biological & pharmaceutical bulletin.

[92]  Herley Casanova,et al.  Insecticide formulations based on nicotine oleate stabilized by sodium caseinate. , 2002, Journal of agricultural and food chemistry.

[93]  B C Eliason,et al.  Dietary Supplement Users: Demographics, Product Use, and Medical System Interaction , 1997, The Journal of the American Board of Family Medicine.

[94]  Jonghoon J. Kim.  Protective Effects of Ginsenoside Rg3 , 2009 .

[95]  S. Rydell,et al.  Prevalence of use of herbal products by adults in the Minneapolis/St Paul, Minn, metropolitan area. , 2001, Mayo Clinic proceedings.

[96]  R. V. van Breemen,et al.  Use of high-performance liquid chromatography-tandem mass spectrometry to distinguish Panax ginseng C. A. Meyer (Asian ginseng) and Panax quinquefolius L. (North American ginseng). , 2000, Analytical chemistry.

[97]  Y. Hwang,et al.  Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells. , 2010, Toxicology and applied pharmacology.

[98]  C. Yuan,et al.  Ginseng pharmacology: multiple constituents and multiple actions. , 1999, Biochemical pharmacology.

[99]  R. Kasai,et al.  Further Studies on Dammarane-Saponins of Sanchi-Ginseng , 1983 .

[100]  K. Kobashi,et al.  Drug Metabolism: Intestinal Bacterial Hydrolysis is Required for the Appearance of Compound K in Rat Plasma after Oral Administration of Ginsenoside Rb1 from Panax ginseng , 1998 .

[101]  Y. Benno,et al.  Role of Human Intestinal Prevotella oris in Hydrolyzing Ginseng Saponins , 1997, Planta medica.

[102]  M. Nagai,et al.  STUDIES ON THE CONSTITUENTS OF JAPANESE AND CHINESE CRUDE DRUGS. XII. PANAXADIOL, A SAPOGENIN OF GINSENG ROOTS. , 1963, Chemical & pharmaceutical bulletin.

[103]  Xiao-ling Fang,et al.  Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. , 2003, Journal of ethnopharmacology.

[104]  M. Bernards,et al.  Ginsenosides as host resistance factors in American ginseng (Panax quinquefolius) , 2002 .

[105]  Guang-Ji Wang,et al.  Uptake and metabolism of ginsenoside Rh2 and its aglycon protopanaxadiol by Caco-2 cells. , 2005, Biological & pharmaceutical bulletin.

[106]  N. Baek,et al.  Ginsenoside Rh4, a genuine dammarane glycoside from Korean red ginseng. , 1996, Planta medica.

[107]  R. Bonneau,et al.  Sulfur ylides generated from the reaction of arylchlorocarbenes with trimethylenesulfide: determination of rate parameters by laser flash photolysis , 2001 .

[108]  D. Choi,et al.  Analysis of transcripts in methyl jasmonate-treated ginseng hairy roots to identify genes involved in the biosynthesis of ginsenosides and other secondary metabolites , 2004, Plant Cell Reports.

[109]  Shiladitya Sengupta,et al.  Modulating Angiogenesis: The Yin and the Yang in Ginseng , 2004, Circulation.

[110]  Y. Umezawa,et al.  Ginsenoside Re, a Main Phytosterol of Panax ginseng, Activates Cardiac Potassium Channels via a Nongenomic Pathway of Sex Hormones , 2006, Molecular Pharmacology.