Download PDF
Planta Med 2018; 84(03): 139-152
DOI: 10.1055/s-0043-124087
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Ginsenoside Rh1: A Systematic Review of Its Pharmacological Properties

Dao Ngoc Hien Tam   *
1   Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
,
Duy Hieu Truong   *
2   Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
,
Thi Thanh Hoa Nguyen
3   Huy Cuong Pharmaceutical Company, Ho Chi Minh City, Vietnam
,
Le Nhat Quynh
4   Hue University of Medicine and Pharmacy, Hue, Vietnam
,
Linh Tran
2   Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
,
Hong Duong Nguyen
5   Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan
,
Bahaa eldin Shamandy
6   Faculty of Medicine, Aswan University, Aswan, Egypt
,
Thi Minh Huong Le
7   Tien Giang General Hospital, Tien Giang, Vietnam
,
Dang Khoa Tran
8   Vo Truong Toan University, Hau Giang, Vietnam
,
Dina Sayed
9   Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt
,
Van Vinh Vu
10   School of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea
,
Shusaku Mizukami
11   Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
,
Kenji Hirayama
11   Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
,
Nguyen Tien Huy
12   Evidence Based Medicine Research Group & Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam
13   Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Leading Graduate School Program, and Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
› Author Affiliations
Further Information

Publication History

received 05 June 2017
revised 15 November 2017

accepted 24 November 2017

Publication Date:
12 January 2018 (online)

   Permissions and Reprints

Abstract

Ginsenoside Rh1 is one of major bioactive compounds extracted from red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. The objective of this study was to review the pharmacological effects of ginsenoside Rh1 in a systematic manner. We performed searches on eight electronic databases including MEDLINE (Pubmed), Scopus, Google Scholar, POPLINE, Global Health Library, Virtual Health Library, the System for Information on Grey Literature in Europe, and the New York Academy of Medicine Grey Literature Report to select the original research publications reporting the biological and pharmacological effects of ginsenoside Rh1 from in vitro and in vivo studies regardless of publication language and study design. Upon applying the inclusion and exclusion criteria, we included a total of 57 studies for our systemic review. Ginsenoside Rh1 exhibited the potent characteristics of anti-inflammatory, antioxidant, immunomodulatory effects, and positive effects on the nervous system. The cytotoxic effects of ginsenoside Rh1 were dependent on different types of cell lines. Other pharmacological effects including estrogenic, enzymatic, anti-microorganism activities, and cardiovascular effects have been mentioned, but the results were considerably diverged. A higher quality of evidence on clinical trial studies is highly recommended to confirm the consistent efficacy of ginsenoside Rh1.

Key words

ginsenoside Rh1 - Panax ginseng - Araliaceae - in vitro - in vivo

* Dao Ngoc Hien Tam and Duy Hieu Truong contributed equally to this work.


Supporting Information

 

  • References

  • 1 Kee CH. The pharmacology of Chinese herbs. CRC Press 1999; 200: 308
    PubMedGoogle Scholar
  • 2 Xiang YZ, Shang HC, Gao XM, Zhang BL. A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials. Phytother Res 2008; 22: 851-858
    CrossrefPubMedGoogle Scholar
  • 3 Baeg IH, So SH. The world ginseng market and the ginseng (Korea). J Ginseng Res 2013; 37: 1-7
    CrossrefPubMedGoogle Scholar
  • 4 Accuray Research LLP. Global Ginseng Market Analysis & Trends – Industry Forecast to 2025. Available at. https://www.researchandmarkets.com/reports/4332998 Accessed November 03, 2017
    PubMedGoogle Scholar
  • 5 Chen JK, Chen TT, Crampton L. Chinese Medical Herbology and Pharmacology. City of Industry: Art of Medicine Press; 2004
    Google Scholar
  • 6 Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, Kwak YS. Characterization of Korean Red Ginseng (Panax ginseng Meyer): History, preparation method, and chemical composition. J Ginseng Res 2015; 39: 384-391
    CrossrefPubMedGoogle Scholar
  • 7 Park J. Recent studies on the chemical constituents of Korean ginseng (Panax ginseng CA Meyer). Korean J Ginseng Sci 1996; 20: 389-415
    PubMedGoogle Scholar
  • 8 Chung HS, Hwang I, Oh KJ, Lee MN, Park K. The effect of Korean red ginseng on sexual function in premenopausal women: placebo-controlled, double-blind, crossover clinical trial. Evid Based Complement Alternat Med 2015; 2015: 91358
    PubMedGoogle Scholar
  • 9 Ganesan P, Ko HM, Kim IS, Choi DK. Recent trends of nano bioactive compounds from ginseng for its possible preventive role in chronic disease models. RSC Adv 2015; 5: 98634-98642
    CrossrefPubMedGoogle Scholar
  • 10 Lee SH, Oh M, Park J, Jang SY, Cheong SH, Lee H, Moon SH. Antioxidant and anti-inflammatory activities of the ethanolic extract of fermented red ginseng marc. Food Sci Biotechnol 2015; 24: 651-657
    CrossrefPubMedGoogle Scholar
  • 11 Shergis JL, Zhang AL, Zhou W, Xue CC. Panax ginseng in randomised controlled trials: a systematic review. Phytother Res 2013; 27: 949-965
    CrossrefPubMedGoogle Scholar
  • 12 Nag SA, Qin J, Wang W, Wang MH, Wang H, Zhang R. Ginsenosides as anticancer agents: in vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action. Front Pharmacol 2012; 3: 25
    PubMedGoogle Scholar
  • 13 Shin BK, Kwon SW, Park JH. Chemical diversity of ginseng saponins from Panax ginseng . J Ginseng Res 2015; 39: 287-298
    CrossrefPubMedGoogle Scholar
  • 14 Court WE. Ginseng, the Genus Panax. Amsterdam: CRC Press; 2000
    Google Scholar
  • 15 Kitagawa I, Yoshiawa M, Yoshihara M, Hayashi T, Taniyama T. Chemical studies on crude drug precession 1. On the constituents of ginseng radix rubra (1). Yakugaku Zasshi 1983; 103: 612-622
    CrossrefPubMedGoogle Scholar
  • 16 Lee S, Lee YH, Park JM, Bai DH, Jang JK, Park YS. Bioconversion of ginsenosides from red ginseng extract using Candida allociferrii JNO301 isolated from Meju . Mycobiology 2014; 42: 368-375
    CrossrefPubMedGoogle Scholar
  • 17 Han BH, Park MH, Han Y, Woo L, Sankawa U, Yahara S, Tanaka O. Degradation of ginseng saponins under mild acidic conditions. Planta Med 1982; 44: 146-149
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 2001; 16: S28-S37
    CrossrefPubMedGoogle Scholar
  • 19 Tawab MA, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M. Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos 2003; 31: 1065-1071
    CrossrefPubMedGoogle Scholar
  • 20 Li XF, Lui CN, Jiang ZH, Ken YK. Neuroprotective effects of ginsenosides Rh 1 and Rg 2 on neuronal cells. Chin Med 2011; 6: 19
    CrossrefPubMedGoogle Scholar
  • 21 Choi YJ, Yoon JH, Cha SW, Lee SG. Ginsenoside Rh1 inhibits the invasion and migration of THP-1 acute monocytic leukemia cells via inactivation of the MAPK signaling pathway. Fitoterapia 2011; 82: 911-919
    CrossrefPubMedGoogle Scholar
  • 22 Li J, Du J, Liu D, Cheng B, Fang F, Weng L, Wang C, Ling C. Ginsenoside Rh1 potentiates dexamethasoneʼs anti-inflammatory effects for chronic inflammatory disease by reversing dexamethasone-induced resistance. Arthritis Res Ther 2014; 16: 1
    CrossrefPubMedGoogle Scholar
  • 23 Yoon JH, Choi YJ, Lee SG. Ginsenoside Rh1 suppresses matrix metalloproteinase-1 expression through inhibition of activator protein-1 and mitogen-activated protein kinase signaling pathway in human hepatocellular carcinoma cells. Eur J Pharmacol 2012; 679: 24-33
    CrossrefPubMedGoogle Scholar
  • 24 Kim YS, Kim JJ, Cho KH, Jung WS, Moon SK, Park EK, Kim DH. Biotransformation of ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, hesperidin, poncirin, glycyrrhizin, and baicalin by human fecal microflora and its relation to cytotoxicity against tumor cells. J Microbiol Biotechnol 2008; 18: 1109-1114
    PubMedGoogle Scholar
  • 25 Wang Y, Hao Y, Lou J, Ma H, Qiu Q. Effect of ginsenoside Rg1 and Rh1 on the anti-tumor activity of dendritic cell. Chin J Pathophysiol 2004; 20: 1759-1764
    PubMedGoogle Scholar
  • 26 Byun BH, Shin I, Yoon YS, Kim SI, Joe CO. Modulation of protein kinase C activity in NIH 3T3 cells by plant glycosides from Panax ginseng . Planta Med 1997; 63: 389-392
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Popovich DG, Kitts DD. Structure–function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line. Arch Biochem Biophys 2002; 406: 1-8
    CrossrefPubMedGoogle Scholar
  • 28 Quan K, Liu Q, Wan JY, Zhao YJ, Guo RZ, Alolga RN, Li P, Qi LW. Rapid preparation of rare ginsenosides by acid transformation and their structure-activity relationships against cancer cells. Sci Rep 2015; 5: 8598
    CrossrefPubMedGoogle Scholar
  • 29 Odashima S, Ohta T, Kohno H, Matsuda T, Kitagawa I, Abe H, Arichi S. Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides. Cancer Res 1985; 45: 2781-2784
    PubMedGoogle Scholar
  • 30 Jung JS, Ahn JH, Le TK, Kim DH, Kim HS. Protopanaxatriol ginsenoside Rh1 inhibits the expression of matrix metalloproteinases and the in vitro invasion/migration of human astroglioma cells. Neurochem Int 2013; 63: 80-86
    CrossrefPubMedGoogle Scholar
  • 31 Park MT, Cha HJ, Jeong JW, Lee HY, Kim SI, Baek NI, Kim O, Kim KW. Anti-invasive Activity of Ginsenoside Rh~ 1 and Rh~ 2 in the HT1080 Cells. J Ginseng Res 1998; 22: 216-221
    PubMedGoogle Scholar
  • 32 Lee YN, Lee HY, Chung HY, Kim SI, Lee SK, Park BC, Kim KW. In vitro induction of differentiation by ginsenosides in F9 teratocarcinoma cells. Eur J Cancer 1996; 32: 1420-1428
    CrossrefPubMedGoogle Scholar
  • 33 Lee YN, Lee HY, Lee YM, Chung HY, Kim SI, Lee SK, Park BC, Kim KW. Involvement of glucocorticoid receptor in the induction of differentiation by ginsenosides in F9 teratocarcinoma cells. J Steroid Biochem Mol Biol 1998; 67: 105-111
    CrossrefPubMedGoogle Scholar
  • 34 He F, Ding Y, Liang C, Song SB, Dou DQ, Song GY, Kim YH. Antitumor effects of dammarane-type saponins from steamed Notoginseng. Pharmacogn Mag 2014; 10: 314
    CrossrefPubMedGoogle Scholar
  • 35 Xing L, Jiang M, Dong L, Gao J, Hou Y, Bai G, Luo G. Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression. J Ethnopharmacol 2013; 148: 239-245
    CrossrefPubMedGoogle Scholar
  • 36 Jung JS, Shin JA, Park EM, Lee JE, Kang YS, Min SW, Kim DH, Hyun JW, Shin CY, Kim HS. Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide-stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase-1 expression. J Neurochem 2010; 115: 1668-1680
    CrossrefPubMedGoogle Scholar
  • 37 Jung JS, Kim DH, Kim HS. Ginsenoside Rh1 suppresses inducible nitric oxide synthase gene expression in IFN-gamma-stimulated microglia via modulation of JAK/STAT and ERK signaling pathways. Biochem Biophys Res Commun 2010; 397: 323-328
    CrossrefPubMedGoogle Scholar
  • 38 Lee SY, Jeong JJ, Eun SH, Kim DH. Anti-inflammatory effects of ginsenoside Rg1 and its metabolites ginsenoside Rh1 and 20 (S)-protopanaxatriol in mice with TNBS-induced colitis. Eur J Pharmacol 2015; 762: 333-343
    CrossrefPubMedGoogle Scholar
  • 39 Park EK, Choo MK, Han MJ, Kim DH. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol 2004; 133: 113-120
    CrossrefPubMedGoogle Scholar
  • 40 Lee DC, Yang CL, Chik SC, Li JC, Rong JH, Chan GC, Lau AS. Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells. J Transl Med 2009; 7: 34
    CrossrefPubMedGoogle Scholar
  • 41 Wang Y, Wang BX, Liu TH, Minami M, Nagata T, Ikejima T. Metabolism of ginsenoside Rg1 by intestinal bacteria. II. Immunological activity of ginsenoside Rg1 and Rh1. Acta Pharmacol Sin 2000; 21: 792-796
    PubMedGoogle Scholar
  • 42 Gu W, Kim KA, Kim DH. Ginsenoside Rh1 ameliorates high fat diet-induced obesity in mice by inhibiting adipocyte differentiation. Biol Pharm Bull 2013; 36: 102-107
    PubMedGoogle Scholar
  • 43 Park YC, Lee CH, Kang HS, Kim KW, Chung HT, Kim HD. Ginsenoside-Rh1 and Rh2 inhibit the induction of nitric oxide synthesis in murine peritoneal macrophages. Biochem Mol Biol Int 1996; 40: 751-757
    PubMedGoogle Scholar
  • 44 Zheng H, Jeong Y, Song J, Ji GE. Oral administration of ginsenoside Rh1 inhibits the development of atopic dermatitis-like skin lesions induced by oxazolone in hairless mice. Int Immunopharmacol 2011; 11: 511-518
    CrossrefPubMedGoogle Scholar
  • 45 Jang SE, Jung IH, Joh EH, Han MJ, Kim DH. Antibiotics attenuate anti-scratching behavioral effect of ginsenoside Re in mice. J Ethnopharmacol 2012; 142: 105-112
    CrossrefPubMedGoogle Scholar
  • 46 Feng Y, Wang C, Cheng S, Wang X, Meng X, Li L, Du J, Liu Q, Guo Y, Meng Y. Ginsenoside Rh1 improves the effect of dexamethasone on autoantibodies production and lymphoproliferation in MRL/lpr mice. Evid Based Complement Alternat Med 2015; 2015: 727650
    PubMedGoogle Scholar
  • 47 Sun H, Yang Z, Ye Y. Structure and biological activity of protopanaxatriol-type saponins from the roots of Panax notoginseng . Int Immunopharmacol 2006; 6: 14-25
    CrossrefPubMedGoogle Scholar
  • 48 Kim MS, Kwon B, Park MS, Ji GE. Isolation of ginsenoside Rh1 and compound K from fermented ginseng and efficacy assessment on systemic anaphylactic shock. Food Sci Biotechnol 2008; 17: 805-808
    PubMedGoogle Scholar
  • 49 Shin YW, Bae EA, Kim SS, Lee YC, Lee BY, Kim DH. The effects of ginsenoside Re and its metabolite, ginsenoside Rh1, on 12-O-tetradecanoylphorbol 13-acetate-and oxazolone-induced mouse dermatitis models. Planta Med 2006; 72: 376-378
    Article in Thieme ConnectPubMedGoogle Scholar
  • 50 Jung JS, Shin JA, Park EM, Lee JE, Kang YS, Min SW, Kim DH, Hyun JW, Shin CY, Kim HS. Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide-stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase-1 expression. J Neurochem 2010; 115: 1668-1680
    CrossrefPubMedGoogle Scholar
  • 51 Jiang Y, Liu W, Wang XM, Zhong GG, Zhang WJ, Chen L, Zhan S, Qi H, Zhao CY, Ma XY, Yang SJ, Li H. Calcium channel blockade and anti-free-radical actions of panaxatriol saponins in cultured myocardiocytes. Acta Pharmacol Sin 1996; 17: 138-141
    PubMedGoogle Scholar
  • 52 Chae S, Kang KA, Youn U, Park JS, Hyun JW. A comparative study of the potential antioxidant activities of ginsenosides. J Food Biochem 2010; 34: 31-43
    PubMedGoogle Scholar
  • 53 He W, Liu G, Chen X, Lu J, Abe H, Huang K, Manabe M, Kodama H. Inhibitory effects of ginsenosides from the root of Panax ginseng on stimulus-induced superoxide generation, tyrosyl or serine/threonine phosphorylation, and translocation of cytosolic compounds to plasma membrane in human neutrophils. J Agric Food Chem 2008; 56: 1921-1927
    CrossrefPubMedGoogle Scholar
  • 54 Liu ZQ, Luo XY, Sun YX, Chen YP, Wang ZC. Can ginsenosides protect human erythrocytes against free-radical-induced hemolysis?. Biochim Biophys Acta 2002; 1572: 58-66
    CrossrefPubMedGoogle Scholar
  • 55 Liu ZQ, Luo XY, Liu GZ, Chen YP, Wang ZC, Sun YX. In vitro study of the relationship between the structure of ginsenoside and its antioxidative or prooxidative activity in free radical induced hemolysis of human erythrocytes. J Agric Food Chem 2003; 51: 2555-2558
    CrossrefPubMedGoogle Scholar
  • 56 Li GX, Liu ZQ. The protective effects of ginsenosides on human erythrocytes against hemin-induced hemolysis. J Agric Food Chem 2008; 56: 1921-1927
    CrossrefPubMedGoogle Scholar
  • 57 Samukawa K, Suzuki Y, Ohkubo N, Aoto M, Sakanaka M, Mitsuda N. Protective effect of ginsenosides Rg2 and Rh1 on oxidation-induced impairment of erythrocyte membrane properties. Biorheology 2008; 45: 689-700
    CrossrefPubMedGoogle Scholar
  • 58 Wang YZ, Chen J, Chu SF, Wang YS, Wang XY, Chen NH, Zhang JT. Improvement of memory in mice and increase of hippocampal excitability in rats by ginsenoside Rg1′s metabolites ginsenoside Rh1 and protopanaxatriol. J Pharmacol Sci 2009; 109: 504-510
    CrossrefPubMedGoogle Scholar
  • 59 Hou J, Xue J, Lee M, Yu J, Sung C. Long-term administration of ginsenoside Rh1 enhances learning and memory by promoting cell survival in the mouse hippocampus. Int J Mol Med 2014; 33: 234-240
    CrossrefPubMedGoogle Scholar
  • 60 Lee SH, Yang SC, Park JK, Jung MW, Lee CJ. Reduction of electrically evoked neural activity by ginseng saponin in rat hippocampal slices. Biol Pharm Bull 2000; 23: 411-414
    CrossrefPubMedGoogle Scholar
  • 61 Dong S, Kiyama R. Characterisation of oestrogenic activity of ginsenosides in MCF-7 cells using a customised DNA microarray. Food Chem 2009; 113: 672-678
    CrossrefPubMedGoogle Scholar
  • 62 Lee Y, Jin Y, Lim W, Ji S, Choi S, Jang S, Lee S. A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells. J Steroid Biochem Mol Biol 2003; 84: 463-468
    CrossrefPubMedGoogle Scholar
  • 63 Bae EA, Shin JE, Kim DH. Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect. Biol Pharm Bull 2005; 28: 1903-1908
    CrossrefPubMedGoogle Scholar
  • 64 Liu Y, Ma H, Zhang JW, Deng MC, Yang L. Influence of ginsenoside Rh1 and F1 on human cytochrome p450 enzymes. Planta Med 2006; 72: 126-131
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Etheridge AS, Black SR, Patel PR, So J, Mathews JM. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents. Planta Med 2007; 73: 731-741
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Li X, Hu J, Wang B, Sheng L, Liu Z, Yang S, Li Y. Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp. Toxicol Appl Pharmacol 2014; 275: 163-175
    CrossrefPubMedGoogle Scholar
  • 67 Masuno H, Kitao H, Okuda H. Ginsenosides increase secretion of lipoprotein lipase by 3T3-L1 adipocytes. Biosci Biotechnol Biochem 1996; 60: 1962-1965
    CrossrefPubMedGoogle Scholar
  • 68 Bae EA, Han MJ, Baek NI, Kim DH. In vitro anti-Helicobacter pylori activity of panaxytriol isolated from ginseng. Arch Pharm Res 2001; 24: 297-299
    CrossrefPubMedGoogle Scholar
  • 69 Jeong JJ, Kim B, Kim DH. Ginsenoside Rh1 eliminates the cytoprotective phenotype of human immunodeficiency virus type 1-transduced human macrophages by inhibiting the phosphorylation of pyruvate dehydrogenase lipoamide kinase isozyme 1. Biol Pharm Bull 2013; 36: 1088-1094
    CrossrefPubMedGoogle Scholar
  • 70 Gai Y, Ma Z, Yu X, Qu S, Sui D. Effect of ginsenoside Rh1 on myocardial injury and heart function in isoproterenol-induced cardiotoxicity in rats. Toxicol Mech Methods 2012; 22: 584-591
    PubMedGoogle Scholar
  • 71 Lee ES, Choi JS, Kim MS, You HJ, Ji GE, Kang YH. Ginsenoside metabolite compound K differentially antagonizing tumor necrosis factor-alpha-induced monocyte-endothelial trafficking. Chem Biol Interact 2011; 194: 13-22
    CrossrefPubMedGoogle Scholar
  • 72 Lee JH, Ahn JY, Shin TJ, Choi SH, Lee BH, Hwang SH, Kang J, Kim HJ, Park CW, Nah SY. Effects of minor ginsenosides, ginsenoside metabolites, and ginsenoside epimers on the growth of Caenorhabditis elegans . J Ginseng Res 2011; 35: 375-383
    CrossrefPubMedGoogle Scholar
  • 73 Tachikawa E, Kudo K, Kashimoto T, Takahashi E. Ginseng saponins reduce acetylcholine-evoked Na+ influx and catecholamine secretion in bovine adrenal chromaffin cells. J Pharmacol Exp Ther 1995; 273: 629-636
    PubMedGoogle Scholar
  • 74 Siddiqi MH, Siddiqi MZ, Ahn S, Kim YJ, Yang DC. Ginsenoside Rh1 induces mouse osteoblast growth and differentiation through the bone morphogenetic protein 2/runt-related gene 2 signalling pathway. J Pharm Pharmacol 2014; 66: 1763-1773
    CrossrefPubMedGoogle Scholar
  • 75 Matsuda H, Kubo M, Tani T, Arichi S, Kitagawa I. Pharmacological study on Panax ginseng CA Meyer V.: Effects of red ginseng on the experimental disseminated intravascular coagulation (4). On ginsenoside-Rg3, Rh1 and Rh2. Jpn J Pharmacol 1985; 39: 123-125
    CrossrefPubMedGoogle Scholar
  • 76 Zhang YW, Dou DQ, Zhang L, Chen YJ, Yao XS. Effects of ginsenosides from Panax ginseng on cell-to-cell communication function mediated by gap junctions. Planta Med 2001; 67: 417-422
    Article in Thieme ConnectPubMedGoogle Scholar
  • 77 Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLEʼs risk of bias tool for animal studies. BMC Med Res Methodol 2014; 14: 43
    CrossrefPubMedGoogle Scholar
  • 78 Buettner C, Yeh GY, Phillips RS, Mittleman MA, Kaptchuk TJ. Systematic review of the effects of ginseng on cardiovascular risk factors. Ann Pharmacother 2006; 40: 83-95
    CrossrefPubMedGoogle Scholar
  • 79 Hur MH, Lee MS, Yang HJ, Kim C, Bae IL, Ernst E. Ginseng for reducing the blood pressure in patients with hypertension: a systematic review and meta-analysis. J Ginseng Res 2010; 34: 342-347
    CrossrefPubMedGoogle Scholar
  • 80 Lee MS, Yang EJ, Kim JI, Ernst E. Ginseng for cognitive function in Alzheimerʼs disease: a systematic review. J Alzheimers Dis 2009; 18: 339-344
    CrossrefPubMedGoogle Scholar
  • 81 Geng J, Dong J, Ni H, Lee MS, Wu T, Jiang K, Wang G, Zhou AL, Malouf R. Ginseng for cognition. CDSR 2010; 12: 007769
    PubMedGoogle Scholar
  • 82 Siraj FM, Natarajan S, Kim YJ, Chun Yang D. In silico screening of ginsenoside Rh1 with PPARγ and in vitro analysis on 3T3-L1 cell line. Mol Simul 2015; 41: 1219-1226
    CrossrefPubMedGoogle Scholar
  • 83 Liu J, Shiono J, Shimizu K, Yu H, Zhang C, Jin F, Kondo R. 20(R)-ginsenoside Rh2, not 20(S), is a selective osteoclastgenesis inhibitor without any cytotoxicity. Bioorg Med Chem Lett 2009; 19: 3320-3323
    CrossrefPubMedGoogle Scholar
  • 84 Kang DI, Lee JY, Yang JY, Jeong SM, Lee JH, Nah SY, Kim Y. Evidence that the tertiary structure of 20(S)-ginsenoside Rg 3 with tight hydrophobic packing near the chiral center is important for Na+ channel regulation. Biochem Biophys Res Commun 2005; 333: 1194-1201
    CrossrefPubMedGoogle Scholar
  • 85 Lai L, Hao H, Liu Y, Zheng C, Wang Q, Wang G, Chen X. Characterization of pharmacokinetic profiles and metabolic pathways of 20(S)-ginsenoside Rh1 in vivo and in vitro . Planta Med 2009; 75: 797-802
    Article in Thieme ConnectPubMedGoogle Scholar
  • 86 Han M, Sha X, Wu Y, Fang X. Oral absorption of ginsenoside Rb1 using in vitro and in vivo models. Planta Med 2006; 72: 398-404
    Article in Thieme ConnectPubMedGoogle Scholar
  • 87 Yang F, Zhou J, Hu X, Yu SK, Liu C, Pan R, Chang Q, Liu X, Liao Y. Preparation and evaluation of self-microemulsions for improved bioavailability of ginsenoside-Rh1 and Rh2. Drug Deliv Transl Res 2017; 7: 731-737
    CrossrefPubMedGoogle Scholar