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Interactions of ginseng with therapeutic drugs

Abstract

Ginseng is the most frequently used herbal medicine for immune system stimulation and as an adjuvant with prescribed drugs owing to its numerous pharmacologic activities. It is important to investigate the beneficial effects and interaction of ginseng with therapeutic drugs. This review comprehensively discusses drug metabolizing enzyme- and transporter-mediated ginseng–drug interaction by analyzing in vitro and clinical results with a focus on ginsenoside, a pharmacologically active marker of ginseng. Impact of ginseng therapy or ginseng combination therapy on diabetic patients and of ginseng interaction with antiplatelets and anticoagulants were evaluated based on ginseng origin and ginsenoside content. Daily administration of Korean red ginseng (0.5–3 g extract; dried ginseng > 60%) did not cause significant herb–drug interaction with drug metabolizing enzymes and transporters. Among various therapeutic drugs administered in combination with ginseng, adjuvant chemotherapy, comprising ginseng (1–3 g extract) and anticancer drugs, was effective for reducing cancer-related fatigue and improving the quality of life and emotional scores. Limited information regarding ginsenoside content in each ginseng product and plasma ginsenoside concentration among patients necessitates standardization of ginseng product and establishment of pharmacokinetic–pharmacodynamic correlation to further understand beneficial effects of ginseng–therapeutic drug interactions in future clinical studies.

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References

  • Agbabiaka TB, Wider B, Watson LK, Goodman C (2017) Concurrent use of prescription drugs and herbal medicinal products in older adults: a systematic review. Drugs Aging 34:891–905

    PubMed  PubMed Central  Article  Google Scholar 

  • Arring NM, Millstine D, Marks LA, Nail LM (2018) Ginseng as a treatment for fatigue: a systematic review. J Altern Complement Med 24:624–633

    PubMed  Article  Google Scholar 

  • Awang DVC, Li MZC (2008) The pharmacologically active constituents of white and red ginseng root. Herbalgram 80:38–49

    Google Scholar 

  • Bang H, Kwak JH, Ahn HY, Shin DY, Lee JH (2014) Korean red ginseng improves glucose control in subjects with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed type 2 diabetes mellitus. J Med Food 17:128–134

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Barton DL, Liu H, Dakhil SR, Linquist B, Sloan JA, Nichols CR, Mcginn TW, Stella PJ, Seeger GR, Sood A, Loprinzi CL (2013) Wisconsin ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst 105:1230–1238

    PubMed  PubMed Central  Article  Google Scholar 

  • Ben-Eltriki M, Hassona M, Meckling G, Adomat H, Deb S, Tomlinson Guns ES (2019) Pharmacokinetic interaction of calcitriol with 20(S)-protopanaxadiol in mice: determined by LC/MS analysis. Eur J Pharm Sci 130:173–180

    CAS  PubMed  Article  Google Scholar 

  • Bilgi N, Bell K, Ananthakrishnan AN, Atallah E (2010) Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother 44:926–928

    PubMed  Article  PubMed Central  Google Scholar 

  • Bogacz AK, Dziekan KP, Górska-Paukszta M, Kowalska A, Mikołajczak P, Ożarowski M, Czerny B (2016) Impact of Panax ginseng and ginkgo biloba extracts on expression level of transcriptional factors and xenobiotic-metabolizing cytochrome p450 enzymes. Herba Polonica 62:42–54

    Article  Google Scholar 

  • Chang YD, Smith J, Portman D, Kim R, Oberoi-Jassal R, Rajasekhara S, Davis M (2018) Single institute experience with methylphenidate and American ginseng in cancer-related fatigue. Am J Hosp Palliat Care 35:144–150

    PubMed  Article  Google Scholar 

  • Chen CF, Chiou WF, Zhang JT (2008) Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium. Acta Pharmacol Sin 29:1103–1108

    CAS  PubMed  Article  Google Scholar 

  • Chen S, Wang Z, Huang Y, O’barr SA, Wong RA, Yeung S, Chow MS (2014) Ginseng and anticancer drug combination to improve cancer chemotherapy: a critical review. Evid Based Complement Alternat Med 2014:168940

    PubMed  PubMed Central  Google Scholar 

  • Choi KT (2008) Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer. Acta Pharmacol Sin 29:1109–1118

    CAS  PubMed  Article  Google Scholar 

  • Choi KM, Lee EJ, Kim YH, Baik SH, Kim YK, Choi DS (1997) Effects of red ginseng on the lipid peroxidation of erythrocyte and antioxidant superoxide dismutase (SOD) activity in NIDDM patients. J Ginseng Res 21:153–159

    Google Scholar 

  • Choi ID, Ryu JH, Lee DE, Lee MH, Shim JJ, Ahn YT, Sim JH, Huh CS, Shim WS, Yim SV, Chung EK, Lee KT (2016) Enhanced absorption study of ginsenoside Compound K (20-O-beta-(d-Glucopyranosyl)-20(S)-protopanaxadiol) after oral administration of fermented red ginseng extract (HYFRG) in healthy Korean volunteers and rats. Evid Based Complement Alternat Med 2016:3908142

    PubMed  PubMed Central  Google Scholar 

  • Choi S, Oh DS, Jerng UM (2017) A systematic review of the pharmacokinetic and pharmacodynamic interactions of herbal medicine with warfarin. PLoS ONE 12:e0182794

    PubMed  PubMed Central  Article  Google Scholar 

  • Choi MK, Jin S, Jeon JH, Kang WY, Seong SJ, Yoon YR, Han YH, Song IS (2018) Tolerability and pharmacokinetics of ginsenosides Rb1, Rb2, Rc, Rd, and compound K after single or multiple administration of red ginseng extract in human beings. J Ginseng Res. https://doi.org/10.1016/j.jgr.2018.1010.1006

    Article  PubMed  PubMed Central  Google Scholar 

  • Council for Responsible Nutrition (2018) Who takes dietary supplements? 2017 CRN consumer survey on dietary supplements. 18 October 2018. https://www.crnusa.org/resources/2017-crn-consumer-survey-dietarysupplements

  • Dong H, Ma J, Li T, Xiao Y, Zhang N, Liu J, Gao Y, Shao J, Jia L (2017a) Global deregulation of ginseng products may be a safety hazard to warfarin takers: solid evidence of ginseng–warfarin interaction. Sci Rep 7:5813

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Dong WW, Zhao J, Zhong FL, Zhu WJ, Jiang J, Wu S, Yang DC, Li D, Quan LH (2017b) Biotransformation of Panax ginseng extract by rat intestinal microflora: identification and quantification of metabolites using liquid chromatography-tandem mass spectrometry. J Ginseng Res 41:540–547

    PubMed  PubMed Central  Article  Google Scholar 

  • Gui QF, Xu ZR, Xu KY, Yang YM (2016) The efficacy of ginseng-related therapies in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Medicine (Baltimore) 95:e2584

    CAS  Article  Google Scholar 

  • Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY (2002) Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 72:276–287

    CAS  PubMed  Article  Google Scholar 

  • Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY (2005) Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging 22:525–539

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P (2002) St John’s wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 54:349–356

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Hwang SW, Han HS, Lim KY (2008) Drug interaction between complementary herbal medicines and gefitinib. J Thorac Oncol 3:942–943

    PubMed  Article  Google Scholar 

  • Jeong JS, Ryu BH, Kim JS, Park JW, Choi WC, Yoon SW (2010) Bojungikki-Tang for cancer-related fatigue: a pilot randomized clinical trial. Integr Cancer Ther 9:331–338

    CAS  PubMed  Article  Google Scholar 

  • Jeurissen SMF, Buurma-Rethans EJM, Beukers MH, Jansen-Van Der Vliet M, Van Rossum CTM, Sprong RC (2018) Consumption of plant food supplements in the Netherlands. Food Funct 9:179–190

    CAS  PubMed  Article  Google Scholar 

  • Jiang X, Williams KM, Liauw WS, Ammit AJ, Roufogalis BD, Duke CC, Day RO, Mclachlan AJ (2004) Effect of St. John’s wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 57:592–599

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Jiang R, Dong J, Li X, Du F, Jia W, Xu F, Wang F, Yang J, Niu W, Li C (2015) Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb–drug interactions on OATP1B3. Br J Pharmacol 172:1059–1073

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Jiang SL, Liu HJ, Liu ZC, Liu N, Rui L, Kang YR, Ji JG, Zhang C, Hua BJ, Kang SJ (2017) Adjuvant effects of fermented red ginseng extract on advanced non-small cell lung cancer patients treated with chemotherapy. Chin J Integr Med 23:331–337

    PubMed  Article  Google Scholar 

  • Jin S, Jeon JH, Lee S, Kang WY, Seong SJ, Yoon YR, Choi MK, Song IS (2019a) Detection of 13 ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, Compound K, 20(S)-Protopanaxadiol, and 20(S)-Protopanaxatriol) in human plasma and application of the analytical method to human pharmacokinetic studies following 2 week-repeated administration of red ginseng extract. Molecules 24:E2618

    PubMed  Article  CAS  Google Scholar 

  • Jin S, Lee S, Jeon JH, Kim H, Choi MK, Song IS (2019b) Enhanced intestinal permeability and plasma concentration of metformin in rats by the repeated administration of red ginseng extract. Pharmaceutics 11:E189

    PubMed  Article  Google Scholar 

  • Jo JJ, Lee S (2017) Investigation of herb-drug interactions between Korean red ginseng extract and five Cyp substrates by LC–MS/MS. Mass Spectrom Lett 8:98–104

    CAS  Google Scholar 

  • Kim HK (2013) Pharmacokinetics of ginsenoside Rb1 and its metabolite compound K after oral administration of Korean Red Ginseng extract. J Ginseng Res 37:451–456

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Kim DH (2018) Gut microbiota-mediated pharmacokinetics of ginseng saponins. J Ginseng Res 42:255–263

    PubMed  Article  Google Scholar 

  • Kim HO, Park M, Han J (2011) Effects of fermented Red Ginseng supplementation on blood glucose and insulin resistance in type 2 diabetic patients. J Korean Soc Food Sci Nutr 40:696

    CAS  Article  Google Scholar 

  • Kim H, Nam W, Kim SH, Jang HR, Lee MK, Kim TW, Lee S (2012) Modulatory effects of Korean red ginseng extract (Panax ginseng C.A. Meyer) on cytochrome P450 after oral administration to mice for 14 days. J Life Sci 22:991–998

    Article  Google Scholar 

  • Kim D, Zheng YF, Min JS, Park JB, Bae SH, Yoon KD, Chin YW, Oh E, Bae SK (2016a) In vitro stereoselective inhibition of ginsenosides toward UDP-glucuronosyltransferase (UGT) isoforms. Toxicol Lett 259:1–10

    CAS  PubMed  Article  Google Scholar 

  • Kim DS, Kim Y, Jeon JY, Kim MG (2016b) Effect of Red Ginseng on cytochrome P450 and P-glycoprotein activities in healthy volunteers. J Ginseng Res 40:375–381

    PubMed  Article  Google Scholar 

  • Kim MG, Kim Y, Jeon JY, Kim DS (2016c) Effect of fermented red ginseng on cytochrome P450 and P-glycoprotein activity in healthy subjects, as evaluated using the cocktail approach. Br J Clin Pharmacol 82:1580–1590

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Kim HS, Kim MK, Lee M, Kwon BS, Suh DH, Song YS (2017a) Effect of red ginseng on genotoxicity and health-related quality of life after adjuvant chemotherapy in patients with epithelial ovarian cancer: a randomized, double blind, placebo-controlled Trial. Nutrients 9:E772

    PubMed  Article  CAS  Google Scholar 

  • Kim JH, Yi YS, Kim MY, Cho JY (2017b) Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res 41:435–443

    PubMed  Article  Google Scholar 

  • Kim SJ, Choi S, Kim M, Park C, Kim GL, Lee SO, Kang W, Rhee DK (2018) Effect of Korean Red Ginseng extracts on drug–drug interactions. J Ginseng Res 42:370–378

    PubMed  Article  Google Scholar 

  • Kuo SC, Teng CM, Lee JC, Ko FN, Chen SC, Wu TS (1990) Antiplatelet components in Panax ginseng. Planta Med 56:164–167

    CAS  PubMed  Article  Google Scholar 

  • Kwon HW (2018) Inhibitory Effect of 20(S)-ginsenoside Rg3 on human platelet aggregation and intracellular Ca(2+) levels via cyclic adenosine monophosphate dependent manner. Prev Nutr Food Sci 23:317–325

    PubMed  PubMed Central  Google Scholar 

  • Lau AJ, Woo SO, Koh HL (2003) Analysis of saponins in raw and steamed Panax notoginseng using high-performance liquid chromatography with diode array detection. J Chromatogr A 1011:77–87

    CAS  PubMed  Article  Google Scholar 

  • Lau AJ, Toh DF, Chua TK, Pang YK, Woo SO, Koh HL (2009) Antiplatelet and anticoagulant effects of Panax notoginseng: comparison of raw and steamed Panax notoginseng with Panax ginseng and Panax quinquefolium. J Ethnopharmacol 125:380–386

    CAS  PubMed  Article  Google Scholar 

  • Laube R, Liu K (2019) An unwanted complement: rare case of potential liver injury induced by an interaction between ginseng and atorvastatin. Br J Clin Pharmacol 85:1612–1613

    PubMed  Article  Google Scholar 

  • Lee CH, Kim JH (2014) A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res 38:161–166

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Lee SH, Ahn YM, Ahn SY, Doo HK, Lee BC (2008) Interaction between warfarin and Panax ginseng in ischemic stroke patients. J Altern Complement Med 14:715–721

    PubMed  Article  Google Scholar 

  • Lee YH, Lee BK, Choi YJ, Yoon IK, Chang BC, Gwak HS (2009) Interaction between warfarin and Korean red ginseng in patients with cardiac valve replacement. Int J Cardiol 145:275–276

    PubMed  Article  Google Scholar 

  • Lee S, Lee MS, Kim CT, Kim IH, Kim Y (2012) Ginsenoside Rg3 reduces lipid accumulation with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Int J Mol Sci 13:5729–5739

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Lee S, Kwon M, Choi MK, Song IS (2018) Effects of red ginseng extract on the pharmacokinetics and elimination of methotrexate via Mrp2 regulation. Molecules 23:E2948

    PubMed  Article  CAS  Google Scholar 

  • Leite PM, Martins MaP, Castilho RO (2016) Review on mechanisms and interactions in concomitant use of herbs and warfarin therapy. Biomed Pharmacother 83:14–21

    PubMed  Article  Google Scholar 

  • Li KK, Gong XJ (2015) A review on the medicinal potential of Panax ginseng saponins in diabetes mellitus. RSC Adv 59:47353–47366

    Article  CAS  Google Scholar 

  • Lu JM, Yao Q, Chen C (2009) Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol 7:293–302

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Ma SW, Benzie IF, Chu TT, Fok BS, Tomlinson B, Critchley LA (2008) Effect of Panax ginseng supplementation on biomarkers of glucose tolerance, antioxidant status and oxidative stress in type 2 diabetic subjects: results of a placebo-controlled human intervention trial. Diabetes Obes Metab 10:1125–1127

    CAS  PubMed  Article  Google Scholar 

  • Maher JM, Slitt AL, Callaghan TN, Cheng X, Cheung C, Gonzalez FJ, Klaassen CD (2006) Alterations in transporter expression in liver, kidney, and duodenum after targeted disruption of the transcription factor HNF1alpha. Biochem Pharmacol 72:512–522

    CAS  PubMed  Article  Google Scholar 

  • Malati CY, Robertson SM, Hunt JD, Chairez C, Alfaro RM, Kovacs JA, Penzak SR (2012) Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants. J Clin Pharmacol 52:932–939

    PubMed  Article  Google Scholar 

  • Martovetsky G, Tee JB, Nigam SK (2013) Hepatocyte nuclear factors 4 alpha and 1 alpha regulate kidney developmental expression of drug-metabolizing enzymes and drug transporters. Mol Pharmacol 84:808–823

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Meng F, Su X, Li W, Zheng Y (2017) Ginsenoside Rb3 strengthens the hypoglycemic effect through AMPK for inhibition of hepatic gluconeogenesis. Exp Ther Med 13:2551–2557

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Mucalo I, Jovanovski E, Vuksan V, Bozikov V, Romic Z, Rahelic D (2014) American ginseng extract (Panax quinquefolius L.) is safe in long-term use in type 2 diabetic patients. Evid Based Complement Alternat Med 2014:969168

    PubMed  PubMed Central  Article  Google Scholar 

  • Na DH, Ji HY, Park EJ, Kim MS, Liu KH, Lee HS (2011) Evaluation of metabolism-mediated herb–drug interactions. Arch Pharm Res 34:1829–1842

    CAS  PubMed  Article  Google Scholar 

  • Nam SJ, Han YJ, Lee W, Kang B, Choi MK, Han YH, Song IS (2018) Effect of red ginseng extract on the pharmacokinetics and efficacy of metformin in streptozotocin-induced diabetic rats. Pharmaceutics 10:E80

    PubMed  Article  CAS  Google Scholar 

  • Oh MR, Park SH, Kim SY, Back HI, Kim MG, Jeon JY, Ha KC, Na WT, Cha YS, Park BH, Park TS, Chae SW (2014) Postprandial glucose-lowering effects of fermented red ginseng in subjects with impaired fasting glucose or type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. BMC Complement Altern Med 14:237

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Park SH, Oh MR, Choi EK, Kim MG, Ha KC, Lee SK, Kim YG, Park BH, Kim DS, Chae SW (2014) An 8-week, randomized, double-blind, placebo-controlled clinical trial for the antidiabetic effects of hydrolyzed ginseng extract. J Ginseng Res 38:239–243

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Park SE, Na CS, Yoo SA, Seo SH, Son HS (2017a) Biotransformation of major ginsenosides in ginsenoside model culture by lactic acid bacteria. J Ginseng Res 41:36–42

    PubMed  Article  Google Scholar 

  • Park TY, Hong M, Sung H, Kim S, Suk KT (2017b) Effect of Korean Red Ginseng in chronic liver disease. J Ginseng Res 41:450–455

    PubMed  PubMed Central  Article  Google Scholar 

  • Qiu F, Zeng J, Liu S, He M, Zhu L, Ye Y, Miao P, Shen S, Jiang J (2014) Effects of danshen ethanol extract on the pharmacokinetics of fexofenadine in healthy volunteers. Evid Based Complement Alternat Med 2014:473213

    PubMed  PubMed Central  Google Scholar 

  • Reeds DN, Patterson BW, Okunade A, Holloszy JO, Pololsky KS, Klein S (2011) Ginseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes. Diabetes Care 34:1071–1076

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Ru W, Wang D, Xu Y, He X, Sun YE, Qian L, Zhou X, Qin Y (2015) Chemical constituents and bioactivities of Panax ginseng (C. A. Mey.). Drug Discov Ther 9:23–32

    CAS  PubMed  Article  Google Scholar 

  • Ryu JY, Song IS, Sunwoo YE, Shon JH, Liu KH, Cha IJ, Shin JG (2007) Development of the “Inje cocktail” for high-throughput evaluation of five human cytochrome P450 isoforms in vivo. Clin Pharmacol Ther 82:531–540

    CAS  PubMed  Article  Google Scholar 

  • Ryu JS, Lee HJ, Bae SH, Kim SY, Park Y, Suh HJ, Jeong YH (2013) The bioavailability of red ginseng extract fermented by Phellinus linteus. J Ginseng Res 37:108–116

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Seong SJ, Kang WY, Heo JK, Jo J, Choi WG, Liu KH, Lee S, Choi MK, Han YH, Lee HS, Ohk B, Lee HW, Song IS, Yoon YR (2018) A comprehensive in vivo and in vitro assessment of the drug interaction potential of red ginseng. Clin Ther 40:1322–1337

    CAS  PubMed  Article  Google Scholar 

  • Shih DQ, Bussen M, Sehayek E, Ananthanarayanan M, Shneider BL, Suchy FJ, Shefer S, Bollileni JS, Gonzalez FJ, Breslow JL, Stoffel M (2001) Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet 27:375–382

    CAS  PubMed  Article  Google Scholar 

  • Shishtar E, Sievenpiper JL, Djedovic V, Cozma AI, Ha V, Jayalath VH, Jenkins DJ, Meija SB, De Souza RJ, Jovanovski E, Vuksan V (2014) The effect of ginseng (the genus panax) on glycemic control: a systematic review and meta-analysis of randomized controlled clinical trials. PLoS ONE 9:e107391

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Sotaniemi EA, Haapakoski E, Rautio A (1995) Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care 18:1373–1375

    CAS  Article  Google Scholar 

  • Teng CM, Kuo SC, Ko FN, Lee JC, Lee LG, Chen SC, Huang TF (1989) Antiplatelet actions of panaxynol and ginsenosides isolated from ginseng. Biochim Biophys Acta 990:315–320

    CAS  PubMed  Article  Google Scholar 

  • Tian Z, Pang H, Du S, Lu Y, Zhang L, Wu H, Guo S, Wang M, Zhang Q (2017) Effect of Panax notoginseng saponins on the pharmacokinetics of aspirin in rats. J Chromatogr B Analyt Technol Biomed Life Sci 1040:136–143

    CAS  PubMed  Article  Google Scholar 

  • Tian Z, Pang H, Zhang Q, Du S, Lu Y, Zhang L, Bai J, Li P, Li D, Zhao M, Chen X (2018) Effect of aspirin on the pharmacokinetics and absorption of panax notoginseng saponins. J Chromatogr B Analyt Technol Biomed Life Sci 1074–1075:25–33

    PubMed  Article  CAS  Google Scholar 

  • Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT, Choi M, Naeem A (2008) Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis 18:46–56

    PubMed  Article  Google Scholar 

  • Won HJ, Kim HI, Park T, Kim HK, Jeon H, Ha SJ, Hyun JM, Jeong A, Kim JS, Park YJ, Eo YH, Lee J (2019) Non-clinical pharmacokinetic behavior of ginsenosides. J Ginseng Res 43:354–360

    PubMed  Article  Google Scholar 

  • Wu X, Ma J, Ye Y, Lin G (2016) Transporter modulation by Chinese herbal medicines and its mediated pharmacokinetic herb–drug interactions. J Chromatogr B Analyt Technol Biomed Life Sci 1026:236–253

    CAS  PubMed  Article  Google Scholar 

  • Xin HW, Wu XC, Li Q, Yu AR, Zhu M, Shen Y, Su D, Xiong L (2007) Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers. Br J Clin Pharmacol 64:469–475

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Xu T, Jin ZC, Yuan Y, Wei HM, Xu XY, He SL, Chen ST, Hou W, Guo QJ, Hua BJ (2016) Ginsenoside Rg3 serves as an adjuvant chemotherapeutic agent and VEGF inhibitor in the treatment of non-small cell lung cancer: a meta-analysis and systematic review. Evid Based Complement Alternat Med 2016:7826753

    PubMed  PubMed Central  Google Scholar 

  • Yennu S, Tannir NM, Williams JL, Hess KR, Frisbee-Hume S, House HL (2016) Effects of high-dose Asian ginseng (Panax ginseng) to improve cancer-related fatigue: results of a double-blind, placebo-controlled randomized controlled trial. J Clin Oncol 34:209

    Article  Google Scholar 

  • Yokozawa T, Kobayashi T, Oura H, Kawashima Y (1985) Studies on the mechanism of the hypoglycemic activity of ginsenoside-Rb2 in streptozotocin-diabetic rats. Chem Pharm Bull (Tokyo) 33:869–872

    CAS  Article  Google Scholar 

  • Yoon SH, Han EJ, Sung JH, Chung SH (2007) Anti-diabetic effects of compound K versus metformin versus compound K-metformin combination therapy in diabetic db/db mice. Biol Pharm Bull 30:2196–2200

    CAS  PubMed  Article  Google Scholar 

  • Yoon JW, Kang SM, Vassy JL, Shin HJ, Lee YH, Ahn HY, Choi SH, Park KS, Jang HC, Lim S (2011) Efficacy and safety of ginsam, a vinegar extract from Panax ginseng, in type 2 diabetic patients: results of a double-blind, placebo-controlled study. J Diabetes Investig 3:309–317

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  • Yuan CS, Wei G, Dey L, Karrison T, Nahlik L, Maleckar S, Kasza K, Ang-Lee M, Moss J (2004) Brief communication: American ginseng reduces warfarin’s effect in healthy patients: a randomized, controlled Trial. Ann Intern Med 141:23–27

    CAS  PubMed  Article  Google Scholar 

  • Yuan HD, Kim JT, Kim SH, Chung SH (2012) Ginseng and diabetes: the evidences from in vitro, animal and human studies. J Ginseng Res 36:27–39

    PubMed  PubMed Central  Article  Google Scholar 

  • Yun TK, Choi SY, Yun HY (2001) Epidemiological study on cancer prevention by ginseng: are all kinds of cancers preventable by ginseng? J Korean Med Sci 16(Suppl):S19–S27

    PubMed  PubMed Central  Article  Google Scholar 

  • Zhang Y, Lu S, Liu YY (2007) Effect of panax quinquefolius saponin on insulin sensitivity in patients of coronary heart disease with blood glucose abnormality. Zhongguo Zhong Xi Yi Jie He Za Zhi 27:1066–1069

    CAS  PubMed  Google Scholar 

  • Zhang R, Jie J, Zhou Y, Cao Z, Li W (2009) Long-term effects of Panax ginseng on disposition of fexofenadine in rats in vivo. Am J Chin Med 37:657–667

    CAS  PubMed  Article  Google Scholar 

  • Zhou J, Wu J, Wu CY, Long F, Shen H, Zhang W, Li SL (2019a) Herb–drug interaction: a case study of effects and involved mechanisms of cisplatin on the pharmacokinetics of ginsenoside Rb1 in tumor-bearing mice. Biomed Pharmacother 110:95–104

    CAS  PubMed  Article  Google Scholar 

  • Zhou L, Chen L, Wang Y, Huang J, Yang G, Tan Z, Wang Y, Liao J, Zhou G, Hu K, Li Z, Ouyang D (2019b) Impact of NR1I2, adenosine triphosphate-binding cassette transporters genetic polymorphisms on the pharmacokinetics of ginsenoside compound K in healthy Chinese volunteers. J Ginseng Res 43:460–474

    PubMed  Article  Google Scholar 

  • Ziemann J, Lendeckel A, Muller S, Horneber M, Ritter CA (2019) Herb–drug interactions: a novel algorithm-assisted information system for pharmacokinetic drug interactions with herbal supplements in cancer treatment. Eur J Clin Pharmacol 75:1237–1248

    PubMed  Article  Google Scholar 

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Choi, MK., Song, IS. Interactions of ginseng with therapeutic drugs. Arch. Pharm. Res. 42, 862–878 (2019). https://doi.org/10.1007/s12272-019-01184-3

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Keywords

  • Korean ginseng
  • Ginsenoside
  • Herb–drug interaction
  • Adjuvant chemotherapy