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http://dx.doi.org/10.1016/j.jgr.2021.03.001

Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects  

Wan, Yan (State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine)
Wang, Jing (State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine)
Xu, Jin-feng (State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine)
Tang, Fei (State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine)
Chen, Lu (State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine)
Tan, Yu-zhu (State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine)
Rao, Chao-long (College of Public Health, Chengdu University of Traditional Chinese Medicine)
Ao, Hui (State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine)
Peng, Cheng (State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine)
Publication Information
Journal of Ginseng Research / v.45, no.6, 2021 , pp. 617-630 More about this Journal
Abstract
Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.
Keywords
Chemotherapy; Side effects; PG; Ginsenosides; Mechanism; Pharmacological effects;
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1 Qi Z, Li W, Tan J, Wang C, Lin H, Zhou B, Liu J, Li P. Effect of ginsenoside Rh2 on renal apoptosis in cisplatin-induced nephrotoxicity in vivo. Phytomedicine 2019;61:152862.   DOI
2 Yousef MI, Hussien HM. Cisplatin-induced renal toxicity via tumor necrosis factor-a, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng. Food Chem Toxicol 2015;78:17-25.   DOI
3 Yokozawa T, Liu ZW. The role of ginsenoside-Rd in cisplatin-induced acute renal failure. Ren Fai 2000;22:115-27.   DOI
4 Yokozawa T, Dong E. Role of ginsenoside-Rd in cisplatin-induced renal injury: special reference to DNA fragmentation. Nephron 2001;89:433-8.   DOI
5 Hu JN, Xu XY, Jiang S, et al. Protective effect of ginsenoside Rk1, a major rare saponin from black ginseng, on cisplatin-induced nephrotoxicity in HEK-293 cells. Kaohsiung J Med Sci 2020;36:732-40.   DOI
6 Li W, Yan MH, Liu Y, Liu Z, Wang Z, Chen C, Zhang J, Sun YS. Ginsenoside Rg5 ameliorates cisplatin-Induced nephrotoxicity in mice through inhibition of inflammation, oxidative Stress, and apoptosis. Nutrients 2016;8:566.   DOI
7 Kim HS, Kim MK, Lee M, Kwon BS, Suh DH, Song YS. 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 2017;9(7):772.   DOI
8 Li L, Ni J, Li M, Chen J, Han L, Zhu Y, Kong D, Mao J, Wang Y, Zhang B, et al. Ginsenoside Rg3 micelles mitigate doxorubicin-induced cardiotoxicity and enhance its anticancer efficacy. Drug Deliv 2017;24:1617-30.   DOI
9 Alberts DS. Protection by amifostine of cyclophosphamide-induced myelosuppression. Semin Oncol 1999;26:37-40.
10 Magdy T, Burmeister BT, Burridge PW. Validating the pharmacogenomics of chemotherapy-induced cardiotoxicity: what is missing? Pharmacol Ther 2016;168:113-25.   DOI
11 You JS, Huang HF, Chang YL. Panax ginseng reduces adriamycin-induced heart failure in rats. Phytother Res 2005;19:1018-22.   DOI
12 Volkova M, Palmeri M, Russell KS, Russell RR. Activation of the aryl hydrocarbon receptor by doxorubicin mediates cytoprotective effects in the heart. Cardiovasc Res 2011;90:305-14.   DOI
13 Xu X, Chen K, Kobayashi S, Timm D, Liang Q. Resveratrol attenuates doxorubicin-induced cardiomyocyte death via inhibition of p70 S6 kinase 1-mediated autophagy. J Pharmacol Exp Ther 2012;341:183-95.   DOI
14 Zhang Y, Wang Y, Ma Z, Liang Q, Tang X, Tan H, Xiao C, Gao Y. Ginsenoside Rb1 inhibits doxorubicin-triggered H9C2 cell apoptosis via aryl hydrocarbon receptor. Biomol Ther 2017;25:202-12.   DOI
15 Han J, Xia J, Zhang L, Cai E, Zhao Y, Fei X, Jia X, Yang H, Liu S. Studies of the effects and mechanisms of ginsenoside Re and Rk3 on myelosuppression induced by cyclophosphamide. J Ginseng Res 2019;43:618-24.   DOI
16 Li LF, Ma ZC, Wang YG, Tang XL, Tan HL, Xiao CR, Gao Y. Protective effect of ginsenoside Rb1 on adriamycin-induced cardiomyocyte autophagy. China J Chin Mater Med 2017;42:1365-9.
17 Rashid HO, Yadav RK, Kim HR, Chae HJ. ER stress: autophagy induction, inhibition and selection. Autophagy 2015;11:1956-77.   DOI
18 Xu ZM, Li CB, Liu QL, Li P, Yang H. Ginsenoside Rg1 prevents doxorubicin-induced cardiotoxicity through the inhibition of autophagy and endoplasmic reticulum stress in mice. Int J Mol Sci 2018;19:3658.   DOI
19 Han J, Wang Y, Cai E, Zhang L, Zhao Y, Sun N, Zheng X, Wang S. Study of the effects and mechanisms of ginsenoside Compound K on myelosuppression. J Agric Food Chem 2019;67:1402-8.   DOI
20 Sun X, Zhao YN, Qian S, Gao RL, Yin LM, Wang LP, Chong BH, Zhang SZ. Ginseng-derived panaxadiol saponins promote hematopoiesis recovery in cyclophosphamide-induced myelosuppressive mice: potential novel treatment of chemotherapy-induced cytopenias. Chin J Integr Med 2018;24:200-6.   DOI
21 Yang Y, Xu S, Xu Q, Liu X, Gao Y, Steinmetz A, Wang N, Wang T, Qiu G. Protective effect of dammarane sapogenins against chemotherapy-induced myelosuppression in mice. Exp Biol Med 2011;236:729-35.   DOI
22 Xu SF, Yu LM, Fan ZH, Wu Q, Yuan Y, Wei Y, Fang N. Improvement of ginsenoside Rg1 on hematopoietic function in cyclophosphamide-induced myelosuppression mice. Eur J Pharmacol 2012;695:7-12.   DOI
23 Wang H, Yu P, Gou H, Zhang J, Zhu M, Wang ZH, Tian JW, Jiang YT, Fu FH. Cardioprotective effects of 20(S)-ginsenoside Rh2 against doxorubicin-induced cardiotoxicity in vitro and in vivo. Evid Based Complement Alternat Med 2012;2012:506214.
24 Wellenstein MD, de Visser KE. Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape. Immunity 2018;48:399-416.   DOI
25 Liu HH, Chen FP, Liu RK, Lin CL, Chang KT. Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen. J Cell Mol Med 2015;19:2575-86.   DOI
26 Wang J, Feng W, Zhang S, Chen L, Sheng Y, Tang F, He J, Xu X, Ao H, Peng C. Ameliorative effect of Atractylodes macrocephala essential oil combined with Panax ginseng total saponins on 5-fluorouracil induced diarrhea is associated with gut microbial modulation. J Ethnopharmacol 2019;238:111887.   DOI
27 Raghavendran HR, Sathyanath R, Shin J, Kim HK, Han JM, Cho J, Son CG. Panax ginseng modulates cytokines in bone marrow toxicity and myelopoiesis: ginsenoside Rg1 partially supports myelopoiesis. PLoS One 2012;7:e33733.   DOI
28 Zhang QH, Wu CF, Yang JY, Mu YH, Chen XX, Zhao YQ. Reduction of cyclophosphamide-induced DNA damage and apoptosis effects of ginsenoside Rb (1) on mouse bone marrow cells and peripheral blood leukocytes. Environ Toxicol Pharmacol 2009;27:384-9.   DOI
29 Qian Y, Huang R, Li S, Xie R, Qian B, Zhang Z, Li L, Wang B, Tian C, Yang J, et al. Ginsenoside Rh2 reverses cyclophosphamide-induced immune deficiency by regulating fatty acid metabolism. J Leukoc Biol 2019;106:1089-100.   DOI
30 Im GJ, Chang JW, Choi J, Chae SW, Ko EJ, Jung HH. Protective effect of Korean red ginseng extract on cisplatin ototoxicity in HEI-OC1 auditory cells. Phytother Res 2010;24:614-21.   DOI
31 Chen C, Zhang H, Xu H, Zheng Y, Wu T, Lian Y. Ginsenoside Rb1 ameliorates cisplatin-induced learning and memory impairments. J Ginseng Res 2019;43:499-507.   DOI
32 Gao Y, Chu S, Shao Q, Zhang M, Xia C, Wang Y, Li Y, Lou Y, Huang H, Chen N. Antioxidant activities of ginsenoside Rg1 against cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice. Free Radical Research 2017;51:1-13.   DOI
33 Lee HL, Kang KS. Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in LLC-PK1 kidney cells. J Ginseng Res 2017;41:227-31.   DOI
34 Xing JJ, Hou JG, Ma ZN, Wang Z, Ren S, Wang YP, Liu WC, Chen C, Li W. Ginsenoside Rb3 provides protective effects against cisplatin-induced nephrotoxicity via regulation of AMPK-/mTOR-mediated autophagy and inhibition of apoptosis in vitro and in vivo. Cell Prolif 2019;52:e12627.   DOI
35 Watanabe S, Suemaru K, Yamaguchi T, Hidaka N, Sakanaka M, Araki H. Effect of oral mucosal adhesive films containing ginsenoside Rb1 on 5-fluorouracil-induced oral mucositis in hamsters. Eur J Pharmacol 2009;616:281-6.   DOI
36 Wang J, Feng W, Zhang S, Chen L, Tang F, Sheng Y, Ao H, Peng C. Gut microbial modulation in the treatment of chemotherapy-induced diarrhea with Shenzhu Capsule. BMC Complement Altern Med 2019;19:126.   DOI
37 Suzuki T, Yamamoto A, Ohsawa M, Motoo Y, Mizukami H, Makino T. Effect of ninjin'yoeito and ginseng extracts on oxaliplatin-induced neuropathies in mice. J Nat Med 2017;71:757-64.   DOI
38 Suzuki T, Yamamoto A, Ohsawa M, Motoo Y, Mizukami H, Makino T. Ninjin'yoeito and ginseng extract prevent oxaliplatin-induced neurodegeneration in PC12 cells. J Nat Med 2015;69:531-7.   DOI
39 Han MS, Han IH, Lee D, An JM, Kim SN, Shin MS, Yamabe N, Hwang GS, Yoo HH, Choi SJ, et al. Beneficial effects of fermented black ginseng and its ginsenoside 20(S)-Rg3 against cisplatin-induced nephrotoxicity in LLC-PK1 cells. J Ginseng Res 2016;40:135-40.   DOI
40 Park JY, Choi P, Kim T, Ko H, Kim HK, Kang KS, Ham J. Protective effects of processed ginseng and its active ginsenosides on cisplatin-induced nephrotoxicity: in vitro and in vivo studies. J Agric Food Chem 2015;63:5964-9.   DOI
41 Xiao Z, Wang C, Zhou M, Hu S, Jiang Y, Huang X, Li N, Feng J, Tang F, Chen X, et al. Clinical efficacy and safety of Aidi injection plus paclitaxel-based chemotherapy for advanced non-small cell lung cancer: a meta-analysis of 31 randomized controlled trials following the PRISMA guidelines. J Ethnopharmacol 2019;228:110-22.   DOI
42 Huang JY, Sun Y, Fan QX, Zhang YQ. Efficacy of Shenyi Capsule combined with gemcitabine plus cisplatin in treatment of advanced esophageal cancer: a randomized controlled trial. Zhong Xi Yi Jie He Xue Bao 2009;7:1047-51.   DOI
43 Pan L, Zhang T, Cao H, Sun H, Liu G. Ginsenoside Rg3 for chemotherapy-induced Myelosuppression: a meta-analysis and systematic review. Front Pharmacol 2020;11:649.   DOI
44 Sathishkumar N, Sathiyamoorthy S, Ramya M, Yang DU, Lee HN, Yang DC. Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng. J Enzyme Inhib Med Chem 2012;27:685-92.   DOI
45 Manohar S, Leung N. Cisplatin nephrotoxicity: a review of the literature. J Nephrol 2018;31:15-25.   DOI
46 Kim SJ, Kwak HJ, Kim DS, Choi HM, Sim JE, Kim SH, Um JY, Hong SH. Protective mechanism of Korean red ginseng in cisplatin-induced ototoxicity through attenuation of nuclear factor-kB and caspase-1 activation. Mol Med Rep 2015;12:315-22.   DOI
47 Gaguski ME, Karcheski T. Dosing done right: a review of common chemotherapy calculations. Clin J Oncol Nurs 2011;15:471-3.   DOI
48 Kang J, Lee Y, No K, Jung E, Sung J, Kim Y, Nam S. Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in the mouse testis. Reprod Toxicol 2002;16:291-8.   DOI
49 Lobina C, Carai MA, Loi B, Gessa GL, Riva A, Cabri W, Petrangolini G, Morazzoni P, Colombo G. Protective effect of Panax ginseng in cisplatin-induced cachexia in rats. Future Oncol 2014;10:1203-14.   DOI
50 Keum DI, Pi LQ, Hwang ST, Lee WS. Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model. J Ginseng Res 2016;40:169-75.   DOI
51 Feng W, Liu J, Ao H, Yue SJ, Peng C. Targeting gut microbiota for precision medicine: focusing on the efficacy and toxicity of drugs. Theranostics 2020. https://doi.org/10.7150/thno.47289.   DOI
52 Lin G, Yu X, Wang J, Qu S, Sui D. Beneficial effects of 20(S)-protopanaxadiol on antitumor activity and toxicity of cyclophosphamide in tumor-bearing mice. Exp Ther Med 2013;5:443-7.   DOI
53 Turk JL, Parker D. Effect of cyclophosphamide on immunological control mechanisms. Immunol Rev 1982;65:99-113.   DOI
54 Chen LX, Qi YL, Qi Z, Gao K, Gong RZ, Shao ZJ, Liu SX, Li SS, Sun YS. A comparative study on the effects of different parts of Panax ginseng on the immune activity of cyclophosphamide-induced immunosuppressed mice. Molecules 2019;24:1096.   DOI
55 Qi Z, Chen L, Li Z, Shao Z, Qi Y, Gao K, Liu S, Sun Y, Li P, Liu J. Immunomodulatory effects of (24R)-pseudo-ginsenoside HQ and (24S)-pseudoginsenoside HQ on cyclophosphamide-induced immunosuppression and their anti-tumor effects study. Int J Mol Sci 2019;20:836.   DOI
56 Chan CW, Chang AM, Molassiotis A, Lee IY, Lee GC. Oral complications in Chinese cancer patients undergoing chemotherapy. Support Care Cancer 2003;11:48-55.   DOI
57 Joy J, Nair CK. Amelioration of cisplatin induced nephrotoxicity in Swiss albino mice by Rubia cordifolia extract. J Cancer Res Ther 2008;4:111-5.   DOI
58 Navari RM. Management of chemotherapy-induced nausea and vomiting: focus on newer agents and new uses for older agents. Drugs 2013;73:249-62.   DOI
59 Guo S, Guo Y, Ergun A, Lu L, Walker WA, Ganguli K. Secreted Metabolites of Bifidobacterium infantis and Lactobacillus acidophilus protect immature human enterocytes from IL-1β-induced inflammation: a transcription profiling analysis. PLoS One 2015;10:e0124549.   DOI
60 Souglakos J, Mavroudis D, Kakolyris S, Kourousis Ch, Vardakis N, Androulakis N, Agelaki S, Kalbakis K, Tsetis D, Athanasiadis N, et al. Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter phase II trial. J Clin Oncol 2002;20:2651-7.   DOI
61 Jodrell DI, Stewart M, Aird R, Knowles G, Bowman A, Wall L, McLean C. 5- fluorouracil steady state pharmacokinetics and outcome in patients receiving protracted venous infusion for advanced colorectal cancer. Br J Cancer 2001;84:600-3.   DOI
62 Saba E, Lee YY, Kim M, Kim SH, Hong SB, Rhee MH. A comparative study on immune-stimulatory and antioxidant activities of various types of ginseng extracts in murine and rodent models. J Ginseng Res 2018;42:577-84.   DOI
63 Launay-Vacher V, Rey JB, Isnard-Bagnis C, Deray G, Daouphars M. European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European society of clinical pharmacy special interest group on cancer care. Cancer Chemother Pharmacol 2008;61:903-9.   DOI
64 Wang X, Chen L, Wang T, Jiang X, Zhang H, Li P, Lv B, Gao X. Ginsenoside Rg3 antagonizes ADM-induced cardiotoxicity by improving endothelial dysfunction from oxidative stress via upregulating the Nrf2-ARE pathway through the activation of akt. Phytomedicine 2015;22:875-84.   DOI
65 Lim TG, Jang M, Cho CW, Hong HD, Kim KT, Lee SY, Jung SK, Rhee YK. White ginseng extract induces immunomodulatory effects via the MKK4-JNK pathway. Food Sci Biotechnol 2016;25:1737-44.   DOI
66 Kim JK, Kim JY, Jang SE, Choi MS, Jang HM, Yoo HH, Kim DH. Fermented red ginseng alleviates cyclophosphamide-induced immunosuppression and 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice by regulating macrophage activation and T cell differentiation. Am J Chin Med 2018;46:1879-97.   DOI
67 Molyneux G, Andrews M, Sones W, York M, Barnett A, Quirk E, Yeung W, Turton J. Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration. Cell Biol Toxicol 2011;27:13-40.   DOI
68 Abdelfattah-Hassan A, Shalaby SI, Khater SI, El-Shetry ES, Abd El Fadil H, Elsayed SA. Panax ginseng is superior to vitamin E as a hepatoprotector against cyclophosphamide-induced liver damage. Complementary Therapies in Medicine 2019;46:95-102.   DOI
69 Zhu H, Long MH, Wu J, Wang MM, Li XY, Shen H, Xu JD, Zhou L, Fang ZJ, Luo Y, et al. Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid. Sci Rep 2015;5:17536.   DOI
70 Shi DD, Huang YH, Lai CSW, Dong CM, Ho LC, Li XY, Wu EX, Li Q, Wang XM, Chen YJ, et al. Ginsenoside Rg1 prevents Chemotherapy-induced cognitive impairment: associations with microglia-mediated cytokines, neuroinflammation, and neuroplasticity. Mol Neurobiol 2019;56:5626-42.   DOI
71 Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins 2010;2:2490-518.   DOI
72 Zhu C, Wang Y, Liu H, Mu H, Lu Y, Zhang J, Huang J. Oral administration of Ginsenoside Rg1 prevents cardiac toxicity induced by doxorubicin in mice through anti-apoptosis. Oncotarget 2017;8:83792-801.   DOI
73 Liu X, Zhang Z, Liu J, Wang Y, Zhou Q, Wang S, Wang X. Ginsenoside Rg3 improves cyclophosphamide-induced immunocompetence in Balb/c mice. Int Immunopharmacol 2019;72:98-111.   DOI
74 Han J, Dai M, Zhao Y, Cai E, Zhang L, Jia X, Sun N, Fei X, Shu H. Compatibility effects of ginseng and Ligustrum lucidum Ait herb pair on hematopoietic recovery in mice with cyclophosphamide-induced myelosuppression and its material basis. J Ginseng Res 2020;44:291-9.   DOI
75 Zhang S, Sun H, Wang C, Zheng X, Jia X, Cai E, Zhao Y. Comparative analysis of active ingredients and effects of the combination of Panax ginseng and Ophiopogon japonicus at different proportions on chemotherapy-induced myelosuppression mouse. Food Funct 2019;10:1563-70.   DOI
76 Joo SS, Won TJ, Kim MS, Lee DI. Hematopoietic effect of ginsenoside Rg3 in ICR mouse primary cultures and its application to a biological response modifier. Fitoterapia 2004;75:337-41.   DOI
77 Baek SH, Piao XL, Lee UJ, Kim HY, Park JH. Reduction of cisplatin-induced nephrotoxicity by ginsenosides isolated from processed ginseng in cultured renal tubular cells. Biol Pharm Bull 2006;29:2051-5.   DOI
78 Wang Z, Li YF, Han XY, Sun YS, Zhang LX, Liu W, Liu XX, Li W, Liu YY. Kidney protection effect of ginsenoside Re and its underlying mechanisms on cisplatin-induced kidney injury. Cell Physiol Biochem 2018;48:2219-29.   DOI
79 Baek SH, Shin BK, Kim NJ, Chang SY, Park JH. Protective effect of ginsenosides Rk3 and Rh4 on cisplatin-induced acute kidney injury in vitro and in vivo. J Ginseng Res 2017;41:233-9.   DOI
80 Wang Z, Zheng Q, Liu K, Li G, Zheng R. Ginsenoside Rh2 enhances antitumour activity and decreases genotoxic effect of cyclophosphamide. Basic Clin Pharmacol Toxicol 2006;98:411-5.   DOI
81 Feng W, Ao H, Peng C, Yan D. Gut microbiota, a new frontier to understand traditional Chinese medicines. Pharmacol Res 2019;142:176-91.   DOI
82 Jo EJ, Kang SJ, Kim AJ. Effects of steam-and dry-processing temperatures on the benzo (a) pyrene content of black and red ginseng. The Korean Journal of Food And Nutrition 2009;22:199-204.
83 Lee CK, Park KK, Chung AS, Chung WY. Ginsenoside Rg3 enhances the chemosensitivity of tumors to cisplatin by reducing the basal level of nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1/NAD(P)H quinone oxidoreductase-1 and prevents normal tissue damage by scavenging cisplatin-induced intracellular reactive oxygen species. Food Chem Toxicol 2012;50:2565-74.   DOI
84 Alrashed AA, El-Kordy EA. Possible protective role of panax ginseng on cisplatin-induced hepatotoxicity in adult male albino rats (Biochemical and Histological Study). J Microsc Ultrastruct 2019;7:84-90.   DOI
85 Olgun Y, Kirkim G, Altun Z, Aktas, S, Kolatan E, Kiray M, Bagriyanik A, Olgun A, Cakir Kizmazoglu D, Ozogul C, et al. Protective Effect of Korean red ginseng on cisplatin ototoxicity: is it effective enough? J Int Adv Otol 2016;12:177-83.   DOI
86 Park HJ, Shim HS, Kim JY, Kim JY, Park SK, Shim I. Ginseng purified dry extract, BST204, improved cancer chemotherapy-related fatigue and toxicity in mice. Evid Based Complement Alternat Med 2015;2015:197459.
87 Zhang QH, Wu CF, Duan L, Yang JY. Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells. Food Chem Toxicol 2008;46:293-302.   DOI
88 Zhang QH, Wu CF, Duan L, Yang JY. Protective effects of ginsenoside Rg (3) against cyclophosphamide-induced DNA damage and cell apoptosis in mice. Arch Toxicol 2008;82:117-23.   DOI