Pharmacological activities of ginsenoside Rg5 (Review)
- Authors:
- Ming-Yang Liu
- Fei Liu
- Yan-Li Gao
- Jia-Ning Yin
- Wei-Qun Yan
- Jian-Guo Liu
- Hai-Jun Li
-
Affiliations: Department of Immunity, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Obstetrics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Tissue Engineering, School of Pharmaceutical Sciences in Jilin University, Changchun, Jilin 130021, P.R. China, Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China - Published online on: June 6, 2021 https://doi.org/10.3892/etm.2021.10272
- Article Number: 840
-
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
De Souza LR, Jenkins AL, Sievenpiper JL, Jovanovski E, Rahelić D and Vuksan V: Korean red ginseng (Panax ginseng C.A. Meyer) root fractions: Differential effects on postprandial glycemia in healthy individuals. J Ethnopharmacol. 137:245–250. 2011.PubMed/NCBI View Article : Google Scholar | |
Zhou QL, Zhu DN, Yang YF, Xu W and Yang XW: Simultaneous quantification of twenty-one ginsenosides and their three aglycones in rat plasma by a developed UFLC-MS/MS assay: Application to a pharmacokinetic study of red ginseng. J Pharm Biomed Anal. 137:1–12. 2017.PubMed/NCBI View Article : Google Scholar | |
Christensen LP: Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 55:1–99. 2009.PubMed/NCBI View Article : Google Scholar | |
Shi W, Wang Y, Li J, Zhang H and Ding L: Investigation of ginsenosides in different parts and ages of Panax ginseng. Food Chem. 102:664–668. 2007. | |
Chen RJ, Chung TY, Li FY, Lin NH and Tzen JTC: Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity. Acta Pharmacol Sin. 30:61–69. 2009.PubMed/NCBI View Article : Google Scholar | |
Shin BK, Kwon SW and Park JH: Chemical diversity of ginseng saponins from Panax ginseng. J Ginseng Res. 39:287–298. 2015.PubMed/NCBI View Article : Google Scholar | |
Shin KC and Oh DK: Classification of glycosidases that hydrolyze the specific positions and types of sugar moieties in ginsenosides. Crit Rev Biotechnol. 36:1036–1049. 2016.PubMed/NCBI View Article : Google Scholar | |
Jin S, Jeon JH, Lee S, Kang WY, Seong SJ, Yoon YR, Choi MK and Song IS: 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 two week-repeated administration of red ginseng extract. Molecules. 24(2618)2019.PubMed/NCBI View Article : Google Scholar | |
Cui CH, Jeon BM, Fu Y, Im WT and Kim SC: High-density immobilization of a ginsenoside-transforming β-glucosidase for enhanced food-grade production of minor ginsenosides. Appl Microbiol Biotechnol. 103:7003–7015. 2019.PubMed/NCBI View Article : Google Scholar | |
Noh KH and Oh DK: Production of the rare ginsenosides compound K, compound Y, and compound Mc by a thermostable beta-glycosidase from sulfolobus acidocaldarius. Biol Pharm Bull. 32:1830–1835. 2009.PubMed/NCBI View Article : Google Scholar | |
Liang LD, He T, Du TW, Fan YG, Chen DS and Wang Y: Ginsenoside-Rg5 induces apoptosis and DNA damage in human cervical cancer cells. Mol Med Rep. 11:940–946. 2015.PubMed/NCBI View Article : Google Scholar | |
Qi LW, Wang CZ and Yuan CS: Ginsenosides from American ginseng: Chemical and pharmacological diversity. Phytochemistry. 72:689–699. 2011.PubMed/NCBI View Article : Google Scholar | |
Kim JH, Yi YS, Kim MY and Cho JY: Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res. 41:435–443. 2017.PubMed/NCBI View Article : Google Scholar | |
Liu Y and Fan D: The preparation of ginsenoside Rg5, its antitumor activity against breast cancer cells and its targeting of PI3K. Nutrients. 12(246)2020.PubMed/NCBI View Article : Google Scholar | |
Kim SJ and Kim AK: Anti-breast cancer activity of fine black ginseng (Panax ginseng Meyer) and ginsenoside Rg5. J Ginseng Res. 39:125–134. 2015.PubMed/NCBI View Article : Google Scholar | |
Zou Y and Liu P: Ginsenoside-Rg5 inhibits proliferation of the breast carcinoma cells through promotion of the proteins involved in AMP kinase pathway. Int J Clin Exp Med. 9:17664–17669. 2016. | |
Liu Y and Fan D: Ginsenoside Rg5 induces apoptosis and autophagy via the inhibition of the PI3K/Akt pathway against breast cancer in a mouse model. Food Funct. 9:5513–5527. 2018.PubMed/NCBI View Article : Google Scholar | |
Liu Y and Fan D: Ginsenoside Rg5 induces G2/M phase arrest, apoptosis and autophagy via regulating ROS-mediated MAPK pathways against human gastric cancer. Biochem Pharmacol. 168:285–304. 2019.PubMed/NCBI View Article : Google Scholar | |
Jin HS, Suh HW, Kim SJ and Jo EK: Mitochondrial control of innate immunity and inflammation. Immune Netw. 17:77–88. 2017.PubMed/NCBI View Article : Google Scholar | |
Medzhitov R: Origin and physiological roles of inflammation. Nature. 454:428–435. 2008.PubMed/NCBI View Article : Google Scholar | |
Harrison DJ, Geller DS, Gill JD, Lewis VO and Gorlick R: Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther. 18:39–50. 2018.PubMed/NCBI View Article : Google Scholar | |
Akram M, Iqbal M, Daniyal M and Khan AU: Awareness and current knowledge of breast cancer. Biol Res. 50(33)2017.PubMed/NCBI View Article : Google Scholar | |
Sun M, Ye Y, Xiao L, Duan X, Zhang Y and Zhang H: Anticancer effects of ginsenoside Rg3 (Review). Int J Mol Med. 39:507–518. 2017.PubMed/NCBI View Article : Google Scholar | |
Baldo BA and Pham NH: Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch. Cancer Metastasis Rev. 32:723–761. 2013.PubMed/NCBI View Article : Google Scholar | |
Majeed F, Malik FZ, Ahmed Z, Afreen A, Afzal MN and Khalid N: Ginseng phytochemicals as therapeutics in oncology: Recent perspectives. Biomed Pharmacother. 100:52–63. 2018.PubMed/NCBI View Article : Google Scholar | |
Nakhjavani M, Hardingham JE, Palethorpe HM, Tomita Y, Smith E, Price TJ and Townsend AR: Ginsenoside Rg3: Potential molecular targets and therapeutic indication in metastatic breast cancer. Medicines (Basel). 6(17)2019.PubMed/NCBI View Article : Google Scholar | |
Zhang D, Wang A, Feng J, Zhang Q, Liu L and Ren H: Ginsenoside Rg5 induces apoptosis in human esophageal cancer cells through the phosphoinositide-3 kinase/protein kinase B signaling pathway. Mol Med Rep. 19:4019–4026. 2019.PubMed/NCBI View Article : Google Scholar | |
Wang YS, Li H, Li Y, Zhu H and Jin YH: Identification of natural compounds targeting annexin A2 with an anti-cancer effect. Protein Cell. 9:568–579. 2018.PubMed/NCBI View Article : Google Scholar | |
Lee KH, Lee YH, Kim SI, Park JH and Lee SK: Ginsenoside-Rg5 suppresses cyclin E-dependent protein kinase activity via up-regulating p21Cip/WAF1 and down-regulating cyclin E in SK-HEP-1 cells. Anticancer Res. 17:1067–1072. 1997.PubMed/NCBI | |
Cui Y, Su Y, Deng L and Wang W: Ginsenoside-Rg5 inhibits retinoblastoma proliferation and induces apoptosis through suppressing BCL2 expression. Chemotherapy. 63:293–300. 2018.PubMed/NCBI View Article : Google Scholar | |
Feng SL, Luo HB, Cai L, Zhang J, Wang D, Chen YJ, Zhan HX, Jiang ZH and Xie Y: Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: In vitro and in vivo study. J Ginseng Res. 44:247–257. 2020.PubMed/NCBI View Article : Google Scholar | |
Dong Y, Fu R, Yang J, Ma P, Liang L, Mi Y and Fan D: Folic acid-modified ginsenoside Rg5-loaded bovine serum albumin nanoparticles for targeted cancer therapy in vitro and in vivo. Int J Nanomedicine. 14:6971–6988. 2019.PubMed/NCBI View Article : Google Scholar | |
Bortolotti P, Faure E and Kipnis E: Inflammasomes in tissue damages and immune disorders after trauma. Front Immunol. 9(1900)2018.PubMed/NCBI View Article : Google Scholar | |
Yi YS: Roles of ginsenosides in inflammasome activation. J Ginseng Res. 43:172–178. 2019.PubMed/NCBI View Article : Google Scholar | |
Kim TW, Joh EH, Kim B and Kim DH: Ginsenoside Rg5 ameliorates lung inflammation in mice by inhibiting the binding of LPS to toll-like receptor-4 on macrophages. Int Immunopharmacol. 12:110–116. 2012.PubMed/NCBI View Article : Google Scholar | |
Park JY, Choi P, Kim T, Ko H, Kim HK, Kang KS and 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. 63:5964–5969. 2015.PubMed/NCBI View Article : Google Scholar | |
Li W, Yan M, Liu Y, Liu Z, Wang Z, Chen C, Zhang J and Sun YS: Ginsenoside Rg5 ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of inflammation, oxidative stress, and apoptosis. Nutrients. 8(566)2016.PubMed/NCBI View Article : Google Scholar | |
Lee SM: Anti-inflammatory effects of ginsenosides Rg5, Rz1, and Rk1: Inhibition of TNF-α-induced NF-κB, COX-2, and iNOS transcriptional expression. Phytother Res. 28:1893–1896. 2014.PubMed/NCBI View Article : Google Scholar | |
Wang Z, Hu JN, Yan MH, Xing JJ, Liu WC and Li W: Caspase-mediated anti-apoptotic effect of ginsenoside Rg5, a main rare ginsenoside, on acetaminophen-induced hepatotoxicity in mice. J Agric Food Chem. 65:9226–9236. 2017.PubMed/NCBI View Article : Google Scholar | |
Zhu Y, Zhu C, Yang H, Deng J and Fan D: Protective effect of ginsenoside Rg5 against kidney injury via inhibition of NLRP3 inflammasome activation and the MAPK signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. Pharmacol Res. 155(104746)2020.PubMed/NCBI View Article : Google Scholar | |
Cecconi M, Evans L, Levy M and Rhodes A: Sepsis and septic shock. Lancet. 392:75–87. 2018.PubMed/NCBI View Article : Google Scholar | |
Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, Janson A, Kokkola R, Zhang M, Yang H and Tracey KJ: High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 192:565–570. 2000.PubMed/NCBI View Article : Google Scholar | |
Bae JS: Role of high mobility group box 1 in inflammatory disease: Focus on sepsis. Arch Pharm Res. 35:1511–1523. 2012.PubMed/NCBI View Article : Google Scholar | |
Kim JE, Lee W, Yang S, Cho SH, Baek MC, Song GY and Bae JS: Suppressive effects of rare ginsenosides, Rk1 and Rg5, on HMGB1-mediated septic responses. Food Chem Toxicol. 124:45–53. 2019.PubMed/NCBI View Article : Google Scholar | |
Shin YW, Bae EA and Kim DH: Inhibitory effect of ginsenoside Rg5 and its metabolite ginsenoside Rh3 in an oxazolone-induced mouse chronic dermatitis model. Arch Pharm Res. 29:685–690. 2006.PubMed/NCBI View Article : Google Scholar | |
Ahn S, Siddiqi MH, Aceituno VC, Simu SY, Zhang J, Jimenez Perez ZE, Kim YJ and Yang DC: Ginsenoside Rg5:Rk1 attenuates TNF-α/IFN-γ-induced production of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-κB/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages. In Vitro Cell Dev Biol Anim. 52:287–295. 2016.PubMed/NCBI View Article : Google Scholar | |
Chu S, Gu J, Feng L, Liu J, Zhang M, Jia X, Liu M and Yang D: Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses. Int Immunopharmacol. 19:317–326. 2014.PubMed/NCBI View Article : Google Scholar | |
Cheng Z, Zhang M, Ling C, Zhu Y, Ren H, Hong C, Qin J, Liu T and Wang J: Neuroprotective effects of ginsenosides against cerebral ischemia. Molecules. 24(1102)2019.PubMed/NCBI View Article : Google Scholar | |
Lee YY, Park JS, Jung JS, Kim DH and Kim HS: Anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide-stimulated BV2 microglial cells. Int J Mol Sci. 14:9820–9833. 2013.PubMed/NCBI View Article : Google Scholar | |
Liu FF, Zhang Z, Chen W, Gu HY and Yan QJ: Regulatory mechanism of microRNA-377 on CDH13 expression in the cell model of Alzheimer's disease. Eur Rev Med Pharmacol Sci. 22:2801–2808. 2018.PubMed/NCBI View Article : Google Scholar | |
Bolognin S, Blanchard J, Wang X, Basurto-Islas G, Tung YC, Kohlbrenner E, Grundke-Iqbal I and Iqbal K: An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide. Acta Neuropathol. 123:133–151. 2012.PubMed/NCBI View Article : Google Scholar | |
Tao X, Finkbeiner S, Arnold D, Shaywitz A and Greenberg M: Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron. 20:709–726. 1998.PubMed/NCBI View Article : Google Scholar | |
Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G and Silva A: Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell. 79:59–68. 1994.PubMed/NCBI View Article : Google Scholar | |
Kim EJ, Jung IH, Van Le TK, Jeong JJ, Kim NJ and Kim DH: Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice. J Ethnopharmacol. 146:294–299. 2013.PubMed/NCBI View Article : Google Scholar | |
Choi SY, Kim KJ, Song JH and Lee BY: Ginsenoside Rg5 prevents apoptosis by modulating heme-oxygenase-1/nuclear factor E2-related factor 2 signaling and alters the expression of cognitive impairment-associated genes in thermal stress-exposed HT22 cells. J Ginseng Res. 42:225–228. 2018.PubMed/NCBI View Article : Google Scholar | |
Wu J, Jeong HK, Bulin SE, Kwon SW, Park JH and Bezprozvanny I: Ginsenosides protect striatal neurons in a cellular model of Huntington's disease. J Neurosci Res. 87:1904–1912. 2009.PubMed/NCBI View Article : Google Scholar | |
Shao J, Zheng X, Qu L, Zhang H, Yuan H, Hui J, Mi Y, Ma P and Fan D: Ginsenoside Rg5/Rk1 ameliorated sleep via regulating the GABAergic/serotoninergic signaling pathway in a rodent model. Food Funct. 11:1245–1257. 2020.PubMed/NCBI View Article : Google Scholar | |
Yuan CS, Attele AS, Wu JA and Liu D: Modulation of American ginseng on brainstem GABAergic effects in rats. J Ethnopharmacol. 62:215–222. 1998.PubMed/NCBI View Article : Google Scholar | |
Sattler R and Tymianski M: Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol. 24:107–129. 2001.PubMed/NCBI View Article : Google Scholar | |
Yuan Q, Joiner WJ and Sehgal A: A sleep-promoting role for the Drosophila serotonin receptor 1A. Curr Biol. 16:1051–1062. 2006.PubMed/NCBI View Article : Google Scholar | |
Cho YL, Hur SM, Kim JY, Kim JH, Lee DK, Choe J, Won MH, Ha KS, Jeoung D, Han S, et al: Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation. J Biol Chem. 290:467–477. 2015.PubMed/NCBI View Article : Google Scholar | |
Yang YL, Li J, Liu K, Zhang L, Liu Q, Liu B and Qi LW: Ginsenoside Rg5 increases cardiomyocyte resistance to ischemic injury through regulation of mitochondrial hexokinase-II and dynamin-related protein 1. Cell Death Dis. 8(e2625)2017.PubMed/NCBI View Article : Google Scholar | |
Wojdasiewicz P, Poniatowski Ł and Szukiewicz D: The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014(561459)2014.PubMed/NCBI View Article : Google Scholar | |
Cheng W, Jing J, Wang Z, Wu D and Huang Y: Chondroprotective effects of ginsenoside Rg1 in human osteoarthritis chondrocytes and a rat model of anterior cruciate ligament transection. Nutrients. 9(263)2017.PubMed/NCBI View Article : Google Scholar | |
Chen Y, Lin S, Sun Y, Pan X, Xiao L, Zou L, Ho KW and Li G: Translational potential of ginsenoside Rb1 in managing progression of osteoarthritis. J Orthop Translat. 6:27–33. 2016.PubMed/NCBI View Article : Google Scholar | |
Zhang P: Ginsenoside-Rg5 treatment inhibits apoptosis of chondrocytes and degradation of cartilage matrix in a rat model of osteoarthritis. Oncol Rep. 37:1497–1502. 2017.PubMed/NCBI View Article : Google Scholar | |
Wang T, Liu Q, Tjhioe W, Zhao J, Lu A, Zhang G, Tan RX, Zhou M, Xu J and Feng HT: Therapeutic potential and outlook of alternative medicine for osteoporosis. Current Drug Targets. 18:1051–1068. 2017.PubMed/NCBI View Article : Google Scholar | |
Siddiqi MH, Siddiqi MZ, Ahn S, Kang S, Kim YJ, Veerappan K, Yang DU and Yang DC: Stimulative effect of ginsenosides Rg5:Rk1 on murine osteoblastic MC3T3-E1 cells. Phytother Res. 28:1447–1455. 2014.PubMed/NCBI View Article : Google Scholar | |
Ponnuraj SP, Siraj F, Kang S, Noh HY, Min JW, Kim YJ and Yang DC: Amelioration of insulin resistance by Rk1 + Rg5 complex under endoplasmic reticulum stress conditions. Pharmacognosy Res. 6:292–296. 2014.PubMed/NCBI View Article : Google Scholar | |
Xiao N, Lou MD, Lu YT, Yang LL, Liu Q, Liu B, Qi LW and Li P: Ginsenoside Rg5 attenuates hepatic glucagon response via suppression of succinate-associated HIF-1α induction in HFD-fed mice. Diabetologia. 60:1084–1093. 2017.PubMed/NCBI View Article : Google Scholar | |
Xiao N, Yang LL, Yang YL, Liu LW, Li J, Liu B, Liu K, Qi LW and Li P: Ginsenoside Rg5 inhibits succinate-associated lipolysis in adipose tissue and prevents muscle insulin resistance. Front Pharmacol. 8(43)2017.PubMed/NCBI View Article : Google Scholar | |
Bai L, Gao J, Wei F, Zhao J, Wang D and Wei J: Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes. Front Pharmacol. 9(423)2018.PubMed/NCBI View Article : Google Scholar | |
Park HJ, Kim JH and Shim I: Anti-obesity effects of ginsenosides in high-fat diet-fed rats. Chin J Integr Med. 25:895–901. 2019.PubMed/NCBI View Article : Google Scholar | |
Liu H, Liu M, Jin Z, Yaqoob S, Zheng M, Cai D, Liu J and Guo S: Ginsenoside Rg2 inhibits adipogenesis in 3T3-L1 preadipocytes and suppresses obesity in high-fat-diet-induced obese mice through the AMPK pathway. Food Funct. 10:3603–3614. 2019.PubMed/NCBI View Article : Google Scholar | |
Liu H, Wang J, Liu M, Zhao H, Yaqoob S, Zheng M, Cai D and Liu J: Antiobesity effects of ginsenoside Rg1 on 3T3-L1 preadipocytes and high fat diet-induced obese mice mediated by AMPK. Nutrients. 10(830)2018.PubMed/NCBI View Article : Google Scholar | |
Zhang L, Zhang L, Wang X and Si H: Anti-adipogenic effects and mechanisms of ginsenoside Rg3 in pre-adipocytes and obese mice. Front Pharmacol. 8(113)2017.PubMed/NCBI View Article : Google Scholar | |
Yesmin Simu S, Ahn S, Castro-Aceituno V and Yang DC: Ginsenoside Rg5: Rk1 exerts an anti-obesity effect on 3T3-L1 Cell Line by the downregulation of PPARγ and CEBPα. Iran J Biotechnol. 15:252–259. 2017.PubMed/NCBI View Article : Google Scholar |