Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the NF-κB and PI3K/Akt/mTOR pathways

International Immunopharmacology

Volumn 23, Issue 1, 2014, Pages 77-84

  Wang, Yao ^a   Liu, Yi ^b   Zhang, Xiao Yu ^a   Xu, Li Hui ^a   Ouyang, Dong Yun ^a   Liu, Kun Peng ^a   Pan, Hao ^a   He, Jian ^a   He, Xian Hui ^a  

^a JINAN UNIVERSITY   (China)

^b PEKING UNION MEDICAL COLLEGE   (China)

Author keywords

Ginsenoside Rg1; Interleukin 6; Lipopolysaccharide; Macrophages; mTOR; Tumor necrosis factor

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; GINSENOSIDE RG 1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; 2-(4-MORPHOLINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE; CHROMONE DERIVATIVE; GINSENOSIDE; MORPHOLINE DERIVATIVE; TARGET OF RAPAMYCIN KINASE; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG CYTOTOXICITY; DRUG DOSE COMPARISON; DRUG MEGADOSE; ENZYME ACTIVATION; IMMUNOMODULATION; IMMUNOREGULATION; INNATE IMMUNITY; LOW DRUG DOSE; MOUSE; NONHUMAN; PERITONEUM MACROPHAGE; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL LINE; DRUG EFFECTS; GENETICS; IMMUNOLOGY; METABOLISM;

ANIMALS; CELL LINE; CHROMONES; GINSENOSIDES; IMMUNITY, INNATE; IMMUNOMODULATION; INTERLEUKIN-6; LIPOPOLYSACCHARIDES; MACROPHAGES, PERITONEAL; MICE; MICE, INBRED C57BL; MORPHOLINES; NF-KAPPA B; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84906960598     PISSN: 15675769     EISSN: 18781705     Source Type: Journal    
DOI: 10.1016/j.intimp.2014.07.028     Document Type: Article

References (43)

1. J.T. Xie, S. McHendale, and C.S. Yuan Ginseng and diabetes Am J Chin Med 33 2005 397 404
2. L. Jia, and Y. Zhao Current evaluation of the millennium phytomedicine - ginseng (I): etymology, pharmacognosy, phytochemistry, market and regulations Curr Med Chem 16 2009 2475 2484
3. Z.Q. Liu, X.Y. Luo, G.Z. Liu, Y.P. Chen, Z.C. Wang, and Y.X. Sun 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 51 2003 2555 2558
4. D.F. Qu, H.J. Yu, Z. Liu, D.F. Zhang, Q.J. Zhou, and H.L. Zhang Ginsenoside Rg1 enhances immune response induced by recombinant Toxoplasma gondii SAG1 antigen Vet Parasitol 179 2011 28 34
5. F. Su, L. Yuan, L. Zhang, and S. Hu Ginsenosides Rg1 and Re act as adjuvant via TLR4 signaling pathway Vaccine 30 2012 4106 4112
6. J. Sun, X. Song, and S. Hu Ginsenoside Rg1 and aluminum hydroxide synergistically promote immune responses to ovalbumin in BALB/c mice Clin Vaccine Immunol 15 2008 303 307
7. K.W. Leung, Y.K. Cheng, N.K. Mak, K.K. Chan, T.P. Fan, and R.N. Wong Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells FEBS Lett 580 2006 3211 3216
8. J. Wu, Z. Pan, M. Cheng, Y. Shen, H. Yu, and Q. Wang Ginsenoside Rg1 facilitates neural differentiation of mouse embryonic stem cells via GR-dependent signaling pathway Neurochem Int 62 2013 92 102
9. L.S. Chan, P.Y. Yue, Y.Y. Wong, and R.N. Wong MicroRNA-15b contributes to ginsenoside-Rg1-induced angiogenesis through increased expression of VEGFR-2 Biochem Pharmacol 86 2013 392 400
10. K.W. Leung, Y.L. Pon, R.N. Wong, and A.S. Wong Ginsenoside-Rg1 induces vascular endothelial growth factor expression through the glucocorticoid receptor-related phosphatidylinositol 3-kinase/Akt and beta-catenin/T-cell factor-dependent pathway in human endothelial cells J Biol Chem 281 2006 36280 36288
11. M. Laplante, and D.M. Sabatini mTOR signaling in growth control and disease Cell 149 2012 274 293
12. A.W. Thomson, H.R. Turnquist, and G. Raimondi Immunoregulatory functions of mTOR inhibition Nat Rev Immunol 9 2009 324 337
13. W.J. Oh, and E. Jacinto mTOR complex 2 signaling and functions Cell Cycle 10 2011 2305 2316
14. C.C. Thoreen, L. Chantranupong, H.R. Keys, T. Wang, N.S. Gray, and D.M. Sabatini A unifying model for mTORC1-mediated regulation of mRNA translation Nature 485 2012 109 113
15. J.D. Powell, K.N. Pollizzi, E.B. Heikamp, and M.R. Horton Regulation of immune responses by mTOR Annu Rev Immunol 30 2012 39 68
16. A.C. Hsieh, Y. Liu, M.P. Edlind, N.T. Ingolia, M.R. Janes, and A. Sher The translational landscape of mTOR signalling steers cancer initiation and metastasis Nature 485 2012 55 61
17. T. Weichhart, G. Costantino, M. Poglitsch, M. Rosner, M. Zeyda, and K.M. Stuhlmeier The TSC-mTOR signaling pathway regulates the innate inflammatory response Immunity 29 2008 565 577
18. F. Schmitz, A. Heit, S. Dreher, K. Eisenacher, J. Mages, and T. Haas Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells Eur J Immunol 38 2008 2981 2992
19. J. He, Y. Wang, L.H. Xu, J. Qiao, D.Y. Ouyang, and X.H. He Cucurbitacin IIa induces caspase-3-dependent apoptosis and enhances autophagy in lipopolysaccharide-stimulated RAW 264.7 macrophages Int Immunopharmacol 16 2013 27 34
20. D.Y. Ouyang, L.H. Xu, X.H. He, Y.T. Zhang, L.H. Zeng, and J.Y. Cai Autophagy is differentially induced in prostate cancer LNCaP, DU145 and PC-3 cells via distinct splicing profiles of ATG5 Autophagy 9 2013 20 32
21. Y.C. Lu, W.C. Yeh, and P.S. Ohashi LPS/TLR4 signal transduction pathway Cytokine 42 2008 145 151
22. B.T. Rouse, and S. Sehrawat Immunity and immunopathology to viruses: what decides the outcome? Nat Rev Immunol 10 2010 514 526
23. Y. Yamamoto, and R.B. Gaynor IkappaB kinases: key regulators of the NF-kappaB pathway Trends Biochem Sci 29 2004 72 79
24. M.S. Hayden, and S. Ghosh Shared principles in NF-kappaB signaling Cell 132 2008 344 362
25. W. Cao, S. Manicassamy, H. Tang, S.P. Kasturi, A. Pirani, and N. Murthy Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway Nat Immunol 9 2008 1157 1164
26. P.J. Murray, and T.A. Wynn Protective and pathogenic functions of macrophage subsets Nat Rev Immunol 11 2011 723 737
27. B. Behm, P. Babilas, M. Landthaler, and S. Schreml Cytokines, chemokines and growth factors in wound healing J Eur Acad Dermatol Venereol 26 2012 812 820
28. A. Bohan, W.S. Chen, L.A. Denson, M.A. Held, and J.L. Boyer Tumor necrosis factor alpha-dependent up-regulation of Lrh-1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis J Biol Chem 278 2003 36688 36698
29. L. Summers deLuca, and J.L. Gommerman Fine-tuning of dendritic cell biology by the TNF superfamily Nat Rev Immunol 12 2012 339 351
30. G.E. Glass, J.K. Chan, A. Freidin, M. Feldmann, N.J. Horwood, and J. Nanchahal TNF-alpha promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells Proc Natl Acad Sci U S A 108 2011 1585 1590
31. J. Wang, V.C. Asensio, and I.L. Campbell Cytokines and chemokines as mediators of protection and injury in the central nervous system assessed in transgenic mice Curr Top Microbiol Immunol 265 2002 23 48
32. L.W. Cheung, K.W. Leung, C.K. Wong, R.N. Wong, and A.S. Wong Ginsenoside-Rg1 induces angiogenesis via non-genomic crosstalk of glucocorticoid receptor and fibroblast growth factor receptor-1 Cardiovasc Res 89 2011 419 425
33. S. Sengupta, S.A. Toh, L.A. Sellers, J.N. Skepper, P. Koolwijk, and H.W. Leung Modulating angiogenesis: the yin and the yang in ginseng Circulation 110 2004 1219 1225
34. J.A. Deane, and D.A. Fruman Phosphoinositide 3-kinase: diverse roles in immune cell activation Annu Rev Immunol 22 2004 563 598
35. J. Du, B. Cheng, X. Zhu, and C. Ling Ginsenoside Rg1, a novel glucocorticoid receptor agonist of plant origin, maintains glucocorticoid efficacy with reduced side effects J Immunol 187 2011 942 950
36. J.W. Hwang, J.H. Oh, H.S. Yoo, Y.W. Lee, C.K. Cho, and K.R. Kwon Mountain ginseng extract exhibits anti-lung cancer activity by inhibiting the nuclear translocation of NF-kappaB Am J Chin Med 40 2012 187 202
37. A.Y. Choo, S.O. Yoon, S.G. Kim, P.P. Roux, and J. Blenis Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation Proc Natl Acad Sci U S A 105 2008 17414 17419
38. L.S. Tain, H. Mortiboys, R.N. Tao, E. Ziviani, O. Bandmann, and A.J. Whitworth Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss Nat Neurosci 12 2009 1129 1135
39. A.K. Baker, R. Wang, N. Mackman, and J.P. Luyendyk Rapamycin enhances LPS induction of tissue factor and tumor necrosis factor-alpha expression in macrophages by reducing IL-10 expression Mol Immunol 46 2009 2249 2255
40. A. Rhule, S. Navarro, J.R. Smith, and D.M. Shepherd Panax notoginseng attenuates LPS-induced pro-inflammatory mediators in RAW264.7 cells J Ethnopharmacol 106 2006 121 128
41. Y. Song, F. Zhao, L. Zhang, Y. Du, T. Wang, and F. Fu Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro Fitoterapia 91 2013 173 179
42. Y. Wang, B.X. Wang, T.H. Liu, M. Minami, T. Nagata, and T. Ikejima Metabolism of ginsenoside Rg1 by intestinal bacteria. II. Immunological activity of ginsenoside Rg1 and Rh1 Acta Pharmacol Sin 21 2000 792 796
43. H.K. Rim, C.H. Yun, J.S. Shin, Y.W. Cho, D.S. Jang, and J.H. Ryu 5,6,7-Trimethoxyflavone suppresses pro-inflammatory mediators in lipopolysaccharide-induced RAW 264.7 macrophages and protects mice from lethal endotoxin shock Food Chem Toxicol 62 2013 847 855