Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Korean Red Ginseng and Korean black ginseng extracts, JP5 and BG1, prevent hepatic oxidative stress and inflammation induced by environmental heat stress

  • Song, Ji-Hyeon (Department of Food Science and Biotechnology, College of Life Science, CHA University) ;
  • Kim, Kui-Jin (Department of Food Science and Biotechnology, College of Life Science, CHA University) ;
  • Chei, Sungwoo (Department of Food Science and Biotechnology, College of Life Science, CHA University) ;
  • Seo, Young-Jin (Department of Food Science and Biotechnology, College of Life Science, CHA University) ;
  • Lee, Kippeum (Department of Food Science and Biotechnology, College of Life Science, CHA University) ;
  • Lee, Boo-Yong (Department of Food Science and Biotechnology, College of Life Science, CHA University)
  • Received : 2018.09.27
  • Accepted : 2018.12.11
  • Published : 2020.03.15
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Abstract

Background: Continuous exposure to high temperatures can lead to heat stress. This stress response alters the expression of multiple genes and can contribute to the onset of various diseases. In particular, heat stress induces oxidative stress by increasing the production of reactive oxygen species. The liver is an essential organ that plays a variety of roles, such as detoxification and protein synthesis. Therefore, it is important to protect the liver from oxidative stress caused by heat stress. Korean ginseng has a variety of beneficial biological properties, and our previous studies showed that it provides an effective defense against heat stress. Methods: We investigated the ability of Korean Red Ginseng and Korean black ginseng extracts (JP5 and BG1) to protect against heat stress using a rat model. We then confirmed the active ingredients and mechanism of action using a cell-based model. Results: Heat stress significantly increased gene and protein expression of oxidative stress-related factors such as catalase and SOD2, but treatment with JP5 (Korean Red Ginseng extract) and BG1 (Korean black ginseng extract) abolished this response in both liver tissue and HepG2 cells. In addition, JP5 and BG1 inhibited the expression of inflammatory proteins such as p-NF-κB and tumor necrosis factor alpha-α. In particular, JP5 and BG1 decreased the expression of components of the NLRP3 inflammasome, a key inflammatory signaling factor. Thus, JP5 and BG1 inhibited both oxidative stress and inflammation. Conclusions: JP5 and BG1 protect against oxidative stress and inflammation induced by heat stress and help maintain liver function by preventing liver damage.

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References

  1. Myers SS, Bernstein A. The coming health crisis: indirect health effects of global climate change. F1000 Biol Rep 2011;3:3. https://doi.org/10.3410/B3-3
  2. McGeehin MA, Mirabelli M. The potential impacts of climate variability and change on temperature-related morbidity and mortality in the United States. Environ Health Perspect 2001;109(Suppl 2):185-9.
  3. Sulman FG, Danon A, Pfeifer Y, Tal E, Weller CP. Urinalysis of patients suffering from climatic heat stress (Sharav). Int J Biometeorol 1970;14:45-53. https://doi.org/10.1007/BF01440676
  4. Keim SM, Guisto JA, Sullivan Jr JB. Environmental thermal stress. Ann Agric Environ Med 2002;9:1-15.
  5. Jian B, Hsieh CH, Chen J, Choudhry M, Bland K, Chaudry I, Raju R. Activation of endoplasmic reticulum stress response following trauma-hemorrhage. Biochim Biophys Acta 2008;1782:621-6. https://doi.org/10.1016/j.bbadis.2008.08.007
  6. Sonna LA, Wenger CB, Flinn S, Sheldon HK, Sawka MN, Lilly CM. Exertional heat injury and gene expression changes: a DNA microarray analysis study. J Appl Physiol (1985) 2004;96:1943-53. https://doi.org/10.1152/japplphysiol.00886.2003
  7. Ando M, Katagiri K, Yamamoto S, Wakamatsu K, Kawahara I, Asanuma S, Usuda M, Sasaki K. Age-related effects of heat stress on protective enzymes for peroxides and microsomal monooxygenase in rat liver. Environ Health Perspect 1997;105:726-33. https://doi.org/10.1289/ehp.97105726
  8. Droge W. Free radicals in the physiological control of cell function. Physiol Rev 2002;82:47-95. https://doi.org/10.1152/physrev.00018.2001
  9. Gutteridge JM, Halliwell B. Comments on review of free radicals in biology and medicine. In: Halliwell Barry, Gutteridge John MC, editors. Free radic biol med. 2nd ed, vol. 12; 1992. p. 93-5.
  10. Xia F,Wang C, Jin Y, Liu Q, Meng Q, Liu K, Sun H. Luteolin protects HUVECs from TNF-alpha-induced oxidative stress andinflammation via its effects onthe Nox4/ROS-NF-kappaB and MAPK pathways. J Atheroscler Thromb 2014;21:768-83. https://doi.org/10.5551/jat.23697
  11. Jiang F, Gao Y, Dong C, Xiong S. ODC1 inhibits the inflammatory response and ROS-induced apoptosis in macrophages. Biochem Biophys Res Commun 2018;504(4):734-41. https://doi.org/10.1016/j.bbrc.2018.09.023
  12. Andersen HR, Nielsen JB, Nielsen F, Grandjean P. Antioxidative enzyme activities in human erythrocytes. Clin Chem 1997;43:562-8. https://doi.org/10.1093/clinchem/43.4.562
  13. Wang H, Wang L, Li NL, Li JT, Yu F, Zhao YL, Wang L, Yi J, Wang L, Bian JF, et al. Subanesthetic isoflurane reduces zymosan-induced inflammation in murine Kupffer cells by inhibiting ROS-activated p38 MAPK/NF-kappaB signaling. Oxid Med Cell Longev 2014;2014:851692. https://doi.org/10.1155/2014/851692
  14. Park J, Min JS, Kim B, Chae UB, Yun JW, Choi MS, Kong IK, Chang KT, Lee DS. Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-kappaB pathways. Neurosci Lett 2015;584:191-6. https://doi.org/10.1016/j.neulet.2014.10.016
  15. Sakurai H. Targeting of TAK1 in inflammatory disorders and cancer. Trends Pharmacol Sci 2012;33:522-30. https://doi.org/10.1016/j.tips.2012.06.007
  16. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 2015;21:677-87. https://doi.org/10.1038/nm.3893
  17. Abdel-Misih SR, Bloomston M. Liver anatomy. Surg Clin North Am 2010;90:643-53. https://doi.org/10.1016/j.suc.2010.04.017
  18. Brockmoller J, Roots I. Assessment of liver metabolic function. Clinical implications. Clin Pharmacokinet 1994;27:216-48. https://doi.org/10.2165/00003088-199427030-00005
  19. Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 2004;431:461-6. https://doi.org/10.1038/nature02924
  20. Bishayee A. The role of inflammation and liver cancer. Adv Exp Med Biol 2014;816:401-35. https://doi.org/10.1007/978-3-0348-0837-8_16
  21. Kim KJ, Hong HD, Lee OH, Lee BY. The effects of Acanthopanax senticosus on global hepatic gene expression in rats subjected to heat environmental stress. Toxicology 2010;278:217-23. https://doi.org/10.1016/j.tox.2010.04.010
  22. Song J-H, Kim K-J, Choi S-Y, Koh E-J, Park J, Lee B-Y. Korean ginseng extract ameliorates abnormal immune response through the regulation of inflammatory constituents in Sprague Dawley rat subjected to environmental heat stress. Journal of Ginseng Research 2018.
  23. Koh EJ, Kim KJ, Choi J, Jeon HJ, Seo MJ, Lee BY. Ginsenoside Rg1 suppresses early stage of adipocyte development via activation of C/EBP homologous protein-10 in 3T3-L1 and attenuates fat accumulation in high fat diet-induced obese zebrafish. J Ginseng Res 2017;41:23-30. https://doi.org/10.1016/j.jgr.2015.12.005
  24. Kim KJ, Yoon KY, Hong HD, Lee BY. Role of the red ginseng in defense against the environmental heat stress in Sprague Dawley rats. Molecules 2015;20:20240-53. https://doi.org/10.3390/molecules201119692
  25. Hou J, Xue J, Lee M, Liu L, Zhang D, Sun M, Zheng Y, Sung C. Ginsenoside Rh2 improves learning and memory in mice. J Med Food 2013;16:772-6. https://doi.org/10.1089/jmf.2012.2564
  26. Hwang J-B, Ha J-H, Hawer W-D, Nahmgung B, Lee B-Y. Ginsenoside contents of Korean white ginseng and taegeuk ginseng with various sizes and cultivation years. Korean Journal of Food Science and Technology 2005;37:508-12.
  27. Lee B-Y, Kim E-J, Park D-J, Hong S-I, Chun H-S. Composition of saponin and free sugar of some white ginsengs with processing conditions. Korean Journal of Food Science and Technology 1996;28:922-7.
  28. Kim S-N, Kang S-J. Effects of black ginseng (9 times-steaming ginseng) on hypoglycemic action and changes in the composition of ginsenosides on the steaming process. Korean Journal of Food Science and Technology 2009;41:77-81.
  29. Gonzalez-Ramos R, Defrere S, Devoto L. Nuclear factor-kappaB: a main regulator of inflammation and cell survival in endometriosis pathophysiology. Fertil Steril 2012;98:520-8. https://doi.org/10.1016/j.fertnstert.2012.06.021
  30. Glover M, Soni S, Ren Q, Maclennan GT, Fu P, Gupta S. Influence of chronic inflammation on Bcl-2 and PCNA expression in prostate needle biopsy specimens. Oncol Lett 2017;14:3927-34. https://doi.org/10.3892/ol.2017.6668
  31. Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR. Cell signaling through protein kinase C oxidation and activation. Int J Mol Sci 2012;13:10697-721. https://doi.org/10.3390/ijms130910697
  32. Sabuncuoglu S, Eken A, Aydin A, Ozgunes H, Orhan H. Cofactor metals and antioxidant enzymes in cisplatin-treated rats: effect of antioxidant intervention. Drug Chem Toxicol 2015;38:375-82. https://doi.org/10.3109/01480545.2014.974107
  33. Sakaida I, Okita K. The role of oxidative stress in NASH and fatty liver model. Hepatol Res 2005;33:128-31. https://doi.org/10.1016/j.hepres.2005.09.019
  34. Natarajan SK, Thangaraj KR, Eapen CE, Ramachandran A, Mukhopadhya A, Mathai M, Seshadri L, Peedikayil A, Ramakrishna B, Balasubramanian KA. Liver injury in acute fatty liver of pregnancy: possible link to placental mitochondrial dysfunction and oxidative stress. Hepatology 2010;51:191-200. https://doi.org/10.1002/hep.23245
  35. Mohanan P, Subramaniyam S, Mathiyalagan R, Yang DC. Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions. J Ginseng Res 2018;42:123-32. https://doi.org/10.1016/j.jgr.2017.01.008
  36. Wang X, Chen L, Wang T, Jiang X, Zhang H, Li P, Lv B, Gao X. Ginsenoside Rg3 antagonizes adriamycin-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. https://doi.org/10.1016/j.phymed.2015.06.010
  37. Wei X, Su F, Su X, Hu T, Hu S. Stereospecific antioxidant effects of ginsenoside Rg3 on oxidative stress induced by cyclophosphamide in mice. Fitoterapia 2012;83:636-42. https://doi.org/10.1016/j.fitote.2012.01.006

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