Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Comparative transcriptome analysis of the protective effects of Korean Red Ginseng against the influence of bisphenol A in the liver and uterus of ovariectomized mice

  • Lee, Jeonggeun (Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University) ;
  • Park, Joonwoo (Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University) ;
  • Lee, Yong Yook (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Lee, YoungJoo (Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University)
  • Received : 2019.07.09
  • Accepted : 2020.01.31
  • Published : 2020.05.15
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Abstract

Background: Bisphenol A (BPA), known as an endocrine disruptor, is widely used in the world. BPA is reported to cause inflammation-related diseases. Korean Red Ginseng (KRG) has been used safely in human for a long time for the treatment of diverse diseases. KRG has been reported of its mitigating effect on menopausal symptoms and suppress adipose inflammation. Here, we investigate the protective effect of orally administered KRG on the impacts of BPA in the liver and uterus of menopausal mice model. Methods: The transcriptome analysis for the effects of BPA on mice liver was evaluated by Gene Expression Omnibus (GEO) database-based data (GSE26728). In vivo assay to evaluate the protective effect of KRG on BPA impact in ovariectomized (OVX) mice were designed and analyzed by RNA sequencing. Results: We first demonstrated that BPA induced 12 kinds of gene set in the liver of normal mice. The administration of BPA and KRG did not change body, liver, and uterine weight in OVX mice. KRG downregulated BPA-induced inflammatory response and chemotaxis-related gene expression. Several gene set enrichment analysis (GSEA)-derived inflammatory response genes increased by BPA were inhibited by KRG in OVX mice. Conclusion: Our data suggest that BPA has commonly influenced inflammatory response effects on both normal and OVX mice. KRG protects against BPA impact of inflammatory response and chemotaxis in OVX mouse models. Our comparative analysis will provide new insight into the efficacy of KRG on endocrine disrupting chemicals and OVX mouse.

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References

  1. Murata M, Kang JH. Bisphenol A (BPA) and cell signaling pathways. Biotechnology Advances 2018;36(1):311-27. https://doi.org/10.1016/j.biotechadv.2017.12.002
  2. Vermeirssen EL, Dietschweiler C, Werner I, Burkhardt M. Corrosion protection products as a source of bisphenol A and toxicity to the aquatic environment. Water Research 2017;123:586-93. https://doi.org/10.1016/j.watres.2017.07.006
  3. Vitku J, Kolatorova L, Franekova L, Blahos J, Simkova M, Duskova M, Skodova T, Starka L. Endocrine disruptors of the bisphenol and paraben families and bone metabolism. Physiological Research 2018;67.
  4. Skledar DG, Masic LP. Bisphenol A and its analogs: do their metabolites have endocrine activity? Environmental Toxicology and Pharmacology 2016;47:182-99. https://doi.org/10.1016/j.etap.2016.09.014
  5. Park C, Lee J, Kong B, Park J, Song H, Choi K, Guon T, Lee Y. The effects of bisphenol A, benzyl butyl phthalate, and di (2-ethylhexyl) phthalate on estrogen receptor alpha in estrogen receptor-positive cells under hypoxia. Environmental Pollution 2019;248:774-81. https://doi.org/10.1016/j.envpol.2019.02.069
  6. Acconcia F, Pallottini V, Marino M. Molecular mechanisms of action of BPA. Dose-response 2015;13(4). 1559325815610582.
  7. Yang M, Chen M, Wang J, Xu M, Sun J, Ding L, Lv X, Ma Q, Bi Y, Liu R. Bisphenol A promotes adiposity and inflammation in a nonmonotonic dose-response way in 5-week-old male and female C57BL/6J mice fed a low-calorie diet. Endocrinology 2016;157(6):2333-45. https://doi.org/10.1210/en.2015-1926
  8. Marmugi A, Ducheix S, Lasserre F, Polizzi A, Paris A, Priymenko N, Bertrand-Michel J, Pineau T, Guillou H, Martin PG. Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver. Hepatology 2012;55(2):395-407. https://doi.org/10.1002/hep.24685
  9. Vabre P, Gatimel N, Moreau J, Gayrard V, Picard-Hagen N, Parinaud J, Leandri RD. Environmental pollutants, a possible etiology for premature ovarian insufficiency: a narrative review of animal and human data. Environmental Health 2017;16(1):37. https://doi.org/10.1186/s12940-017-0242-4
  10. Kopalli SR, Cha KM, Ryu JH, Lee SH, Jeong MS, Hwang SY, Lee YJ, Song HW, Kim SN, Kim JC. Korean red ginseng improves testicular ineffectiveness in aging rats by modulating spermatogenesis-related molecules. Experimental Gerontology 2017;90:26-33. https://doi.org/10.1016/j.exger.2017.01.020
  11. Shin BK, Kwon SW, Park JH. Chemical diversity of ginseng saponins from Panax ginseng. Journal of Ginseng Research 2015;39(4):287-98. https://doi.org/10.1016/j.jgr.2014.12.005
  12. Song H, Lee YJ. Inhibition of hypoxia-induced cyclooxygenase-2 by Korean red ginseng is dependent on peroxisome proliferator-activated receptor gamma. Journal of Ginseng Research 2017;41(3):240-6. https://doi.org/10.1016/j.jgr.2016.04.001
  13. Kim K. Effect of ginseng and ginsenosides on melanogenesis and their mechanism of action. Journal of Ginseng Research 2015;39(1):1-6. https://doi.org/10.1016/j.jgr.2014.10.006
  14. Lee DC, Lau AS. Effects of Panax ginseng on tumor necrosis factor-a-mediated inflammation: a mini-review. Molecules 2011;16(4):2802-16. https://doi.org/10.3390/molecules16042802
  15. Kang SW, Park JH, Seok H, Park HJ, Chung JH, Kim CJ, Kim YO, Han YR, Hong D, Kim YS. The effects of Korea red ginseng on inflammatory cytokines and apoptosis in rat model with chronic nonbacterial prostatitis. BioMed Research International 2019. 2019.
  16. Lee H, Choi J, Shin SS, Yoon M. Effects of Korean red ginseng (Panax ginseng) on obesity and adipose inflammation in ovariectomized mice. Journal of Ethnopharmacology 2016;178:229-37. https://doi.org/10.1016/j.jep.2015.12.017
  17. Takemura H, Ma J, Sayama K, Terao Y, Zhu BT, Shimoi K. In vitro and in vivo estrogenic activity of chlorinated derivatives of bisphenol A. Toxicology 2005;207(2):215-21. https://doi.org/10.1016/j.tox.2004.09.015
  18. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences 2005;102(43):15545-50. https://doi.org/10.1073/pnas.0506580102
  19. Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov JP, Tamayo P. The molecular signatures database hallmark gene set collection. Cell Systems 2015;1(6):417-25. https://doi.org/10.1016/j.cels.2015.12.004
  20. In G, Ahn NG, Bae B-S, Lee MW, Park HW, Jang KH, Cho BG, Han CK, Park CK, Kwak YS. In situ analysis of chemical components induced by steaming between fresh ginseng, steamed ginseng, and red ginseng. Journal of Ginseng Research 2017;41(3):361-9. https://doi.org/10.1016/j.jgr.2016.07.004
  21. Matthews JB, Twomey K, Zacharewski TR. In vitro and in vivo interactions of bisphenol A and its metabolite, bisphenol A glucuronide, with estrogen receptors ${\alpha}$ and ${\beta}$. Chemical Research in Toxicology 2001;14(2):149-57. https://doi.org/10.1021/tx0001833
  22. An BS, Kang SK, Shin JH, Jeung EB. Stimulation of calbindin-D9k mRNA expression in the rat uterus by octyl-phenol, nonylphenol and bisphenol. Molecular and Cellular Endocrinology 2002;191(2):177-86. https://doi.org/10.1016/S0303-7207(02)00042-4
  23. Jie D, Ying X, Xiaoping M, Jinna A, Xiudong Y, Zhiqiang L, Na L. Estrogenic effect of the extract of Renshen (Radix Ginseng) on reproductive tissues in immature mice. Journal of Traditional Chinese Medicine 2015;35(4):460-7. https://doi.org/10.1016/S0254-6272(15)30125-4
  24. Lee JH, Lee HJ, Yang M, Moon C, Kim JC, Bae CS, Jo SK, Jang JS, Kim SH. Effect of Korean Red Ginseng on radiation-induced bone loss in C3H/HeN mice. Journal of Ginseng Research 2013;37(4):435. https://doi.org/10.5142/jgr.2013.37.435
  25. Xu Y, Ding J, An JN, Qu YK, Li X, Ma XP, Zhang YM, Dai GJ, Lin N. Effect of the interaction of veratrum nigrum with panax ginseng on estrogenic activity in vivo and in vitro. Scientific Reports 2016;6:26924. https://doi.org/10.1038/srep26924
  26. Kim B-B, Kim M, Park YH, Ko Y, Park JB. Short-term application of dexamethasone on stem cells derived from human gingiva reduces the expression of RUNX2 and ${\beta}$-catenin. Journal of International Medical Research 2017;45(3):993-1006. https://doi.org/10.1177/0300060517701035
  27. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols 2009;4(1):44. https://doi.org/10.1038/nprot.2008.211
  28. Wang J, Cui C, Fu L, Xiao Z, Xie N, Liu Y, Yu L, Wang H, Luo B. Genomic expression profiling and bioinformatics analysis on diabetic nephrology with ginsenoside Rg3. Molecular Medicine Reports 2016;14(2):1162-72. https://doi.org/10.3892/mmr.2016.5349
  29. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nature Reviews Genetics 2009;10(1):57. https://doi.org/10.1038/nrg2484
  30. Wang K, Jiang S, Sun C, Lin Y, Yin R, Wang Y, Zhang M. The spatial and temporal transcriptomic landscapes of ginseng, Panax ginseng CA Meyer. Scientific Reports 2015;5:18283. https://doi.org/10.1038/srep18283
  31. Satoh Ji, Yamamoto Y, Asahina N, Kitano S, Kino Y. RNA-Seq data mining: downregulation of NeuroD6 serves as a possible biomarker for alzheimer's disease brains, vol. 2014. Disease markers; 2014.
  32. Yang M, Lee HS, Hwang MW, Jin M. Effects of Korean red ginseng (Panax Ginseng Meyer) on bisphenol A exposure and gynecologic complaints: single blind, randomized clinical trial of efficacy and safety. BMC Complementary and Alternative Medicine 2014;14(1):265. https://doi.org/10.1186/1472-6882-14-265
  33. Yuan M, Hu M, Lou Y, Wang Q, Mao L, Zhan Q, Jin F. Environmentally relevant levels of bisphenol A affect uterine decidualization and embryo implantation through the estrogen receptor/serum and glucocorticoid-regulated kinase 1/epithelial sodium ion channel ${\alpha}$-subunit pathway in a mouse model. Fertility and Sterility 2018;109(4):735-44. e1. https://doi.org/10.1016/j.fertnstert.2017.12.003
  34. Hong M, Lee YH, Kim S, Suk KT, Bang CS, Yoon JH, Baik GH, Kim DJ, Kim MJ. Anti-inflammatory and antifatigue effect of Korean Red Ginseng in patients with nonalcoholic fatty liver disease. Journal of Ginseng Research 2016;40(3):203-10. https://doi.org/10.1016/j.jgr.2015.07.006
  35. Lee HJ, Cho SH. Therapeutic effects of Korean red ginseng extract in a murine model of atopic dermatitis: anti-pruritic and anti-inflammatory mechanism. Journal of Korean Medical Science 2017;32(4):679-87. https://doi.org/10.3346/jkms.2017.32.4.679
  36. Hong CE, Lyu SY. Anti-inflammatory and anti-oxidative effects of Korean red ginseng extract in human keratinocytes. Immune Network 2011;11(1):42-9. https://doi.org/10.4110/in.2011.11.1.42
  37. Saba E, Jeong D, Irfan M, Lee YY, Park SJ, Park CK, Rhee MH. Anti-inflammatory activity of Rg3-enriched Korean red ginseng extract in murine model of sepsis. Evidence-Based Complementary and Alternative Medicine 2018;2018.
  38. Song H, Park J, Choi K, Lee J, Chen J, Park HJ, Yu BI, Iida M, Rhyu MR, Lee Y. Ginsenoside Rf inhibits cyclooxygenase-2 induction via peroxisome proliferatoreactivated receptor gamma in A549 cells. Journal of Ginseng Research 2019;43(2):319-25. https://doi.org/10.1016/j.jgr.2018.11.007

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