Korean Journal of Plant Resources (한국자원식물학회지)

The Plant Resources Society of Korea (한국자원식물학회)
권호 표지
DOI QR코드

DOI QR Code

Red Ginseng Extract Improves Liver Fibrosis in Mice Treated with the Endocrine Disruptor Bisphenol A

내분비교란물질 비스페놀 A를 처리한 마우스에서 홍삼 추출물의 간 섬유화 개선

  • Choi, Jehun (Herbal Crop Utilization Research Team, National Institute of Horticultural and Herbal Science, RDA) ;
  • Park, Chun Geon (Herbal Crop Utilization Research Team, National Institute of Horticultural and Herbal Science, RDA) ;
  • Seo, Kyoung Hee (Department of Biomedical Chemistry, Konkuk University) ;
  • Kim, Hyung Don (Herbal Crop Utilization Research Team, National Institute of Horticultural and Herbal Science, RDA) ;
  • Yoon, Ji Hye (Herbal Crop Utilization Research Team, National Institute of Horticultural and Herbal Science, RDA) ;
  • Ahn, Young Sup (Herbal Crop Utilization Research Team, National Institute of Horticultural and Herbal Science, RDA) ;
  • Kim, Jin Seong (Department of Biomedical Chemistry, Konkuk University)
  • 최재훈 (농촌진흥청 국립원예특작과학원 인삼특작이용팀) ;
  • 박춘근 (농촌진흥청 국립원예특작과학원 인삼특작이용팀) ;
  • 서경희 (건국대학교 의료생명대학 의생명화학과) ;
  • 김형돈 (농촌진흥청 국립원예특작과학원 인삼특작이용팀) ;
  • 윤지혜 (농촌진흥청 국립원예특작과학원 인삼특작이용팀) ;
  • 안영섭 (농촌진흥청 국립원예특작과학원 인삼특작이용팀) ;
  • 김진성 (건국대학교 의료생명대학 의생명화학과)
  • Received : 2016.05.25
  • Accepted : 2016.11.07
  • Published : 2017.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Bisphenol A (BPA), a known endocrine disruptor, induces toxicity in cells and in experimental animals. Ginseng extracts were evaluated to determine whether they can inhibit BPA-induced toxicity. The antioxidant activity of fresh ginseng extract (WGE), dried white ginseng extract (DGE), and dried red ginseng extract (RGE) was measured using the DPPH assay. WGE and RGE increased DPPH free radical scavenging activity. Cell viability was measured in HepG2 cells following treatment with BPA and ginseng extracts using the MTT assay. DGE and RGE increased HepG2 cell viability following treatment with $200{\mu}M$ BPA. RGE reduced levels of biochemical markers of liver damage, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that increased in mice following treatment with BPA. In addition, the regeneration and proliferation of damaged liver cells were significantly increased in RGE-treated mice. Moreover, RGE inhibited hepatic fibrosis in the surrounding area and in the central vein of the liver microstructure. RGE also significantly inhibited BPA-induced cytotoxicity. In addition, RGE protected liver damage and regenerated liver tissues in BPA-treated animals. These results show that RGE may represent a potential candidate drug for the treatment and prevention of liver damage caused by environmental toxins.

BPA는 내분비교란물질로 널리 알려져 있다. BPA를 세포와 실험동물에 처리하여 독성을 유도하고 이를 인삼 추출물들이 BPA로 유도된 독성에 어떠한 영향을 미칠 것인지 살펴보았다. WGE, DGE, RGE에 대한 항산화능을 DPPH 분석법으로 측정하였다. DGE 및 RGE는 DPPH 소거 항산화 활성을 증가시켰다. 간암세포주 HepG2에 BPA 처리하여 세포독성을 유도하고, 이를 인삼추출물에 의해 세포생존이 증가되는지 MTT법으로 측정하였다. BPA $200{\mu}M$ 처리하여 유도된 세포독성에 DGE 및 RGE는 세포 생존 능력을 증가시켰다. 실험동물에 BPA를 처리하여 독성을 유도하고 이를 인삼추출물들이 방어하는지 살펴보았다. 혈청에서 간 손상 생화학적 마커인 AST와 ALT가 RGE 투여군에서 증가했다. 또한, 손상된 간세포 재생및 증식이 RGE 투여군에서 현저하게 증가하였다. 또한, RGE 주변 영역 및 간 미세 구조의 중심 정맥의 문맥에서 간 섬유화를 억제하였다. 이상의 결과를 종합하면 RGE가 간 세포주에서 BPA로 유도된 세포독성을 유의적으로 저해하였으며, 동물실험을 통하여 BPA에 의해 손상된 간에서 RGE가 간의 보호와 간 조직 재생이 발생하는 것을 확인하였다. 이 결과는 RGE가 외부에서 유입된 화학물질에 대한 간 손상 개선제로 사용될 수 있음을 보여준다. 그러므로, RGE는환경독성 물질로 인한 질환치료약물에 대한 잠재적인 후보가 될 수 있을 것이라 사료된다.

Keywords

References

  1. Abdel-Wahhab, M.A., N.S. Hassan, A.A. El-Kady, Y.A. Khadrawy, A.A. El-Nekeety, S.R. Mohamed, H.A. Sharaf and F.A. Mannaa. 2010. Red ginseng extract protects against aflatoxin B1 and fumonisins-induced hepatic pre-cancerous lesions in rats. Food. Chem. Toxicol. 48:733-742. https://doi.org/10.1016/j.fct.2009.12.006
  2. Baillie-Hamilton, P.F. 2002. Chemical toxins: a hypothesis to explain the global obesity epidemic. J. Altern. Complement Med. 8:185-192. https://doi.org/10.1089/107555302317371479
  3. Bang, C.S., S.H. Hong, K.T. Suk, J.B. Kim, S.H. Han, H. Sung, E.J. Kim, M.J. Kim, M.Y. Kim and S.K. Baik. 2014. Effects of Korean red ginseng (Panax ginseng), urushiol (Rhus vernicifera Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) on the gut-liver axis of alcoholic liver disease. J. Ginseng Res. 38:167-172. https://doi.org/10.1016/j.jgr.2014.04.002
  4. Blois, M.S. 1958. Antioxidant determinations by the use of a stable free radical. Nature 181:1199-1200. https://doi.org/10.1038/1811199a0
  5. Di Sario, A., E. Bendia, G.S. Baroni, F. Ridolfi, A. Casini, E. Ceni, S. Saccomanno, M. Marzioni, L. Trozzi and P. Sterpetti. 2002. Effect of pirfenidone on rat hepatic stellate cell proliferation and collagen production. J. Hepatol. 37:584-591. https://doi.org/10.1016/S0168-8278(02)00245-3
  6. Diamanti-Kandarakis, E., J.-P. Bourguignon, L.C. Giudice, R. Hauser, G.S. Prins, A.M. Soto, R.T. Zoeller and A.C. Gore. 2009. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr. Rev. 30:293-342. https://doi.org/10.1210/er.2009-0002
  7. Grun, F. and B. Blumberg. 2006. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 147:s50-s55. https://doi.org/10.1210/en.2005-1129
  8. Heo, J.H., S.T. Lee, M.J. Oh, H.J. Park, J.Y. Shim, K. Chu and M.H. Kim. 2011. Improvement of cognitive deficit in Alzheimer's disease patients by long term treatment with Korean red ginseng. J. Ginseng Res. 35:457-461. https://doi.org/10.5142/jgr.2011.35.4.457
  9. Hwang, E.K. 2013. Protective effect of rutin on carbon tetrachloride-Induced acute hepatotoxicity in rats. J. Vet. Clin. 30:12-16.
  10. Hwang, J.T., M.S. Lee, H.J. Kim, M.J. Sung, H.Y. Kim, M.S. Kim and D.Y. Kwon. 2009. Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-${\gamma}$ signal pathways. Phytother. Res. 23:262-266. https://doi.org/10.1002/ptr.2606
  11. Jenkins, S., A. Grandison, J. Baxter, D. Day, I. Taylor and R. Shields. 1985. A dimethylnitrosamine-induced model of cirrhosis and portal hypertension in the rat. J. Hepatol. 1:489-499. https://doi.org/10.1016/S0168-8278(85)80747-9
  12. Kaneko, H. and K. Nakanishi. 2004. Proof of the mysterious efficacy of ginseng: basic and clinical trials: clinical effects of medical ginseng, Korean red ginseng: specifically, its anti-stress action for prevention of disease. J. Pharmacol. Sci. 95:158-162. https://doi.org/10.1254/jphs.FMJ04001X5
  13. Kavlock, R.J., G.P. Daston, C. DeRosa, P. Fenner-Crisp, L.E. Gray, S. Kaattari, G. Lucier, M. Luster, M.J. Mac and C. Maczka. 1996. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the US EPA-sponsored workshop. Environ. Health. Persp. 104:715. https://doi.org/10.1289/ehp.96104s4715
  14. Ki, S.H., J.H. Yang, S.K. Ku, S.C. Kim, Y.W. Kim and I.J. Cho. 2013. Red ginseng extract protects against carbon tetrachloride-induced liver fibrosis. J. Ginseng Res. 37:45-53. https://doi.org/10.5142/jgr.2013.37.45
  15. Kim, H.Y., K.S. Kang, N. Yamabe and T. Yokozawa. 2008. Comparison of the effects of Korean ginseng and heat-processed Korean ginseng on diabetic oxidative stress. Am. J. Chin. Med. 36:989-1004. https://doi.org/10.1142/S0192415X08006417
  16. Kretschmer, X.C. and W.S. Baldwin. 2005. CAR and PXR: xenosensors of endocrine disrupters? Chem. Biol. Interact. 155:111-128. https://doi.org/10.1016/j.cbi.2005.06.003
  17. Lee, D.H. 2012. Endocrine disrupting chemicals and environmental diseases. J. Korean Med. Assoc. 55:243-249. https://doi.org/10.5124/jkma.2012.55.3.243
  18. Lee, H.J., Y.H. Lee, S.K. Park, E.S. Kang, H.J. Kim, Y.C. Lee, C.S. Choi, S.E. Park, C.W. Ahn and B.S. Cha. 2009. Korean red ginseng (Panax ginseng) improves insulin sensitivity and attenuates the development of diabetes in Otsuka Long-Evans Tokushima fatty rats. Metabolism 58:1170-1177. https://doi.org/10.1016/j.metabol.2009.03.015
  19. Lee, J.S., G.N. Kim and H.D. Jang. 2008. Effect of Red Ginseng Extract on Storage and Antioxidant Activity of Tofu. J. Korean Soc. Food Sci. Nutr. 37:1497-1509. https://doi.org/10.3746/jkfn.2008.37.11.1497
  20. Lee, S., M.S. Lee, C.T. Kim, I.H. Kim and Y. Kim. 2012a. Ginsenoside Rg3 reduces lipid accumulation with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Int. J. Mol. Sci. 13:5729-5739. https://doi.org/10.3390/ijms13055729
  21. Lee, S.H., H.J. Lee, Y.H. Lee, B.W. Lee, B.S. Cha, E.S. Kang, C.W. Ahn, J.S. Park, H.J. Kim and E.Y. Lee. 2012b. Korean red ginseng (Panax ginseng) improves insulin sensitivity in high fat fed Sprague-Dawley rats. Phytother. Res. 26:142-147. https://doi.org/10.1002/ptr.3610
  22. Olaso, E. and S.L. Friedman. 1998. Molecular regulation of hepatic fibrogenesis. J. Hepatol. 29:836-847. https://doi.org/10.1016/S0168-8278(98)80269-9
  23. Park, H.J., D.H. Jung, H. Joo, N.S. Kang, S.A. Jang, J.G. Lee and E.H. Sohn. 2010. The comparative study of anti-allergic and anti-inflammatory effects by fermented red ginseng and red ginseng. Korean J. Plant Res. 23:415-422.
  24. Quan, H.Y., H.D. Yuan, M.S. Jung, S.K. Ko, Y.G. Park and S.H. Chung. 2012. Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice. Int. J. Mol. Med. 29:73-80.
  25. Seo, E.Y. and W.K. Kim. 2011. Red ginseng extract reduced metastasis of colon cancer cells in vitro and in vivo. J. Ginseng. Res. 35:315-324. https://doi.org/10.5142/jgr.2011.35.3.315
  26. Sohn, E.H., J.W. Yoon, H.J. Koo, D.W. Park, Y.J. Jeong, S. Namkoong, H.S. Han and S.C. Kang. 2012. Immunomodulating effects of red ginseng on the regulation of cytokine release in vivo. Korean J. Plant Res. 25:578-585. https://doi.org/10.7732/kjpr.2012.25.5.578
  27. Sung, S.K., Y.K. Rhee, C.W. Cho, Y.C. Kim, O.H. Lee and H.D. Hong. 2013. Physicochemical properties and antioxidative activity of fermented Rhodiola sachalinensis and Korean red ginseng mixture by Lactobacillus acidophilus. Korean J. Food. Nutr. 26:358-365. https://doi.org/10.9799/ksfan.2013.26.3.358
  28. Svegliati Baroni, G., L. D'Ambrosio, G. Ferretti, A. Casini, A. Di Sario, R. Salzano, F. Ridolfi, S. Saccomanno, A.M. Jezequel and A. Benedetti. 1998. Fibrogenic effect of oxidative stress on rat hepatic stellate cells. Hepatology 27:720-726. https://doi.org/10.1002/hep.510270313
  29. Vandenberg, L.N., M.V. Maffini, C. Sonnenschein, B.S. Rubin and A.M. Soto. 2009. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr. Rev. 30:75-95. https://doi.org/10.1210/er.2008-0021
  30. Wang, L., J. Hao, J. Hu, J. Pu, Z. Lü, L. Zhao, Q. Wang, Q. Yu, Y. Wang and G. Li. 2012. Protective effects of ginsenosides against bisphenol A-induced cytotoxicity in 15P-1 sertoli cells via extracellular signal-regulated kinase 1/2 signalling and antioxidant mechanisms. Basic Clin. Pharmacol. Toxicol. 111:42-49.
  31. Xu, Y., M. Rojkind and M.J. Czaja. 1996. Regulation of monocyte chemoattractant protein 1 by cytokines and oxygen free radicals in rat hepatic fat-storing cells. Gastroenterology 110:1870-1877. https://doi.org/10.1053/gast.1996.v110.pm8964413