생명과학회지 (Journal of Life Science)

  • 제28권9호
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  • Pages.999-1006
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  • 2018
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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비쑥 추출물이 3T3-L1 지방세포 분화 및 MAPK 신호 전달 경로에 미치는 영향

Artemisia scoparia Inhibits Adipogenesis in 3T3-L1 Pre-adipocytes by Downregulating the MAPK Pathway

  • 오정환 (신라대학교 의생명과학대학 식품영양학과) ;
  • 파티 카라데니즈 (신라대학교 해양식의약소재융합기술연구소) ;
  • 서영완 (한국해양대학교 해양과학기술대학 해양환경.생명과학부) ;
  • 공창숙 (신라대학교 의생명과학대학 식품영양학과)
  • Oh, Jung Hwan (Department of Food and Nutrition, College of Medical and Life Sciences, Silla University) ;
  • Karadeniz, Fatih (Department of Food and Nutrition, College of Medical and Life Sciences, Silla University) ;
  • Seo, Youngwan (Division of Marine Bioscience, College of Ocean Science and Technology, Korea Maritime and Ocean University) ;
  • Kong, Chang-Suk (Department of Food and Nutrition, College of Medical and Life Sciences, Silla University)
  • 투고 : 2018.04.30
  • 심사 : 2018.07.04
  • 발행 : 2018.09.30
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초록

비쑥(Atermisia scoparia)은 국화과에 속하는 한해살이 풀로서 유라시아 지역 분포하며, 염생습지에 자생하는 염생식물의 일종이다. 비쑥은 민간요법에서 이뇨제, 소염제, 간염치료제로 사용되어 왔으며, 비쑥에서 분리한 플라보노이드, 쿠마린 화합물의 항산화, 항염증 등의 생리활성이 보고되어 있다. 본 연구에서는 비쑥 추출물이 3T3-L1 지방전구세포 모델에서 지방세포 내에서의 중성지방 생성 및 지방세포 분화조절 인자 발현에 미치는 영향을 검토하였다. 지방전구세포 3T3-L1을 지방세포로 분화하여 Oil Red O 염색법으로 지방세포 분화 정도를 측정한 결과, 비쑥 추출물 처리군에서 농도 의존적으로 지방세포 형성이 억제되었다. 또한 지방세포 분화 관련 인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP-1c의 발현을 mRNA 및 단백질 수준에서 확인한 결과, 비쑥 추출물을 처리한 군에서 지방세포분화 인자 발현이 감소하는 것으로 나타났다. 지방세포 분화 및 증식에 관여하는 것으로 알려져 있는 MAPK 신호전달 경로를 확인한 결과 비쑥 추출물을 처리한 군에서 p38, ERK, JNK의 인산화가 억제되었다. 이를 통해 비쑥 추출물은 MAPK 신호전달 경로를 통한 지방세포 분화 인자 조절을 통해 지방 생성과 합성을 억제하는 것으로 사료된다. 따라서 본 연구 결과로부터 비쑥 추출물의 MAPK 신호전달 경로 억제를 통한 항비만 효과를 확인하였으며, 나아가 건강 기능성 식품 소재로서의 개발 가능성이 기대된다.

Obesity is epidemic worldwide and has reportedly been linked to the progression of several metabolic and cardiovascular diseases. The natural products are decreasing the side effects of medicines used for obesity and also have health benefits dut to their numerous bioactive compounds. In this context, Artemisia scoparia is a widespread plant that has been suggested as possessing various types of bioactivity. In this study, the crude extract from A. scoparia (ASE) was tested for its ability to suppress adipogenesis in mouse 3T3-L1 pre-adipocytes. The molecular pathway by which ASE affects differentiation of 3T3-L1 cells was also investigated. The introduction of ASE to differentiating 3T3-L1 pre-adipocytes resulted in suppressed adipogenesis, as confirmed by decreased intracellular lipid accumulation. The differentiating cells treated with 10 and $100{\mu}g/ml$ of ASE showed 21.9 and 29.0% less lipid accumulation, respectively, than untreated adipocytes. In addition, the results indicated that ASE treatment lowered the expression of the adipogenesis-related factors $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP-1c. Furthermore, treating with ASE notably decreased levels of phosphorylated p38, ERK, and JNK in 3T3-L1 adipocytes. These results indicate that ASE exhibits significant anti-adipogenesis activity by downregulating the MAPK and $PPAR{\gamma}$ pathways during the differentiation of 3T3-L1 pre-adipocytes. Therefore, A. scoparia may be a potential source of natural products against obesity.

키워드

참고문헌

  1. Anderson, A. S. and Caswell, S. 2009. Obesity management - an opportunity for cancer prevention. Surgeon 7, 282-285. https://doi.org/10.1016/S1479-666X(09)80005-X
  2. Bost, F., Aouadi, M., Caron, L. and Binetruy, B. 2005. The role of MAPKs in adipocyte differentiation and obesity. Biochimie 87, 51-56. https://doi.org/10.1016/j.biochi.2004.10.018
  3. Cha, J. D., Jeong, M. R., Jeong, S. I., Moon, S. E., Kim, J. Y., Kil, B. S. and Song, Y. H. 2005. Chemical composition and antimicrobial activity of the essential oils of Artemisia scoparia and A. capillaris. Planta Med. 71, 186-190. https://doi.org/10.1055/s-2005-837790
  4. Choi, J. H., Banks, A. S., Estall, J. L., Kajimura, S., Bostrom, P., Laznik, D., Ruas, J. L., Chalmers, M. J., Kamenecka, T. M., Bluher, M., Griffin, P. R. and Spiegelman, B. M. 2010. Obesity-linked phosphorylation of PPAR${\gamma}$ by cdk5 is a direct target of the anti-diabetic PPAR${\gamma}$ ligands. Nature 466, 451-456. https://doi.org/10.1038/nature09291
  5. de Ferranti, S. and Mozaffarian, D. 2008. The perfect storm: Obesity, adipocyte dysfunction, and metabolic consequences. Clin. Chem. 54, 945-955. https://doi.org/10.1373/clinchem.2007.100156
  6. Fajas, L., Fruchart, J. C. and Auwerx, J. 1998. Transcriptional control of adipogenesis. Curr. Opin. Cell Biol. 10, 165-173. https://doi.org/10.1016/S0955-0674(98)80138-5
  7. Habib, M. and Waheed, I. 2013. Evaluation of anti-nociceptive, anti-inflammatory and antipyretic activities of Artemisia scoparia hydromethanolic extract. J. Ethnopharmacol. 145, 18-24. https://doi.org/10.1016/j.jep.2012.10.022
  8. Hajer, G. R., van Haeften, T. W. and Visseren, F. L. J. 2008. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur. Heart J. 29, 2959-2971. https://doi.org/10.1093/eurheartj/ehn387
  9. Hsu, C. L. and Yen, G. C. 2007. Effects of flavonoids and phenolic acids on the inhibition of adipogenesis in 3T3-L1 adipocytes. J. Agric. Food Chem. 55, 8404-8410. https://doi.org/10.1021/jf071695r
  10. Kawada, T., Takahashi, N. and Fushiki, T. 2001. Biochemical and physiological characteristics of fat cell. J. Nutr. Sci. Vitaminol. 47, 1-12. https://doi.org/10.3177/jnsv.47.1
  11. Kim, J., Karadeniz, F., Ahn, B., Kwon, M. S., Mun, O., Bae, M. J., Seo, Y., Kim, M., Lee, S., Kim, Y. Y., Mi Soon, J. and Kong, C. 2016. Bioactive quinone derivatives from the marine brown alga Sargassum thunbergii induce anti-adipogenic and pro-osteoblastogenic activities. J. Sci. Food Agric. 96, 783-790. https://doi.org/10.1002/jsfa.7148
  12. Kim, T., Jo, C., Kim, H. S., Park, Y. M., Wu, Y. X., Cho, J. H. and Kim, T. H. 2016. Chemical constituents from Ainsliaea acerifolia as potential anti-obesity agents. Phytochem. Lett. 16, 146-151. https://doi.org/10.1016/j.phytol.2016.04.005
  13. Kim, Y. and Lee, J. 2015. Esculetin, a coumarin derivative, suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes. J. Func. Foods 12, 509-515. https://doi.org/10.1016/j.jff.2014.12.004
  14. Kim, J. A., Karadeniz, F., Ahn, B. N., Kwon, M. S., Mun, O. J., Kim, M., Lee. S. H., Yu, K. H., Kim, Y. Y. and Kong, C. S. 2014. Sargassum sp. attenuates oxidative stress and suppresses lipid accumulation in vitro. J. Life Sci. 24, 274-283. https://doi.org/10.5352/JLS.2014.24.3.274
  15. Lavie, C. J., Milani, R. V. and Ventura, H. O. 2009. Obesity and cardiovascular disease: Risk factor, paradox, and impact of weight loss. J. Am. College Cardiol. 53, 1925-1932. https://doi.org/10.1016/j.jacc.2008.12.068
  16. Lee, M. H., Chen, Y. Y., Tsai, J. W., Wang, S. C., Watanabe, T. and Tsai, Y. C. 2011. Inhibitory effect of ${\beta}$-asarone, a component of Acorus calamusessential oil, on inhibition of adipogenesis in 3T3-L1 cells. Food Chem. 126, 1-7. https://doi.org/10.1016/j.foodchem.2010.08.052
  17. Malnick, S. D. and Knobler, H. 2006. The medical complications of obesity. QJM. 99, 565-579. https://doi.org/10.1093/qjmed/hcl085
  18. Marti, A., Martinez-Gonzalez, M. A. and Martinez, J. A. 2008. Interaction between genes and lifestyle factors on obesity. Proc. Nutr. Soc. 67, 1-8. https://doi.org/10.1017/S002966510800596X
  19. Mcpherron, A. and Lee, S. 2002. Suppression of body fat accumulation in myostatin-deficient mice. J. Clin. Investig. 109, 595-602. https://doi.org/10.1172/JCI0213562
  20. Nam, S. Y., Han, N. R., Rah, S. Y., Seo, Y., Kim, H. M. and Jeong, H. J. 2017. Anti-inflammatory effects of Artemisia scoparia and its active constituent, 3,5-dicaffeoyl-epi-quinic acid against activated mast cells. Immunopharm. Immunotoxicol. 40, 52-58.
  21. Nawrocki, A. R. and Scherer, P. E. 2005. Keynote review: the adipocyte as a drug discovery target. Drug Discov. Today 10, 1219-1230. https://doi.org/10.1016/S1359-6446(05)03569-5
  22. Negahban, M., Moharramipour, S. and Sefidkon, F. 2006. Chemical composition and insecticidal activity of Artemisia scoparia essential oil against three coleopteran stored-product insects. J. Asia-Pac. Entomol. 9, 381-388. https://doi.org/10.1016/S1226-8615(08)60318-0
  23. Ordovas, J. M. and Shen, J. 2008. Gene-environment interactions and susceptibility to metabolic syndrome and other chronic diseases. J. Periodontol. 79, 1508-1513. https://doi.org/10.1902/jop.2008.080232
  24. Otto, T. C. and Lane, M. D. 2005. Adipose development: from stem cell to adipocyte. Crit. Rev. Biochem. Mol. Biol. 40, 229-242. https://doi.org/10.1080/10409230591008189
  25. Park, J. H. 1999. Korean Folk Medicine pp. 68, Busan National University Publisher: Busan, Korea.
  26. Pettinelli, P. and Videla, L. A. 2011. Up-regulation of PPAR-${\gamma}$ mRNA expression in the liver of obese patients: An additional reinforcing lipogenic mechanism to SREBP-1c induction. J. Clin. Endocrinol. Metab. 96, 1424-1430. https://doi.org/10.1210/jc.2010-2129
  27. Shin, E., Choi, M. K., Yoo, H. S., Lee, C. K., Hwang, B. Y. and Lee, M. K. 2010. Inhibitory effects of coumarins from the stem barks of Fraxinus rhynchophylla on adipocyte differentiation in 3T3-L1 cells. Biol. Pharm. Bull. 33, 1610-1614. https://doi.org/10.1248/bpb.33.1610
  28. Singh, H. P., Mittal, S., Kaur, S., Batish, D. R. and Kohli, R. K. 2009. Chemical composition and antioxidant activity of essential oil from residues of Artemisia scoparia. Food Chem. 114, 642-645. https://doi.org/10.1016/j.foodchem.2008.09.101
  29. Song, Y., Lee, S. J., Jang, S. H., Kim, T. H., Kim, H. D., Kim, S. W., Won, C. K. and Cho, J. H. 2017. Annual wormwood leaf inhibits the adipogenesis of 3T3-L1 and obesity in high-fat diet-induced obese rats. Nutrients 9, 554. https://doi.org/10.3390/nu9060554
  30. Sun, K., Kusminski, C. M. and Scherer, P. E. 2011. Adipose tissue remodeling and obesity. J. Clin. Investig. 121, 2094-2101. https://doi.org/10.1172/JCI45887
  31. Wofford, M. R. and Hall, J. E. 2004. Pathophysiology and treatment of obesity hypertension. Curr. Pharm. Des. 10, 3621-3637. https://doi.org/10.2174/1381612043382855
  32. Xie, T., Liang, J. Y., Liu, J., Wang, M., Wei, X. L. and Yang, C. H. 2004. Chemical study on Artemisia scoparia. J. China Pharm. Univ. 35, 401-403.
  33. Yang, Y., Yang, X., Xu, B., Zeng, G., Tan, J., He, X., Hu, C. and Zhou, Y. 2014. Chemical constituents of Morus alba L. and their inhibitory effect on 3T3-L1 preadipocyte proliferation and differentiation. Fitoterapia 98, 222-227. https://doi.org/10.1016/j.fitote.2014.08.010