DOI QR코드

DOI QR Code

Anti-obesity Effects of Water and Ethanol Extracts of Black Ginseng

흑삼의 열수 및 에탄올 추출물의 항비만 효과

  • Park, Hye-Jin (Research Institute of Obesity Sciences, Sungshin Women's University) ;
  • Kim, Ae-Jung (The Graduate School of Alternative Medicine, Kyonggi University) ;
  • Cheon, Yong-Pil (Division of Developmental Biology and Physiology, School of Biosciences and Chemistry, Sungshin Women's University) ;
  • Lee, Myoungsook (Research Institute of Obesity Sciences, Sungshin Women's University)
  • 박혜진 (성신여자대학교 비만과학연구소) ;
  • 김애정 (경기대학교 대체의학대학원) ;
  • 전용필 (성신여자대학교 생명과학화학부) ;
  • 이명숙 (성신여자대학교 비만과학연구소)
  • Received : 2014.11.05
  • Accepted : 2014.12.02
  • Published : 2015.03.31

Abstract

Black ginseng was made by steaming raw white ginseng nine times at $100^{\circ}C$ for 2 h and drying. We then performed pilot experiments using the nine black ginseng extracts for different steaming and drying times to determine their anti-obesity effects. Two ginseng extracts, steaming and drying five times (FSFD) and steaming and drying nine times (NSND), prepared in water or ethanol solution decreased lipid accumulation of 3T3-L1 cells. FSFD in water and ethanol extracts showed higher levels of ginsenosides, in particular, Rh1, Rg2, and Rb1 than NSND, and levels of the three ginsenosides were higher in ethanol extracts than in water extracts. Treatment with FSFD and/or NSND in ethanol extracts significantly regulated $PPAR{\gamma}$, C/$EBP{\alpha}$ and AMPK phosphorylation in 3T3-L1 cells. We verified doubling time of stem cells from both abdominal fat and subcutaneous fat after FSFD and NSND in ethanol and water extracts were added. Although addition of FSFD and NSFD in water extracts had no effects on proliferation, ethanol extracts with FSFD and NSND increased doubling time of stem cells in subcutaneous fat. FSFD and NSND in ethanol extracts more effectively reduced adipogenesis compared to those in water extracts. FSFD in ethanol extracts promoted secretion of anti-inflammatory cytokine such as IL-10 and depressed MCP-1 infiltration in 3T3-L1 preadipocytes co-cultured with RAW264.7 cells. We concluded that FSFD and NSND ethanol extracts may be developed as a functional food for its anti-obesity effect, but anti-inflammatory effect was shown in ethanol extracted FSFD rather than in NSND.

본 연구는 구중구포법 과정의 흑삼 1~9포를 대상으로 열수 및 70% 에탄올 추출물의 ginsenosides을 분석한 결과 생리 활성이 높다고 판단한 흑삼 5포와 9포 열수 및 에탄올 추출물을 각각 3T3-L1 지방세포, RAW264.7 대식세포, 지방유래 줄기세포에 처치하여 세포독성, 지질축적(adipogenesis) 및 염증인자 변화를 관찰하였다. 본 연구에서는 열수 추출물보다 에탄올 추출물 흑삼에서 효율적으로 ginsenosides가 추출되었다. 또한 흑삼 에탄올 추출물이 $PPAR{\gamma}$ 및 C/$EBP{\alpha}$ 감소, AMPK의 인산화 증가 등 adipogenesis 관련인자를 억제하였으며, 아울러 염증성 사이토카인의 분비를 억제하였다. 따라서 비만 및 대사성 질환의 예방에도 잠정적으로 이용될 수 있을 것으로 기대되지만 ginsenosides와 비만과의 조절기전 연구 및 항염증성 기전 등에 대한 정확한 기전 규명이 필요하다. 현재 인삼에 함유된 ginsenosides를 이용하여 체지방 감소 등의 기능성식품으로 많이 개발되고 있는 현실을 감안해 볼 때 홍삼 및 흑삼의 제조 기술인 구증구포법의 효율적인 표준화 공정기술, 유효 생리활성 성분의 대량 생산 및 안전성 기술 등이 개발된다면 항비만에 대한 고부가 가치 상품개발이 가능할 것으로 기대된다.

Keywords

References

  1. Faust IM, Johnson PR, Stern JS, Hirsch J. 1978. Diet-induced adipocyte number increase in adult rats-new model of obesity. Am J Physiol 235: E279-E286.
  2. Klyde BJ, Hirsch J. 1979. Increased cellular proliferation in adipose tissue of adult rats fed a high-fat diet. J Lipid Res 20: 705-715.
  3. Choi SH, Kim TH, Lim S, Park KS, Jang HC, Cho NH. 2011. Hemoglobin A1c as a diagnostic tool for diabetes screening and new-onset diabetes prediction: a 6-year community-based prospective study. Diabetes Care 34: 944-949. https://doi.org/10.2337/dc10-0644
  4. Kim DM, Ahn CW, Nam SY. 2005. Prevalence of obesity in Korea. Obes Rev 6: 117-121. https://doi.org/10.1111/j.1467-789X.2005.00173.x
  5. Kim S, Moon S, Popkin BM. 2000. The nutrition transition in South Korea. Am J Clin Nutr 71: 44-53.
  6. Ministry of Health & Welfare, Korea Centers for Disease Control and Prevention. 2014. Korea Health Statistics 2013: Korea National Health and Nutrition Examination Survey (KNHANES VI-1). http://knhanes.cdc.go.kr.
  7. Oh NR, Hwang AR, Jeong JI, Park SH, Yang JS, Lee YH. 2012. Effects of long-term high-fat diet feeding on gene expression of inflammatory cytokines in mouse adipose tissue. J Exp Biomed Sci 18: 56-62.
  8. Lee YH, Pratley RE. 2005. The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diabetes Rep 5: 70-75. https://doi.org/10.1007/s11892-005-0071-7
  9. Lee YH, Pratley RE. 2007. Abdominal obesity and cardiovascular disease risk: the emerging role of the adipocyte. J Cardiopulm Rehabil Prev 27: 2-10. https://doi.org/10.1097/01.HCR.0000265014.36587.dd
  10. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS. 2005. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46: 2347-2355. https://doi.org/10.1194/jlr.M500294-JLR200
  11. Surmi BK, Hasty AH. 2008. Macrophage infiltration into adipose tissue: initiation, propagation and remodeling. Future Lipidol 3: 545-556. https://doi.org/10.2217/17460875.3.5.545
  12. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. 2003. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796-1808. https://doi.org/10.1172/JCI200319246
  13. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821-1830. https://doi.org/10.1172/JCI200319451
  14. Jie YH, Cammisuli S, Baggiolini M. 1984. Immunomodulatory effects of Panax ginseng C.A. Meyer in the mouse. Agents Actions 15: 386-391. https://doi.org/10.1007/BF01972376
  15. Kim YC, Kim SR, Markelonis GJ, Oh TH. 1998. Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration. J Neurosci Res 53: 426-432. https://doi.org/10.1002/(SICI)1097-4547(19980815)53:4<426::AID-JNR4>3.0.CO;2-8
  16. Tahara M, Kono H, Mune S, Odashima S. 1985. Action of ginsenosides on tumor cells growth inhibition and redifferentiation of neoplasia. Wakan Iyaku Gakkaishi 2: 170-171.
  17. Yokozawa T, Kobayashi T, Oura H, Kawashima Y. 1985. Studies on the mechanism of the hypoglycemic activity of ginsenoside-Rb2 in streptozotocin-diabetic rats. Chem Pharm Bull (Tokyo) 33: 869-872. https://doi.org/10.1248/cpb.33.869
  18. Kwon SW, Han SB, Park IH, Park JM, Park MK. 2001. Liquid chromatographic determination of less polar ginsenosides in processed ginseng. J Chromatogr A 921: 335-339. https://doi.org/10.1016/S0021-9673(01)00869-X
  19. Ko SK, Lee KH, Hong JK, Kang SA, Sohn UD, Im BO, Han ST, Yang BW, Chung SH, Lee BY. 2005. Change of ginsenoside composition in ginseng extract by vinegar process. Food Sci Biotechnol 14: 509-513.
  20. Nam KY, Choi JE, Park JD. 2013. Transformation techniques for the large scale production of ginsenoside Rg3. Korean J Medicinal Crop Sci 21: 401-414. https://doi.org/10.7783/KJMCS.2013.21.5.401
  21. Kitagawa I. 1992. Chemical investigation of naturally occurring drug materials: elucidation of scientific basis for traditional medicines and exploitation of new naturally occurring drugs. Yakugaku Zasshi 112: 1-41. https://doi.org/10.1248/yakushi1947.112.1_1
  22. Shoji J. 1999. Studies on the constituents of ginseng. Nat Med 53: 55-59.
  23. Nam KY, Lee NR, Moon BD, Song GY, Shin HS, Choi JE. 2012. Changes of ginsenosides and color from black ginsengs prepared by steaming-drying cycles. Korean J Medicinal Crop Sci 20: 27-35. https://doi.org/10.7783/KJMCS.2012.20.1.027
  24. Xu TM, Cui MH, Xin Y, Gu LP, Jiang X, Su MM, Wang DD, Wang WJ. 2008. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis. Chin Med J 121: 1394-1397.
  25. Lee MS, Kim IH, Kim CT, Kim YH. 2011. Effects of ginsenoside Rg3 on adipocyte fatty acid binding protein mRNA expression and glycerol-3-phosphate dehydrogenase activity during adipocytes differentiation. Korean J Lipidol 21: 67-75.
  26. Gu W, Kim KA, Kim DH. 2013. Ginsenoside Rh1 ameliorates high fat diet-induced obesity in mice by inhibiting adipocyte differentiation. Chem Pharm Bull 36: 102-107.
  27. Kim SN. 2008. Study on ginsenoside patterns on the steam processing of Korean ginseng and hypoglycemic action on streptozotocin induced diabetic rats of 9 time-steamings ginsengs. PhD Dissertation. Joongbu University, Chungnam, Korea. p 3.
  28. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Piegelman BM, Mortensen RM. 1999. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4: 611-617. https://doi.org/10.1016/S1097-2765(00)80211-7
  29. Wu Z, Rosen ED, Erun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM. 1999. Crossregulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell 3: 151-158. https://doi.org/10.1016/S1097-2765(00)80306-8
  30. Hwang JT, Lee MS, Kim HJ, Sung MJ, Kim HY, Kim MS, Kwon DY. 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
  31. Shang W, Yang Y, Jiang B, Jin H, Zhou L, Liu S, Chen M. 2007. Ginsenoside Rb1 promotes adipogenesis in 3T3- L1 cells by enhancing $PPAR{\gamma}2$ and $C/EBP{\alpha} gene expression. Life Sci 80: 618-625. https://doi.org/10.1016/j.lfs.2006.10.021
  32. Kim SN, Lee JH, Shin HS, Son SH, Kim YS. 2009. Effects of in vitro-digested ginsenosides on lipid accumulation in 3T3-L1 adipocytes. Planta Med 75: 596-601. https://doi.org/10.1055/s-0029-1185358
  33. Lee S, Lee MS, Kim CT, Kim IH, Kim Y. 2012. 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
  34. Choi HC. 2012. AMP-activated protein kinase activating agent and its implication. Endocrinol Metab 27: 109-115. https://doi.org/10.3803/EnM.2012.27.2.109
  35. Quan HY, Yuan HD, Jung MS, Ko SK, Park YG, Chung SH. 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.
  36. Song GY, Oh HJ, Seong SR, Seo YB, Park YJ, Myung CS. 2006. Effect of black ginseng on body weight and lipid profiles in male rats and fed normal diets. Yakhak Hoeji 50: 381-385.
  37. Wisse BE. 2004. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 15: 2792-2800. https://doi.org/10.1097/01.ASN.0000141966.69934.21
  38. Chawla A, Nguyen KD, Goh YPS. 2011. Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol 11: 738-749. https://doi.org/10.1038/nri3071
  39. Lumeng CN, Saltiel AR. 2011. Inflammatory links between obesity and metabolic disease. J Clin Invest 121: 2111-2117. https://doi.org/10.1172/JCI57132
  40. Kim AJ, Kang SJ, Lee KH, Lee M, Ha SD, Cha YS, Kim SY. 2010. The chemopreventive potential and anti-inflammatory activities of Korean black ginseng in colon26-M3.1 carcinoma cells and marcrophages. J Korean Soc Appl Biol Chem 53: 101-105.
  41. Shin YJ, Jang HH, Song GY. 2012. Study on anti-atopic effects of black ginseng. Kor J Aesthet Cosmetol 10: 91-97.

Cited by

  1. Anti-Adipogenic Effects of Ethanol Extracts Prepared from Selected Medicinal Herbs in 3T3-L1 Cells vol.21, pp.3, 2016, https://doi.org/10.3746/pnf.2016.21.3.227
  2. Effects of Red or Black Ginseng Extract in a Rat Model of Inflammatory Temporomandibular Joint Pain vol.17, pp.1, 2017, https://doi.org/10.17135/jdhs.2017.17.1.65
  3. Antioxidant and anti-adipogenic activities of the nuts of Castanopsis cuspidata var. thunbergii 2017, https://doi.org/10.1007/s10068-017-0183-2
  4. Inhibitory Activities of Water Extracts of Black Ginseng on HCl/Ethanol-Induced Acute Gastritis through Anti-Oxidant Effect vol.45, pp.9, 2016, https://doi.org/10.3746/jkfn.2016.45.9.1249
  5. Potential of Fisetin as a Nutri-cosmetics Material through Evaluating Anti-oxidant and Anti-adipogenic Activities vol.14, pp.1, 2016, https://doi.org/10.20402/ajbc.2016.0003
  6. HPLC와 DPPH radical 소거능 측정 방법의 결합에 의한 약용 식물 추출물의 항산화 활성 비교 vol.27, pp.1, 2015, https://doi.org/10.5352/jls.2017.27.1.44
  7. Black Ginseng and Its Saponins: Preparation, Phytochemistry and Pharmacological Effects vol.24, pp.10, 2015, https://doi.org/10.3390/molecules24101856
  8. Metabolic Changes in Serum Metabolome of Beagle Dogs Fed Black Ginseng vol.10, pp.12, 2015, https://doi.org/10.3390/metabo10120517
  9. The effects of ginseng on the metabolic syndrome: An updated review vol.9, pp.9, 2021, https://doi.org/10.1002/fsn3.2475
  10. Anti-Aging Effects of Black Ginseng Extract via H2O2-Induced Oxidative Stress Regulation in Human Keratinocytes vol.50, pp.10, 2021, https://doi.org/10.3746/jkfn.2021.50.10.1019
  11. Black Ginseng Extract Attenuates TNF-ɑ-Induced Inflammation via Downregulation of NF-κB Signaling in Human Keratinocytes vol.50, pp.10, 2015, https://doi.org/10.3746/jkfn.2021.50.10.1030