Journal of the East Asian Society of Dietary Life (동아시아식생활학회지)

The East Asian Society of Dietary Life (동아시아식생활학회)
권호 표지

Anti-Obese Effects of Ginseng/Ginsenosides : A Literature Review from 1983 to 2012

인삼과 진세노사이드의 항비만 효과에 대한 문헌 고찰

  • Choi, Munji (Research Institute of Obesity Sciences, Sungshin Women's University) ;
  • An, Jinpyo (Graduate School of Alternative Medicine, Kyonggi University) ;
  • Kim, Ae Jung (Graduate School of Alternative Medicine, Kyonggi University) ;
  • Lee, Myoungsook (Research Institute of Obesity Sciences, Sungshin Women's University)
  • 최문지 (성신여자대학교 비만과학연구소) ;
  • 안진표 (경기대학교 대체의학대학원) ;
  • 김애정 (경기대학교 대체의학대학원) ;
  • 이명숙 (성신여자대학교 비만과학연구소)
  • Received : 2014.04.15
  • Accepted : 2014.06.14
  • Published : 2014.06.30
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Abstract

Compared to the large numbers of studies on the diabetes, hyperlipidemia and cancer therpeutic effects of ginseng, the anti-obese effect and mechanisms of ginsengs have not been studied as much. To determine the effects of ginseng on obesity, 14 keywords (ginseng, ginsenoside, obesity, weight, fat, diet, overeat, appetite, lipid, 3T3-L1, adipocyte, food intake, adipogenesis and lipolysis) were combined in searching a database. Fifty-six articles published from 1983 to 2012 as well as 656 patents registered until Aug $17^{th}$, 2012, were screened for anti-obese effects of ginseng. In the classification of experimental methods, 16 papers on 3T3-L1 cells, 38 papers on animals and three papers on human were reviewed. In terms of obese mechanisms of action, the most commonly used biomarkers were in order of lipid profiles > weight change > blood glucose > adipocytokine. Most ginseng studies on obesity focused on AMPK, $PPAR{\gamma}$, GLUT-4, PI3K and SREBP-1. Korean white ginseng extracts and Re repressed the lipogenesis genes such as PPARc2, SREBP-1c, LPL, FAS and DGAT1. However, ginseng or ginsenosides, PD (Rb1) and PT (Re), showed different or contradictory results. Water and ethanol extraction of ginseng showed contradictory effects on the secretion of inflammatory cytokines, wheras IL-6 was repressed by ethanol extracts and TNF-${\alpha}$ repressed by Re in vitro. Based on the literature, further studies on anti-obese mechanisms of ginseng, such as the inflammation-related obesity or cross signals between the adipocytes and the environments, are needed, instead of more studies on its hypolipidemic and hypoglycemic effects.

Keywords

References

  1. Attle AS, Wu JA, Yuan CS (1999) Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 58: 1685-1693. https://doi.org/10.1016/S0006-2952(99)00212-9
  2. Chen ZH, Li J, Liu J, Zhao Y, Zhang P, Zhang MX, Zhang L (2008) Saponins isolated from the root of Panax notoginseng showed significant anti-diabetic effects in KK-Ay mice. Am J Chin Med 36: 939-951. https://doi.org/10.1142/S0192415X08006363
  3. Cho WC, Chung WS, Lee SK, Leung AW, Cheng CH, Yue KK (2006) Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats. Eur J Pharmacol 550: 173-179. https://doi.org/10.1016/j.ejphar.2006.08.056
  4. Cicero AF, Vitale G, Savino G, Arletti R (2003) Panax notoginseng (Burk.) effects on fibrinogen and lipid plasma level in rats fed on a high-fat diet. Phytother Res 17: 174-178. https://doi.org/10.1002/ptr.1262
  5. De Morais EC, Stefanuto A, Klein GA, Boaventura BC, de Andrade F, Wazlawik E, Di Pietro PF, Maraschin M, da Silva EL (2009) Consumption of yerba mate (Ilex paraguariensis) improves serum lipid parameters in healthy dyslipidemic subjects and provides an additional LDL-cholesterol reduction in individuals on statin therapy. J Agric Food Chem. 57: 8316-8324. https://doi.org/10.1021/jf901660g
  6. Dey L, Xie JT, Wang A, Wu J, Maleckar SA, Yuan CS (2003) Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine 10: 600-605. https://doi.org/10.1078/094471103322331908
  7. Galloway SD, Craig TP, Cleland SJ (2011) Effects of oral Lcarnitine supplementation on insulin sensitivity indices in reponse to glucose feeding in lean and overweight/obese males. Amino Acids 41: 507-515. https://doi.org/10.1007/s00726-010-0770-5
  8. Gwak JH (2010) The effect of isoflavone and gamma-linolenic acid supplementation on serum lipids and menopausal symptoms in postmenopausal women. Korean J Nutr 43: 123-131. https://doi.org/10.4163/kjn.2010.43.2.123
  9. Han EJ, Park KJ, Chung SH, Ko SK, A(2008) Vinegar-processed ginseng radix (Ginsam) ameliorates hyperglycemia and dyslipidemia in C57BL/KsJ db/db mice. Food Sci and Biotechnol 17: 1228-1234.
  10. Han GC, Ko SK, Sung JH, Chung SH (2007) Compound K enhances insulin secretion with beneficial metabolic effects in db/db mice. J Agric Food Chem 55: 10641-10648. https://doi.org/10.1021/jf0722598
  11. Han KL, Jung MH, Sohn JH, Hwang JK (2006) Ginsenoside 20(S)-protopanaxatriol (PPT) activates peroxisome proliferator- activated receptor $\gamma$ (PPAR$\gamma$) in 3T3-L1 adipocytes. Biol Pharm Bull 29: 110-113. https://doi.org/10.1248/bpb.29.110
  12. Han LK, Zheng YN, Yoshikawa M, Okuda H, Kimura Y (2005) Anti-obesity effects of chikusetsu saponins isolated from Panax japonicus rhizomes. BMC Complement Altern Med 5: 1-9. https://doi.org/10.1186/1472-6882-5-1
  13. Henderson S, Magu B, Rasmussen C, Lancaster S, Kerksick C, Smith P, Melton C, Cowan P, Greenwood M, Earnest C, Almada A, Milnor P, Magrans T, Bowden R, Ounpraseuth S, Thomas A, Kreider RB (2005) Effects of Coleus forskohlii supplementation on body composition and hematological profiles in mildly overweight women. J Int Soc Sports Nutr 2: 54-62. https://doi.org/10.1186/1550-2783-2-2-54
  14. Huang YC, Lin CY, Huang SF, Lin HC, Chang WL, Chang TC (2010) Effect of mechanism of ginsenoside CK and Rg1 on stimulation of glucose uptake in 3T3-L1 adipocytes. J Agric Food Chem 58: 6039-6047. https://doi.org/10.1021/jf9034755
  15. Hwang JT, Kim SH, Lee MS, Kim SH, Yang HJ, Kim MJ, Kim HS, Ha J, Kim MS, Kwon DY (2007) Anti-obesity effects of ginsenoside Rh2 are associated with the activation of AMPK signaling pathway in 3T3-L1 adipocyte. Biochem Biophys Res Commun 364: 1002-1008. https://doi.org/10.1016/j.bbrc.2007.10.125
  16. Hwang JT, Lee MS, Kim HJ, Sung MJ, Kim HY, Kim MS, Kwon DY (2009) Antiobesity effect of ginsenoside $Rg_{3}$ involves the AMPK and PPAR-$\gamma$ signal pathways. Phytother Res 23: 262-266. https://doi.org/10.1002/ptr.2606
  17. Ji W, Gong BQ (2007) Hypolipidemic effects and mechanisms of Panax notoginseng on lipid profile in hyperlipidemic rats. J Ethnopharmacol 113: 318-324. https://doi.org/10.1016/j.jep.2007.06.022
  18. Kang KS, Kim HY, Yamabe N, Park JH, Yokozawa T (2007) Preventive effect of (S)-ginsenoside $Rg_{3}$ against lipopolysaccharide- induced hepatic and renal injury in rats. Free Radic Res 41: 1181-1188. https://doi.org/10.1080/10715760701581740
  19. Kang KS, Yamabe N, Kim HY, Park JH, Yokozawa T (2008) Therapeutic potential of 20 (S)-ginsenoside $Rg_{3}$ against streptozotocin-induced diabetic renal damage in rats. Eur J Pharmacol 591: 266-272. https://doi.org/10.1016/j.ejphar.2008.06.077
  20. Karu N, Reifen R, Kerem Z (2007) Weight gain reduction in mice fed Panax ginseng saponin, a pancreatic lipase inhibitor. J Agric Food Chem 55: 2824-2828. https://doi.org/10.1021/jf0628025
  21. Kim DY, Park JS, Yuan HD, Chung SH (2009a) Fermented ginseng attenuates hepatic lipid accumulation and hyperglycemia through AMPK activation. Food Sci Biotechnol 18: 172-178.
  22. Kim EJ, Lee HI, Chung KJ, Noh YH, Ro Y, Koo JH (2009b) The ginsenoside-Rb2 lowers cholesterol and triacylglycerol levels in 3T3-L1 adipocytes cultured under high cholesterol or fatty acids conditions. BMB Rep 42: 194-199. https://doi.org/10.5483/BMBRep.2009.42.4.194
  23. Kim JH, Hahm DH, Yang DC, Kim JH, Lee HJ, Shim I (2005) Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat. J Pharmacol Sci 97: 124-131. https://doi.org/10.1254/jphs.FP0040184
  24. Kim JH, Kang SA, Han SM, Shim I (2009c) Comparison of the antiobesity effects of the protopanaxadiol and protopanaxatriol type saponins of red ginseng. Phytother Res 23: 78-85. https://doi.org/10.1002/ptr.2561
  25. Kim MJ, Kim HK (2009) Perilla leaf extract ameliorates obesity and dyslipidemia induced by high-fat diet. Phytother Res 23: 1685-1690. https://doi.org/10.1002/ptr.2811
  26. Kim MS, Kim JK, Kim HJ, Moon SR, Shin BC, Park KW, Yang HO, Kim SM, Park R (2003) Hibiscus extract inhibits the lipid droplet accumulation and adipogenic transcription factors expression of 3T3-L1 preadipocytes. J Altern Complement Med 9: 499-504. https://doi.org/10.1089/107555303322284785
  27. Kim SH, Park KS (2003) Effects of Panax ginseng extract on lipid metabolism in humans. Pharmacol Res 48: 511-513. https://doi.org/10.1016/S1043-6618(03)00189-0
  28. Kim SN, Kang SJ (2009) Effects of black ginseng (9 timessteaming ginseng) on hypoglycemic action and changes in the composition of ginsenosides on the steaming process. Kor J Food Sci Technol 41: 77-81.
  29. Kim ST, Kim HB, Lee KH, Choi YR, Kim HJ, Shin IS, Gyoung YS, Joo SS (2012) Steam-dried ginseng berry fermented with Lactobacillus plantarum controls the increase of blood glucose and body weight in type 2 obese diabetic db/db mice. J Agric Food Chem 60: 5438-5445. https://doi.org/10.1021/jf300460g
  30. KNHANES (2010) 2007 Korean National Health and Nutrition Examination Survey.
  31. Kwak YS, Kyung JS, Kim JS, Cho JY, Rhee MH (2010) Antihyperlipidemic effects of red ginseng acidic polysaccharide from Korean red ginseng. Biol Pharm Bull 33: 468-472. https://doi.org/10.1248/bpb.33.468
  32. Laclaustra M, Corella D, Ordovas JM (2007) Metabolic syndrome pathophysiology: the role of adipose tissue. Nutr Metab Cardiovasc Dis 17: 125-139. https://doi.org/10.1016/j.numecd.2006.10.005
  33. Lee HJ, Lee YH, Park SK, Kang ES, Kim HJ, Lee YC, Choi CS, Park SE, Ahn CW, Cha BS, Lee KW, Kim KS, Lim SK, Lee HC (2009) Korean red 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
  34. Lee J, Chae K, Ha J, Park BY, Lee HS, Jeong S, Kim MY, Yoon M (2008) Regulation of obesity and lipid disorders by herbal extracts from Morus alba, Melissa officinalis and Artemisia capillaris in high-fat diet-induced obese mice. J Ethnopharmacol 115: 263-270. https://doi.org/10.1016/j.jep.2007.09.029
  35. Lee JY, Shin JW, Chun KS, Park KK, Chung WY, Bang YJ, Sung JH, Surh YJ (2005) Antitumor promotional effects of a novel intestinal bacterial metabolite (IH-901) derived from the protopanaxadiol-type ginsenosides in mouse skin. Carcinogenesis 26: 359-367.
  36. Lee OH, Lee HH, Kim JH, Lee BY (2011) Effect of ginsenosides $Rg_{3}$ and Re on glucose transport in mature 3T3-L1 adipocytes. Phytother Res 25: 768-773. https://doi.org/10.1002/ptr.3322
  37. Lee SH, Lee HJ, Lee YH, Lee BW, Cha BS, Kang ES, Ahn CW, Park JS, Kim HJ, Lee EY, Lee HC (2012) 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
  38. Lee YS, Cha BY, Yamaguchi K, Choi SS, Yonezawa T, Teruya T, Nagai K, Woo JT (2010) Effects of Korean white ginseng extracts on obesity in high-fat diet-induced obese mice. Cytotechnology 62: 367-376. https://doi.org/10.1007/s10616-010-9288-7
  39. Leung KW, Wong AST (2010) Review pharmacology of ginsenosides: a literature review. Chin Med 5: 20. doi: 10.1186/ 1749-8546-5-20.
  40. Li W, Zhang M, Gu J, Meng ZJ, Zhao LC, Zheng YN, Chen L, Yang GL (2012) Hypoglycemic effect of protopanaxadioltype ginsenosides and compound K on Type 2 diabetes mice induced by high-fat diet combining with streptozotocin via suppression of hepatic gluconeogenesis. Fitoterapia 83: 192-198. https://doi.org/10.1016/j.fitote.2011.10.011
  41. Lim S, Yoon JW, Choi SH, Cho BJ, Kim JT, Chang HS, Park HS, Park KS, Lee HK, Kim YB, Jang HC (2009) Effect of ginsam, a vinegar extract from Panax ginseng, on body weight and glucose homeostasis in an obese insulin-resistant rat model. Metabolism 58: 8-15. https://doi.org/10.1016/j.metabol.2008.07.027
  42. Liu R, Zhang J, Liu W, Kimura Y, Zheng Y (2010) Anti-obesity effects of protopanaxdiol types of ginsenosides isolated from the leaves of American ginseng (Panax quinquefolius L.) in mice fed with a high-fat diet. Fitoterapia 81: 1079-1087. https://doi.org/10.1016/j.fitote.2010.07.002
  43. Liu W, Zheng Y, Han L, Wang H, Saito M, Ling M, Kimura Y, Feng Y (2008) Saponins (ginsenosides) from stems and leaves of Panax quinquefolium prevented high-fat dietinduced obesity in mice. Phytomedicine 15: 1140-1145. https://doi.org/10.1016/j.phymed.2008.07.002
  44. Maki KC, Davidson MH, Tsushima R, Matsuo N, Tokimitsu I, Umporowicz DM, Dicklin MR, Foster GS, Ingram KA, Anderson BD, Frost SD, Bell M (2002) Consumption of diacylglycerol oil as part of a reduced-energy diet enhances loss of body weight and fat in comparison with consumption of a triacylglycerol control oil. Am J Clin Nutr 76: 1230-1236.
  45. Maki KC, Reeves MS, Farmer M, Yasunaga K, Matsuo N, Katsuragi Y, Komikado M, Tokimitsu I, Wilder D, Jones F, Blumberg JB, Cartwright Y (2009) Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. J Nutr 139: 264-270.
  46. Masuno H, Kitao T, Okuda H (1996) Ginsenosides increase secretion of lipoprotein lipase by 3T3-L1 adipocyte. Biosci. Biotech. Biochem 60: 1962-1965. https://doi.org/10.1271/bbb.60.1962
  47. Mehta S, Farmer JA (2007) Obesity and inflammation: a new look at an old problem. Current Atherosclerosis Rep 9: 134-138. https://doi.org/10.1007/s11883-007-0009-4
  48. Min SW, Jung SH, Cho KH, Kim DH (2008) Antihyperlipidemic effects of red ginseng, Crataegii fructus and their main constituents ginsenoside $Rg_{3}$ and ursolic acid in mice. Biomolecules & Therapeutics 16: 364-369. https://doi.org/10.4062/biomolther.2008.16.4.364
  49. Mollah ML, Cheon YP, In JG, Yang DC, Kim YC, Song JC, Kim KS (2011) Inhibitory effects of cultivated wild ginseng on the differentiation of 3T3-L1 pre-adipocytes. J Ginseng Res 35: 45-51. https://doi.org/10.5142/jgr.2011.35.1.045
  50. Mollah ML, Kim GS, Moon HK, Chung SK, Cheon YP, Kim JK, Kim KS (2009) Antiobesity effects of wild ginseng (Panax ginseng CA Meyer) mediated by PPAR-$\gamma$, GLUT-4 and LPL in ob/ob mice. Phytother Res 23: 220-225. https://doi.org/10.1002/ptr.2593
  51. Nagao T, Komine Y, Soga S, Meguro S, Hase T, Tanaka Y, Tokimitsu I (2005) Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men. Am J Clin Nutr 81: 122-129.
  52. Park D, Yoon M (2012) Compound K, a novel ginsenoside metabolite, inhibits adipocyte differentiation in 3T3-L1 cells: Involvement of angiogenesis and MMPS. Biochem Biophys Res Commun 422: 263-267. https://doi.org/10.1016/j.bbrc.2012.04.142
  53. Park JS, Park EM, Kim DH, Jung K. Jung JS, Lee, EJ, Hyun JW, Kang JL, Kim HS (2009) Anti-inflammatory mechanism of ginseng saponins in activated microglia. J Neuroimmunol 209: 40-49. https://doi.org/10.1016/j.jneuroim.2009.01.020
  54. Park KH, Shin HJ, Song YB, Hyun HC, Cho HJ, Ham HS, Yoo YB, Ko YC, Jun WT, Park HJ (2002) Possible role of ginsenoside $Rb_{1}$ on regulation of rat liver triglycerides. Biol Pharm Bull 25: 457-460. https://doi.org/10.1248/bpb.25.457
  55. Park MW, Ha J, Chung SH (2008a) 20 (S)-ginsenoside $Rg_{3}$ enhances glucose-stimulated insulin secretion and activates AMPK. Biol Pharm Bull 31: 748-751. https://doi.org/10.1248/bpb.31.748
  56. Park MY, Lee KS, Sung MK (2005) Effects of dietary mulberry, Korean red ginseng, and banaba on glucose homeostasis in relation to PPAR-$\alpha$, PPAR-$\gamma$, and LPL mRNA expressions. Life Sci 77: 3344-3354. https://doi.org/10.1016/j.lfs.2005.05.043
  57. Park S, Ahn IS, Kwon DY, Ko BS, Jun WK (2008b) Ginsenosides $Rb_{1}$ and Rg1 suppress triglyceride accumulation in 3T3-L1 adipocytes and enhance $\beta$-cell insulin secretion and viability in Min6 cells via PKA-dependent pathways. Bio sci Biotechnol Biochem 72: 2815-2823. https://doi.org/10.1271/bbb.80205
  58. Pi-Sunyer FX (1996) A review of long-term studies evaluating the efficacy of weight loss in ameliorating disorders associated with obesity. Clin Ther 18: 1006-1035. https://doi.org/10.1016/S0149-2918(96)80057-9
  59. 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.
  60. Rahman SM, Wang YM, Yotsumoto H, Cha JY, Han SY, Inoue S, Yanagita T (2001) Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation and $\beta$-oxidation of fatty acid in OLETF rats. Nutrition 17: 385-390. https://doi.org/10.1016/S0899-9007(00)00584-0
  61. Rao RN, Sakariah KK (1988) Lipid-lowering and antiobesity effect of (−)hydroxycitric acid. Nutr Res 8: 209-212. https://doi.org/10.1016/S0271-5317(88)80024-1
  62. Reeds DN, Patterson BW, Okunade A, Holloszy JO, Polonsky KS, Klein S (2011) Ginseng and ginsenoside Re do not improve $\beta$-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes. Diabetes care 34: 1071-1076. https://doi.org/10.2337/dc10-2299
  63. Sanders SR, Teachey MK, Ptock A, Kraemer K, Hasselwander O, Henriksen EJ, Baumgard LH (2004) Effects of specific conjugated linoleic acid isomers on growth characteristics in obese Zucker rats. Lipids 39: 537-543. https://doi.org/10.1007/s11745-004-1260-0
  64. Shang W, Yanga Y, Jianga B, Jina H, Zhoua L, Liua S, Chen M (2007) Ginsenoside $Rb_{1}$ 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
  65. Shang W, Yang Y, Zhou L, Jiang B, Jin H, Chen M (2008) Ginsenoside $Rb_{1}$ stimulates glucose uptake through insulinlike signaling pathway in 3T3-L1 adipocytes. J Endocrinol 198: 561-569. https://doi.org/10.1677/JOE-08-0104
  66. Shinkai K, Akedo H, Mukai M, Imamura F, Isoai A, Kobayashi M, Kitagawa I (1996) Inhibition of in vitro tumor cell invasion by ginsenoside $Rg_{3}$. Cancer Sci 87: 357-362. https://doi.org/10.1111/j.1349-7006.1996.tb00230.x
  67. Song YB, An YR, Kim SJ, Park HW, Jung JW, Kyung JS, Hwang SY, Kim YS (2012) Lipid metabolic effect of Korean red ginseng extract in mice fed on a high-fat diet. J Sci Food Agric 92: 388-396. https://doi.org/10.1002/jsfa.4589
  68. Wan JB, Lee SMY, Wang JD, Wang N, He CW, Wang YT, Kang JX (2009) Panax notoginseng reduces atherosclerotic lesions in ApoE-deficient mice and inhibits TNF-$\alpha$-induced endothelial adhesion molecule expression and monocyte adhesion. J Agric Food Chem 57: 6692-6697. https://doi.org/10.1021/jf900529w
  69. Wilson SA, Wong MH, Stryjecki C, De Boer A, Lui EM, Mutch DM (2012) Unraveling the adipocyte inflammomodulatory pathways activated by North American ginseng. Int J Obes (Lond) 37: 350-356.
  70. Xia W, Sun C, Zhao Y, Wu L (2011) Hypolipidemic and antioxidant activities of Sanchi (Radix Notoginseng) in rats fed with a high fat diet. Phytomedicine 18: 516-520. https://doi.org/10.1016/j.phymed.2010.09.007
  71. Xie JT, Aung HH, Wu JA, Attel AS, Yuan CS (2002) Effects of American ginseng berry extract on blood glucose levels in ob/ob mice. Am J Chin Med 30: 187-194. https://doi.org/10.1142/S0192415X02000442
  72. Xie JT, Wang CZ, Ni M, Wu JA, Mehendale SR, Aung HH, Foo A, Yuan CS (2007) American ginseng berry juice intake reduces blood glucose and body weight in ob/ob mice. J food sci 72: S590-S594. https://doi.org/10.1111/j.1750-3841.2007.00481.x
  73. Xie JT, Mchendale S, Yuan CS (2005a) Ginseng and diabetes. Am J Chin Med 33: 397-404. https://doi.org/10.1142/S0192415X05003004
  74. Xie JT, Mehendale SR, Li X, Quigg R, Wang X, Wang CZ, Wu JA, Aung HH, A Rue P, Bell GI, Yuan CS (2005b) Anti-diabetic effect of ginsenoside Re in ob/ob mice. Biochim Biophys Acta 1740: 319-325. https://doi.org/10.1016/j.bbadis.2004.10.010
  75. Xie JT, Wang CZ, Wang AB, Wu J, Basila D, Yuan CS (2005c) Antihyperglycemic effects of total ginsenosides from leaves and stem of Panax ginseng. Acta Pharmacol Sin 26: 1104-1110. https://doi.org/10.1111/j.1745-7254.2005.00156.x
  76. Xiong Y, Shen L, Liu KJ, Tso P, Xiong Y, Wang G, Woods SC, Liu M (2010) Antiobesity and antihyperglycemic effects of ginsenoside $Rb_{1}$ in rats. Diabetes 59: 2505-2512. https://doi.org/10.2337/db10-0315
  77. Yeo CR, Lee SM, Popovich DG (2011a) Ginseng (Panax quinquefolius) reduces cell growth, lipid acquisition and increases adiponectin expression in 3T3-L1 cells. Evid Based Complement Alternat Med 8: 1-9. https://doi.org/10.1625/jcam.8.1
  78. Yeo CR, Yang C, Wong TY, Popovich DG (2011b) A quantified ginseng (Panax ginseng C.A. Meyer) extract influences lipid acquisition and increases adiponectin expression in 3T3-L1 cells. Molecules 16: 477-492. https://doi.org/10.3390/molecules16010477
  79. Yuan HD, Kim SJ, Quan HY, Huang B, Chung SH (2010) Ginseng leaf extract prevents high fat diet-induced hyperglycemia and hyperlipidemia through AMPK activation. J Ginseng Res 34: 369-375. https://doi.org/10.5142/jgr.2010.34.4.369
  80. Yuan HD, Kim JT, Chung SH (2012) Pectinase-processed ginseng radix (GINST) ameliorates hyperglycemia and hyperlipidemia in high fat diet-fed ICR mice. Biomolecules & Therapeutics 200: 220-225.
  81. Yun SN, Ko SK, Lee KH, Chung SH (2007) Vinegar-processed ginseng radix improves metabolic syndrome induced by a high fat diet in ICR mice. Arch Pharm Res 30: 587-595. https://doi.org/10.1007/BF02977653
  82. Zhang Z, Li X, Lv W, Yang Y, Gao H, Yang J, Shen Y, Ning G (2008) Ginsenoside Re reduces insulin resistance through inhibition of c-Jun $NH_{2}$-terminal kinase and nuclear factor- B. Mol Endocrinol 22: 186-195. https://doi.org/10.1210/me.2007-0119
  83. http://www.pubmed.com Accessed July 17, 2012
  84. http://www.webofscience.com Accessed July 10, 2012