Pancreatic lipase inhibitory activity of taraxacum officinale in vitro and in vivo

  • Zhang, Jian ;
  • Kang, Min-Jung ;
  • Kim, Myung-Jin ;
  • Kim, Mi-Eun ;
  • Song, Ji-Hyun ;
  • Lee, Young-Min ;
  • Kim, Jung-In
  • Published : 2008.12.31

Abstract

Obesity has become a worldwide health problem. Orlistat, an inhibitor of pancreatic lipase, is currently approved as an anti-obesity drug. However, gastrointestinal side effects caused by Orlistat may limit its use. In this study the inhibitory activities of dandelion (Taraxacum officinale) against pancreatic lipase in vitro and in vivo were measured to determine its possible use as a natural anti-obesity agent. The inhibitory activities of the 95% ethanol extract of T. officinale and Orlistat were measured using 4-methylumbelliferyl oleate (4-MU oleate) as a substrate at concentrations of 250, 125, 100, 25, 12.5 and $4\;{\mu}g/ml$. To determine pancreatic lipase inhibitory activity in vivo, mice (n=16) were orally administered with com oil emulsion (5 ml/kg) alone or with the 95% ethanol extract of T. officinale (400 mg/kg) following an overnight fast. Plasma triglyceride levels were measured at 0, 90, 180, and 240 min after treatment and incremental areas under the response curves (AUC) were calculated. The 95% ethanol extract of T. officinale and Orlistat, inhibited, porcine pancreatic lipase activity by 86.3% and 95.7% at a concentration of $250\;{\mu}g/ml$, respectively. T. officinale extract showed dose-dependent inhibition with the $IC_{50}$ of $78.2\;{\mu}g/ml$. A single oral dose of the extract significantly inhibited increases in plasma triglyceride levels at 90 and 180 min and reduced AVC of plasma triglyceride response curve (p<0.05). The results indicate that T. officinale exhibits inhibitory activities against pancreatic lipase in vitro and in vivo. Further studies to elucidate anti-obesity effects of chronic consumption of T. officinale and to identify the active components responsible for inhibitory activity against pancreatic lipase are necessary.

Keywords

mouse;pancreatic lipase;Taraxacum officinale;triglyceride

References

  1. Arai I, Amagaya S, Komatsu Y, Okada M, Hayashi T, Kasai M, Arisawa M & Momose Y (1999). Improving effects of the extracts from Eugenia uniflora on hyperglycemia and hypertriglyceridemia in mice. J Ethnopharmacol 68:307-314 https://doi.org/10.1016/S0378-8741(99)00066-5
  2. Aronne LJ (1998). Modern medical management of obesity: the role of pharmaceutical intervention. J Am Diet Assoc 98:S23-26 https://doi.org/10.1016/S0002-8223(98)00008-X
  3. Cho SY, Oh YJ, Park JY, Lee MK & Kim MJ (2003). Effect of dandelion (Taraxacum officinale) leaf extracts on hepatic antioxidative system in rats fed high cholesterol diet. J Korean Soc Food Sci Nutr 32:458-463 https://doi.org/10.3746/jkfn.2003.32.3.458
  4. Han LK, Kimura Y, Kawashima M, Takaku T, Taniyama T, Hayashi T, Zheng YN & Okuda H (2001). Anti-obesity effects in rodents of dietary teasaponin, a lipase inhibitor. Int J Obes 25:1459-1464 https://doi.org/10.1038/sj.ijo.0801747
  5. Hochuli E, Kupfer E, Maurer R, Meister W, Mercadal Y & Schmidt K (1987). Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. II. Chemistry and structure elucidation. J Antibiot (Tokyo) 40:1086-109 https://doi.org/10.7164/antibiotics.40.1086
  6. Kurihara H, Asami S, Shibata H, Fukami H & Tanaka T (2003). Hypolipemic effect of Cyclocarya paliurus (Batal) Iljinskaja in lipid-loaded mice. Biol Pharm Bull 26:383-385 https://doi.org/10.1248/bpb.26.383
  7. Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, Hayflick L, Butler RN, Allison DB & Ludwig DS (2005). A potential decline in life expectancy in the United States in the 21st century. N Engl J Med 352:1135-1137 https://doi.org/10.1056/NEJMe058009
  8. Shin JE, Han MJ & Kim DH (2003). 3-Methylethergalangin isolated from Alpinia officinarum inhibits pancreatic lipase. Biol Pharm Bull 26:854-857 https://doi.org/10.1248/bpb.26.854
  9. Thompson ABR (1978). Disturbance in lipid metabolism, p.31. American Physiological Society New York, USA
  10. Weibel EK, Hadvary P, Hochuli E, Kupfer E & Lengsfeld H. Lipstatin (1987). An inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity. J Antibiot (Tokyo) 40:1081-1085 https://doi.org/10.7164/antibiotics.40.1081
  11. Yamamoto M, Shimura S, Itoh Y, Ohsaka T, Egawa M & Inoue S (2000). Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet. Int J Obes 24:758-764 https://doi.org/10.1038/sj.ijo.0801222
  12. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, & Marks JS (2003). Prevalence of obesity, diabetes, and obesity-related health risk factors. JAMA 289:76-79 https://doi.org/10.1001/jama.289.1.76
  13. Weigle DS (2003). Pharmacological therapy of obesity: past, present, and future. J Clin Endocrinol Metab 88:2462-2469 https://doi.org/10.1210/jc.2003-030151
  14. Kurihara H, Shibata H, Fukui Y, Kiso Y, Xu JK, Yao XS & Fukami H (2006). Evaluation of the hypolipidemic property of Camellia sinensis Var. ptilophylla on postprandial hypertriglyceridemia J Agric Food Chem 54:4977-4981 https://doi.org/10.1021/jf0603681
  15. Ballinger A & Peikin SR (2002). Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol 440:109-117 https://doi.org/10.1016/S0014-2999(02)01422-X
  16. Birari RB & Bhutani KK (2007). Pancreatic lipase inhibitors from natural sources: unexplored potential. Drug Discov Today 12: 879-889 https://doi.org/10.1016/j.drudis.2007.07.024
  17. Cho SY, Park JY, Park EM, Choi MS, Lee MK, Jeon MJ, Jang MK, Kim MJ & Park YB (2002). Alternation of hepatic antioxidant enzyme activities and lipid profile in streptozotocin-induced diabetic rats by supplementation of dandelion water extract. Clin Chim Acta 317:109-117 https://doi.org/10.1016/S0009-8981(01)00762-8
  18. Jandacek RJ & Woods SC (2004). Pharmaceutical approaches to the treatment of obesity. Drug Discov Today 15:874-880
  19. Juhel C, Armand M, Pafumi Y, Rosier C, Vandermander J & Lairon D (2000). Green tea extract (AR25) inhibits lipolysis of triglycerides in gastric and duodenal medium in vitro. J Nutr Biochem 11:45-51 https://doi.org/10.1016/S0955-2863(99)00070-4
  20. Bisset NG (1994). Taraxaci radix cum herba. In: Herbal Drugs and Phytopharmaceuticals, Medpharm, p.486-489. Stuttgart, Germany
  21. Mascolo N, Autore G, Capasso F, Menghini A & Fasulo MP (1987). Biological screening of Italian medical plants for anti-inflammatory activity. Phytother Res 1:28-31 https://doi.org/10.1002/ptr.2650010107
  22. Williams CA, Goldstone F & Greenham J (1996). Flavonoids, cinnamic acids and coumarins from the different tissues and medical preparations of Taraxacum officinale. Phytochemistry 42:121-127 https://doi.org/10.1016/0031-9422(95)00865-9
  23. Han LK, Zheng YN, Xu BJ, Okuda H & Kimura Y (2002). Saponins from Platycodi Radix ameliorate high fat diet-induced obesity in mice. J Nutr 132:2241-2245
  24. Karamanos BG, Thanopoulou AC & Roussi-Penesi DP (2001). Maximal post-prandial triglyceride increases reflects post-prandial hypertriglyceridaemia and is associated with the insulin resistance syndrome. Diabet Med 18:32-39 https://doi.org/10.1046/j.1464-5491.2001.00386.x
  25. Moreno DA, Ilic N, Poulev A, Brasaemle DL, Fried SK & Raskin I (2003). Inhibitory effects of grape seed extract on lipases. Nutrition 19:876-879 https://doi.org/10.1016/S0899-9007(03)00167-9
  26. Kim HY (2007). Effect of onion (Allium cepa) skin extract on pancreatic lipase and body weight-related parameters. Food Science and Biotechnology 16:434-438
  27. Hu C & Kitts DD (2005). Dandelion (Taraxacum officinale) flow extract suppresses both reactive oxygen species and nitric oxide and prevents lipid oxidation in vitro. Phytomedicine 12:588-597 https://doi.org/10.1016/j.phymed.2003.12.012
  28. Cho SY, Park JY, Oh YJ, Jang JY, Park EM & Kim MJ (2000). Effect of dandelion leaf extracts on lipid metabolism in rats fed high cholesterol diet. J Korean Soc Food Sci Nutr 29:676-682
  29. Moreno DA, Ripoll C, Ilic N, Poulev A, Aubin C & Raskin I (2006). Inhibition of lipid metabolic enzymes using Mangifera indica extracts. J Food Agric Environ 4:21-26