DOI QR코드

DOI QR Code

Pinus Densiflora Bark Extract (PineXol) Decreases Adiposity in Mice by Down-Regulation of Hepatic De Novo Lipogenesis and Adipogenesis in White Adipose Tissue

  • Ahn, Hyemyoung (Department of Foods and Nutrition, Kookmin University) ;
  • Go, Gwang-woong (Department of Foods and Nutrition, Kookmin University)
  • Received : 2016.12.30
  • Accepted : 2017.01.09
  • Published : 2017.04.28

Abstract

PineXol, extracted from Korean red pine bark, has beneficial effects, such as antioxidant, antiinflammatory, and antilipogenic activities in vitro. We tested the hypothesis that PineXol supplementation could have anti-obesity effects on mice fed a high-fat diet (HFD). Four-week-old male C57BL/6 mice were fed normal chow (18% kcal from fat) or a HFD (60% kcal from fat). HFD-fed animals were also subjected to PineXol treatment at a dose of 10 or 50 mg/kg body weight (BW) (PX10 or PX50, respectively) body weight. The body weight and body fat mass in the PX50 group were statistically lower than those in the HFD group (p < 0.05 and p < 0.001, respectively). The concentration of hepatic triglycerides, total cholesterol, and low-density lipoprotein cholesterol were reduced in the PX50 group compared with the HFD group (p < 0.01). Acetyl CoA carboxylase (p < 0.01), elongase of very long chain fatty acids 6 (p < 0.01), stearoyl CoA desaturase 1 (p < 0.05), microsomal triglyceride transfer protein (p < 0.01), and sterol regulatory element-binding protein 1 (p < 0.05) were significantly decreased in the PX50 group compared with that in the HFD group. In white adipose tissue, CCAAT-enhancer-binding protein alpha (p < 0.05), peroxisome proliferator-activated receptor gamma (p < 0.001), and perilipin (p < 0.01) were decreased in the PX50 group compared with those in the HFD group. Therefore, the current study implies the potential of PineXol for the prevention and/or amelioration of obesity, in part by inhibition of both hepatic lipid synthesis and adipogenesis in white adipose tissue.

Keywords

References

  1. Popkin BM, Doak CM. 1998. The obesity epidemic is a worldwide phenomenon. Nutr. Rev. 56: 106-114.
  2. Das U. 2001. Is obesity an inflammatory condition? Nutrition 17: 953-966. https://doi.org/10.1016/S0899-9007(01)00672-4
  3. Kopelman PG. 2000. Obesity as a medical problem. Nature 404: 635-643. https://doi.org/10.1038/35007508
  4. Biddinger SB, Kahn CR. 2006. From mice to men: insights into the insulin resistance syndromes. Annu. Rev. Physiol. 68: 123-158. https://doi.org/10.1146/annurev.physiol.68.040104.124723
  5. Spiegelman BM, Flier JS. 2001. Obesity and the regulation of energy balance. Cell 104: 531-543. https://doi.org/10.1016/S0092-8674(01)00240-9
  6. Kang JG, Park C-Y. 2012. Anti-obesity drugs: a review about their effects and safety. Diabetes Metab. J. 36: 13-25. https://doi.org/10.4093/dmj.2012.36.1.13
  7. 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
  8. Heal D, Aspley S, Prow M, Jackson H, Martin K, Cheetham S. 1998. Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from Damphetamine and D-fenfluramine. Int. J. Obes. Relat. Metab. Disord. 22: S18-S28; discussion S9.
  9. Ioannides-Demos LL, Proietto J, Tonkin AM, McNeil JJ. 2006. Safety of drug therapies used for weight loss and treatment of obesity. Drug Saf. 29: 277-302. https://doi.org/10.2165/00002018-200629040-00001
  10. Sergent T, Vanderstraeten J, Winand J, Beguin P, Schneider Y-J. 2012. Phenolic compounds and plant extracts as potential natural anti-obesity substances. Food Chem. 135: 68-73. https://doi.org/10.1016/j.foodchem.2012.04.074
  11. Maimoona A, Naeem I, Saddiqe Z, Jameel K. 2011. A review on biological, nutraceutical and clinical aspects of French maritime pine bark extract. J. Ethnopharmacol. 133: 261-277. https://doi.org/10.1016/j.jep.2010.10.041
  12. Grimm T, Schafer A, Högger P. 2004. Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (Pycnogenol). Free Radic. Biol. Med. 36: 811-822. https://doi.org/10.1016/j.freeradbiomed.2003.12.017
  13. Packer L, Rimbach G, Virgili F. 1999. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, Pycnogenol. Free Radic. Biol. Med. 27: 704-724. https://doi.org/10.1016/S0891-5849(99)00090-8
  14. Virgili F, Kobuchi H, Packer L. 1998. Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine RAW 264.7 macrophages. Free Radic. Biol. Med. 24: 1120-1129. https://doi.org/10.1016/S0891-5849(97)00430-9
  15. Nocun M, Ulicna O, Muchova J, Durackova Z, Watala C. 2008. French maritime pine bark extract (Pycnogenol) reduces thromboxane generation in blood from diabetic male rats. Biomed. Pharmacother. 62: 168-172. https://doi.org/10.1016/j.biopha.2007.07.002
  16. Lee OH, Seo MJ, Choi HS, Lee BY. 2012. Pycnogenol inhibits l ipid a ccumulation i n 3T3- L1 a dipocytes w ith t he modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses. Phytother. Res. 26: 403-411.
  17. Canali R, Comitato R, Schonlau F, Virgili F. 2009. The anti-inflammatory pharmacology of Pycnogenol in humans involves COX-2 and 5-LOX mRNA expression in leukocytes. Int. Immunopharmacol. 9: 1145-1149. https://doi.org/10.1016/j.intimp.2009.06.001
  18. Bayeta E, Lau BH. 2000. Pycnogenol inhibits generation of inflammatory mediators in macrophages. Nutr. Res. 20: 249-259. https://doi.org/10.1016/S0271-5317(99)00157-8
  19. Hasegawa N. 1999. Stimulation of lipolysis by Pycnogenol. Phytother. Res. 13: 619-620. https://doi.org/10.1002/(SICI)1099-1573(199911)13:7<619::AID-PTR498>3.0.CO;2-B
  20. Hasegawa N. 2000. Inhibition of lipogenesis by Pycnogenol. Phytother. Res. 14: 472-473. https://doi.org/10.1002/1099-1573(200009)14:6<472::AID-PTR649>3.0.CO;2-S
  21. Ho JN, Kim OK, Nam DE, Jun W, Lee J. 2014. Pycnogenol supplementation promotes lipolysis via activation of cAMP-dependent PKA in ob/ob mice and primary-cultured adipocytes. J. Nutr. Sci. Vitaminol. (Tokyo) 60: 429-435. https://doi.org/10.3177/jnsv.60.429
  22. Kim KD, Kim HJ, P ark K- R, Kim S-M, Na Y- C, Shim BS, et al. 2011. Pinexol inhibits in vitro inflammatory biomarkers by blocking $NF-{\kappa}B$ signaling pathway and protects mice from lethal endotoxemia. Orient. Pharm. Exp. Med. 11: 61-70. https://doi.org/10.1007/s13596-011-0003-9
  23. Lee YJ, Han OT, Choi H-S, Lee BY, Chung H-J, Lee O-H. 2013. Antioxidant and anti-adipogenic effects of PineXol. Kor. J. Food Sci. Technol. 45: 97-103. https://doi.org/10.9721/KJFST.2013.45.1.97
  24. Saliou C, Rimbach G, Moini H, McLaughlin L, Hosseini S, Lee J, et al. 2001. Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic. Biol. Med. 30: 154-160. https://doi.org/10.1016/S0891-5849(00)00445-7
  25. Hwang YJ. 2016. Quantitative analysis of taxifolin, (+)-catechin and procyanidin B1 from the preparation of Pinus densiflora (PineXol). Kor. J. Pharmacogn. 47: 246-250.
  26. Go G-W, Srivastava R, Hernandez-Ono A, Gang G, Smith SB, Booth CJ, et al. 2014. The combined hyperlipidemia caused by impaired Wnt-LRP6 signaling is reversed by Wnt3a rescue. Cell Metab. 19: 209-220. https://doi.org/10.1016/j.cmet.2013.11.023
  27. Michael SL, Pumford NR, Mayeux PR, Niesman MR, Hinson JA. 1999. Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species. Hepatology 30: 186-195. https://doi.org/10.1002/hep.510300104
  28. Krisko TI, LeClair KB, Cohen DE. 2017. Genetic ablation of phosphatidylcholine transfer protein/starD2 in ob/ob mice improves glucose tolerance without increasing energy expenditure. Metabolism 68: 145-149. https://doi.org/10.1016/j.metabol.2016.11.012
  29. Choi J-H, Choi M-K, Han O-T, Han S - J, Chung S-J, Shim C-K, et al. 2007. Evaluation of skin absorption of catechin from topical formulations containing Korean pine bark extract (Pinexol). J. Pharm. Investig. 37: 359-364. https://doi.org/10.4333/KPS.2007.37.6.359
  30. Hsu CL, Yen GC. 2008. Phenolic compounds: evidence for inhibitory effects against obesity and their underlying molecular signaling mechanisms. Mol. Nutr. Food Res. 52: 53-61. https://doi.org/10.1002/mnfr.200700393
  31. Sato M, Yamada Y, Matsuoka H, Nakashima S, Kamiya T, Ikeguchi M, et al. 2009. Dietary pine bark extract reduces atherosclerotic lesion development in male ApoE-deficient mice by lowering the serum cholesterol level. Biosci. Biotechnol. Biochem. 73: 1314-1317. https://doi.org/10.1271/bbb.80838
  32. Powell EE, Cooksley WGE, Hanson R, Searle J, Halliday JW, Powell W. 1990. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 11: 74-80. https://doi.org/10.1002/hep.1840110114
  33. Trevaskis JL, Griffin PS, Wittmer C, Neuschwander-Tetri BA, Brunt EM, Dolman CS, et al. 2012. Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 302: G762-G772. https://doi.org/10.1152/ajpgi.00476.2011
  34. Chen Y, Sun R, Jiang W, Wei H, Tian Z. 2007. Liver-specific HBsAg transgenic mice are over-sensitive to poly(I: C)-induced liver injury in NK cell- and $IFN-{\gamma}$-dependent manner. J. Hepatol. 47: 183-190. https://doi.org/10.1016/j.jhep.2007.02.020
  35. Giannini E, Botta F, Fasoli A, Ceppa P, Risso D, Lantieri PB, et al. 1999. Progressive liver functional impairment is associated with an increase in AST/ALT ratio. Dig. Dis. Sci. 44: 1249-1253. https://doi.org/10.1023/A:1026609231094
  36. Devaraj S, Vega-Lopez S, Kaul N, Schonlau F, Rohdewald P, Jialal I. 2002. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids 37: 931-934. https://doi.org/10.1007/s11745-006-0982-3
  37. Koch R. 2002. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother. Res. 16: 1-5.
  38. Guerrero L, Margalef M, Pons Z, Quiñones M, Arola L, Arola-Arnal A, et al. 2013. Serum metabolites of proanthocyanidin-administered rats decrease lipid synthesis in HepG2 cells. J. Nutr. Biochem. 24: 2092-2099. https://doi.org/10.1016/j.jnutbio.2013.08.001
  39. Yang J, Jang J-Y, Nam D-E, Lee J, Hwang K-T, Jun W-J, et al. 2010. Pcynogenol inhibits adipogenesis and simulate antilipogenic effect in 3T3-L1 adipocytes. FASEB J. 24: lb254.

Cited by

  1. Downregulation of Hepatic De Novo Lipogenesis and Adipogenesis in Adipocytes by Pinus densiflora Bark Extract vol.27, pp.11, 2017, https://doi.org/10.4014/jmb.1707.07030
  2. 마우스를 이용한 비만연구에서 활용되는 물리적 표현형 분석 기술 vol.51, pp.1, 2017, https://doi.org/10.23093/fsi.2018.51.1.37
  3. Pinus densiflora bark extract ameliorates 2,4‐dinitrochlorobenzene‐induced atopic dermatitis in NC/Nga mice by regulating Th1/Th2 balance and skin barrier function vol.32, pp.6, 2018, https://doi.org/10.1002/ptr.6061
  4. Sesamol intervention ameliorates obesity-associated metabolic disorders by regulating hepatic lipid metabolism in high-fat diet-induced obese mice vol.63, pp.None, 2017, https://doi.org/10.29219/fnr.v63.3637
  5. Pinus Species as Prospective Reserves of Bioactive Compounds with Potential Use in Functional Food-Current State of Knowledge vol.10, pp.7, 2021, https://doi.org/10.3390/plants10071306