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Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice

Abstract

Visceral obesity induces insulin resistance and is recognized as an important risk factor for metabolic syndrome (MS). Therefore, inhibition of lipid absorption from the intestine is regarded as an effective way of preventing MS. Terminalia bellirica is extensively used in Ayurvedic medicine in India and neighboring countries, and the fruit of this plant has been reported to have hypoglycemic and hypolipidemic effects. In this study, we investigated the preventive effect of a hot water extract of T. bellirica fruit (TB) on obesity and various metabolic disorders, and explored its molecular mechanisms and active ingredients. TB treatment had a preventive effect on obesity, insulin resistance, and hyperlipidemia in spontaneously obese type 2 diabetic TSOD mice. To clarify the molecular mechanisms of TB in preventing obesity, we investigated the inhibitory effect on lipid absorption. TB suppressed absorption of triacylglycerol in an olive oil loading test (in vivo) and showed a strong inhibitory effect on pancreatic lipase activity (in vitro). Furthermore, a search for the active ingredients in TB revealed that gallic acid is the component primarily responsible for the inhibition of pancreatic lipase activity. Thus, our findings indicate that TB could be useful in preventing MS. The mechanisms probably involve suppression of the absorption of meal-derived lipids mediated by gallic acid.

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References

  1. Yoshikawa M, Shimoda H, Nishida N, Takada M, Matsuda H (2002) Salacia reticulata and its polyphenolic constituents with lipase inhibitory and lipolytic activities have mild antiobesity effects in rats. J Nutr 132:1819–1824

    PubMed  CAS  Google Scholar 

  2. Nakai M, Fukui Y, Asami S, Toyoda-Ono Y, Iwashita T, Shibata H, Mitsunaga T, Hashimoto F, Kiso Y (2005) Inhibitory effects of oolong tea polyphenols on pancreatic lipase in vitro. J Agric Food Chem 53:4593–4598

    PubMed  Article  CAS  Google Scholar 

  3. Ikeda I, Tsuda K, Suzuki Y, Kobayashi M, Unno T, Tomoyori H, Goto H, Kawata Y, Imaizumi K, Nozawa A, Kakuda T (2005) Tea catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by delaying lymphatic transport of dietary fat in rats. J Nutr 135:155–159

    PubMed  CAS  Google Scholar 

  4. Ninomiya K, Matsuda H, Shimoda H, Nishida N, Kasajima N, Yoshino T, Morikawa T, Yoshikawa M (2004) Carnosic acid, a new class of lipid absorption inhibitor from sage. Bioorg Med Chem Lett 14:1943–1946

    PubMed  Article  CAS  Google Scholar 

  5. Birari RB, Bhutani KK (2007) Pancreatic lipase inhibitors from natural sources: unexplored potential. Drug Discov Today 12:879–889

    PubMed  Article  CAS  Google Scholar 

  6. Modak M, Dixit P, Londhe J, Ghaskadbi S, Paul A, Devasagayam T (2007) Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr 40:163–173

    PubMed  Article  Google Scholar 

  7. Williamson EM (2002) Major herbs of Ayurveda. Churchill Livingstone, Philadelphia, pp 294–297

    Google Scholar 

  8. Duke JA, Bogenschutz-Godwin MJ, Ducelliar J, Duke PAK (2002) Handbook of medicinal herbs, 2nd edn. CRC, Boca Raton, pp 70–71

    Book  Google Scholar 

  9. Row JR, MURTY PS (1970) Chemical examination of Terminalia bellerica Roxb. Indian J Chem 8:1047–1048

    CAS  Google Scholar 

  10. Pfundstein B, El Desouky SK, Hull WE, Haubner R, Erben G, Owen RW (2010) Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): characterization, quantitation and determination of antioxidant capacities. Phytochemistry 71:1132–1148

    PubMed  Article  CAS  Google Scholar 

  11. Awasthi L, Nath B (1968) Chemical examination of Terminalia belerica Roxb., part I—a new cardiac glycoside. J Indian Chem Soc 45:913–917

    CAS  Google Scholar 

  12. Valsaraj R, Pushpangadan P, Smitt UW, Adsersen A, Christensen SB, Sittie A, Nyman U, Nielsen C, Olsen CE (1997) New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica. J Nat Prod 60:739–742

    PubMed  Article  CAS  Google Scholar 

  13. Kar A, Choudhary BK, Bandyopadhyay NG (2003) Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic rats. J Ethnopharmacol 84:105–108

    PubMed  Article  Google Scholar 

  14. Latha RC, Daisy P (2010) Influence of Terminalia bellerica Roxb. Fruit extracts on biochemical parameters in streptozotocin diabetic rats. Int J Pharmacol 6:89–96

    Article  Google Scholar 

  15. Latha RC, Daisy P (2011) Insulin-secretagogue, antihyperlipidemic and other protective effects of gallic acid isolated from Terminalia bellerica Roxb. in streptozotocin-induced diabetic rats. Chem Biol Interact 189:112–118

    PubMed  Article  CAS  Google Scholar 

  16. Thakur CP, Thakur B, Singh S, Sinha PK, Sinha SK (1988) The Ayurvedic medicines Haritaki, Amala and Bahira reduce cholesterol-induced atherosclerosis in rabbits. Int J Cardiol 21:167–175

    PubMed  Article  CAS  Google Scholar 

  17. Shaila HP, Udupa AL, Udupa SL (1995) Preventive actions of Terminalia belerica in experimentally induced atherosclerosis. Int J Cardiol 49:101–106

    PubMed  Article  CAS  Google Scholar 

  18. Shaila HP, Udupa SL, Udupa AL (1998) Hypolipidemic activity of three indigenous drugs in experimentally induced atherosclerosis. Int J Cardiol 67:119–124

    PubMed  Article  CAS  Google Scholar 

  19. Khan A, Gilani A (2008) Pharmacodynamic evaluation of Terminalia bellerica for its anti hypertensive effect. J Food Drug Anal 16:6–14

    Google Scholar 

  20. Anand KK, Singh B, Saxena AK, Chandan BK, Gupta VN, Bhardwaj V (1997) 3,4,5-Trihydroxy benzoic acid (gallic acid), the hepatoprotective principle in the fruits of Terminalia belerica-bioassay guided activity. Pharmacol Res 36:315–321

    PubMed  Article  CAS  Google Scholar 

  21. Jadon A, Bhadauria M, Shukla S (2007) Protective effect of Terminalia belerica Roxb and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharmacol 109:214–218

    PubMed  Article  CAS  Google Scholar 

  22. Sabu MC, Kuttan R (2002) Anti-diabetic activity of medicinal plants and its relationship with their antioxidant property. J Ethnopharmacol 81:155–160

    PubMed  Article  CAS  Google Scholar 

  23. Sabu MC, Kuttan R (2009) Antidiabetic and antioxidant activity of Terminalia belerica Roxb. Indian J Exp Biol 47:270–275

    PubMed  CAS  Google Scholar 

  24. Suzuki W, Iizuka S, Tabuchi M, Funo S, Yanagisawa T, Kimura M, Sato T, Endo T, Kawamura H (1999) A new mouse model of spontaneous diabetes derived from ddY strain. Exp Anim 48:181–189

    PubMed  Article  CAS  Google Scholar 

  25. Iizuka S, Suzuki W, Tabuchi M, Nagata M, Imamura S, Kobayashi Y, Kanitani M, Yanagisawa T, Kase Y, Takeda S, Aburada M, Takahashi KW (2005) Diabetic complications in a new animal model (TSOD mouse) of spontaneous NIDDM with obesity. Exp Anim 54:71–83

    PubMed  Article  CAS  Google Scholar 

  26. Takahashi A, Tabuchi M, Suzuki W, Iizuka S, Nagata M, Ikeya Y, Takeda S, Shimada T, Aburada M (2006) Insulin resistance and low sympathetic nerve activity in the Tsumura Suzuki obese diabetic mouse: a new model of spontaneous type 2 diabetes mellitus and obesity. Metabolism 55:1664–1669

    PubMed  Article  CAS  Google Scholar 

  27. Hirayama I, Yi Z, Izumi S, Arai I, Suzuki W, Nagamachi Y, Kuwano H, Takeuchi T, Izumi T (1999) Genetic analysis of obese diabetes in the TSOD mouse. Diabetes 48:1183–1191

    PubMed  Article  CAS  Google Scholar 

  28. Shimada T, Kudo T, Akase T, Aburada M (2008) Preventive effects of Bofutsushosan on obesity and various metabolic disorders. Biol Pharm Bull 31:1362–1367

    PubMed  Article  CAS  Google Scholar 

  29. Shimada T, Akase T, Kosugi M, Aburada M (2011) Preventive effect of Boiogito on metabolic disorders in the TSOD mouse, a model of spontaneous obese type II diabetes mellitus. Evid Based Complement Alternat Med. doi:10.1093/ecam/nep012

  30. Shimada T, Kosugi M, Tokuhara D, Tsubata M, Kamiya T, Sameshima M, Nagamine R, Takagaki K, Miyamoto K, Aburada M (2011) Preventive effect of pine bark extract (flavangenol) on metabolic disease in Western diet-loaded Tsumura Suzuki obese diabetes mice. Evid Based Complement Alternat Med. doi: 10.1093/ecam/nep231

  31. Shimada T, Nagai E, Harasawa Y, Akase T, Aburada T, Iizuka S, Miyamoto K, Aburada M (2010) Metabolic disease prevention and suppression of fat accumulation by Salacia reticulata. J Nat Med 64:266–274

    PubMed  Article  Google Scholar 

  32. Akase T, Shimada T, Harasawa Y, Ikeya Y, Nagai E, Iizuka S, Nakagami G, Iizaka S, Sanada H, Aburada M (2011) Preventive effects of Salacia reticulata on obesity and metabolic disorders in TSOD mice. Evid Based Complement Alternat Med. doi:10.1093/ecam/nep052

  33. Akase T, Shimada T, Terabayashi S, Ikeya Y, Sanada H, Aburada M (2011) Antiobesity effects of Kaempferia parviflora in spontaneously obese type II diabetic mice. J Nat Med 65:73–80

    PubMed  Article  Google Scholar 

  34. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    PubMed  Article  CAS  Google Scholar 

  35. Freedman BD, Lee EJ, Park Y, Jameson JL (2005) A dominant negative peroxisome proliferator-activated receptor-gamma knock-in mouse exhibits features of the metabolic syndrome. J Biol Chem 280:17118–17125

    PubMed  Article  CAS  Google Scholar 

  36. Kasabri V, Flatt PR, Abdel-Wahab YH (2010) Terminalia bellirica stimulates the secretion and action of insulin and inhibits starch digestion and protein glycation in vitro. Br J Nutr 103:212–217

    PubMed  Article  CAS  Google Scholar 

  37. McDougall GJ, Stewart D (2005) The inhibitory effects of berry polyphenols on digestive enzymes. Biofactors 23:189–195

    PubMed  Article  CAS  Google Scholar 

  38. Gowadia N, Vasudevan TN (2000) Studies on effect of some medicinal plants on pancreatic lipase activity using spectrophotometric method. Asian J Chem 12:847–852

    CAS  Google Scholar 

  39. Hsu CL, Yen GC (2007) Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. Br J Nutr 98:727–735

    PubMed  Article  CAS  Google Scholar 

  40. Jang A, Srinivasan P, Lee NY, Song HP, Lee JW, Lee M, Jo C (2008) Comparison of hypolipidemic activity of synthetic gallic acid–linoleic acid ester with mixture of gallic acid and linoleic acid, gallic acid, and linoleic acid on high-fat diet induced obesity in C57BL/6 Cr Slc mice. Chem Biol Interact 174:109–117

    PubMed  Article  CAS  Google Scholar 

  41. Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, Du LJ (2007) Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond) 31:1023–1029

    Article  CAS  Google Scholar 

  42. Gao H, Huang YN, Xu PY, Kawabata J (2007) Inhibitory effect on alpha-glucosidase by the fruits of Terminalia chebula Retz. Food Chem 105:628–634

    Article  CAS  Google Scholar 

  43. Zoechling A, Liebner F, Jungbauer A (2011) Red wine: a source of potent ligands for peroxisome proliferator-activated receptor γ. Food Funct 2:28–38

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Masaki Aburada.

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H. Makihara and T. Shimada contributed equally to this work.

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Makihara, H., Shimada, T., Machida, E. et al. Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice. J Nat Med 66, 459–467 (2012). https://doi.org/10.1007/s11418-011-0606-y

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  • DOI: https://doi.org/10.1007/s11418-011-0606-y

Keywords

  • Terminalia bellirica
  • Gallic acid
  • Lipid absorption
  • Anti-obesity
  • Metabolic disorders