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Protein tyrosine phosphatase 1B inhibitory activity of Indonesian herbal medicines and constituents of Cinnamomum burmannii and Zingiber aromaticum

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Abstract

We screened water and methanol extracts of 28 Indonesian medicinal plants for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activities. Nine water extracts, i.e., Alstonia scholaris leaf, Blumea balsamifera, Cinnamomum burmannii, Cymbopogon nardus, Melaleuca leucadendra, Phyllanthus niruri, Piper nigrum, Syzygium aromaticum, and Sy. polyanthum, exhibited ≥70 % inhibition at 25 μg/mL, whereas 11 methanol extracts, i.e., Als. scholaris, Andrographis paniculata, B. balsamifera, Ci. burmannii, Curcuma heyneana, Glycyrrhiza glabra, M. leucadendra, Punica granatum, Rheum palmatum, Sy. polyanthum, and Z. aromaticum, exhibited ≥70 % inhibition at 25 μg/mL. Water extracts of B. balsamifera (IC50, 2.26 μg/mL) and M. leucadendra (IC50, 2.05 μg/mL), and methanol extracts of Ci. burmannii (IC50, 2.47 μg/mL), Pu. granatum (IC50, 2.40 μg/mL), and Sy. polyanthum (IC50, 1.03 μg/mL) exhibited strong inhibitory activity, which was comparable with that of the positive control, RK-682 (IC50, 2.05 μg/mL). The PTP1B inhibitory activity of the constituents of Ci. burmannii and Z. aromaticum was then evaluated. 5′-Hydroxy-5-hydroxymethyl-4″,5″-methylenedioxy-1,2,3,4-dibenzo-1,3,5-cycloheptatriene (2; IC50, 29.7 μM) and trans-cinnamaldehyde (5; IC50, 57.6 μM) were the active constituents of Ci. burmannii, while humulatrien-5-ol-8-one (21; IC50, 27.7 μM), kaempferol-3,4′-di-O-methyl ether (32; IC50, 17.5 μM), and (S)-6-gingerol (33; IC50, 28.1 μM) were those of Z. aromaticum. These results suggest that these medicinal plants may contribute to the treatment and/or prevention of type II diabetes and/or obesity through PTP1B inhibition.

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References

  1. Byon JCH, Kusari AB, Kusari J (1998) Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal transduction. Mol Cell Biochem 182:101–108

    Article  PubMed  CAS  Google Scholar 

  2. Tonks NK, Diltz CD, Fischer EH (1988) Characterization of the major protein-tyrosine-phosphatases of human placenta. J Biol Chem 263:6731–6737

    PubMed  CAS  Google Scholar 

  3. González-Rodríguez Á, Gutierrez JAM, Sanz-González S, Ros M, Burks DJ, Valverde ÁM (2010) Inhibition of PTP1B restores IRS1-mediated hepatic insulin signaling in IRS2-deficient mice. Diabetes 59:588–599

    Article  PubMed  Google Scholar 

  4. Ahmad F, Li P-M, Meyerovitch J, Goldstein BJ (1995) Osmotic loading of neutralizing antibodies demonstrates a role for protein-tyrosine phosphatase 1B in negative regulation of the insulin action pathway. J Biol Chem 270:20503–20508

    Article  PubMed  CAS  Google Scholar 

  5. Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan C-C, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP (1999) Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283:1544–1548

    Article  PubMed  CAS  Google Scholar 

  6. Haj FG, Zabolotny JM, Kim Y-B, Kahn BB, Neel BG (2005) Liver-specific protein-tyrosine phosphatase 1B (PTP1B) re-expression alters glucose homeostasis of PTP1B−/− mice. J Biol Chem 280:15038–15046

    Article  PubMed  CAS  Google Scholar 

  7. Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, Haj F, Wang Y, Minokoshi Y, Kim Y-B, Elmquist JK, Tartaglia LA, Kahn BB, Neel BG (2002) PTP1B regulates leptin signal transduction in vivo. Dev Cell 2:489–495

    Article  PubMed  CAS  Google Scholar 

  8. Bence KK, Delibegovic M, Xue B, Gorgun CZ, Hotamisligil GS, Neel BG, Kahn BB (2006) Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat Med 12:917–924

    Article  PubMed  CAS  Google Scholar 

  9. Liu G, Trevillyan JM (2002) Protein tyrosine phosphatase 1B as a target for the treatment of impaired glucose tolerance and type II diabetes. Curr Opin Investig Drugs 3:1608–1616

    PubMed  CAS  Google Scholar 

  10. Tonks NK (2003) PTP1B: from the sidelines to the front lines! FEBS Lett 546:140–148

    Article  PubMed  CAS  Google Scholar 

  11. Zhang Y-Z, Lee S-Y (2003) PTP1B inhibitors as potential therapeutics in the treatment of type 2 diabetes and obesity. Expert Opin Investig Drugs 12:223–233

    Article  PubMed  CAS  Google Scholar 

  12. Taylor SD, Hill B (2004) Recent advances in protein tyrosine phosphatase 1B inhibitors. Expert Opin Investig Drugs 13:199–214

    Article  PubMed  CAS  Google Scholar 

  13. Combs AP (2010) Recent advances in the discovery of competitive protein tyrosine phosphatase 1B inhibitors for the treatment of diabetes, obesity, and cancer. J Med Chem 53:2333–2344

    Article  PubMed  CAS  Google Scholar 

  14. Mukherjee PK, Maiti K, Mukherjee K, Houghton PJ (2006) Leads from Indian medicinal plants with hypoglycemic potentials. J Ethnopharmacol 106:1–28

    Article  PubMed  CAS  Google Scholar 

  15. Broadhurst CL, Polansky MM, Anderson RA (2000) Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro. J Agric Food Chem 48:849–852

    Article  PubMed  CAS  Google Scholar 

  16. Mueller M, Jungbauer A (2009) Culinary plants, herbs and spices—a rich source of PPARγ ligands. Food Chem 117:660–667

    Article  CAS  Google Scholar 

  17. Khan A, Safdar M, Khan MMA, Khattak KN, Anderson RA (2003) Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 26:3215–3218

    Article  PubMed  Google Scholar 

  18. Otto AD (2010) Cinnamon as a supplemental treatment for impaired glucose tolerance and type 2 diabetes. Curr Diab Rep 10:170–172

    Article  PubMed  Google Scholar 

  19. Prasad RC, Herzog B, Boone B, Sims L, Waltner-Law M (2005) An extract of Syzygium aromaticum represses genes encoding hepatic gluconeogenic enzymes. J Ethnopharmacol 96:295–301

    Article  PubMed  Google Scholar 

  20. Chen RM, Hu LH, An TY, Li J, Shen Q (2002) Natural PTP1B inhibitors from Broussonetia papyrifera. Bioorg Med Chem Lett 12:3387–3390

    Article  PubMed  CAS  Google Scholar 

  21. Bae EY, Na MK, Njamen D, Mbafor JT, Fomum ZT, Cui L, Choung DH, Kim BY, Oh WK, Ahn JS (2006) Inhibition of protein tyrosine phosphatase 1B by prenylated isoflavonoids isolated from the stem bark of Erythrina addisoniae. Planta Med 72:945–948

    Article  PubMed  CAS  Google Scholar 

  22. Na MK, Yang S, He L, Oh H, Kim BS, Oh WK, Kim BY, Ahn JS (2006) Inhibition of protein tyrosine phosphatase 1B by ursane-type triterpenes isolated from Symplocos paniculata. Planta Med 72:261–263

    Article  PubMed  CAS  Google Scholar 

  23. Baumgartner RR, Steinmann D, Heiss EH, Atanas GA, Ganzera M, Stuppner H, Dirsch VM (2010) Bioactivity-guided isolation of 1,2,3,4,6-penta-O-galloyl-d-glucopyranose from Paeonia lactiflora roots as a PTP1B inhibitor. J Nat Prod 73:1578–1581

    Article  PubMed  CAS  Google Scholar 

  24. Sastroamidjojo S (1997) Tumbuh-tumbuhan yang dipergunakan sebagai obat asli Indonesia. In: Tjokronegoro A (ed) Obat asli Indonesia. Dian Rakyat, Indonesia, pp 27–266

  25. PT Eisai Indonesia (1995) Medicinal herb index in Indonesia. PT Eisai Indonesia, Jakarta

    Google Scholar 

  26. Subehan Kadota S, Tezuka Y (2008) In vitro mechanism-based inactivation of cytochrome P450 3A4 by a new constituent of Cinnamomum burmani. Planta Med 74:1474–1480

    Article  PubMed  CAS  Google Scholar 

  27. Usia T, Iwata H, Hiratsuka A, Watabe T, Kadota S, Tezuka Y (2004) Sesquiterpenes and flavonol glycosides from Zingiber aromaticum and their CYP3A4 and CYP2D6 inhibitory activities. J Nat Prod 67:1079–1083

    Article  PubMed  CAS  Google Scholar 

  28. Cui L, Na MK, Oh H, Bae EY, Jeong DG, Ryu SE, Kim S, Kim BY, Oh WK, Ahn JS (2006) Protein tyrosine phosphatase 1B inhibitors from Morus root bark. Bioorg Med Chem Lett 16:1426–1429

    Article  PubMed  CAS  Google Scholar 

  29. Hamaguchi T, Sudo T, Osada H (1995) RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1 phase. FEBS Lett 372:54–58

    Article  PubMed  CAS  Google Scholar 

  30. Tsuruga T, Chun Y-T, Ebizuka Y, Sankawa U (1991) Biologically active constituents of Melaleuca leucadendron: inhibitors of induced histamine release from rat mast cells. Chem Pharm Bull 39:3276–3278

    Article  PubMed  CAS  Google Scholar 

  31. Lee S, Wang Q (2007) Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B. Med Res Rev 27:553–573

    Article  PubMed  CAS  Google Scholar 

  32. Shan B, Cai Y-Z, Brooks JD, Corke H (2007) Antibacterial properties and major bioactive components of cinnamon stick (Cinnamomum burmannii): activity against foodborne pathogenic bacteria. J Agric Food Chem 55:5484–5490

    Article  PubMed  CAS  Google Scholar 

  33. Anand P, Muraly KY, Tandon V, Murthy PS, Chandra R (2010) Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats. Chem Biol Interact 186:72–81

    Article  PubMed  CAS  Google Scholar 

  34. Mishra A, Bhatti R, Singh A, Ishar MPS (2010) Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy. Planta Med 76:412–417

    Article  PubMed  CAS  Google Scholar 

  35. Huang B, Yuan HD, Kim DY, Quan HY, Chung SH (2011) Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferator-activated receptor-γ (PPARγ) and AMP-activated protein kinase (AMPK) pathways. J Agric Food Chem 59:3666–3673

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are thankful to Dr. Sucipto (PJ. Bintang Terang Lestari, Traditional Medicine Supplier, Jakarta) and Dr. Aty Widyawaruyanti (Faculty of Pharmacy, Airlangga University) for their authentication of the plant materials. One of the authors (A.S.) would like to thank the Indonesian Ministry of Education for a Ph.D. grant.

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  1. Institute of Natural Medicine, University of Toyama, Toyama, Japan

    Azis Saifudin, Shigetoshi Kadota & Yasuhiro Tezuka

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  1. Azis Saifudin
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  2. Shigetoshi Kadota
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  3. Yasuhiro Tezuka
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Correspondence to Yasuhiro Tezuka.

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Saifudin, A., Kadota, S. & Tezuka, Y. Protein tyrosine phosphatase 1B inhibitory activity of Indonesian herbal medicines and constituents of Cinnamomum burmannii and Zingiber aromaticum . J Nat Med 67, 264–270 (2013). https://doi.org/10.1007/s11418-012-0674-7

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  • DOI: https://doi.org/10.1007/s11418-012-0674-7

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