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β-Sitosterol and flavonoids isolated from Bauhinia malabarica found during screening for Wnt signaling inhibitory activity

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Abstract

Screening with a cell-based luciferase assay was conducted to identify bioactive natural products which inhibit Wnt signaling activity-guided separation of an MeOH extract of Bauhinia malabarica (Caesalpiniaceae) leaves yielded five compounds, which were identified as β-sitosterol (1), quercetin (2), 6,8-C-dimethyl kaempferol-3-O-rhamnopyranoside (3), hyperin (4), and 6,8-C-dimethyl kaempferol-3-methyl ether (5). The tested compounds 1, 3, and 5 exhibited Wnt signaling inhibitory activity, with IC50 values of 0.77, 0.74, and 16.6 μM, respectively.

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References

  1. Schneikert J, Behrens J (2007) The canonical Wnt signalling pathway and its APC partner in colon cancer development. Gut 56:417–425

    Article  PubMed  CAS  Google Scholar 

  2. Bienz M, Clevers H (2000) Linking colorectal cancer to Wnt signaling. Cell 103:311–320

    Article  PubMed  CAS  Google Scholar 

  3. Maiese K, Li F, Chong ZZ, Shang YC (2008) The Wnt signaling pathway: aging gracefully as a protectionist? Pharmacol Ther 118(1):58–81

    Article  PubMed  CAS  Google Scholar 

  4. Rawadi G, Roman-Roman S (2005) Wnt signalling pathway: a new target for the treatment of osteoporosis. Expert Opin Ther Targets 9(5):1063–1077

    Article  PubMed  CAS  Google Scholar 

  5. De Ferrari GV, Inestrosa NC (2000) Wnt signaling function in Alzheimer’s disease. Brain Res Brain Res Rev 33(1):1–12

    Article  PubMed  Google Scholar 

  6. Jin T (2008) The Wnt signalling pathway and diabetes mellitus. Diabetologia 51:1771–1780

    Article  PubMed  CAS  Google Scholar 

  7. Liu Z, Brooks RS, Ciappio ED, Kim SJ, Crott JW, Bennett G, Greenberg AS, Mason JB (2012) Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer. J Nutr Biochem 23(10):1207–1213

    Article  PubMed  CAS  Google Scholar 

  8. Li X, Ohtsuki T, Koyano T, Kowithayakorn T, Ishibashi M (2009) New Wnt/β-catenin signaling inhibitors isolated from Eleutherine palmifolia. Chem Asian J 4:540–547

    Article  PubMed  CAS  Google Scholar 

  9. Mori N, Toume K, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M (2011) 2-Methoxy-1,4-naphthoquinone isolated from Impatiens balsamina in a screening program for activity to inhibit Wnt signaling. J Nat Med 65:234–236

    Article  PubMed  CAS  Google Scholar 

  10. Kongduang D, Wungsintaweekul J, De-Eknamkul W (2008) Biosynthesis of β-sitosterol and stigmasterol proceeds exclusively via the mevalonate pathway in cell suspension cultures of Croton stellatopilosus. Tetrahedron Lett 49:4067–4072

    Article  CAS  Google Scholar 

  11. Güvenalp Z, Demirezer LO (2005) Flavonol glycosides from Asperula arvensis L. Turk J Chem 29:163–169

    Google Scholar 

  12. Tran HQ, Nguyen XC, Chau VM, Phan VK (2008) New flavonoids from Baeckea frutescens and their antioxidant activity. Nat Prod Commun 3(5):755–758

    CAS  Google Scholar 

  13. Benyahia S, Benayache S, Benayache F, Quintana J, López M, León F, Hernández JC, Estévez F, Bermejo J (2004) Isolation from Eucalyptus occidentalis and identification of a new kaempferol derivative that induces apoptosis in human myeloid leukemia cells. J Nat Prod 67(4):527–531

    Article  PubMed  CAS  Google Scholar 

  14. Ikeda I, Sugano M (1983) Some aspects of mechanism of inhibition of cholesterol absorption by β-sitosterol. Biochim Biophys Acta 732:651–658

    Article  PubMed  CAS  Google Scholar 

  15. Christiansen L, Karjalainen M, Seppänen-Laakso T, Hiltunen R, Yliruusi J (2003) Effect of β-sitosterol on precipitation of cholesterol from non-aqueous and aqueous solutions. Int J Pharm 254:155–166

    Article  PubMed  CAS  Google Scholar 

  16. Fan YF, Chen ZW, Guo Y, Wang QH, Song B (2011) Cellular mechanisms underlying hyperin-induced relaxation of rat basilar artery. Fitoterapia 82:626–631

    Article  PubMed  CAS  Google Scholar 

  17. Park CH, Chang JY, Hahm ER, Park S, Kim HK, Yang CH (2005) Quercetin, a potent inhibitor against β-catenin/Tcf signaling in SW480 colon cancer cells. Biochem Biophys Res Commun 328:227–234

    Article  PubMed  CAS  Google Scholar 

  18. Shan BE, Wang MX, Li RQ (2009) Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/β-catenin signaling pathway. Cancer Invest 27:604–612

    Article  PubMed  CAS  Google Scholar 

  19. Yang J, Zhang W, Evans PM, Chen X, He X, Liu C (2006) Adenomatous polyposis coli (APC) differentially regulates β-catenin phosphorylation and ubiquitination in colon cancer cells. J Biol Chem 281(26):17751–17757

    Article  PubMed  CAS  Google Scholar 

  20. Baskar AA, Ignacimuthu S, Paulraj GM, Al Numair KS (2010) Chemopreventive potential of β-sitosterol in experimental colon cancer model—an in vitro and in vivo study. BMC Complement Altern Med 10:24–33

    Article  PubMed  Google Scholar 

  21. Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL, Kim HY, Moon SH, Ha JR, Kahn M (2004) A small molecule inhibitor of β-catenin/CREB-binding protein transcription. Proc Natl Acad Sci USA 101(34):12682–12687

    Article  PubMed  CAS  Google Scholar 

  22. Park SY, Gwak JS, Cho MJ, Song TY, Won JJ, Kim D-E, Shin J-G, Oh ST (2006) Hexachlorophene inhibits Wnt/β-catenin pathway by promoting Siah-mediated β-catenin degradation. Mol Pharmacol 70:960–966

    Article  PubMed  CAS  Google Scholar 

  23. Lepourcelet M, Chen YNP, France DS, Wang H, Crews P, Petersen F, Bruseo C, Wood AW, Shivdasani RA (2004) Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex. Cancer Cell 5:91–102

    Article  PubMed  CAS  Google Scholar 

  24. Lindhagen E, Nygren P, Larsson R (2008) The fluorometric microculture cytotoxicity assay. Nat Protoc 3(8):1364–1369

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are grateful to Prof. J. Nathans (Johns Hopkins University School of Medicine) for the STF/293 cells and Prof. R. T. Moon (University of Washington) for the SuperTOPFlash plasmid. This study was supported by Grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS), the Cosmetology Research Foundation, and Sekisui Chemical Innovations Inspired by Nature Research Support Program.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo, Chiba, 260-8675, Japan

    Hyun Young Park, Kazufumi Toume, Midori A. Arai & Masami Ishibashi

  2. Temko Corporation, 4-27-4 Honcho, Nakano, Tokyo, 164-0012, Japan

    Takashi Koyano

  3. Faculty of Agriculture, Khon Kaen University, Khon Kaen, 40002, Thailand

    Thaworn Kowithayakorn

Authors
  1. Hyun Young Park
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  2. Kazufumi Toume
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  3. Midori A. Arai
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  4. Takashi Koyano
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  5. Thaworn Kowithayakorn
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  6. Masami Ishibashi
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Correspondence to Masami Ishibashi.

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Park, H.Y., Toume, K., Arai, M.A. et al. β-Sitosterol and flavonoids isolated from Bauhinia malabarica found during screening for Wnt signaling inhibitory activity. J Nat Med 68, 242–245 (2014). https://doi.org/10.1007/s11418-013-0762-3

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  • DOI: https://doi.org/10.1007/s11418-013-0762-3

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