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Chemical constituents from the leaves of Ilex paraguariensis inhibit human neutrophil elastase

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Abstract

Human neutrophil elastase (HNE), a serine protease with broad target specificity, is the only enzyme responsible for the degradation of elastin which is an insoluble elastic fibrous protein in animal connective tissue. Biologically, elastase activity significantly increased with age, which results in a reduced skin elasticity and in the appearance of wrinkles or stretchmarks. In the course of our screening program for HNE inhibitors from natural source, the MeOH extract of Ilex paraguariensis leaves showed strong HNE inhibitory effect. Bioassay-guided fractionation led to the isolation of a new pyrrole alkaloid (1), along with seventeen known compounds (2–18) from the MeOH extract of Ilex paraguariensis leaves, and their chemical structures were elucidated on the basis of spectroscopic analysis. All isolated compounds were evaluated for HNE inhibitory activity, and the result demonstrated that dicaffeoylquinic acid derivatives (12, 13, 14, 15 and 16) and flavonoids (8 and 17) exhibited potent HNE inhibitory activity with IC50 values ranging from 1.4 to 7.3 µM.

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References

  • Abreu, P. M., Braham, H., Ben-Jannet, H., Mighri, Z., and Matthew, S., Antioxidant compounds from Ebenus pinnata. Fitoterapia, 78, 32–34 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Alikaridis, F., Natural constituents of Ilex species. J. Ethnopharmacol., 20, 121–144 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Antonicelli, F., Bellon, G., Debelle, L., and Hornebeck, W., Elastin-elastases and inflamm-aging. Curr. Top. Dev. Biol., 79, 99–155 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Ban, J. Y., Cho, S. O., Jeon, S. Y., Bae, K., Song, K. S., and Seong, Y. H., 3, 4-Dihydroxybenzoic acid from Smilacis chinae rhizome protects amyloid beta protein (25–35)-induced neurotoxicity in cultured rat cortical neurons. Neurosci. Lett., 420, 184–188 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Basnet, P., Matsushige, K., Hase, K., Kadota, S., and Namba, T., Four di-O-caffeoyl quinic acid derivatives from propolis. Potent hepatoprotective activity in experimental liver injury models. Biol. Pharm. Bull., 19, 1479–1484 (1996).

    PubMed  CAS  Google Scholar 

  • Benedek, B., Kopp, B., and Melzig, M. F., Achillea millefolium L. s.l. — Is the anti-inflammatory activity mediated by protease inhibition? J. Ethnopharmacol., 113, 312–317 (2007).

    Article  PubMed  Google Scholar 

  • Bernstein, E. F. and Uitto, J., The effect of photodamage on dermal extracellular matrix. Clin. Dermatol., 14, 143–151 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Chin, Y. W., Lim, S. W., Kim, S. H., Shin, D. Y., Suh, Y. G., Kim, Y. B., Kim, Y. C., and Kim, J., Hepatoprotective pyrrole derivatives of Lycium chinense fruits. Bioorg. Med. Chem. Lett., 13, 79–81 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Choi, S. Z., Lee, S. O., Choi, S. U., and Lee, K. R., A new sesquiterpene hydroperoxide from the aerial parts of Aster oharai. Arch. Pharm. Res., 26, 521–525 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Elisabeth, P., Yoshioka, M., Yamauchi, Y., and Saito, M., Infrared and nuclear magnetic resonance spectrometry of caffeine in roasted coffee after separation by preparative supercritical fluid chromatography. Anal. Sci., 7, 427–431 (1991).

    Article  CAS  Google Scholar 

  • Filip, R., Lotito, S. B., Ferraro, G., and Fraga, C. G., Antioxidant activity of Ilex paraguariensis and related species. Nutr. Res., 20, 1437–1446 (2000).

    Article  CAS  Google Scholar 

  • Filip, R., Lopez, P., Giberti, G., Coussio, J., and Ferraro, G., Phenolic compounds in seven South American Ilex species. Fitoterapia, 72, 774–778 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Gorgen, M., Turatti, K., Medeiros, A. R., Buffon, A., Bonan, C. D., Sarkis, J. J., and Pereira, G. S., Aqueous extract of Ilex paraguariensis decreases nucleotide hydrolysis in rat blood serum. J. Ethnopharmacol., 97, 73–77 (2005).

    Article  PubMed  Google Scholar 

  • Gorzalczany, S., Filip, R., Alonso, M. R., Mino, J., Ferraro, G. E., and Acevedo, C., Choleretic effect and intestinal propulsion of ‘Mate’ (Ilex paraguariensis) and its substitutes or adulterants. J. Ethnopharmacol., 75, 291–294 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Gosmann, G., Guillaume, D., Taketa, A. T., and Schenkel, E. P., Triterpenoid saponins from Ilex paraguariensis. J. Nat. Prod., 58, 438–441 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Grigioni, G, Carduzam, F., Iruruetam, M., and Pensel, N., Flavour characteristics of Ilex paraguariensis infusion, a typical Argentine product, assessed by sensory evaluation and electronic nose. J. Sci. Food Agric., 84, 427–432 (2004).

    Article  CAS  Google Scholar 

  • Gugliucci, A. and Stahl, A. J., Low density lipoprotein oxidation is inhibited by extracts of Ilex paraguariensis. Biochem. Mol. Biol. Int., 35, 47–56 (1995).

    PubMed  CAS  Google Scholar 

  • Han, J. T., Bang, M. H., Chun, O. K., Kim, D. O., Lee, C. Y., and Baek, N. I., Flavonol glycosides from the aerial parts of Aceriphyllum rossii and their antioxidant activities. Arch. Pharm. Res., 27, 390–395 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Hung, T. M., Thuong, P. T., Youn, U. J., Zhang, X. F., Min, B. S., Woo, M. H., Lee, H. K., and Bae, K. H., Antioxidant activities of phenolic derivatives from Dipsacus asper Wall. (II). Nat. Prod. Sci., 14, 107–112 (2008).

    CAS  Google Scholar 

  • Kim, Y. C., Kim, M. Y., Takaya, Y., Niwa, M., and Chung, S. K., Phenolic antioxidants isolated from Mulberry leaves. Food Sci. Biotechnol., 16, 854–857 (2007).

    CAS  Google Scholar 

  • Kuo, W. L., Huang, Y. L., Wang, S. T., Ni, C. L., Shien, B. J., and Chen, C. C., Chemical constituents of Trema orientalis. J. Chin. Med., 18, 27–36 (2007).

    Google Scholar 

  • Lee, J. Y., Moon, S. O., Kwon, Y. J., Rhee, S. J., Park, H. R., and Choi, S. W., Identification and quantification of anthocyanins and flavonoids in Mulberry (Morus sp.) cultivars. Food Sci. Biotechnol., 13, 176–184 (2004).

    CAS  Google Scholar 

  • Lee, K. K., Kim, J. H., Cho, J. J., and Choi, J. D., Inhibitory effects of 150 plant extracts on elastase activity, and their anti-inflammatory effects. Int. J. Cosmet. Sci., 21, 71–82 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Martinet, A., Hostettmann, K., and Schutz, Y., Thermogenic effects of commercially available plant preparations aimed at treating human obesity. Phytomedicine, 6, 231–238 (1999).

    PubMed  CAS  Google Scholar 

  • Melzig, M. F., Löser, B., and Ciesielski, S., Inhibition of neutrophil elastase activity by phenolic compounds from plants. Die Pharmazie, 56, 967–970 (2001).

    PubMed  CAS  Google Scholar 

  • Oh, S. R., Jung, K. Y., and Lee, H. K., In vitro anticomplementary activity of phenylpropanoids from Agastache rugosa. Kor. J. Pharmacogn., 27, 20–25 (1996).

    CAS  Google Scholar 

  • Ohem, N. and Holzl, J., Some new investigations on Ilex paraguariensis: flavonoids and triterpenes. Planta Med., 54, 576 (1988).

    Article  PubMed  CAS  Google Scholar 

  • Puizina-Ivic, N., Skin aging. Acta Dermatoven. APA., 17, 47–54 (2008).

    Google Scholar 

  • Saldana, M. D. A., Zetzl, C., Mohamed, R. S., and Brunner, G., Extraction of methylxanthines from guarana seeds, mate leaves, and cocoa beans using supercritical carbon dioxide and ethanol. J. Agric. Food Chem., 50, 4820–4826 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Seite, S., Zucchi, H., Septier, D., Igondjo-Tchen, S., Senni, K., and Godeau, G., Elastin changes during chronological and photo-ageing: the important role of lysozyme. J. Eur. Acad. Dermatol. Venereol., 20, 980–987 (2006).

    PubMed  CAS  Google Scholar 

  • Starcher, B., Aycock, R. L., and Hill, C. H., Multiple roles for elastic fibers in the skin. J. Histochem. Cytochem., 53, 431–443 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Tatefuji, T., Izumi, N., Ohta, T., Arai, S., Ikeda, M., and Kurimoto, M., Isolation and identification of compounds from Brazilian propolis which enhance macrophage spreading and mobility. Biol. Pharm. Bull., 19, 966–970 (1996).

    PubMed  CAS  Google Scholar 

  • Teramachi, F., Koyano, T., Kowithayakorn, T., Hayashi, M., Komiyama, K., and Ishibashi, M., Collagenase inhibitory quinic acid esters from Ipomoea pes-caprae. J. Nat. Prod., 68, 794–796 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Wiltried, M., Klaus, N., and Lin, Z. F., Elastic fibre arrangement in the skin of the pig. Arch. Derm. Res., 270, 397–401 (1994).

    Google Scholar 

  • Yang, Y. P., Cheng, M. J., Teng, C. M., Chang, Y. L., Tsai, I. L., and Chen, I. S., Chemical and anti-platelet constituents from Formosan Zanthoxylum simulans. Phytochemistry, 61, 567–572 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Zhao, N., Gao, H. Y., Sun, B. H., and Wu, L. J., Chemical constituents from the leaves of Camellia sinensis. J. ShenYang Pharm. Univ., 24, 211–214 (2007).

    CAS  Google Scholar 

  • Zhu, X., Dong, X., Wang, Y., Peng, J., and Luo, S., Phenolic compounds from Viburnum cylindricum. Helv. Chim. Acta, 88, 339–342 (2005).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea

    Guang-Hua Xu, Young-Hee Kim, Soo-Jin Choo, In-Ja Ryoo, Jong-Seog Ahn & Ick-Dong Yoo

  2. Han Kook Shin Yak, Yangchonmyeon, Nonsan, Chungnam, 320-854, Korea

    Jae-Kuk Yoo

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  1. Guang-Hua Xu
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  2. Young-Hee Kim
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  3. Soo-Jin Choo
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Correspondence to Ick-Dong Yoo.

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Xu, GH., Kim, YH., Choo, SJ. et al. Chemical constituents from the leaves of Ilex paraguariensis inhibit human neutrophil elastase. Arch. Pharm. Res. 32, 1215–1220 (2009). https://doi.org/10.1007/s12272-009-1905-7

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  • DOI: https://doi.org/10.1007/s12272-009-1905-7

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