Inhibition of metalloproteinase-9 activity and gene expression by polyphenolic compounds isolated from the bark of Tristaniopsis calobuxus (Myrtaceae)

S. Bellosta, M. Dell'Agli, M. Canavesi, N. Mitro, M. Monetti, M. Crestani, L. Verotta, N. Fuzzati, F. Bernini, E. Bosisio

Research output: Contribution to journalArticle

Abstract

Excessive breakdown of extracellular matrix by metalloproteinases (MMPs) occurs in many pathological conditions, and thus inhibition of MMP activity might have therapeutic potential. The methanolic extract and the identified compounds from the bark of Tristaniopsis calobuxus Brongniart & Gris (Myrtaceae) were tested on the activity, production, and gene expression of MMP-9. The extract produced a concentration-dependent inhibition (50-95% at 10-50 μg/ml) of MMP-9 activity. The inhibitory activity was retained in the ethyl acetate-soluble fraction (50-95% inhibition at 10-50 μg/ml) which also reduced the release of MMP-9 by mouse peritoneal macrophages up to 80%. In the ethyl acetate-soluble fraction, two active fractions, 5A and 5B were identified. HPLC-MS and NMR analyses of these fractions indicated the presence of gallocatechin, ellagic acid, and its glycoside derivatives. Since the absolute configuration of gallocatechin was not determined, in the next experiments both (+)-gallocatechin (2R,3S) and (-)-gallocatechin (2S,3R) were tested, and (-)-epigallocatechin (2R,3R) was included for comparison. 5A and 5B inhibited MMP-9 secretion, an observation which correlated with the decrease of MMP-9 promoter activity and the downregulation of mRNA levels. All compounds decreased MMP-9 mRNA levels and secretion. Ellagic acid, (+)-gallocatechin and (-)-epigallocatechin, but not (-)-gallocatechin inhibited promoter-driven transcription. Thus configuration at C2 (R) of the flavanol seem to be critical for the interaction with the promoter.

Original languageEnglish
Pages (from-to)1440-1448
Number of pages9
JournalCellular and Molecular Life Sciences
Volume60
Issue number7
DOIs
Publication statusPublished - Jul 1 2003

Keywords

  • (+)-gallocatechin
  • (-)-epigallocatechin
  • (-)-gallocatechin
  • Ellagic acid
  • Gene expression
  • Metalloproteinase-9
  • Plant polyphenols
  • Secretion
  • Tristaniopsis calobuxus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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  • Cite this

    Bellosta, S., Dell'Agli, M., Canavesi, M., Mitro, N., Monetti, M., Crestani, M., Verotta, L., Fuzzati, N., Bernini, F., & Bosisio, E. (2003). Inhibition of metalloproteinase-9 activity and gene expression by polyphenolic compounds isolated from the bark of Tristaniopsis calobuxus (Myrtaceae). Cellular and Molecular Life Sciences, 60(7), 1440-1448. https://doi.org/10.1007/s00018-003-3119-3