QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.116459v1 321/2/492    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dell'Aica, I. Articles by Garbisa, S. Search for Related Content PubMed PubMed Citation Articles by Dell'Aica, I. Articles by Garbisa, S.

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Hyperforin Blocks Neutrophil Activation of Matrix Metalloproteinase-9, Motility and Recruitment, and Restrains Inflammation-Triggered Angiogenesis and Lung Fibrosis

Department of Experimental Biomedical Sciences, Medical School, Padova, Italy (I.D.A., L.S., C.C., S.G.); Venetian Institute of Molecular Medicine, Padova, Italy (R.N., F.P., A.C., E.B., C.A.); Department of Clinical and Experimental Medicine, Medical School, Padova, Italy (F.P., A.C., E.B., C.A.); IRCCS Multimedica, Milano, Italy (G.L., A.A.); Molecular Biology Laboratory, National Institute for Research on Cancer, Genova, Italy (R.B.); and Department of Pathology, Medical School, Padova, Italy (F.C.)

Hyperforin (Hyp), a polyphenol-derivative of St. John's wort (Hypericum perforatum), has emerged as key player not only in the antidepressant activity of the plant but also as an inhibitor of bacteria lymphocyte and tumor cell proliferation, and matrix proteinases. We tested whether as well as inhibiting leukocyte elastase (LE) activity, Hyp might be effective in containing both polymorphonuclear neutrophil (PMN) leukocyte recruitment and unfavorable eventual tissue responses. The results show that, without affecting in vitro human PMN viability and chemokine-receptor expression, Hyp (as stable dicyclohexylammonium salt) was able to inhibit in a dose-dependent manner their chemotaxis and chemoinvasion (IC₅₀ = 1 µM for both); this effect was associated with a reduced expression of the adhesion molecule CD11b by formyl-Met-Leu-Phe-stimulated neutrophils and block of LE-triggered activation of the gelatinase matrix metalloproteinase-9. PMN-triggered angiogenesis is also blocked by both local injection and daily i.p. administration of the Hyp salt in an interleukin-8-induced murine model. Furthermore, i.p. treatment with Hyp reduces acute PMN recruitment and enhances resolution in a pulmonary bleomycin-induced inflammation model, significantly reducing consequent fibrosis. These results indicate that Hyp is a powerful anti-inflammatory compound with therapeutic potential, and they elucidate mechanistic keys.

Address correspondence to: Dr. Spiridione Garbisa, Department of Experimental Biomedical Sciences, viale G. Colombo 3, 35121 Padova, Italy. E-mail garbisa{at}unipd.it

This article has been cited by other articles:

				A. Cabrelle, I. Dell'Aica, L. Melchiori, S. Carraro, E. Brunetta, R. Niero, E. Scquizzato, G. D'Intino, L. Calza, S. Garbisa, et al. Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease J. Leukoc. Biol., January 1, 2008; 83(1): 212 - 219. [Abstract] [Full Text] [PDF]