Hyperforin Blocks Neutrophil Activation of Matrix Metalloproteinase-9, Motility and Recruitment, and Restrains Inflammation-triggered Angiogenesis and Lung Fibrosis.
From: Department of Experimental Biomedical Sciences, Medical School, Padova, Italy.
The Journal of pharmacology and experimental therapeutics
- Publish Date: May 2007
- ISSN: 0022-3565
- Volume: 321
- Issue: 2
- Pages: 492-500
- Medium: Print
- Language: English
- Citation (JAMA): Dell'Aica Isabella, Niero Raffaele, Piazza Francesco, et al. Hyperforin Blocks Neutrophil Activation of Matrix Metalloproteinase-9, Motility and Recruitment, and Restrains Inflammation-triggered Angiogenesis and Lung Fibrosis.. J. Pharmacol. Exp. Ther. May 2007;321:492-500
Abstract
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 microM 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.
Mesh Headings (Keywords): Animals, Anti-Inflammatory Agents, Bicyclo Compounds, Cell Movement, Chemotaxis, Leukocyte, Cyclohexylamines, Dose-Response Relationship, Drug, Enzyme Activation, Humans, Inflammation, Male, Matrix Metalloproteinase 9, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic, Neutrophils, Phloroglucinol, Pulmonary Fibrosis, Terpenes
Check for Full Text / PubMed Unique Identifier (PMID): 17289834
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