Matrix proteases, green tea, and St. John's wort: biomedical research catches up with folk medicine

Background: Some proteases involved in extracellular matrix degradation are instrumental not only in overcoming tissue barriers to allow normal extravasation of hematic cells, but also in facilitating pathological processes such as inflammation, angiogenesis and tumor invasion. The possibility of blocking these enzymes has led to the development of synthetic inhibitors, though clinical trials have been disappointing owing to considerable side effects. However, long before enzymes were first isolated, these same pathologies were being treated in plant-based folk remedies, and today science is screening them for their reputed beneficial effects. State of the art: We present studies of 2 vegetable components as protease inhibitors. The first, (-)epigallocatechin-3-gallate - from green tea, has proved a good weapon for inhibiting gelatinases MMP-2 and MMP-9, but an even better inhibitor of leukocyte elastase (LE) activity; in vivo it blocks inflammation, angiogenesis and tumor invasion. The second, hyperforin - from Hypericum sp, inhibits LE-triggered activation of MMP-9, PMN chemotaxis and chemoinvasion, PMN-triggered angiogenesis, and inflammation-triggered pulmonary fibrosis; it also represses tumor-cell expression of MMP-2, thereby restraining invasion and metastasis. Conclusion: Modern research clearly vindicates epidemiological and historical evidence of the beneficial effects of two long-used allies from the plant kingdom, going a step beyond by shedding light on mechanistic keys.