In Vitro Activity of St. John's Wort Against Cytochrome P450 Isozymes and P-Glycoprotein

Abstract

The inhibitory activity of 18 commercial St. John's wort products (Hypericum perforatum L. Hypericaceae) against human cytochrome P450 enzymes was assessed because recent studies have found that this herb can markedly affect disposition of concurrently used conventional drugs. For the most part, these studies have employed ethanolic extracts. However, many of the two dozen reported constituents or groups of compounds having pharmacological effects in Hypericum extracts have widely differing solubility characteristics and hence the interpretation of the results is problematic. Sequential extracts from hexane through to water demonstrated a strong effect of several lipophilic fractions on the cytochrome P450 3A4 mediated-metabolism of 7-benzyloxyresorufin (7-BR), suggesting that many different classes of compounds are active. In this study we sought to investigate 18 single-entity and blended products containing St. John's wort, including 7 caplets/tablets, 6 capsules, 4 teas and 1 tincture, for biomarker content and affect on cytochrome P450-mediated metabolism. Our results show that there is a wide variation in hyperforin, hypericin and pseudohypericin levels and that most standardized products did not meet specification. Furthermore, all aqueous extracts from the products tested exhibited a marked capacity to inhibit cytochrome P450-mediated metabolism. Four of the five extracts tested also inhibited P-glycoprotein activity. These findings support the notion that a wide range of therapeutic products used in conjunction with St. John's wort could lead to adverse side effects.