Assessment of Extracts from Mistletoe (Viscum album) for Herb–Drug Interaction by Inhibition and Induction of Cytochrome P450 Activities

Abstract

Three commercially available extracts from mistletoe (Viscum album L.) grown on ash tree (abnobaVISCUM(®) Fraxini 20 mg), on fir (abnobaVISCUM(®) Abietis 20 mg), and on pine (abnobaVISCUM(®) Pini 20 mg) were tested in vitro for their potential to interfere with the major drug metabolizing cytochromes P450 by hepatocyte viability, by inhibition of cytochromes P450 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4, and by the induction of cytochromes P450 1A2, 2B6, 2C9, 2E1 and 3A4. As the three extracts are produced from mistletoe plants belonging to three different subspecies of Viscum album L. they have explicit differences in the content and spectrum of various active ingredients, e.g. mistletoe specific lectins. Cytotoxic effects on liver cells were observed for abnobaVISCUM(®) Fraxini with a high lectin content with an EC(50) value of 2.56 µg/mL, for abnobaVISCUM(®) Abietis with a moderate lectin content with an EC(50) value of 5.79 µg/mL and for abnobaVISCUM(®) Pini with a low lectin content with an EC(50) value of 30.86 µg/mL. The induction of cytochromes P450 was tested on human liver cells from three donors. Inhibition of cytochromes P450 was carried out on human liver microsomes. No or minor induction and inhibition was observed for all three extracts. The data indicate no or minor potential for herb-drug interactions by interference with cytochromes P450 by any of the three mistletoe extracts.

Mistletoe as complementary treatment in patients with advanced non-small-cell lung cancer treated with carboplatin-based combinations: A randomised phase II study

“…However, no such interaction was found in a recent in vitro study. 19 Reduction of chemotherapy-related toxicity was reported in another prospective randomised study involving 224 patients with breast carcinoma, ovarian carcinoma or NSCLC. 20 The randomisation was between treatment with ME or Lentinan (Chinas immunomodulating phytopharmacon).…”

Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro

“…Mistletoe was reported to be an inhibitor of CYP3A4 in vitro [22], however, the corresponding IC 50 values are physiologically irrelevant. The investigation of interferences of mistletoe with cytochrome P450 isoforms in human hepatocytes indicated no or only minor potential for herb-drug interactions [23], suggesting that clinically significant systemic interaction is unlikely.…”

Die Misteltherapie in der Behandlung von Patienten mit einer Krebserkrankung

“…Die Ergebnisse einiger weniger hierzu bisher durchgeführter Untersuchungen weisen darauf hin, dass Mistelextrakte kein oder nur ein geringes Risiko für klinische Interaktionen aufweisen. Es handelt sich dabei vorwiegend um präklinische Studien [40][41][42][43][44][45][46]. Eine erste Phase-I-Studie zeigte für ein Mistelpräparat am Patienten, dass die Pharmakokinetik des Zytostatikums Gemcitabin bei paralleler Anwendung von hohen Dosierungen bis zu 250 mg Mistelextrakt nicht beeinflusst wurde [47].…”