Plant Coumarins: Myths and Realities

Abstract

Plant coumarins are structurally distinct, nonanticoagulant compounds that have significant medical activity. They can be fermented by various fungi to metabolites, which then dimerize to vitamin K-antagonist anticoagulants, but these are not inherently found in any known plants. Plant coumarins are often described as being anticoagulant and as interacting with drug anticoagulants, despite all evidence to the contrary. Coumarin itself does have potential to cause hepatotoxicity, perhaps in the tiny subset of people who take enough and have insufficient CYP2A6 activity to break coumarin down into safe catabolites. The particular concern over Cinnamomum aromaticum (cassia) versus Cinnamomum zeylanicum (true cinnamon) is discussed. Plant coumarins and plants rich in these compounds, including Melilotus spp. (sweet clover), Angelica keiskei (ashitaba), Angelica pubescens (pubescent angelica), Artemisia scoparia (yin-chen wormwood), Citrus spp. (orange), Glycyrrhiza uralensis (licorice), Justicia pectoralis (chambá), Mikania glomerata (guaco), Pelargonium sidoides (African geranium), and Leonurus heterophyllus (Chinese motherwort), have demonstrated inflammation-modulating, antiedema, and anticancer activities. The time is long past to stop looking at these compounds as anticoagulants and instead focus on the true benefits and potential harms associated with them.

Safety Assessment of Osthole Isolated from Prangos ferulacea: Acute and Subchronic Toxicities and Modulation of Cytochrome P450

“…It was previously indicated that coumarin itself is potent to cause hepatotoxicity, perhaps in the tiny subset of people who take enough and have insufficient CYP2A6 activity to break coumarin down into safe catabolites. Since cytochrome 2A6 is responsible for 7-hydroxylation of coumarin, people who lack significant CYP2A6 activity may be at increased risk of coumarin hepatotoxicity (26).…”

“…Hemorrhage was observed in the lung, kidney, and heart. These damages mediated by osthole might be due to the anticoagulant effects of coumarins, something that is not prevalent in all coumarins despite common knowledge (26). Coumarins, which are vitamin K antagonists, exert their anticoagulant effects by interfering with the cyclic inter conversion of vitamin K and vitamin K epoxide.…”

Nutraceuticals: Curative Integrative Cancer Treatment

“…Coumarins are also found in Artemisiascoparia (yin-chen wormwood), Citrus spp. (orange), and Glycyrrhiza uralensis (licorice) [37]. Fungi convert coumarin from moldy Melilotus spp.…”

“…Fungi convert coumarin from moldy Melilotus spp. (sweet clover) to 4-hydroxycoumarin that dimerizes to dicoumarol, a variant of which is warfarin [37]. Comparatively high coumarin content differentiates cassia cinnamon (Cinnamomun cassia) from true Ceylon cinnamon, C. verum that has minuscule coumarin content [38].…”

“…Comparatively high coumarin content differentiates cassia cinnamon (Cinnamomun cassia) from true Ceylon cinnamon, C. verum that has minuscule coumarin content [38]. Coumarin's reduction of melanoma recurrence and inhibition of renal-cell carcinoma did not withstand corroborating trials [37]. Coumarin has dose dependent cytotoxicity against the Hep2 cell line [39].…”