Effects of herbal products and their constituents on human cytochrome P4502E1 activity

Abstract

Ethanolic extracts from fresh Echinacea purpurea and Spilanthes acmella and dried Hydrastis canadensis were examined with regard to their ability to inhibit cytochrome P4502E1 mediated oxidation of p-nitrophenol in vitro. In addition, individual constituents of these extracts, including alkylamides from E. purpurea and S. acmella, caffeic acid derivatives from E. purpurea, and several of the major alkaloids from H. canadensis, were tested for inhibition using the same assay. H. canadensis (goldenseal) was a strong inhibitor of the P450 2E1 , and the inhibition appeared to be related to the presence of the alkaloids berberine, hydrastine and canadine in the extract. These compounds inhibited 2E1 with K I values ranging from 2.8 µM for hydrastine to 18 µM for berberine. The alkylamides present in E. purpurea and S. acmella also showed significant inhibition at concentrations as low as 25 µM, whereas the caffeic acid derivatives had no effect. Commercial green tea preparations, along with four of the individual tea catechins, were also examined and were found to have no effect on the activity of P450 2E1 .

Echinacea metabolism and drug interactions: The case for standardization of a complementary medicine

“…From a comparison of the likely bioavailable serum concentrations of the relevant alkylamides (Table 2) with the IC 50 values obtained in vitro (Table 3), the authors of both these studies concluded that clinically significant inhibition was unlikely but could not be excluded (Modarai et al 2007;Raner et al 2007). Unfortunately, when estimating in vivo drug-drug interactions from in vitro data, numerous pharmacokinetic parameters need to be considered, such as: inhibition potencies (K i ) for each active phytochemical component; percentage of the administered dose that reaches the liver enzymes as intact and unbound compound, in order to use clinically relevant concentrations in in vitro studies; intersubject variability, with regard to pharmacogenetics of metabolizing enzymes, transporters and receptors; estimates of the abundance of each metabolizing enzyme in the liver; and finally, the contribution of extrahepatic modes of clearance to the total body clearance of the active compounds (Butterweck and Derendorf 2008;Pelkonen and Turpeinen 2007;Rostami-Hodjegan and Tucker 2007).…”

“…In another study (Raner et al 2007) the inhibitory potency of two ethanolic Echinacea extracts and three Echinacea alkylamides was assessed against CYP2E1 activity, both in human liver microsomes and with the recombinant human enzyme. Interestingly, the 95% ethanolic extract showed inhibition, whereas the extract in 33% ethanol did not.…”

Drug—Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals

“…The akylamides, not the caffeic acids, can inhibit CYP2E1 activity in human liver microsomes and baculovirus-expressed enzymes. 45 Collectively, these data indicate that Echinacea can inhibit several CYPs, such as CYP1A2, -2C9, -2E1, -3A4, and -2D6, based on the findings from these laboratory studies, but the proportion of the constituents will likely determine the overall effect on CYP metabolism.…”

Synthesis of N-[5-alkoxy-2(5H)-furanonyl] amino acid propargyl esters

“…At the same time, many compounds containing terminal alkyne structure are not only important intermediates, especially for the syntheses of different 1,2,3-triazoles [23][24][25][26][27], but also have different bioactivities [28,29], and even some propargyl ester can be used as a herbicide [30]. However, there is no report on the synthesis of propargyl esters simultaneously containing the structure of 2(5H)-furanone and amino acid as the bioactive units.…”