Echinacea sanguinea and Echinacea pallida Extracts Stimulate Glucuronidation and Basolateral Transfer of Bauer Alkamides 8 and 10 and Ketone 24 and Inhibit P-glycoprotein Transporter in Caco-2 Cells

Abstract

The use of Echinacea as a medicinal herb is prominent in the United States, and many studies have assessed the effectiveness of Echinacea as an immunomodulator. We hypothesized that Bauer alkamides 8, 10 and 11 and ketone 24 were absorbed similarly either as pure compounds or from Echinacea sanguinea and Echinacea pallida ethanol extracts, and that these Echinacea extracts could inhibit P-glycoprotein transporter (P-gp) in Caco-2 human intestinal epithelial cells. Using HPLC analysis, the permeation rate of Bauer alkamides by passive diffusion across Caco-2 cells corresponded with compound hydrophilicity (alkamide 8 > 10 > 11), independent of the plant extract matrix. Both Echinacea ethanol extracts stimulated apparent glucuronidation and basolateral efflux of glucuronides of alkamides 8 and 10 but not alkamide 11. Bauer ketone 24 was totally metabolized to more hydrophilic metabolites when administered as a single compound, but was also glucuronidated when present in Echinacea extracts. Bauer alkamides 8, 10 and 11 (175–230 μM) and ethanol extracts of E. sanguinea (1 mg/mL, containing ~90 μM total alkamides) and E. pallida (5 mg/mL, containing 285 μM total alkamides) decreased the efflux of the P-gp probe calcein-AM from Caco-2 cells. These results suggest that other constituents in these Echinacea extracts facilitated the metabolism and efflux of alkamides and ketones, which might improve therapeutic benefits. Alkamides and Echinacea extracts might be useful in potentiating some chemotherapeutics which are substrates for P-gp.

One-pot formation of 2,4-di- or 2,4,6-tri-olefinic monocarboxylic acids by straight chain C4-extension

“…We mention here specifically 2,4,6-octatrienoic acid ( 3b in Table 1 ) that may be used as tanning promoter and antioxidant in skin care products [13] . Moreover, a large class of natural polyunsaturated monocarboxylic acid amides [ 14 , 15 , 16 , 17 , 18 ] of the formula R-CH CH-CH CH-CO-NH-isobutyl, wherein R signifies a saturated or an unsaturated aliphatic group may now come into facile synthesis. They exhibit a wide range of biological properties and a corresponding range of possible utilities, notably as modulators or enhancers for the immune system [ 14 , 15 , 16 ] or as insecticides [ 17 , 18 ].…”

Echinacea for preventing and treating the common cold

“…Since then, however, studies have reported immunoactivity attributable to alkamides (Lalone 2009; Matthias 2008) and have suggested that influences on inflammatory pathways are complex, with both pro- and anti-inflammatory effects reported (Birt 2008; Qiang 2013; Yu 2013). Echinacea alkamides have been shown to be absorbed into the blood (Matthias 2005; Woelkart 2005b; Woelkart 2006; Woelkart 2008) and appear to exert a variety of effects through the endocannabinoid system (Chicca 2009; Woelkart 2005a; Woelkart 2007).…”