Transport of Alkamides from Echinacea Species through Caco-2 Monolayers1

Institute for Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany
Planta Medica (Impact Factor: 2.15). 06/2002; 68(5):469-71. DOI: 10.1055/s-2002-32076
Source: PubMed


To gain more insights into the human intestinal absorption of alkamides from Echinacea species, transport studies were performed with the human adenocarcinoma colonic cell line Caco-2 (ATCC) as a model to assess the epithelial transport of dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides (1/ 2). 30 minutes after apical loading of 25 microg/ml 1/ 2, about 15 % of these alkamides were detectable on the basolateral side. Close monitoring of the transport during 6 hours revealed a nearly complete transport to the basolateral side after 4 hours and no significant metabolism was observable. Transport experiments performed at 4 degrees C showed only a slight decrease in transport, which is a strong hint that dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides (1/ 2) cross biological membranes by passive diffusion. Nearly the same results were obtained after preincubation of the Caco-2 cells with lipopolysaccharides (LPS) or phorbol 12-myristate-13-acetate (PMA) to mimic an inflammatory status. These results support the assumption that the alkamides can be easily transported from the intestinum and hence may contribute to the in vivo effects of Echinacea preparations.

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    • "The compounds studied were used as isolated chemical compounds dissolved in incubation medium or as extract attempting to achieve concentrations sufficiently above the limit of detection in the basal compartment. Lacking cytotoxicity of the test substance concentrations was determined in Caco-2 cells, using the methylthiazolyltetrazoliumbromide (MTT) method (Jager et al., 2002). "
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    ABSTRACT: To correlate the pharmacological effects of the fixed herbal combination STW 5 (Iberogast) containing nine extract components with its confirmed clinical efficacy, ex vivo/in vitro absorption tests were performed. For the investigation, the everted gut sac technique and, in a pilot study, the Caco-2-cell model were used. The absorption rate of the extracts was determined by measuring characteristic marker substances of each of the individual extracts using HPLC or GC techniques. The results allow us to conclude that the investigated substances from STW 5 possess a good bioavailability, which is in accordance with the rapid onset of the therapeutic efficacy and explains its known pharmacological effects and clinical efficacy in terms of multiple drug action and multi-target therapy, respectively.
    Phytomedicine 02/2006; 13 Suppl 5:107-13. DOI:10.1016/j.phymed.2006.07.002 · 3.13 Impact Factor
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    • "Free radical scavenging activity has been documented for alcoholic extracts of the roots and leaves of E. purpurea, E. angustifolia and E. pallida in-vitro (Sloley et al 2001). Dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides found in Echinacea species (but isolated in this experiment from E. atrorubens root) were transported across Caco-2 monolayers, an in-vitro model for the intestinal epithelial barrier, over a 6-h period (Jager et al 2002). Transport kinetics did not differ significantly following modification of the model (by pre-incubation of Caco-2 cells with lipopolysaccharide and phorbol 12-myr- istate-13-acetate) to mimic inflammation. "
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    ABSTRACT: This paper reviews the chemistry, pharmacology and clinical properties of Echinacea species used medicinally. The Echinacea species Echinacea angustifolia, Echinacea pallida and Echinacea purpurea have a long history of medicinal use for a variety of conditions, particularly infections, and today echinacea products are among the best-selling herbal preparations in several developed countries. Modern interest in echinacea is focused on its immunomodulatory effects, particularly in the prevention and treatment of upper respiratory tract infections. The chemistry of Echinacea species is well documented, and several groups of constituents, including alkamides and caffeic acid derivatives, are considered important for activity. There are, however, differences in the constituent profile of the three species. Commercial echinacea samples and marketed echinacea products may contain one or more of the three species, and analysis of samples of raw material and products has shown that some do not meet recognized standards for pharmaceutical quality. Evidence from preclinical studies supports some of the traditional and modern uses for echinacea, particularly the reputed immunostimulant (or immunomodulatory) properties. Several, but not all, clinical trials of echinacea preparations have reported effects superior to those of placebo in the prevention and treatment of upper respiratory tract infections. However, evidence of efficacy is not definitive as studies have included different patient groups and tested various different preparations and dosage regimens of echinacea. On the basis of the available limited safety data, echinacea appears to be well tolerated. However, further investigation and surveillance are required to establish the safety profiles of different echinacea preparations. Safety issues include the possibility of allergic reactions, the use of echinacea by patients with autoimmune diseases and the potential for echinacea preparations to interact with conventional medicines.
    Journal of Pharmacy and Pharmacology 09/2005; 57(8):929-54. DOI:10.1211/0022357056127 · 2.26 Impact Factor
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