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Title: Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

item QIANG, ZHIYI - Iowa State University
item ZHONG, YE - University Of California
item HAUCK, CATHY - Iowa State University
item MURPHY, PATRICIA - Iowa State University
item MCCOY, JOE-ANN - Bent Creek Institute
item Widrlechner, Mark
item REDDY, MANJU - Iowa State University
item HENDRICH, SUZANNE - Iowa State University

Submitted to: Journal of Ethnopharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/10/2011
Publication Date: 7/20/2011
Citation: Qiang, Z., Zhong, Y., Hauck, C., Murphy, P., McCoy, J., Widrlechner, M.P., Reddy, M., Hendrich, S. 2011. Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers. Journal of Ethnopharmacology. 137(3):1107-1112. Available:

Interpretive Summary: Rosmarinic acid (RA) and ursolic acid (UA) are two organic acids found in mint-family plants used as botanical dietary supplements. These two compounds are known antioxidants, but are also being studied for their ability to reduce inflammation and fight microbial and viral infections. In order to understand how these compounds may act in humans, it is important to know how they are absorbed by the body. Thus, we conducted experiments by using monolayers of Caco-2 cells as a model system to determine the permeability of RA and UA both for pure compounds and for these compounds found in extracts of self-heal (Prunella vulgaris) and sage (Salvia officinalis). We initially determined the concentrations of RA and UA that were toxic to Caco-2 cells. Then we determined permeability of these compounds in Caco-2 cells grown in two media, Hank's Buffered Salt Solution (HBSS) and Dulbecco's modified Eagle's medium (DMEM). The permeabilities of RA and UA were not significantly different when tested in pure form or as part of the plant extracts. UA passed through the basolateral membrane of Caco-2 cells without significant chemical modification. RA permeability was very low, but after a treatment with the enzymes ß-glucuronidase and sulfatase, basolateral transport of increased fivefold, when Caco-2 cells were cultured in HBSS. However, no RA was found basolaterally when using DMEM. Paracellular transfer of bioactive compounds, as modeled by RA, may better simulate uptake in Caco-2 cells with HBSS rather than with DMEM. These results are of interest to nutritionists, physiologists and medicinal-plant researchers, who are expanding our understanding of bioactive compound uptake, ultimately leading to the more effective use of botanical dietary supplements for improving human health.

Technical Abstract: Rosmarinic acid (RA), a caffeic acid derivative found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be of benefit to gastrointestinal health in general. The aim of the study is to investigate the permeabilities and metabolism of RA and UA as pure compounds and in P. vulgaris and S. officinalis ethanol extracts across human intestinal epithelial Caco-2 cell monolayers. The permeabilities and Phase II biotransformation of RA and UA as pure compounds and in herbal extracts were compared using Caco-2 cells with HPLC detection. The apparent permeability coefficient (Papp) for RA and RA in P. vulgaris extracts was 0.2 ± 0.05 x 10-6 cm/s, significantly increased to 0.9 ± 0.2 x 10-6 cm/s after ß-glucuronidase/sulfatase treatment. Papp for UA and UA in S. officinalis extract was 2.7 ± 0.3 x 10-6 cm/s and 2.3 ± 0.5 x 10-6 cm/s before and after ß-glucuronidase/sulfatase treatment, respectively. Neither compound was affected in permeability by the herbal extract matrix. RA and UA in herbal extracts had similar uptake as that found using the pure compounds, which may simplify the prediction of compound efficacy, but the apparent lack of intestinal glucuronidation/sulfation of UA is likely to further enhance the bioavailability of that compound compared with RA.