4.7 Article

Intestinal permeability and gut microbiota interactions of pharmacologically active compounds in valerian and St. John?s wort

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 162, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2023.114652

Keywords

Valerenic acid; Hyperforin; Hypericin; Caco-2 cells; Gut microbiota; Short -chain fatty acids

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The results of the experiments showed that valerenic acid and hyperforin are highly permeable, while hypericin has low-to-moderate permeability. Valerenic acid may undergo an active transport process. Hyperforin and hypericin are mainly transported through passive diffusion across the cell layer. None of the compounds were metabolized in the artificial gut microbiota. The compounds or herbal extracts had no substantial effect on microbial short-chain fatty acid production or bacterial viability.
Phytomedicines such as valerian and St. John's wort are widely used for the treatment of sleeping disorders, anxiety and mild depression. They are perceived as safe alternatives to synthetic drugs, but limited information is available on the intestinal absorption and interaction with human intestinal microbiota of pharmacologically relevant constituents valerenic acid in valerian, and hyperforin and hypericin in St. John's wort. The intestinal permeability of these compounds and the antidepressant and anxiolytic drugs citalopram and diazepam was investigated in the Caco-2 cell model with bidirectional transport experiments. In addition, interaction of compounds and herbal extracts with intestinal microbiota was evaluated in artificial human gut microbiota. Microbiota-mediated metabolisation of compounds was assessed, and bacterial viability and short-chain fatty acids (SCFA) production were measured in the presence of compounds or herbal extracts. Valerenic acid and hyperforin were highly permeable in Caco-2 cell monolayers. Hypericin showed low-to-moderate permeability. An active transport process was potentially involved in the transfer of valerenic acid. Hyperforin and hypericin were mainly transported through passive transcellular diffusion. All compounds were not metabolized over 24 h in the artificial gut microbiota. Microbial SCFA production and bacterial viability was not substantially impaired nor promoted by exposure to the compounds or herbal extracts.

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