Hypericum perforatum L.: in vitro upper gastrointestinal tract digestion and fermentation with human fecal samples

Hypericum perforatum is frequently used for mild to moderate depressive disorders [1]. Oral bioavailability of key constituents is known [2] [3]. However, to understand the pharmacological response and the mechanism of action of herbal medicinal products, an important step is the investigation of the complex metabolic processes within the human digestive tract. The aim of this study was to assess the impact of the digestive processes in the upper GI tract and the colon on the chemical profile of a H. perforatum ethanolic extract.

We have used the Infogest 2.0 protocol, a standardized static in vitro model mimicking upper GI tract digestion [4], which was subsequently followed by ex vivo incubation with fecal samples from 10 donors [5]. Analysis and annotation of the constituents present in the ethanolic extract, in the gastric and intestinal phases after digestion, as well as after incubation with gut microbiota was accomplished by UHPLC-HRMS (ultrahigh performance liquid chromatography coupled with high resolution mass spectrometry).

Analysis indicated the presence of flavonoids, hydroxycinnamic acids, xanthones, hypericins and phloroglucinols in the ethanolic extract, with more than 60 constituents being annotated. Apart from a few exceptions (such as hypericins), the levels of most annotated constituents remained basically unchanged through the three digestive phases in the Infogest model, indicating their stability towards simulated upper GI tract digestion. In contrast, incubation with gut microbiota led to an intensive metabolization of the constituents of the extract. Although there were differences between the donors, the majority of the annotated constituents have been metabolized by gut microbiota similarly in most samples, including hypericin. Metabolites may possess different pharmacokinetics and pharmacodynamics, indicating that gut microbial metabolization could play a role for the overall pharmacological effects of H. perforatum extracts.

Publication History

Article published online:
14 June 2023

• References

• 1 www.ema.europa.eu/en/medicines/herbal/hyperici-herba
• 2 Schulz HU. et al. Arzneimittelforschung 2005; 55: 15-22
• 3 Schulz HU. et al. Arzneimittelforschung 2006; 56: 212-221
• 4 Brodkorb A. et al. Nat Protoc 2019; 14: 991-1014
• 5 Pérez-Burillo S. et al. Nat Protoc 2021; 16: 3186-3209