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. 2026 Apr 24:361:121254.
doi: 10.1016/j.jep.2026.121254. Epub 2026 Jan 22.

Safety and anti-inflammatory activity of Gentiana lutea L. in human bronchial epithelial cell cultures

Joanne Wildhaber  1 , Bedia Begum Karakocak  2 , Mauro Sousa de Almeida  2 , Barbara Rothen-Rutishauser  2 , Alke Petri-Fink  2 , Johannes Wildhaber  3 , Benedikt Maria Huber  4
Affiliations
Free article

Safety and anti-inflammatory activity of Gentiana lutea L. in human bronchial epithelial cell cultures

Joanne Wildhaber et al. J Ethnopharmacol. .
Free article

Abstract

Ethnopharmacological relevance: Gentiana lutea L. is a famous bitter plant frequently used to treat digestive disorders. Ethnopharmacological studies have also revealed a little-known traditional use for respiratory diseases. Although this approach is supported by the recent discovery of bitter taste receptors in the airways, it has not yet been established in clinical practice.

Aim of the study: To evaluate the safety and anti-inflammatory effects of an aqueous G. lutea root extract on human bronchial epithelial cells in vitro.

Materials and methods: The extract was chemically characterized by ultra-high-performance liquid chromatography (UHPLC). Human Calu-3 bronchial epithelial cells were exposed to different concentrations of G. lutea (0.1-12.5 mg/mL) in monoculture and co-culture with immune cells. Cytotoxicity and epithelial tissue integrity were assessed by lactate dehydrogenase release and transepithelial electrical resistance. Interleukin (IL)-6 and IL-8 secretion were quantified by ELISA in unstimulated and lipopolysaccharide (LPS)-stimulated conditions, and selected gene transcripts (IL6, CXCL8, IL33, TNF, TJP1, MUC5AC, TAS2R4/14) were analyzed by qPCR. Methylprednisolone and quinine served as anti-inflammatory references.

Results: UHPLC confirmed the presence of bitter secoiridoids in the extract. G. lutea showed no cytotoxicity and preserved epithelial barrier integrity in mono- and co-cultures. It significantly reduced LPS-induced IL-6 and IL-8 secretion and downregulated IL6, CXCL8, and IL33 expression.

Conclusion: An aqueous G. lutea root extract is safe to use and exhibits direct anti-inflammatory effects in bronchial epithelial tissues in vitro. These findings provide the first experimental support of its traditional use in respiratory diseases and warrant further preclinical and clinical evaluation.

Keywords: Anti-inflammatory; Bitter substances; Bitter taste receptors; Bronchial epithelial cells; Epithelial barrier; Gentiana lutea; Immune cells.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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