Parthenolide promotes glucagon-like peptide-1 secreting in human Caco-2 cells via regulation of bitter taste receptor-induced of calcium signaling.

Shanshan Li, Ye Chen, Zhaosu Song, Penghui Ou, Yujing Duan, Qinglei Liu, Wei Wang

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Article in Molecular and cellular biochemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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7 authors.

Shanshan LiSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, 201418, PR China.

Ye ChenSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, 201418, PR China.

Zhaosu SongSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, 201418, PR China.

Penghui OuSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, 201418, PR China.

Yujing DuanSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, 201418, PR China.

Qinglei LiuSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, 201418, PR China.

Wei WangSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, 201418, PR China. wangwei_sit@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bitter taste receptors (TAS2Rs), in addition to being expressed in oral tissues, are also present in the gastrointestinal tract and are promising targets for inducing glucagon-like peptide-1 (GLP-1) secretion and treating type 2 diabetes mellitus (T2DM). However, natural bitter agonists capable of enhancing endogenous GLP-1 secretion remain scarce. In this study, we aimed to identify natural bitter agonists with GLP-1-inducing potential through comprehensive screening of the BitterDB and BitterX databases, and to evaluate their effects and underlying mechanisms in human enteroendocrine Caco-2 cells. Parthenolide (PTL) was identified as a high-affinity TAS2R4 agonist candidate. Cellular thermal shift assays (CETSA) confirmed its direct binding to TAS2R4, enhancing its thermal stability. Molecular docking revealed strong interactions, including hydrogen bonding with ASN-65 and hydrophobic contacts with PHE-62 and PHE-88. Functionally, PTL promotes GLP-1 secretion in a dose-dependent manner. Mechanistically, PTL treatment enhances TAS2R4 expression and upregulates its key downstream signaling molecule, phospholipase C β2 (PLCβ2), which catalyzes the production of inositol trisphosphate (IP3). This indicates that PTL promotes secretion by activating the TAS2R4 signaling pathway. PTL treatment leads to increase in intracellular calcium ion (Ca

Indexed as

Calcium SignalingGlucagon-Like Peptide 1Receptors, G-Protein-CoupledSesquiterpenesCaco-2 CellsHumansLactonesTaste Receptors, Type 2Glucagon-Like Peptide 1LactonesparthenolideReceptors, G-Protein-CoupledSesquiterpenesTaste Receptors, Type 2Bitter taste receptors (TAS2Rs)Calcium signalingGlucagon-like peptide 1 (GLP-1)Parthenolide (PTL)

Identifiers

PMID41182647

DOI10.1007/s11010-025-05425-6

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.