TUDCA: An Agonist of the Bile Acid Receptor GPBAR1/TGR5 With Anti‐Inflammatory Effects in Microglial Cells
Abstract
Bile acids are steroid acids found in the bile of mammals. The bile acid conjugate tauroursodeoxycholic acid (TUDCA) is neuroprotective in different animal models of stroke and neurological diseases. We have previously shown that TUDCA has anti‐inflammatory effects on glial cell cultures and in a mouse model of acute neuroinflammation. We show now that microglial cells (central nervous system resident macrophages) express the G protein‐coupled bile acid receptor 1/Takeda G protein‐coupled receptor 5 (GPBAR1/TGR5) in vivo and in vitro. TUDCA binding to GPBAR1/TGR5 caused an increase in intracellular cAMP levels in microglia that induced anti‐inflammatory markers, while reducing pro‐inflammatory ones. This anti‐inflammatory effect of TUDCA was inhibited by small interference RNA for GPBAR1/TGR5 receptor, as well as by treatment with a protein kinase A (PKA) inhibitor. In the mouse model of acute neuroinflammation, treating the animals with TUDCA was clearly anti‐inflammatory. TUDCA biased the microglial phenotype in vivo and in vitro toward the anti‐inflammatory. The bile acid receptor GPBAR1/TGR5 could be a new therapeutic target for pathologies coursing with neuroinflammation and microglia activation, such as traumatic brain injuries, stroke, or neurodegenerative diseases. TUDCA and other GPBAR1/TGR5 agonists need to be further investigated, to determine their potential in attenuating the neuropathologies associated with microglia activation. J. Cell. Physiol. 232: 2231–2245, 2017. © 2016 Wiley Periodicals, Inc.
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The anti-inflammatory activity of TUDCA has been demonstrated in LPS-stimulated primary microglial cells and BV-2 microglial cells.
“The anti-inflammatory activity of TUDCA has been demonstrated in LPS-stimulated primary microglial cells and BV-2 microglial cells.367–369”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [367]
TUDCA is effective in attenuating microglial reactivity in LPS-treated mice.
“In addition, TUDCA is effective in attenuating microglial reactivity in LPS-treated mice.367,370,371”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [367]
Specific BAs demonstrate neuroprotective effects in cellular and animal models.
“Specific BAs demonstrate neuroprotective effects in cellular and animal models, with human clinical trials underway (306–308).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [308]
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- Authors
- Yanguas‐Casás, N., Barreda‐Manso, M. A., Nieto‐Sampedro, M., & Romero‐Ramírez, L.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Departamento de Neurobiología Funcional y de Sistemas Instituto Cajal (CSIC) Madrid Spain
- Servicio de Salud de Castilla La Mancha (ES)
- Corresponding author
- Romero‐Ramírez, Lorenzo
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2017-03-03
- Volume
- 232
- Issue
- 8
- Pages
- 2231-2245
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W2565880658
- Cited by
- 223
- References
- 69
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 30 · 2023: 25 · 2022: 34 · 2021: 29 · 2020: 27 · 2019: 12 · 2018: 10 · 2017: 4
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Ciencia e Innovación (SAF2009‐11257)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- tauroursodeoxycholic acid, bile acid receptors, microglia, neuroinflammation, anti-inflammatory activity, cAMP signaling, protein kinase A, receptor agonists, microglial activation, traumatic brain injury, stroke, neurodegenerative diseases
- MeSH terms
- Cyclic AMP, Animals, Animals, Newborn, Anti-Inflammatory Agents, Cells, Cultured, Disease Models, Animal, Encephalitis, Hippocampus, Mice, Inbred C57BL, Taurochenodeoxycholic Acid, Time Factors, Transfection, Signal Transduction, Prosencephalon, Rats, Wistar, Microglia, Cyclic AMP-Dependent Protein Kinases, Neuroprotective Agents, Inflammation Mediators, RNA Interference, Receptors, G-Protein-Coupled, Protein Kinase Inhibitors
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