Caffeic Acid Regulates High Glucose-Induced Inflammatory Responses in BV-2 Microglial Cells: Implications for Purinergic Signaling.
- 1Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, University Campus, Camobi District, Santa Maria, RS, 97105-900, Brazil.
- 2Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, University Campus, Camobi District, Santa Maria, RS, 97105-900, Brazil. [email protected].
Abstract
High glucose-induced microglial activation contributes to inflammatory processes associated with diabetic complications. Thus, the effects of caffeic acid (CA) on inflammatory responses and purinergic signaling parameters in high glucose-challenged BV-2 microglial cells were investigated. A) Oxidative stress; b) Enzymatic activities of Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), Ecto-5-nucleotidase (E-5'-NT), and Adenosine deaminase (ADA); c) Density of P2X7R, A1R, and A2AR purinoceptors; d) Inflammatory markers (IBA-1, NLRP3, and IL-1β); and e) Apoptosis and cell cycle were assessed. Treatment with CA (50 and 75 µM, 24 h) in cells exposed to high glucose medium (GL 25 mM, 48 h) increased viability and reduced nitric oxide (NO), reactive species (RS), and thiobarbituric acid reactive substances (TBARS) levels compared to high glucose-challenged cells. CA also restored ATP and ADP hydrolysis and reduced ADA activity. Furthermore, CA increased the density of the A1R while reversing the high glucose-induced increase in P2X7R and A2AR densities. Moreover, CA treatment attenuated the increase in IL-1β density in high glucose medium, whereas only CA (75 µM) treatment reduced NLRP3 and IBA-1 densities. Besides, this phenolic compound decreased apoptosis and promoted cell cycle progression by increasing the proportion of cells in the S and G2/M phases. Overall, findings suggest that CA attenuates high glucose-induced inflammatory and oxidative alterations in BV-2 microglial cells, besides modulating purinergic enzyme activities and purinoceptor density. These results support the potential involvement of purinergic signaling in the cellular effects of CA and provide possible mechanistic insights into its antioxidant and anti-inflammatory actions under high glucose conditions.
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BibTeX
@article{castro2026caffeic,
title = {{Caffeic Acid Regulates High Glucose-Induced Inflammatory Responses in BV-2 Microglial Cells: Implications for Purinergic Signaling.}},
author = {Milagros Fanny Vera Castro and Charles Elias Assmann and Bianca Vedoin Copês Rambo and Mairin Schott and Marcylene Vieira da Silveira and Vitor Bastianello Mostardeiro and Adriel Antonio Schirmann and Pâmela de Almeida Milioni and Michele Goulart Dos Santos and Vera Maria Melchiors Morsch and Roselia Maria Spanevello and Maria Rosa Chitolina Schetinger},
journal = {Neurochemical research},
year = {2026},
month = oct,
doi = {10.1007/s11064-026-04893-6},
url = {https://europepmc.org/article/MED/42963498},
note = {CC BY},
}
RIS
TY - JOUR
TI - Caffeic Acid Regulates High Glucose-Induced Inflammatory Responses in BV-2 Microglial Cells: Implications for Purinergic Signaling.
AU - Milagros Fanny Vera Castro
AU - Charles Elias Assmann
AU - Bianca Vedoin Copês Rambo
AU - Mairin Schott
AU - Marcylene Vieira da Silveira
AU - Vitor Bastianello Mostardeiro
AU - Adriel Antonio Schirmann
AU - Pâmela de Almeida Milioni
AU - Michele Goulart Dos Santos
AU - Vera Maria Melchiors Morsch
AU - Roselia Maria Spanevello
AU - Maria Rosa Chitolina Schetinger
PY - 2026
DA - 2026/10/31
JO - Neurochemical research
DO - 10.1007/s11064-026-04893-6
UR - https://europepmc.org/article/MED/42963498
AB - High glucose-induced microglial activation contributes to inflammatory processes associated with diabetic complications. Thus, the effects of caffeic acid (CA) on inflammatory responses and purinergic signaling parameters in high glucose-challenged BV-2 microglial cells were investigated. A) Oxidative stress; b) Enzymatic activities of Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), Ecto-5-nucleotidase (E-5'-NT), and Adenosine deaminase (ADA); c) Density of P2X7R, A1R, and A2AR purinoceptors; d) Inflammatory markers (IBA-1, NLRP3, and IL-1β); and e) Apoptosis and cell cycle were assessed. Treatment with CA (50 and 75 µM, 24 h) in cells exposed to high glucose medium (GL 25 mM, 48 h) increased viability and reduced nitric oxide (NO), reactive species (RS), and thiobarbituric acid reactive substances (TBARS) levels compared to high glucose-challenged cells. CA also restored ATP and ADP hydrolysis and reduced ADA activity. Furthermore, CA increased the density of the A1R while reversing the high glucose-induced increase in P2X7R and A2AR densities. Moreover, CA treatment attenuated the increase in IL-1β density in high glucose medium, whereas only CA (75 µM) treatment reduced NLRP3 and IBA-1 densities. Besides, this phenolic compound decreased apoptosis and promoted cell cycle progression by increasing the proportion of cells in the S and G2/M phases. Overall, findings suggest that CA attenuates high glucose-induced inflammatory and oxidative alterations in BV-2 microglial cells, besides modulating purinergic enzyme activities and purinoceptor density. These results support the potential involvement of purinergic signaling in the cellular effects of CA and provide possible mechanistic insights into its antioxidant and anti-inflammatory actions under high glucose conditions.
SN - 0364-3190
SN - 1573-6903
ER -