TY - JOUR
T1 - Involvement of NLRP3 inflammasome pathway in the protective mechanisms of ferulic acid and p-coumaric acid in LPS-induced sickness behavior and neuroinflammation in mice
AU - Kinra, Manas
AU - Ranadive, Niraja
AU - Nampoothiri, Madhavan
AU - Arora, Devinder
AU - Mudgal, Jayesh
N1 - Funding Information:
Open access funding provided by Manipal Academy of Higher Education, Manipal The senior research fellowship [CSIR-SRF Direct, File no. 08/602(0005)/19EMR-I] to MK was provided by the Council of Scientific and Industrial Research (CSIR), Human Resource Development Group, Government of India. This work was supported by Griffith University, Australia for the collaborative work and funding (MAHE/RG0618111) to carry out this research work.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Ferulic acid (FA) and p-coumaric acid (PCA) are abundantly present in commonly consumed food and beverages. Being polyphenolic compounds, they have been explored for their antioxidant and anti-inflammatory properties. Based on our previous study, we selected these two compounds to further investigate their potential in lipopolysaccharide (LPS)-induced sickness behavior and the ensuing neuroinflammation by specifically focusing on the NLRP3 inflammasome pathway. Male Swiss albino mice were divided into nine groups (n = 6) consisting of Normal Control, LPS, fluoxetine (FLX), FA40, FA160, FA640, PCA40, PCA160, and PCA640 respectively. Each group received respective FA or PCA treatment except Normal Control and LPS, which received the vehicle, carboxymethylcellulose 0.25% w/v. All groups were challenged with LPS 1.5 mg/kg, intraperitoneally except the Normal Control group, which received saline. Behavioral assessments were performed between 1–2 h, and the whole brains were collected at 3 h post-LPS administration. LPS-induced sickness behavior was characterized by significantly reduced spontaneous activity and high immobility time. The expression of NLRP3, ASC, caspase-1 and IL-1β was significantly increased, along with the levels of brain IL-1β suggesting the assembly and activation of NLRP3 inflammasome pathway. Furthermore, the major cytokines involved in sickness behavior, IL-6 and TNF-α were also significantly elevated with the accompanied lipid peroxidation. The results of this study emphasize that within the employed dose ranges of both FA and PCA, both the compounds were effective at blocking the activation of the NLRP3 inflammasome pathway and thereby reducing the release of IL-1β and the sickness behavior symptoms. There was a prominent effect on cytokine levels and lipid peroxidation as well. Graphical abstract: [Figure not available: see fulltext.].
AB - Ferulic acid (FA) and p-coumaric acid (PCA) are abundantly present in commonly consumed food and beverages. Being polyphenolic compounds, they have been explored for their antioxidant and anti-inflammatory properties. Based on our previous study, we selected these two compounds to further investigate their potential in lipopolysaccharide (LPS)-induced sickness behavior and the ensuing neuroinflammation by specifically focusing on the NLRP3 inflammasome pathway. Male Swiss albino mice were divided into nine groups (n = 6) consisting of Normal Control, LPS, fluoxetine (FLX), FA40, FA160, FA640, PCA40, PCA160, and PCA640 respectively. Each group received respective FA or PCA treatment except Normal Control and LPS, which received the vehicle, carboxymethylcellulose 0.25% w/v. All groups were challenged with LPS 1.5 mg/kg, intraperitoneally except the Normal Control group, which received saline. Behavioral assessments were performed between 1–2 h, and the whole brains were collected at 3 h post-LPS administration. LPS-induced sickness behavior was characterized by significantly reduced spontaneous activity and high immobility time. The expression of NLRP3, ASC, caspase-1 and IL-1β was significantly increased, along with the levels of brain IL-1β suggesting the assembly and activation of NLRP3 inflammasome pathway. Furthermore, the major cytokines involved in sickness behavior, IL-6 and TNF-α were also significantly elevated with the accompanied lipid peroxidation. The results of this study emphasize that within the employed dose ranges of both FA and PCA, both the compounds were effective at blocking the activation of the NLRP3 inflammasome pathway and thereby reducing the release of IL-1β and the sickness behavior symptoms. There was a prominent effect on cytokine levels and lipid peroxidation as well. Graphical abstract: [Figure not available: see fulltext.].
UR - https://www.scopus.com/pages/publications/85172888571
UR - https://www.scopus.com/pages/publications/85172888571#tab=citedBy
U2 - 10.1007/s00210-023-02743-8
DO - 10.1007/s00210-023-02743-8
M3 - Article
C2 - 37755515
AN - SCOPUS:85172888571
SN - 0028-1298
VL - 397
SP - 1829
EP - 1839
JO - Naunyn-Schmiedeberg's Archives of Pharmacology
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
IS - 3
ER -