Agathisflavone, purified from (Tul.) has been shown to be neuroprotective in in vitro models of glutamate-induced excitotoxicity and inflammatory damage. However, the potential role of microglial regulation by agathisflavone in these neuroprotective effects is unclear. Here we investigated the effects of agathisflavone in microglia submitted to inflammatory stimulus in view of elucidating mechanisms of neuroprotection. Microglia isolated from cortices of newborn Wistar rats were exposed to lipopolysaccharide (LPS, 1 µg/mL) and treated or not with agathisflavone (1 µM). Neuronal PC12 cells were exposed to a conditioned medium from microglia (MCM) treated or not with agathisflavone. We observed that LPS induced microglia to assume an activated inflammatory state (increased CD68, more rounded/amoeboid phenotype). However, most microglia exposed to LPS and agathisflavone, presented an anti-inflammatory profile (increased CD206 and branched-phenotype), associated with the reduction in NO, GSH mRNA for NRLP3 inflammasome, IL1-β, IL-6, IL-18, TNF, CCL5, and CCL2. Molecular docking also showed that agathisflavone bound at the NLRP3 NACTH inhibitory domain. Moreover, in PC12 cell cultures exposed to the MCM previously treated with the flavonoid most cells preserved neurites and increased expression of β-tubulin III. Thus, these data reinforce the anti-inflammatory activity and the neuroprotective effect of agathisflavone, effects associated with the control of NLRP3 inflammasome, standing out it as a promising molecule for the treatment or prevention of neurodegenerative diseases.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10223401PMC
http://dx.doi.org/10.3390/pharmaceutics15051410DOI Listing

Publication Analysis

Top Keywords

nlrp3 inflammasome
8
agathisflavone
8
treated agathisflavone
8
mcm treated
8
microglia
5
flavonoid agathisflavone
4
agathisflavone directs
4
directs brain
4
brain microglia/macrophages
4
neuroprotective
4

Similar Publications

Ulcerative colitis (UC), a persistent immune-mediated disorder lacking effective treatment, is distinguished by gut microbiota dysbiosis, abnormal activation of the NLRP3 inflammasome pathway, and apoptosis. Despite growing attention to these factors, understanding their significance in UC pathogenesis remains a challenge. The present study explores the potential therapeutic impact of (Bc) spores in a murine UC model induced by drinking 4 % (w/v) dextran sulfate sodium (DSS) in C57BL/6 mice.

View Article and Find Full Text PDF

Chitosan, a biodegradable and biocompatible natural polymer composed of β-(1-4)-linked -acetyl glucosamine (GlcNAc) and d-glucosamine (GlcN) and derived from crustacean shells, has been widely studied for various biomedical applications, including drug delivery, cartilage repair, wound healing, and tissue engineering, because of its unique physicochemical properties. One of the most promising areas of research is the investigation of the immunomodulatory properties of chitosan, since the biopolymer has been shown to modulate the maturation, activation, cytokine production, and polarization of dendritic cells and macrophages, two key immune cells involved in the initiation and regulation of innate and adaptive immune responses, leading to enhanced immune responses. Several signaling pathways, including the cGAS-STING, STAT-1, and NLRP3 inflammasomes, are involved in chitosan-induced immunomodulation.

View Article and Find Full Text PDF

Introduction: . Pyroptosis is closely related to many chronic diseases including atherosclerosis, but the potential pathomechanisms are still unclear. This research aimed to explore how lncRNAs may contribute to pyroptosis and the potential mechanisms.

View Article and Find Full Text PDF

Background: Hepatic ischemia/reperfusion (I/R) injury (HIRI) is an intrinsic phenomenon observed in the process of various liver surgeries. Unfortunately, there are currently few options available to prevent HIRI. Accordingly, we aim to explore the role and key downstream effects of B-cell lymphoma 6 (BCL6) in hepatic I/R (HIR).

View Article and Find Full Text PDF

CMPK2 promotes NLRP3 inflammasome activation via mtDNA-STING pathway in house dust mite-induced allergic rhinitis.

Clin Transl Med

January 2025

Allergy Center, Department of Otolaryngology, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China.

Background: House dust mite (HDM) is the leading allergen for allergic rhinitis (AR). Although allergic sensitisation by inhaled allergens renders susceptible individuals prone to developing AR, the molecular mechanisms driving this process remain incompletely elucidated.

Objective: This study aimed to elucidate the molecular mechanisms underlying HDM-induced AR.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!