The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome
Agathisflavone, purified from <i>Cenostigma pyramidale</i> (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 i...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/5/1410 |
| _version_ | 1827740388775952384 |
|---|---|
| author | Balbino Lino dos Santos Cleonice Creusa dos Santos Janaina R. P. Soares Karina C. da Silva Juciele Valeria R. de Oliveira Gabriele S. Pereira Fillipe M. de Araújo Maria de Fátima D. Costa Jorge Mauricio David Victor Diogenes A. da Silva Arthur Morgan Butt Silvia Lima Costa |
| author_facet | Balbino Lino dos Santos Cleonice Creusa dos Santos Janaina R. P. Soares Karina C. da Silva Juciele Valeria R. de Oliveira Gabriele S. Pereira Fillipe M. de Araújo Maria de Fátima D. Costa Jorge Mauricio David Victor Diogenes A. da Silva Arthur Morgan Butt Silvia Lima Costa |
| author_sort | Balbino Lino dos Santos |
| collection | DOAJ |
| description | Agathisflavone, purified from <i>Cenostigma pyramidale</i> (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 <i>Escherichia coli</i> 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. |
| first_indexed | 2024-03-11T03:24:16Z |
| format | Article |
| id | doaj.art-46ce0413114040f591754b545aafa679 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:16Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-46ce0413114040f591754b545aafa6792023-11-18T02:51:11ZengMDPI AGPharmaceutics1999-49232023-05-01155141010.3390/pharmaceutics15051410The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 InflammasomeBalbino Lino dos Santos0Cleonice Creusa dos Santos1Janaina R. P. Soares2Karina C. da Silva3Juciele Valeria R. de Oliveira4Gabriele S. Pereira5Fillipe M. de Araújo6Maria de Fátima D. Costa7Jorge Mauricio David8Victor Diogenes A. da Silva9Arthur Morgan Butt10Silvia Lima Costa11Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilGroup of Studies and Research for Health Development, University Salvador, Salvador 40140-110, Bahia, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilDepartment of General and Inorganic Chemistry, Institute of Chemistry, University Federal da Bahia, Salvador 40170-110, Bahia, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilSchool of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2UP, UKLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Bahia, BrazilAgathisflavone, purified from <i>Cenostigma pyramidale</i> (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 <i>Escherichia coli</i> 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.https://www.mdpi.com/1999-4923/15/5/1410anti-neuroinflammatoryagathisflavoneneuroprotectionNRLP3 inflammasome |
| spellingShingle | Balbino Lino dos Santos Cleonice Creusa dos Santos Janaina R. P. Soares Karina C. da Silva Juciele Valeria R. de Oliveira Gabriele S. Pereira Fillipe M. de Araújo Maria de Fátima D. Costa Jorge Mauricio David Victor Diogenes A. da Silva Arthur Morgan Butt Silvia Lima Costa The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome Pharmaceutics anti-neuroinflammatory agathisflavone neuroprotection NRLP3 inflammasome |
| title | The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome |
| title_full | The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome |
| title_fullStr | The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome |
| title_full_unstemmed | The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome |
| title_short | The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome |
| title_sort | flavonoid agathisflavone directs brain microglia macrophages to a neuroprotective anti inflammatory and antioxidant state via regulation of nlrp3 inflammasome |
| topic | anti-neuroinflammatory agathisflavone neuroprotection NRLP3 inflammasome |
| url | https://www.mdpi.com/1999-4923/15/5/1410 |
| work_keys_str_mv | AT balbinolinodossantos theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT cleonicecreusadossantos theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT janainarpsoares theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT karinacdasilva theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT jucielevaleriardeoliveira theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT gabrielespereira theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT fillipemdearaujo theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT mariadefatimadcosta theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT jorgemauriciodavid theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT victordiogenesadasilva theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT arthurmorganbutt theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT silvialimacosta theflavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT balbinolinodossantos flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT cleonicecreusadossantos flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT janainarpsoares flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT karinacdasilva flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT jucielevaleriardeoliveira flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT gabrielespereira flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT fillipemdearaujo flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT mariadefatimadcosta flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT jorgemauriciodavid flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT victordiogenesadasilva flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT arthurmorganbutt flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome AT silvialimacosta flavonoidagathisflavonedirectsbrainmicrogliamacrophagestoaneuroprotectiveantiinflammatoryandantioxidantstateviaregulationofnlrp3inflammasome |