Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated Microglia
<b>Background/Objectives</b>: Chronic inflammation and inappropriate NLRP3 inflammasome regulation are related to many brain diseases. Purinergic mediators may play an important role in inflammation regulation and could be targeted for effective therapies for these illnesses. We evaluate...
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2025-06-01
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| author | Bianca Fagan Bissacotti Marcylene Vieira da Silveira Charles Elias Assmann Priscila Marquezan Copetti André Flores dos Santos Solange Binotto Fagan João Augusto Pereira da Rocha Maria Rosa Chitolina Schetinger Vera Maria Melchiors Morsch Nathieli Bianchin Bottari Alencar Kolinski Machado Aleksandro Schafer da Silva |
| author_facet | Bianca Fagan Bissacotti Marcylene Vieira da Silveira Charles Elias Assmann Priscila Marquezan Copetti André Flores dos Santos Solange Binotto Fagan João Augusto Pereira da Rocha Maria Rosa Chitolina Schetinger Vera Maria Melchiors Morsch Nathieli Bianchin Bottari Alencar Kolinski Machado Aleksandro Schafer da Silva |
| author_sort | Bianca Fagan Bissacotti |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Chronic inflammation and inappropriate NLRP3 inflammasome regulation are related to many brain diseases. Purinergic mediators may play an important role in inflammation regulation and could be targeted for effective therapies for these illnesses. We evaluated resveratrol’s anti-neuroinflammatory potential in BV-2 microglia cells using an innovative in vitro method of NLRP3 inflammasome activation, correlating with the P2X7 purinergic receptor. <b>Methods</b>: In silico analyses were used to estimate resveratrol’s interaction with NLRP3, and its cytotoxicity was measured for 24, 48, and 72 h. Moreover, microglia were exposed to lipopolysaccharide and nigericin to activate the NLRP3 inflammasome and treated with resveratrol between these inflammatory agents. <b>Results</b>: It was found that resveratrol has binding compatible with modulating NLRP3. Specifically, 0.1–25 µM of resveratrol presented a favorable safety profile in BV-2 cells. Microglia exposed to the inflammatory agents had increased levels of oxidative species, the P2X7 receptor, and pro-inflammatory cytokines. However, resveratrol decreased the NLRP3, caspase-1, IL-1β, IL-6, and TNF-α mRNA levels and protein density; on the other hand, IL-10 was increased, acting as a protector, preventing exacerbated inflammation. Under resveratrol exposure, P2X7 was negatively expressed, regulating inflammation to establish homeostasis and microglial proliferation. Additionally, resveratrol activates the A1 adenosine receptor, possibly correlated with neuroprotective effects. <b>Conclusions</b>: We confirmed the anti-neuroinflammatory action of resveratrol via the P2X7 receptor and NLRP3’s combined modulation, regulating the cell cycle and reducing pro-inflammatory and oxidant agents. Considering this pathway, resveratrol could be a candidate for further investigations as a potential treatment against neuroinflammatory diseases. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-8b3e4b99b58a495f992fa69b37b8269e2025-08-20T03:32:33ZengMDPI AGPharmaceuticals1424-82472025-06-0118795010.3390/ph18070950Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated MicrogliaBianca Fagan Bissacotti0Marcylene Vieira da Silveira1Charles Elias Assmann2Priscila Marquezan Copetti3André Flores dos Santos4Solange Binotto Fagan5João Augusto Pereira da Rocha6Maria Rosa Chitolina Schetinger7Vera Maria Melchiors Morsch8Nathieli Bianchin Bottari9Alencar Kolinski Machado10Aleksandro Schafer da Silva11Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, BrazilGraduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, BrazilGraduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, BrazilGraduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, BrazilGraduate Program in Nanosciences, Franciscan University (UFN), Santa Maria 97010-032, RS, BrazilGraduate Program in Nanosciences, Franciscan University (UFN), Santa Maria 97010-032, RS, BrazilLaboratory of Modeling and Computational Chemistry, Federal Institute of Education, Science and Technology of Pará (IFPA), Bragança Campus, Bragança 68600-000, PA, BrazilGraduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, BrazilGraduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, BrazilDepartment of Microbiology and Parasitology, Federal University of Pelotas (UFPel), Pelotas 96010-610, RS, BrazilGraduate Program in Nanosciences, Franciscan University (UFN), Santa Maria 97010-032, RS, BrazilGraduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil<b>Background/Objectives</b>: Chronic inflammation and inappropriate NLRP3 inflammasome regulation are related to many brain diseases. Purinergic mediators may play an important role in inflammation regulation and could be targeted for effective therapies for these illnesses. We evaluated resveratrol’s anti-neuroinflammatory potential in BV-2 microglia cells using an innovative in vitro method of NLRP3 inflammasome activation, correlating with the P2X7 purinergic receptor. <b>Methods</b>: In silico analyses were used to estimate resveratrol’s interaction with NLRP3, and its cytotoxicity was measured for 24, 48, and 72 h. Moreover, microglia were exposed to lipopolysaccharide and nigericin to activate the NLRP3 inflammasome and treated with resveratrol between these inflammatory agents. <b>Results</b>: It was found that resveratrol has binding compatible with modulating NLRP3. Specifically, 0.1–25 µM of resveratrol presented a favorable safety profile in BV-2 cells. Microglia exposed to the inflammatory agents had increased levels of oxidative species, the P2X7 receptor, and pro-inflammatory cytokines. However, resveratrol decreased the NLRP3, caspase-1, IL-1β, IL-6, and TNF-α mRNA levels and protein density; on the other hand, IL-10 was increased, acting as a protector, preventing exacerbated inflammation. Under resveratrol exposure, P2X7 was negatively expressed, regulating inflammation to establish homeostasis and microglial proliferation. Additionally, resveratrol activates the A1 adenosine receptor, possibly correlated with neuroprotective effects. <b>Conclusions</b>: We confirmed the anti-neuroinflammatory action of resveratrol via the P2X7 receptor and NLRP3’s combined modulation, regulating the cell cycle and reducing pro-inflammatory and oxidant agents. Considering this pathway, resveratrol could be a candidate for further investigations as a potential treatment against neuroinflammatory diseases.https://www.mdpi.com/1424-8247/18/7/950brain inflammationBV-2 cellsimmunomodulationpolyphenolpurinergic receptors |
| spellingShingle | Bianca Fagan Bissacotti Marcylene Vieira da Silveira Charles Elias Assmann Priscila Marquezan Copetti André Flores dos Santos Solange Binotto Fagan João Augusto Pereira da Rocha Maria Rosa Chitolina Schetinger Vera Maria Melchiors Morsch Nathieli Bianchin Bottari Alencar Kolinski Machado Aleksandro Schafer da Silva Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated Microglia Pharmaceuticals brain inflammation BV-2 cells immunomodulation polyphenol purinergic receptors |
| title | Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated Microglia |
| title_full | Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated Microglia |
| title_fullStr | Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated Microglia |
| title_full_unstemmed | Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated Microglia |
| title_short | Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated Microglia |
| title_sort | resveratrol alleviates inflammatory response through p2x7 nlrp3 signaling pathway in silico and in vitro evidence from activated microglia |
| topic | brain inflammation BV-2 cells immunomodulation polyphenol purinergic receptors |
| url | https://www.mdpi.com/1424-8247/18/7/950 |
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