Berberine Attenuates Microglial Inflammation by Targeting the SAE1/UBA2 Complex and Suppressing NLRP3 SUMOylation
Qianlu Li, Chunfeng Cao, Minghua Zhang, Hao Qiu, Chao HeBackground
Neuroinflammation contributes to the pathogenesis of multiple neurodegenerative diseases. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is regulated by posttranslational modifications, including small ubiquitin-like modifier (SUMO)ylation initiated by the SAE1/UBA2 complex.
Purpose
To investigate whether berberine (BBR) attenuates microglial inflammation by modulating SAE1/UBA2-associated NLRP3 SUMOylation.
Materials and Methods
Molecular docking was performed to predict interactions between BBR and the SAE1/UBA2 complex. An inflammatory model was established in BV2 microglia using lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Cell viability, cytokine secretion, and apoptosis were evaluated using cell counting kit-8 assays, enzyme-linked immunosorbent assays, and flow cytometry, respectively. Western blotting and coimmunoprecipitation were used to examine inflammasome-related proteins and NLRP3 SUMOylation.
Results
Molecular docking predicted a potential interaction between BBR and the SAE1/UBA2 complex, with a docking score of −6.747 kcal/mol. BBR improved cell viability and reduced interleukin-1β and interleukin-18 secretion and apoptosis in LPS/ATP-stimulated BV2 cells. SAE1 overexpression aggravated inflammatory responses, whereas BBR partially reversed these effects. BBR also reduced NLRP3 SUMOylation and attenuated ASC expression and caspase-1 activation.
Conclusion
BBR attenuates LPS/ATP-induced inflammatory responses in BV2 microglia, potentially through modulation of SAE1/UBA2-associated NLRP3 SUMOylation and inflammasome activation.