ABSTRACT
Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.
Subject(s)
Lauraceae , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Inflammasomes , Zebrafish , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Adenosine Triphosphatases , Plant Extracts/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, antibacterial, antiviral, and immune-enhancing properties. AIM OF THE STUDY: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by water soluble tetrazolium salt (WST) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. Reactive oxygen species (ROS) production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebrafish was used in the in vivo experiments. RESULTS: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular ROS production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos. CONCLUSION: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.
Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Zebrafish , Reactive Oxygen Species/metabolism , Lipopolysaccharides/pharmacology , Caspase 1/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Inflammation/drug therapy , NF-kappa B/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Adenosine Triphosphatases , Interleukin-1beta/metabolismABSTRACT
A hybrid composite membrane is prepared by coating nano-sized Al2O3 powder (13 and 50 nm) and poly(vinylidene fluoride-co-hexafluoropropene) (P(VdF-co-HFP)) binder on both sides of polyethylene separator. The composite membrane shows better thermal stability and improved wettability for organic liquid electrolyte than polyethylene separator, due to the presence of heat-resistant Al2O3 particles with high-surface area in the coating layer. By using the composite membrane, the lithium-ion cells composed of carbon anode and LiNi1/3Co1/3Mn1/3O2 cathode are assembled and their cycling performances are evaluated. The cells assembled with the composite membranes are proven to have better capacity retention than the cell prepared with polyethylene separator, due to the enhanced ability to retain the electrolyte solution in the cell. The cell assembled with the composite membrane containing 13 nm-sized Al2O3 particles has an initial discharge capacity of 173.2 mA h g(-1) with good capacity retention.