PUBLICATION
Guarea microcarpa C. DC. extract inhibits NLRP3 inflammasome by suppressing its ATPase activity
- Authors
- Lee, S., Yun, S., Yang, H., Lee, N., Kim, Y., Lee, S., Zamora, N.A., Montero, S.S., Yi, D.K., Kim, S.Y., Choi, S., Choi, T., Kim, M.S., Lee, Y., Park, Y.H.
- ID
- ZDB-PUB-240105-30
- Date
- 2024
- Source
- Journal of ethnopharmacology 323: 117711 (Journal)
- Registered Authors
- Lee, Nahyun, Lee, Yoonsung, Yun, Sojin
- Keywords
- Guarea microcarpa, Inflammation, Inflammatory diseases, Meliaceae family, NLRP3 inflammasome
- MeSH Terms
-
- Adenosine Triphosphatases
- Animals
- Anti-Inflammatory Agents/pharmacology
- Anti-Inflammatory Agents/therapeutic use
- Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
- Caspase 1/metabolism
- Inflammasomes*/metabolism
- Inflammation/drug therapy
- Interleukin-1beta/metabolism
- Lipopolysaccharides/pharmacology
- NF-kappa B/metabolism
- NLR Family, Pyrin Domain-Containing 3 Protein*/metabolism
- Reactive Oxygen Species/metabolism
- Zebrafish
- PubMed
- 38176663 Full text @ J. Ethnopharmacol.
Citation
Lee, S., Yun, S., Yang, H., Lee, N., Kim, Y., Lee, S., Zamora, N.A., Montero, S.S., Yi, D.K., Kim, S.Y., Choi, S., Choi, T., Kim, M.S., Lee, Y., Park, Y.H. (2024) Guarea microcarpa C. DC. extract inhibits NLRP3 inflammasome by suppressing its ATPase activity. Journal of ethnopharmacology. 323:117711.
Abstract
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 WST (water soluble tetrazolium salt) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. ROS production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebra fish 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 reactive oxygen species 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.
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