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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

Inflammasomes are intricate protein complexes initiating caspase-1 activation, resulting in the release of inflammatory cytokines and pyroptosis. In canines, the conserved NLRP3 gene and observed caspase-1/4 activity implicate the NLRP3 inflammasome in specific inflammatory ailments. Andrographolide, sourced from Andrographis paniculate, exhibits diverse biological effects, notably antioxidant and anti-inflammatory properties, with clinical studies hinting at its therapeutic potential across various diseases. This study seeks to explore andrographolide’s impact on gene expression linked to the NLRP3 inflammasome and cytokines in canine blood cells. The findings indicate that andrographolide diminishes the expression of NLRP3, caspase-1/4, IL-1β, IL-18, and proinflammatory cytokines, alongside reducing IL-1β secretion. This underscores andrographolide’s ability to impede inflammasome activation, thereby mitigating inflammation. Nonetheless, further research is imperative to comprehensively unravel its mechanisms and therapeutic efficacy concerning canine inflammatory conditions.

Abstract

Inflammasomes are multiprotein complexes that trigger processes through caspase-1 activation, leading to the maturation of proinflammatory cytokines, such as IL-1β and IL-18. The gene encoding the inflammasome stimulatory protein NLRP3 is conserved in canines. Caspase-1/4 homologues have been identified in multiple carnivores, including canines, and caspase-1 activity has been shown in humans. The NLRP3 inflammasome has also been described in some canine inflammatory diseases. Andrographolide, a labdane diterpene, is the principal active ingredient in the herb Andrographis paniculate. The objective of this study was to determine the effect of andrographolide on the gene expression of the components of the NLRP3 inflammasome, proinflammatory cytokines, and IL-1β secretion in canine peripheral blood mononuclear cells. For this, MTT assays and real-time PCR were employed to assess the cytotoxicity and gene expression. Further, an ELISA test was performed to measure the IL-1β concentration. The findings reveal that andrographolide significantly reduces the expression of NLRP3, caspase-1/4, IL-1β, and IL-18. Additionally, it decreases the secretion of IL-1β and other proinflammatory cytokines, including IL-6, IL-8, and TNF-α. The results show that andrographolide decreases the expression of NLRP3, caspase-1/4, IL-1β, and IL-18. Andrographolide also reduces proinflammatory cytokines expression, and decreases IL-1β secretion. This indicates that andrographolide can interfere with the activation and function of the inflammasome, resulting in a decrease in the inflammatory response in canines. Research in this area is still budding, and more studies are necessary to fully understand andrographolide’s mechanisms of action and its therapeutic potential in relation to the NLRP3 inflammasome in dogs.

Details

Title
Andrographolide Inhibits Expression of NLPR3 Inflammasome in Canine Mononuclear Leukocytes
Author
Albornoz, Alejandro 1 ; Pardo, Bibiana 2 ; Apaoblaza, Sofia 1 ; Henriquez, Claudio 1   VIAFID ORCID Logo  ; Ojeda, Javier 3 ; Uberti, Benjamín 3 ; Hancke, Juan 4 ; Burgos, Rafael A 1   VIAFID ORCID Logo  ; Moran, Gabriel 1 

 Laboratory of Inflammation Pharmacology and Immunometabolism, Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile; [email protected] (A.A.); [email protected] (B.P.); [email protected] (S.A.); [email protected] (C.H.) 
 Laboratory of Inflammation Pharmacology and Immunometabolism, Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile; [email protected] (A.A.); [email protected] (B.P.); [email protected] (S.A.); [email protected] (C.H.); Graduate School, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile 
 Institute of Veterinary Clinical Sciences, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile; [email protected] (J.O.); [email protected] (B.U.) 
 HP Animal Health, Valdivia 5090000, Chile; [email protected] 
First page
2036
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
20762615
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3084702195
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.