PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Involvement of the Soluble Guanylate Cyclase, Nitric Oxide Synthase and Cytokines Pathway in the Anti-inflammatory Profile of N-acylhydrazone Derivatives (JR19)
Version 1
: Received: 27 July 2023 / Approved: 28 July 2023 / Online: 31 July 2023 (10:51:13 CEST)
How to cite:
Da Silva, P.R.; Apolinário, N.D.M.; Da Silva, S.Â.S.; Araruna, M.E.C.; Costa, T.B.; Silva, Y.M.S.D.M.E.; Da Silva, T.G.; Dos Santos, V.L.L.; De Moura, R.O. Involvement of the Soluble Guanylate Cyclase, Nitric Oxide Synthase and Cytokines Pathway in the Anti-inflammatory Profile of N-acylhydrazone Derivatives (JR19). Preprints2023, 2023072069. https://doi.org/10.20944/preprints202307.2069.v1
Da Silva, P.R.; Apolinário, N.D.M.; Da Silva, S.Â.S.; Araruna, M.E.C.; Costa, T.B.; Silva, Y.M.S.D.M.E.; Da Silva, T.G.; Dos Santos, V.L.L.; De Moura, R.O. Involvement of the Soluble Guanylate Cyclase, Nitric Oxide Synthase and Cytokines Pathway in the Anti-inflammatory Profile of N-acylhydrazone Derivatives (JR19). Preprints 2023, 2023072069. https://doi.org/10.20944/preprints202307.2069.v1
Da Silva, P.R.; Apolinário, N.D.M.; Da Silva, S.Â.S.; Araruna, M.E.C.; Costa, T.B.; Silva, Y.M.S.D.M.E.; Da Silva, T.G.; Dos Santos, V.L.L.; De Moura, R.O. Involvement of the Soluble Guanylate Cyclase, Nitric Oxide Synthase and Cytokines Pathway in the Anti-inflammatory Profile of N-acylhydrazone Derivatives (JR19). Preprints2023, 2023072069. https://doi.org/10.20944/preprints202307.2069.v1
APA Style
Da Silva, P.R., Apolinário, N.D.M., Da Silva, S.Â.S., Araruna, M.E.C., Costa, T.B., Silva, Y.M.S.D.M.E., Da Silva, T.G., Dos Santos, V.L.L., & De Moura, R.O. (2023). Involvement of the Soluble Guanylate Cyclase, Nitric Oxide Synthase and Cytokines Pathway in the Anti-inflammatory Profile of N-acylhydrazone Derivatives (JR19). Preprints. https://doi.org/10.20944/preprints202307.2069.v1
Chicago/Turabian Style
Da Silva, P.R., Vanda Lucia Lucia Dos Santos and Ricardo Olímpio De Moura. 2023 "Involvement of the Soluble Guanylate Cyclase, Nitric Oxide Synthase and Cytokines Pathway in the Anti-inflammatory Profile of N-acylhydrazone Derivatives (JR19)" Preprints. https://doi.org/10.20944/preprints202307.2069.v1
Abstract
The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
,
,
,
