Cargando…

Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice

Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects...

Descripción completa

Detalles Bibliográficos
Autores principales: Boo, Kyung-Jun, Gonzales, Edson Luck, Remonde, Chilly Gay, Seong, Jae Young, Jeon, Se Jin, Park, Yeong-Min, Ham, Byung-Joo, Shin, Chan Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Applied Pharmacology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970841/
https://www.ncbi.nlm.nih.gov/pubmed/36203404
http://dx.doi.org/10.4062/biomolther.2022.073
_version_ 1784897981334421504
author Boo, Kyung-Jun
Gonzales, Edson Luck
Remonde, Chilly Gay
Seong, Jae Young
Jeon, Se Jin
Park, Yeong-Min
Ham, Byung-Joo
Shin, Chan Young
author_facet Boo, Kyung-Jun
Gonzales, Edson Luck
Remonde, Chilly Gay
Seong, Jae Young
Jeon, Se Jin
Park, Yeong-Min
Ham, Byung-Joo
Shin, Chan Young
author_sort Boo, Kyung-Jun
collection PubMed
description Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.
format Online
Article
Text
id pubmed-9970841
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher The Korean Society of Applied Pharmacology
record_format MEDLINE/PubMed
spelling pubmed-99708412023-02-28 Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice Boo, Kyung-Jun Gonzales, Edson Luck Remonde, Chilly Gay Seong, Jae Young Jeon, Se Jin Park, Yeong-Min Ham, Byung-Joo Shin, Chan Young Biomol Ther (Seoul) Original Article Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression. The Korean Society of Applied Pharmacology 2023-03-01 2022-10-07 /pmc/articles/PMC9970841/ /pubmed/36203404 http://dx.doi.org/10.4062/biomolther.2022.073 Text en Copyright © 2023, The Korean Society of Applied Pharmacology https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Boo, Kyung-Jun
Gonzales, Edson Luck
Remonde, Chilly Gay
Seong, Jae Young
Jeon, Se Jin
Park, Yeong-Min
Ham, Byung-Joo
Shin, Chan Young
Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice
title Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice
title_full Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice
title_fullStr Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice
title_full_unstemmed Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice
title_short Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice
title_sort hycanthone inhibits inflammasome activation and neuroinflammation-induced depression-like behaviors in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970841/
https://www.ncbi.nlm.nih.gov/pubmed/36203404
http://dx.doi.org/10.4062/biomolther.2022.073
work_keys_str_mv AT bookyungjun hycanthoneinhibitsinflammasomeactivationandneuroinflammationinduceddepressionlikebehaviorsinmice
AT gonzalesedsonluck hycanthoneinhibitsinflammasomeactivationandneuroinflammationinduceddepressionlikebehaviorsinmice
AT remondechillygay hycanthoneinhibitsinflammasomeactivationandneuroinflammationinduceddepressionlikebehaviorsinmice
AT seongjaeyoung hycanthoneinhibitsinflammasomeactivationandneuroinflammationinduceddepressionlikebehaviorsinmice
AT jeonsejin hycanthoneinhibitsinflammasomeactivationandneuroinflammationinduceddepressionlikebehaviorsinmice
AT parkyeongmin hycanthoneinhibitsinflammasomeactivationandneuroinflammationinduceddepressionlikebehaviorsinmice
AT hambyungjoo hycanthoneinhibitsinflammasomeactivationandneuroinflammationinduceddepressionlikebehaviorsinmice
AT shinchanyoung hycanthoneinhibitsinflammasomeactivationandneuroinflammationinduceddepressionlikebehaviorsinmice