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The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms
Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648619/ https://www.ncbi.nlm.nih.gov/pubmed/37958777 http://dx.doi.org/10.3390/ijms242115793 |
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author | Iwaniak, Paulina Dobrowolski, Piotr Wróbel, Jan Kluz, Tomasz Wdowiak, Artur Bojar, Iwona Stangel-Wójcikiewicz, Klaudia Poleszak, Ewa Jakimiuk, Artur Misiek, Marcin Zapała, Łukasz Wróbel, Andrzej |
author_facet | Iwaniak, Paulina Dobrowolski, Piotr Wróbel, Jan Kluz, Tomasz Wdowiak, Artur Bojar, Iwona Stangel-Wójcikiewicz, Klaudia Poleszak, Ewa Jakimiuk, Artur Misiek, Marcin Zapała, Łukasz Wróbel, Andrzej |
author_sort | Iwaniak, Paulina |
collection | PubMed |
description | Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I—control, II—rats with rapamycin (RA)-induced OAB, III—rats administered IMP at a dose of 10 mg/kg/day, and IV—rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB. |
format | Online Article Text |
id | pubmed-10648619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106486192023-10-31 The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms Iwaniak, Paulina Dobrowolski, Piotr Wróbel, Jan Kluz, Tomasz Wdowiak, Artur Bojar, Iwona Stangel-Wójcikiewicz, Klaudia Poleszak, Ewa Jakimiuk, Artur Misiek, Marcin Zapała, Łukasz Wróbel, Andrzej Int J Mol Sci Article Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I—control, II—rats with rapamycin (RA)-induced OAB, III—rats administered IMP at a dose of 10 mg/kg/day, and IV—rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB. MDPI 2023-10-31 /pmc/articles/PMC10648619/ /pubmed/37958777 http://dx.doi.org/10.3390/ijms242115793 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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/). |
spellingShingle | Article Iwaniak, Paulina Dobrowolski, Piotr Wróbel, Jan Kluz, Tomasz Wdowiak, Artur Bojar, Iwona Stangel-Wójcikiewicz, Klaudia Poleszak, Ewa Jakimiuk, Artur Misiek, Marcin Zapała, Łukasz Wróbel, Andrzej The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms |
title | The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms |
title_full | The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms |
title_fullStr | The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms |
title_full_unstemmed | The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms |
title_short | The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms |
title_sort | assessment of the efficacy of imperatorin in reducing overactive bladder symptoms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648619/ https://www.ncbi.nlm.nih.gov/pubmed/37958777 http://dx.doi.org/10.3390/ijms242115793 |
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