Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785135380442382336
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
work_keys_str_mv AT iwaniakpaulina theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT dobrowolskipiotr theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT wrobeljan theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT kluztomasz theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT wdowiakartur theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT bojariwona theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT stangelwojcikiewiczklaudia theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT poleszakewa theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT jakimiukartur theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT misiekmarcin theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT zapałałukasz theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT wrobelandrzej theassessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT iwaniakpaulina assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT dobrowolskipiotr assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT wrobeljan assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT kluztomasz assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT wdowiakartur assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT bojariwona assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT stangelwojcikiewiczklaudia assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT poleszakewa assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT jakimiukartur assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT misiekmarcin assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT zapałałukasz assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms
AT wrobelandrzej assessmentoftheefficacyofimperatorininreducingoveractivebladdersymptoms