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6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis

Introduction: Benign prostatic hyperplasia (BPH) is a common disease among elderly men. Its pharmacological treatment is still unsatisfactory. 6-Paradol (6-PD) is an active metabolite found in many members of the Zingiberaceae family. It was reported to possess anti-proliferative, antioxidant, and a...

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Autores principales: Binmahfouz, Lenah S., Almukadi, Haifa, Alamoudi, Abdulmohsin J., El-Halawany, Ali M., Abdallah, Hossam M., Algandaby, Mardi M., Mohamed, Gamal A., Ibrahim, Sabrin R. M., Alghamdi, Faraj A., Al-Shaeri, Majed, Abdel-Naim, Ashraf B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9571361/
https://www.ncbi.nlm.nih.gov/pubmed/36235468
http://dx.doi.org/10.3390/plants11192602
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author Binmahfouz, Lenah S.
Almukadi, Haifa
Alamoudi, Abdulmohsin J.
El-Halawany, Ali M.
Abdallah, Hossam M.
Algandaby, Mardi M.
Mohamed, Gamal A.
Ibrahim, Sabrin R. M.
Alghamdi, Faraj A.
Al-Shaeri, Majed
Abdel-Naim, Ashraf B.
author_facet Binmahfouz, Lenah S.
Almukadi, Haifa
Alamoudi, Abdulmohsin J.
El-Halawany, Ali M.
Abdallah, Hossam M.
Algandaby, Mardi M.
Mohamed, Gamal A.
Ibrahim, Sabrin R. M.
Alghamdi, Faraj A.
Al-Shaeri, Majed
Abdel-Naim, Ashraf B.
author_sort Binmahfouz, Lenah S.
collection PubMed
description Introduction: Benign prostatic hyperplasia (BPH) is a common disease among elderly men. Its pharmacological treatment is still unsatisfactory. 6-Paradol (6-PD) is an active metabolite found in many members of the Zingiberaceae family. It was reported to possess anti-proliferative, antioxidant, and anti-inflammatory activities. The present study aimed at exploring the potential of 6-PD to inhibit testosterone-induced BPH in rats as well as the probable underlying mechanism. Methods: Male Wistar rats were divided into 6 groups and treated as follows: Group 1 (control group) received vehicles only, Group 2 testosterone only, Groups 3 and 4 received 6-PD (2.5 and 5.0 mg/kg; respectively) and testosterone, and Group 6 received finasteride and testosterone. Results: Daily treatment of animals with 6-PD at the two dose levels of 2.5 and 5 mg/kg significantly ameliorated a testosterone-induced rise in prostate index and weight. This was confirmed by histological examinations of prostatic tissues that indicated a reduction in the pathological changes as well as inhibition of the rise in glandular epithelial height in 6-PD treated rats. Immunohistochemical investigations showed that 6-PD prevented the up-regulation of cyclin D1 induced by testosterone injections. Further, 6-PD significantly modulated mRNA expression of both Bcl2 and Bax in prostate tissues of testosterone-treated rats in favor of anti-proliferation. It also showed antioxidant activities as evidenced by inhibition of accumulation of malondialdehyde (MDA) and exhaustion of catalase (CAT) activity. In addition, 6-PD displayed significant anti-inflammatory activities as it prevented up-regulation of interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB). Immunoblotting analysis revealed that 6-PD significantly inhibited testosterone-induced activation of AKT and mTOR in prostate tissues. Conclusions: 6-PD protects against testosterone-induced BPH in rats. This can be attributed, at least partly, to its antiproliferative, antioxidant, and anti-inflammatory properties as well as its ability to inhibit activation of the AKT/mTOR axis.
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spelling pubmed-95713612022-10-17 6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis Binmahfouz, Lenah S. Almukadi, Haifa Alamoudi, Abdulmohsin J. El-Halawany, Ali M. Abdallah, Hossam M. Algandaby, Mardi M. Mohamed, Gamal A. Ibrahim, Sabrin R. M. Alghamdi, Faraj A. Al-Shaeri, Majed Abdel-Naim, Ashraf B. Plants (Basel) Article Introduction: Benign prostatic hyperplasia (BPH) is a common disease among elderly men. Its pharmacological treatment is still unsatisfactory. 6-Paradol (6-PD) is an active metabolite found in many members of the Zingiberaceae family. It was reported to possess anti-proliferative, antioxidant, and anti-inflammatory activities. The present study aimed at exploring the potential of 6-PD to inhibit testosterone-induced BPH in rats as well as the probable underlying mechanism. Methods: Male Wistar rats were divided into 6 groups and treated as follows: Group 1 (control group) received vehicles only, Group 2 testosterone only, Groups 3 and 4 received 6-PD (2.5 and 5.0 mg/kg; respectively) and testosterone, and Group 6 received finasteride and testosterone. Results: Daily treatment of animals with 6-PD at the two dose levels of 2.5 and 5 mg/kg significantly ameliorated a testosterone-induced rise in prostate index and weight. This was confirmed by histological examinations of prostatic tissues that indicated a reduction in the pathological changes as well as inhibition of the rise in glandular epithelial height in 6-PD treated rats. Immunohistochemical investigations showed that 6-PD prevented the up-regulation of cyclin D1 induced by testosterone injections. Further, 6-PD significantly modulated mRNA expression of both Bcl2 and Bax in prostate tissues of testosterone-treated rats in favor of anti-proliferation. It also showed antioxidant activities as evidenced by inhibition of accumulation of malondialdehyde (MDA) and exhaustion of catalase (CAT) activity. In addition, 6-PD displayed significant anti-inflammatory activities as it prevented up-regulation of interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB). Immunoblotting analysis revealed that 6-PD significantly inhibited testosterone-induced activation of AKT and mTOR in prostate tissues. Conclusions: 6-PD protects against testosterone-induced BPH in rats. This can be attributed, at least partly, to its antiproliferative, antioxidant, and anti-inflammatory properties as well as its ability to inhibit activation of the AKT/mTOR axis. MDPI 2022-10-03 /pmc/articles/PMC9571361/ /pubmed/36235468 http://dx.doi.org/10.3390/plants11192602 Text en © 2022 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
Binmahfouz, Lenah S.
Almukadi, Haifa
Alamoudi, Abdulmohsin J.
El-Halawany, Ali M.
Abdallah, Hossam M.
Algandaby, Mardi M.
Mohamed, Gamal A.
Ibrahim, Sabrin R. M.
Alghamdi, Faraj A.
Al-Shaeri, Majed
Abdel-Naim, Ashraf B.
6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis
title 6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis
title_full 6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis
title_fullStr 6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis
title_full_unstemmed 6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis
title_short 6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis
title_sort 6-paradol alleviates testosterone-induced benign prostatic hyperplasia in rats by inhibiting akt/mtor axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9571361/
https://www.ncbi.nlm.nih.gov/pubmed/36235468
http://dx.doi.org/10.3390/plants11192602
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