Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia
Benign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, wh...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/7/1014 |
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| author | Ramona D’Amico Tiziana Genovese Marika Cordaro Rosalba Siracusa Enrico Gugliandolo Alessio Filippo Peritore Livia Interdonato Rosalia Crupi Salvatore Cuzzocrea Rosanna Di Paola Roberta Fusco Daniela Impellizzeri |
| author_facet | Ramona D’Amico Tiziana Genovese Marika Cordaro Rosalba Siracusa Enrico Gugliandolo Alessio Filippo Peritore Livia Interdonato Rosalia Crupi Salvatore Cuzzocrea Rosanna Di Paola Roberta Fusco Daniela Impellizzeri |
| author_sort | Ramona D’Amico |
| collection | DOAJ |
| description | Benign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, which are common conditions in BPH, contribute to disrupting the homeostasis between cell proliferation and cell death. With this background in mind, we investigated the effect of ultramicronized palmitoylethanolamide (um-PEA), baicalein (Baic) and co-ultramicronized um-PEA/Baic in a fixed ratio of 10:1 in an experimental model of BPH. BPH was induced in rats by daily administration of testosterone propionate (3 mg/kg) for 14 days. Baic (1 mg/kg), um-PEA (9 mg/kg) and um-PEA/Baic (10 mg/kg) were administered orally every day for 14 days. This protocol led to alterations in prostate morphology and increased levels of dihydrotestosterone (DHT) and of androgen receptor and 5α-reductase expression. Moreover, testosterone injections induced a significant increase in markers of inflammation, apoptosis and oxidative stress. Our results show that um-PEA/Baic is capable of decreasing prostate weight and DHT production in BPH-induced rats, as well as being able to modulate apoptotic and inflammatory pathways and oxidative stress. These effects were most likely related to the synergy between the anti-inflammatory properties of um-PEA and the antioxidant effects of Baic. These results support the view that um-PEA/Baic should be further studied as a potent candidate for the management of BPH. |
| first_indexed | 2024-03-10T10:05:50Z |
| format | Article |
| id | doaj.art-bb1a39d5e0b844b79fb2038ff0de8d97 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T10:05:50Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-bb1a39d5e0b844b79fb2038ff0de8d972023-11-22T01:34:47ZengMDPI AGAntioxidants2076-39212021-06-01107101410.3390/antiox10071014Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic HyperplasiaRamona D’Amico0Tiziana Genovese1Marika Cordaro2Rosalba Siracusa3Enrico Gugliandolo4Alessio Filippo Peritore5Livia Interdonato6Rosalia Crupi7Salvatore Cuzzocrea8Rosanna Di Paola9Roberta Fusco10Daniela Impellizzeri11Department of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyDepartment of Veterinary Science, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyDepartment of Veterinary Science, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, ItalyBenign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, which are common conditions in BPH, contribute to disrupting the homeostasis between cell proliferation and cell death. With this background in mind, we investigated the effect of ultramicronized palmitoylethanolamide (um-PEA), baicalein (Baic) and co-ultramicronized um-PEA/Baic in a fixed ratio of 10:1 in an experimental model of BPH. BPH was induced in rats by daily administration of testosterone propionate (3 mg/kg) for 14 days. Baic (1 mg/kg), um-PEA (9 mg/kg) and um-PEA/Baic (10 mg/kg) were administered orally every day for 14 days. This protocol led to alterations in prostate morphology and increased levels of dihydrotestosterone (DHT) and of androgen receptor and 5α-reductase expression. Moreover, testosterone injections induced a significant increase in markers of inflammation, apoptosis and oxidative stress. Our results show that um-PEA/Baic is capable of decreasing prostate weight and DHT production in BPH-induced rats, as well as being able to modulate apoptotic and inflammatory pathways and oxidative stress. These effects were most likely related to the synergy between the anti-inflammatory properties of um-PEA and the antioxidant effects of Baic. These results support the view that um-PEA/Baic should be further studied as a potent candidate for the management of BPH.https://www.mdpi.com/2076-3921/10/7/1014benign prostatic hyperplasiaandrogen receptorpalmitoylethanolamidebaicaleininflammationoxidative stress |
| spellingShingle | Ramona D’Amico Tiziana Genovese Marika Cordaro Rosalba Siracusa Enrico Gugliandolo Alessio Filippo Peritore Livia Interdonato Rosalia Crupi Salvatore Cuzzocrea Rosanna Di Paola Roberta Fusco Daniela Impellizzeri Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia Antioxidants benign prostatic hyperplasia androgen receptor palmitoylethanolamide baicalein inflammation oxidative stress |
| title | Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia |
| title_full | Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia |
| title_fullStr | Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia |
| title_full_unstemmed | Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia |
| title_short | Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia |
| title_sort | palmitoylethanolamide baicalein regulates the androgen receptor signaling and nf κb nrf2 pathways in benign prostatic hyperplasia |
| topic | benign prostatic hyperplasia androgen receptor palmitoylethanolamide baicalein inflammation oxidative stress |
| url | https://www.mdpi.com/2076-3921/10/7/1014 |
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