Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury

Peripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA...

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Main Authors: Fortuna Iannuzzo, Annunziata Gaetana Cicatiello, Serena Sagliocchi, Elisabetta Schiano, Annarita Nappi, Caterina Miro, Mariano Stornaiuolo, Adriano Mollica, Gian Carlo Tenore, Monica Dentice, Ettore Novellino
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/25/2/902
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author Fortuna Iannuzzo
Annunziata Gaetana Cicatiello
Serena Sagliocchi
Elisabetta Schiano
Annarita Nappi
Caterina Miro
Mariano Stornaiuolo
Adriano Mollica
Gian Carlo Tenore
Monica Dentice
Ettore Novellino
author_facet Fortuna Iannuzzo
Annunziata Gaetana Cicatiello
Serena Sagliocchi
Elisabetta Schiano
Annarita Nappi
Caterina Miro
Mariano Stornaiuolo
Adriano Mollica
Gian Carlo Tenore
Monica Dentice
Ettore Novellino
author_sort Fortuna Iannuzzo
collection DOAJ
description Peripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA from white grape pomace (WGPO) on neuronal regeneration in mice with induced sciatic nerve resection, administered concurrently with the induced damage (the WGPO group) and 10 days prior (the PRE-WGPO group). The experiment was monitored at two-time points (4 and 10 days) after injury. After 10 days, the WGPO group demonstrated a reduction in muscle atrophy, evidenced by an increased number and diameter of muscle fibers and a decreased Atrogin-1 and Murf-1 expression relative to the denervated control. It was also observed that 85.7% of neuromuscular junctions (NMJs) were fully innervated, as indicated by the colocalization of α-bungarotoxin and synaptophysin, along with the significant modulation of Oct-6 and S-100. The PRE-WGPO group showed a more beneficial effect on nerve fiber reformation, with a significant increase in myelin protein zero and 95.2% fully innervated NMJs, and a pro-hypertrophic effect in resting non-denervated muscles. Our findings suggest WGPO as a potential treatment for various conditions that require the repair of nerve and muscle injuries.
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spelling doaj.art-8119256d51ae4325bbb09a60d5ab99022024-01-29T13:55:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125290210.3390/ijms25020902Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve InjuryFortuna Iannuzzo0Annunziata Gaetana Cicatiello1Serena Sagliocchi2Elisabetta Schiano3Annarita Nappi4Caterina Miro5Mariano Stornaiuolo6Adriano Mollica7Gian Carlo Tenore8Monica Dentice9Ettore Novellino10Department of Pharmacy, G. d’Annunzio University of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Napoli, ItalyHealthcare Food Research Center, Inventia Biotech s.r.l., S. S. Sannitica, 81020 Caserta, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, Via Domenico Montesano 59, 80131 Napoli, ItalyDepartment of Pharmacy, G. d’Annunzio University of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Pharmacy, University of Naples Federico II, Via Domenico Montesano 59, 80131 Napoli, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Napoli, ItalyHealthcare Food Research Center, Inventia Biotech s.r.l., S. S. Sannitica, 81020 Caserta, ItalyPeripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA from white grape pomace (WGPO) on neuronal regeneration in mice with induced sciatic nerve resection, administered concurrently with the induced damage (the WGPO group) and 10 days prior (the PRE-WGPO group). The experiment was monitored at two-time points (4 and 10 days) after injury. After 10 days, the WGPO group demonstrated a reduction in muscle atrophy, evidenced by an increased number and diameter of muscle fibers and a decreased Atrogin-1 and Murf-1 expression relative to the denervated control. It was also observed that 85.7% of neuromuscular junctions (NMJs) were fully innervated, as indicated by the colocalization of α-bungarotoxin and synaptophysin, along with the significant modulation of Oct-6 and S-100. The PRE-WGPO group showed a more beneficial effect on nerve fiber reformation, with a significant increase in myelin protein zero and 95.2% fully innervated NMJs, and a pro-hypertrophic effect in resting non-denervated muscles. Our findings suggest WGPO as a potential treatment for various conditions that require the repair of nerve and muscle injuries.https://www.mdpi.com/1422-0067/25/2/902peripheral nerve injuriesursolic acidneuronal regenerationgrape pomaceneuromuscular junctionoleolyte
spellingShingle Fortuna Iannuzzo
Annunziata Gaetana Cicatiello
Serena Sagliocchi
Elisabetta Schiano
Annarita Nappi
Caterina Miro
Mariano Stornaiuolo
Adriano Mollica
Gian Carlo Tenore
Monica Dentice
Ettore Novellino
Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury
International Journal of Molecular Sciences
peripheral nerve injuries
ursolic acid
neuronal regeneration
grape pomace
neuromuscular junction
oleolyte
title Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury
title_full Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury
title_fullStr Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury
title_full_unstemmed Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury
title_short Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury
title_sort therapeutic effect of an ursolic acid based nutraceutical on neuronal regeneration after sciatic nerve injury
topic peripheral nerve injuries
ursolic acid
neuronal regeneration
grape pomace
neuromuscular junction
oleolyte
url https://www.mdpi.com/1422-0067/25/2/902
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