# Ursolic Acid-Based Nutraceutical Mitigates Muscle Atrophy and Improves Exercise Performance in Mouse Model of Peripheral Neuropathy

**Authors:** Caterina Miro, Fortuna Iannuzzo, Lucia Acampora, Annunziata Gaetana Cicatiello, Serena Sagliocchi, Elisabetta Schiano, Annarita Nappi, Federica Restolfer, Mariano Stornaiuolo, Gian Carlo Tenore, Monica Dentice, Ettore Novellino

PMC · DOI: 10.3390/ijms26115418 · 2025-06-05

## TL;DR

A natural compound from white grape pomace helps reduce muscle loss and improve physical performance in mice with nerve damage.

## Contribution

WGPO, a source of ursolic acid, is shown to mitigate muscle atrophy and inflammation in a mouse model of peripheral neuropathy.

## Key findings

- WGPO-fed mice had larger muscle fibers and reduced Atrogin-1 and Murf-1 expression.
- WGPO improved exercise performance and reduced pro-inflammatory interleukins in injured mice.

## Abstract

Peripheral nerve injuries, caused by trauma or iatrogenic damage, often lead to permanent disabilities with limited effectiveness of current therapeutic treatments. This has driven the growing interest toward natural bioactive molecules, including ursolic acid (UA). Literature studies have shown that white grape pomace oleolyte (WGPO), a natural source of UA, is a promising candidate for promoting peripheral nerve regeneration. Considering that many neurological injuries involve compression or partial damage, the present study examined the effects of WGPO on peripheral neuropathy using a neuropathic pain mouse model. Briefly, 14 days after starting the WGPO-enriched diet, mice underwent cuffing of the right sciatic nerve to induce nerve injury and inflammation. At sacrifice, the WGPO-fed mice exhibited reduced muscle atrophy, as indicated by a greater number and larger diameter of muscle fibers, along with decreased expression of Atrogin-1 and Murf-1, compared with the injured control-diet group. To determine the functional impact of the WGPO treatment, the WGPO-supplemented group was compared with a control group receiving only sunflower oil, evaluating exercise performance post-cuffing via a treadmill test. Mice on the WGPO diet exhibited improved physical performance and a significantly lower expression of pro-inflammatory interleukins than controls. Our findings suggest WGPO as a promising candidate for managing peripheral neuropathy and related muscular impairments.

## Linked entities

- **Genes:** Fbxo32 (F-box protein 32) [NCBI Gene 67731], TRIM63 (tripartite motif containing 63) [NCBI Gene 84676]
- **Chemicals:** ursolic acid (PubChem CID 64945)
- **Diseases:** peripheral neuropathy (MONDO:0003620)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Fbxo32 (F-box protein 32) [NCBI Gene 67731] {aka 4833442G10Rik, ATROGIN1, Gm20361, MAFbx}, Trim63 (tripartite motif-containing 63) [NCBI Gene 433766] {aka MuRF1, RF1, Rnf28}
- **Diseases:** muscular impairments (MESH:D009135), Peripheral nerve injuries (MESH:D059348), neurological injuries (MESH:D020196), trauma (MESH:D014947), nerve injury (MESH:D000080902), neuropathic pain (MESH:D009437), Muscle Atrophy (MESH:D009133), inflammation (MESH:D007249), Peripheral Neuropathy (MESH:D010523)
- **Chemicals:** WGPO (-), UA (MESH:C005466)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12155626/full.md

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Source: https://tomesphere.com/paper/PMC12155626