Urolithin A improves motor function and attenuates muscle fibrosis in a mouse model of Duchenne muscular dystrophy
10.3969/j.issn.1000-4718.2025.00.020
- VernacularTitle:尿石素A改善杜氏肌营养不良症小鼠的运动功能并减轻肌肉纤维化
- Author:
Hongyi JIA
1
;
Chaoming QIU
;
Dan LIU
;
Luchen SHAN
;
Pei YU
;
Xifei YANG
Author Information
1. 暨南大学药学院生物活性分子与成药性评价国家重点实验室,广东 广州 511436;深圳市现代毒理学重点实验室,深圳市医学健康毒理学重点学科,深圳市疾病预防控制中心,广东 深圳 518055
- Publication Type:Journal Article
- Keywords:
urolithin A;
Duchenne muscular dystrophy;
motor function;
muscle fibrosis;
mitochondria
- From:
Chinese Journal of Pathophysiology
2025;41(11):2184-2190
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effects of urolithin A on motor function and muscle fibrosis in dystrophin-deficient mdx mice,a model of Duchenne muscular dystrophy.METHODS:Twelve 26-week-old SPF male dystrophin gene deficient C57BL/10ScSnJNju-Dmdem3Cd4/Gpt(mdx)mice were randomly divided into model group and urolithin A treatment group,with 6 mice in each group.Additionally,six wild-type SPF male mice were selected as the normal con-trol.The motor ability of the mice was evaluated by pole climbing test,inverted suspension test,grip strength test and en-durance test.The body mass,mitochondrial relative copy number,ATP level and malondialdehyde(MDA)level were compared among the mice in different groups.Hematoxylin-eosin staining,Masson staining and immunohistochemistry were performed to analyze the atrophy and pathological changes of the gastrocnemius muscle.RESULTS:Compared with normal control group,the mdx mice in model group exhibited significantly impaired motor function,as evidenced by pro-longed pole-climbing time(P<0.01),reduced suspension time and forelimb/hindlimb grip strength(P<0.01),and in-creased number of electrical stimuli required to induce movement(P<0.01).Additionally,mitochondrial relative copy number and ATP level were significantly decreased(P<0.01),while MDA level was significantly elevated(P<0.01).Histological analysis revealed marked inflammatory cell infiltration and extensive tissue fibrosis in the gastrocnemius mus-cle.In contrast,urolithin A treatment significantly improved motor performance(P<0.01),attenuated inflammatory cell infiltration and muscle fibrosis,increased mitochondrial copy number,restored ATP level(P<0.05),and reduced MDA level(P<0.01).CONCLUSION:Urolithin A ameliorates motor dysfunction and alleviates muscle fibrosis in mdx mice,suggesting its potential therapeutic benefits for Duchenne muscular dystrophy.
