PPARβ agonist ZLY16 promotes muscle regeneration and improves motor performance of mdx mice
10.11665/j.issn.1000-5048.2024093001
- VernacularTitle:PPARβ激动剂ZLY16促进肌再生及改善mdx小鼠运动能力
- Author:
Guangyao GUO
1
;
Qian LU
;
Shusheng FAN
;
Qinwei YU
;
Luyong ZHANG
;
Zhenzhou JIANG
Author Information
1. 中国药科大学多靶标天然药物全国重点实验室新药筛选与药效评价中心, 江苏省药效研究与评价服务中心, 南京210009;广东药科大学新药研发中心, 广州510006
- Publication Type:Journal Article 期刊文章
- Keywords:
ZLY16;
PPARβ agonists;
Duchenne muscular dystrophy;
skeletal muscle function;
lipid accumulation;
mdx mice
- From:
Journal of China Pharmaceutical University
2025;56(4):469-477
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the therapeutic effects of ZLY16, a novel peroxisome proliferator-activated receptor (PPAR) β agonist, on Duchenne muscular dystrophy (DMD), C57BL/10ScSnJGpt-Dmdem3Cd4/Gpt (mdx) mice were gavaged with 30 mg/kg ZLY16 for 6 weeks. Expression of proteins associated with muscle regeneration, exercise ability, blood lipids content and skeletal muscle damage in mdx mice were investigated by behavioral experiments, histopathology, blood biochemical analysis, immunofluorescence and Western blot. A high-fat-induced myoblast differentiation inhibition model was established to examine lipid content and myoblast differentiation-related protein expression in myoblasts using Nile Red staining, immunofluorescence and Western blot. The results demonstrated that ZLY16 increased muscle grip strength, reduced triglyceride (TG) and total cholesterol (TC) levels, attenuated muscle fiber necrosis, fibrosis and inflammatory cell infiltration, and promoted muscle regeneration in mdx mice. ZLY16 promoted myoblast differentiation and myotube fusion in vitro by reducing lipid accumulation in murine skeletal muscle myoblast line (C2C12) cells. These findings suggest that ZLY16 improves motor function in mdx mice by decreasing lipid accumulation and promoting muscle regeneration.
