Abstract
Background/Objectives: Our previous study demonstrated that 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) administration improved grip strength and reduced blood urea nitrogen levels, but its underlying mechanisms remain unclear. This study aimed to investigate the effects of HMPA on oxidative stress and muscle fiber composition, emphasizing its potential role in modulating redox signaling pathways and influencing muscle development. Methods: Eight-week-old male C57BL/6 mice were orally administered HMPA solution (50 or 500 mg/kg/day) or distilled water (10 mL/kg) for 14 days, and then divided into sedentary and exhaustive exercise groups to evaluate oxidative stress status, myosin heavy chain (MHC) isoform expression, and underlying mechanisms. Results: Both low and high doses of HMPA reduced oxidative stress by decreasing plasma reactive oxygen metabolites. High-dose HMPA reduced plasma nitrite/nitrate levels and enhanced antioxidant capacity post-exercise, accompanied by changes in the mRNA abundance of antioxidant enzymes (e.g., Sod1 and Nqo1) and reductions in the mRNA abundance of nitric oxide synthases (e.g., Nos2 and Nos3) in the soleus. Additionally, high-dose HMPA administration increased the protein expression of MYH4 in the soleus, while low-dose HMPA enhanced the gene expression of Myh4 and Igf1, suggesting that HMPA may promote fast-twitch fiber hypertrophy through the activation of the IGF-1 pathway. Furthermore, low-dose HMPA significantly increased the gene expression of Sirt1 and Nrf1, as well as AMPK phosphorylation post-exercise, suggesting low-dose HMPA may improve mitochondrial biogenesis and exercise adaptation. Conclusions: These findings suggest that HMPA may serve as a dietary supplement to regulate redox balance, enhance antioxidant defenses, and promote the formation of fast-twitch fibers.