Mitohormesis and Regeneration: Natural Compounds Chlorogenic Acid (CGA) and Isovanillic Acid 3-O-sulfate (IVAS) Boost Muscle Cell Recovery in the Equine Athlete Model

作者：O. Witkowska-Piłaszewicz, Małgorzata Nowicka-Kazmierczak, Patrycja Pietrzak, Krzysztof Marycz · 发表于：Stem Cell Reviews and Reports · 年份：2025 · DOI：10.1007/s12015-025-10959-9 · 研究领域：Medicine

Skeletal muscle satellite cells ( SCs), essential for muscle regeneration, are a valuable model for studying exercise-induced stress relevant to human athletes. This study examined the effects of two natural compounds—chlorogenic acid (CGA) and isovanillic acid 3-O-sulfate (IVAS)—increasingly recognized as components of modern, nature-based recovery strategies. Their combination (Hybrid) was also tested on equine model of skeletal muscle satellite cells (ESCs) exposed to heat shock (40 °C, 1 h), mimicking exercise stress. Cells were treated with CGA (0.005%), IVAS (0.0005%), or both for 24 h post-stress. Cell viability (MTS), mitochondrial membrane potential, apoptosis (Annexin V/7-AAD), nitric oxide (NO) production, and gene expression (RT-qPCR) were assessed. CGA significantly improved viability under both normothermia and heat stress (216–227%, p < 0.05), while IVAS was effective only without stress. Only the Hybrid group maintained elongated morphology post-heat shock. CGA increased NO levels (p < 0.05), with no effect from IVAS or Hybrid. Antioxidant gene expression remained unchanged, but proinflammatory cytokines IL-6 and IL-1β were upregulated in the Hybrid group (2.74- and 5.64-fold, p < 0.01), suggesting a controlled, adaptive immune response. Early apoptosis rose in CGA and Hybrid groups (~ 34%, p < 0.05), but total cell death was lowest in the Hybrid group (6.26%). BCL2 was downregulated (p < 0.05), while BAX increased only in the Hybrid group (8.14-fold, p < 0.01...