(-)-Epicatechin modulates skeletal muscle inflammatory response in a mouse model of Limb-Girdle Muscular Dystrophy 2F

Cancino-Bello, A.; Hernandez-Somilleda, M.; Bahena-Culhuac, E.; Garcia-Gonzalez, E. G.; Hernandez-Hernandez, O.; Ramirez-Ramirez, M.; Coral-Vazquez, R. M.; Hernandez-Hernandez, J. M.

doi:10.64898/2026.05.01.722369

bioRxiv · 10.64898/2026.05.01.722369

(-)-Epicatechin modulates skeletal muscle inflammatory response in a mouse model of Limb-Girdle Muscular Dystrophy 2F

Cancino-Bello, A.·Hernandez-Somilleda, M.·Bahena-Culhuac, E.·Garcia-Gonzalez, E. G.·Hernandez-Hernandez, O.·Ramirez-Ramirez, M.·Coral-Vazquez, R. M.·Hernandez-Hernandez, J. M.

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Abstract

Skeletal muscle possesses remarkable regenerative capacity. However, in limb-girdle muscular dystrophy-2F (LGMD2F), this capacity is compromised by persistent innate immune activation, whose transcriptional landscape remains unexplored. In parallel, (-)-Epicatechin has emerged as a promising compound with beneficial effects on muscle and notable anti-inflammatory properties. We therefore used (-)-Epicatechin treatment to test whether it can alleviate LGMD2F-associated transcriptional and immune dysregulation. Here we provide the first transcriptomic characterization of LGMD2F using the Sgcd-/- mouse model, along with the first RNA-sequencing-based evaluation of (-)-Epicatechin treatment. We profiled two functionally distinct muscles -- the soleus and EDL -- through bulk RNA-sequencing coupled with immune cell-deconvolution. Sgcd-/- muscles exhibited marked transcriptional dysregulation, more pronounced in the soleus and associated with enhanced innate immune signaling. (-)-Epicatechin induced a muscle- and genotype-dependent transcriptional response: in wild-type animals, the EDL displayed the highest number of differentially expressed transcripts, whereas in Sgcd-/- mice, the soleus showed the most prominent response. This shift was accompanied by downregulation of Toll-like receptor and RIG-I-like receptor pathways, along with suppression of NF-{kappa}B2 and interferon-stimulated genes. Together, these findings identify innate immune overactivation as a central feature of LGMD2F and reveal (-)-Epicatechin as a context-dependent modulator of muscle-specific transcriptional responses.

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Cancino-Bello, A., Hernandez-Somilleda, M., Bahena-Culhuac, E., Garcia-Gonzalez, E. G., Hernandez-Hernandez, O., Ramirez-Ramirez, M., Coral-Vazquez, R. M., Hernandez-Hernandez, J. M.. 2026-05-06. (-)-Epicatechin modulates skeletal muscle inflammatory response in a mouse model of Limb-Girdle Muscular Dystrophy 2F. https://doi.org/10.64898/2026.05.01.722369

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