Tart cherry extract improves skeletal muscle recovery by increasing type II MHC expression, MCP-1 and HGF secretion, and attenuating ROS production by neutrophils

Abstract Ingestion of tart cherry extract (TCE), a rich source of polyphenolic anti-oxidant/anti-inflammatory compounds, improves skeletal muscle (SM) recovery following exercise-induced muscle damage. This response may be due in part to attenuated oxidative/pro-inflammatory activities of recruited neutrophils and macrophages during SM regeneration. How TCE promotes the molecular mechanisms regulating SM regeneration or attenuates those controlling myeloid cell pro-inflammatory responses is unknown. Herein, we describe how TCE affects two murine cell models optimized to recapitulate in vivo interactions between regenerating SM and recruited pro-inflammatory myeloid cells: 1) strained skeletal muscle tissue derived from C2C12 myoblasts, and 2) mature myeloid lineages derived from ex vivo-cultured primary bone marrow. We show that TCE treatment may improve SM regeneration by increasing MHC protein expression plus MCP-1 and HGF secretion. Importantly, TCE treatment modestly reduced myoblast proliferation but without affecting viability, and did not affect proliferation or differentiation-specific protein expression profiles (via imaging flow cytometry) of myeloblasts or derived progenitors. Moreover, TCE treatment reduced levels of reactive oxygen species (ROS) released by activated neutrophils. Our continued analyses will identify how TCE either independently affects damaged SM regeneration or myeloid cell functional responses, or dependently affects the interactions between these disparate cell types upon muscle injury. Our studies may reveal that this natural compound not only improves muscle recovery following damage but also attenuates pro-inflammatory responses of recruited myeloid cells.