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Background: Activation of the nuclear factor-kappa β (NF-ΚB) signaling results in releasing of a variety of inflammatory cytokines that can induce skeletal muscle wasting (MW) in mammals. Curcumin is a natural product from spice turmeric that can block biological events in which NF-ΚB plays a critical role. Objective: The present study was conducted to evaluate the beneficial effects of curcumin on the NF-ΚB-dependent MW in rats. Methods: The MW rats were induced by lipopolysaccharide (LPS) injection and rats were fed 15 g curcumin per kg diet for 16 d. Results: LPS not only decreased the growth performance of rat, but significantly elevated its serum IL-1 concentration and muscle proteolysis rate. Interestingly, curcumin significantly prevented the muscle proteolysis rate and down-regulated expression levels of two critical muscle-specific ubiquitin ligases (Atrogin-1 and MuRF-1). When muscles from MW rats were incubated with curcumin in vitro, the calpain-, cathepsin L-, and proteasome-dependent muscle proteolysis were significantly decreased. Moreover, the nuclear NF-ΚB/p65 protein abundance were also decreased by curcumin. Conclusion: The results not only suggest a molecular mechanism by which curcumin modulates the inflammatory responses, but also offer a feasible avenue to ameliorate the NF-ΚB-dependent muscle proteolysis.