Naringenin alleviates cisplatin induced muscle atrophy by regulating RIPK1/AMPK/NF-κB pathway

Abstract

Cisplatin (DDP) is a commonly used chemotherapy drug, but DDP can cause skeletal muscle atrophy and cachexia. This study combined the DDP-induced C2C12 myotube atrophy model and the LLC tumour-bearing mouse cachexia model under DDP treatment to explore the effect and mechanism of naringenin (NAR) in alleviating skeletal muscle atrophy and cachexia. NAR alleviated the decreases in body weight, food intake, muscle, adipose tissue and kidney weight and forelimb grip strength in LLC tumour-bearing mice under DDP treatment and reduced the serum level of TNF-α. High dose NAR also enhanced the antitumour effect of DDP. NAR can prevent the cross-sectional area reduction of skeletal muscle fibres and prevent the change in fibre type ratio induced by DDP. NAR intervention inhibits the RIPK1/AMPK/NF-κB pathway in skeletal muscle, downregulates the expression of Atrogin1 and MuRF1, and inhibits the degradation of skeletal muscle protein. In C2C12 myotubes treated with DDP, NAR inhibited the RIPK1/AMPK/NF-κB pathway to reduce myotube cell atrophy, and the overexpression of RIPK1 reversed the therapeutic effect of NAR. These results indicate that NAR downregulates the expression of Atrogin1 and MuRF1 by regulating the RIPK1/AMPK/NF-κB pathway and alleviates DDP-induced skeletal muscle atrophy.

Keywords

• Naringenin
• Cisplatin
• Cachexia
• Muscle atrophy
• RIPK1/AMPK/NF-κB pathway