Tanshinone IIA alleviates inflammation-induced skeletal muscle atrophy by regulating mitochondrial dysfunction

Abstract

Skeletal muscle atrophy, characterized by loss of muscle mass and function, is often linked to systemic inflammation. Tanshinone IIA (Tan IIA), a major active constituent of Salvia miltiorrhiza, has anti-inflammatory and antioxidant properties. However, the effect of Tan IIA on inflammation-induced skeletal muscle atrophy remains unclear. Here, a mice model of the inflammatory muscle atrophy was established using lipopolysaccharide (LPS). Tan IIA intervention significantly increased muscle mass and strength, improved muscle fiber size, and maintained the integrity of skeletal muscle mitochondrial morphology in LPS-treated mice. Myotubes derived from myosatellite cells (MUSCs) were exposed to LPS in vitro. Tan IIA treatment inhibited LPS-induced muscle protein degradation and increased myotube diameter. Notably, Tan IIA attenuated LPS-induced inflammatory response and hyperactive mitophagy both in vivo and in vitro. In addition, Tan IIA treatment effectively diminished oxidative stress, inhibited the accumulation of mitochondrial reactive oxygen species (mtROS), and attenuated mitochondrial fission in LPS-treated myotubes. Reducing mtROS production helped to inhibit LPS-induced excessive mitophagy and myotubes atrophy. Together, our results reveal that Tan IIA can protect against inflammation-induced skeletal muscle atrophy by regulating mitochondrial dysfunction, presenting innovative potential therapeutics for skeletal muscle atrophy.