Abstract: Objective To evaluate the effects of Yifei Sanjie Pills (YFSJ) on weight, strength, pathology, glycogen and lipid contents and metabolism of skeletal muscles in tumor-bearing mice and explore the therapeutic mechanism of YFSJ for cancer-related skeletal muscle atrophy. Methods Sixteen female ICR mice bearing intraperitoneal Lewis lung adenocarcinoma xenografts were randomized into model group and YFSJ treatment group (daily dose of 4 g/kg for 21 days, n=8), with another 8 normal mice as the normal control group. The changes in body weight and gastrocnemius muscle weight of the mice were recorded. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the drug components in YFSJ entering the blood. Enzyme-linked immunosorbent assay was used to detect serum blood glucose and insulin concentrations and inflammatory cytokine levels in the serum and gastrocnemius. RNA-seq was performed to analyze the signaling pathways involved in the pathologies of the gastrocnemius muscle, and lipid contents in the muscle were observed using Oil red O staining. Adenosine triphosphatase staining was used to assess the metabolic intensity of the gastrocnemius muscle, and inflammatory cell infiltration and P-AKT level were evaluated using immunohistochemical staining; the contents of creatine kinase, lactate dehydrogenase and myoglobin in the gastrocnemius muscle were also detected. Results Treatment with YFSJ significantly increased skeletal muscle strength and gastrocnemius muscle weight (P<0.001) and reduced the levels of gastrocnemius muscle injury markers in the tumor-bearing mice (P<0.01). RNA-seq and LC-MS showed that YFSJ alleviated gastrocnemius muscle injury in the tumor-bearing mice possibly by improving inflammatory infiltration, insulin resistance and lipid metabolism (P<0.05). YFSJ lowered inflammatory cytokine levels in both the serum and gastrocnemius muscle (P<0.05), reduced pro-inflammatory cell infiltration, increased P-AKT level, and improved glycogen and lipid contents and metabolic levels in the gastrocnemius muscle. Conclusion YFSJ alleviates cancer-related skeletal muscle atrophy possibly by reducing inflammatory insulin resistance.

Key words: Yifei Sanjie Pills, inflammatory insulin resistance, cancer-related skeletal muscle atrophy