Genistein Alleviates Fatigue in Immunosuppressed Rats through the AMPK/SIRT1/PGC-1α Signaling Pathway

Objective: To explore the effect of genistein (GEN) on relieving fatigue in immunosuppressed rats and the underlying mechanism. Methods: A total of 96 male SD rats were randomly divided into six groups with 16 rats in each group, including blank control (CG), immunosuppression model (MG), low-dose GEN (LG), medium-dose GEN (MG), high-dose GEN (HG) and positive control (PG). All rats except those in the blank control group were injected intraperitoneally with cyclophosphamide at a dose of 40 mg/kg mb for three days to establish an immunosuppressed rat model. The rats in the LG, MG and HG groups were gavaged with GEN at doses of 10, 20, and 40 mg/kg mb, respectively. The positive control group was gavaged with 3.125 g/kg mb of Zhenqi Fuzheng granule, and the blank control group was gavaged with an equal amount of peanut oil. After the experiment, the exhaustive swimming time of rats was recorded. The activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in rat serum were detected by colorimetry. The concentrations of immunoglobulin G (IgG) and tumor necrosis factor-α (TNF-α) in rat serum were detected by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative PCR was used to detect adenylate-activated protein kinase (AMPK), silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptorγ coactivator-1α (PGC-1α) and peroxisome proliferators-activated receptor-γ (PPARγ) mRNA expression levels. The protein expression levels of AMPK, SIRT1, PGC-1α and PPARγ in the skeletal muscle of rats were detected by Western blot. Results: Compared with the MG group, GEN supplementation significantly prolonged the exhaustive swimming time of rats (P < 0.01), and high-dose GEN significantly decreased CK and LDH activities and increased the concentrations of IgG and TNF-α in the serum (P < 0.01), and significantly increased the gene and protein expression levels of AMPK, SIRT1, PGC-1α and PPARγ in the skeletal muscle of rats (P < 0.05 and P < 0.01). Conclusion: GEN relieves fatigue in immunosuppressed rats, and the underlying mechanism may be related to activating the AMPK/SIRT1/PGC-1α signaling pathway in the skeletal muscle and improving the exercise endurance, energy production and immunomodulatory capacity of rats.