Effect and Mechanism of Whey Protein Isolate-Epigallocatechin Gallate Non-Covalent Complex on Skeletal Muscle Attenuation in Aging Mice

Abstract

With the increasing aging population, there is a growing concern regarding the impact of skeletal muscle decay on the quality of life of the elderly. In this study, the anti-sarcopenia effect of the whey protein isolate-epigallocatechin gallate (WPI-EGCG) complex and its underlying mechanisms were investigated using a D-galactose induced senescence C2C12 cell model and skeletal muscle sarcopenia mouse model. The results showed that the optimal preparation conditions of the complex were pH 5.5, reaction time 1.5 h, and WPI:EGCG = 1:2.5. Under this condition, the DPPH free radical scavenging rate of the complex was 71.61%, and the protein digestibility was 80.95%. Compared with WPI, the antioxidant activity of the complex was significantly increased by 66.23%, and the protein digestibility was significantly decreased by 5.39% (p < 0.05). After the intervention with 0.32 mol/L and 0.16 mol/L D-galactose, the cell proliferation rate of 4.0 mg/mL WPI-EGCG complex treatment was significantly increased by 63.81% and 69.92% compared with the model group (p < 0.05), respectively. In addition, gavage of a low dose WPI-EGCG complex (250 mg/kg/d.bw) significantly increased skeletal muscle mass index (SMI) and muscle cross-sectional area (p < 0.05), and improved muscle mass and muscle fiber morphology in the sarcopenia mouse model compared with the model group. Compared with the model group, the low-dose WPI-EGCG complex significantly increased SOD activity by 16.14% and decreased 8-hydroxydeoxyguanosine (8-OHdG) content by 17.18% (p < 0.05), which was beneficial to reduce the oxidative stress level of mice. In addition, the protein expression of PI3K was increased after gavage of a low dose WPI-EGCG complex compared with the model group. After gavage of a high dose of the WPI-EGCG complex, the expression of AKT and mTOR protein was significantly increased compared with the model group (p < 0.05). In conclusion, the WPI-EGCG complex ameliorated the inhibitory effect of D-galactose on protein synthesis in mouse skeletal muscle by up-regulating the phosphorylation levels of PI3K, AKT, and mTOR proteins. It can promote protein anabolism in the skeletal muscle of mice, thereby improving aging-induced skeletal muscle decay. It provided new ideas for improving skeletal muscle health and quality of life in the elderly.

Keywords: EGCG; WPI; mechanism; sarcopenia.