18β-glycyrrhetinic acid improves high-intensity exercise performance by promoting glucose-dependent energy production and inhibiting oxidative stress in mice.

It has been shown that 18β-glycyrrhetinic acid (18β-GA), the main bioactive compound of licorice, can modulate oxidative stress and metabolic processes in liver and skin. Given the critical role of oxidative stress and energy metabolism in exercise-induced fatigue, we hypothesized that 18β-GA could exert an ergogenic action by inhibiting excess reactive oxygen species (ROS) induction and promoting energy production in muscles. Mice were gavage-fed with 18β-GA for four consecutive days. Running ability was assessed based on the exhaustive treadmill test with high- and moderate-intensity. Western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence staining were used to measure the changes of muscle fatigue-related markers, oxidative stress status, and energy metabolism in response to 18β-GA exposure. Treatment with 18β-GA significantly increased the exhaustive running distance (~37%) in the high-intensity exercise, but not in the moderate-intensity exercise. Mechanistically, reduction of oxidative stress and induction of antioxidants (SOD, CAT, and GSH) by 18β-GA were observed. Moreover, 18β-GA treatment caused an improved preservation of muscle glycogen (12%), which was associated with upregulation of glucose transporter 4 (GLUT4) (91%) and increased insulin level (17%). The findings of the present study clearly suggest that 18β-GA holds excellent potential as a novel bioactive agent against high-intensity exercise-induced fatigue.