Ameliorating effect of Trigonella foenum-graecum L. (fenugreek) extract tablet on exhaustive exercise-induced fatigue in rats by suppressing mitophagy in skeletal muscle.

Abstract

Trigonella foenum-graecum L. (fenugreek) is widely used as a leafy vegetable and spice in China and North Africa. Recent studies have reported that fenugreek can reduce fatigue; however, its antifatigue mechanism remains unclear. Therefore, this study aimed to investigate the potential antifatigue effects of fenugreek extract (FE) on mitophagy and the underlying mechanisms. We evaluated the potential effects of FE tablet on an exhaustive exercise-induced fatigue (EEF) rat model. Oxidative stress indicators and fatigue biomarkers in the serum and skeletal muscle were detected. Mitophagy and mitochondrial morphology were observed using transmission electron microscopy. The expression levels of mitochondrial autophagy-related proteins were detected using western blot and immunofluorescence. Compared with the model group, FE enhanced the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase as well as total antioxidant capacity; however, it decreased the level of malondialdehyde in the serum and skeletal muscle after a 7-day treatment. Moreover, certain indicators of mitochondrial function, such as reactive oxygen species levels, ATP levels, cellular and mitochondrial Ca2+ levels, and ATPase activity, were significantly improved in the FE group compared with the model group. Finally, we found that mitophagy was induced by exhaustive exercise and inhibited by FE. Regarding mitochondrial autophagy-related proteins, the expression levels of LC3B, FUNDC1, PGAM5, PARKIN, and PINK1 in the skeletal muscle tissue were increased in the EEF group compared with the control group. After administration of FE and a positive control drug, a significant reversal in the expression of the above-mentioned proteins was noted. Our findings demonstrate that FE exerted antifatigue effects in the EEF rat model by regulating the mitophagy-related FUNDC1/LC3B signaling pathway rather than the PINK1/PARKIN signaling pathway.