The macamide relieves fatigue by acting as inhibitor of inflammatory response in exercising mice: From central to peripheral.

Macamides are the major and unique bioactive compounds of Lepidium meyenii (Walp.) or Maca. N-benzyl-(9Z, 12Z)-octadecadienamide (N-benzyl-linoleamide) is one of the most biologically active macamides with various pharmacological activities - anti-fatigue, neuroprotective, antioxidant, anti-tumoral activities, anti-inflammatory, and analgesic. In this study, the anti-fatigue properties of N-benzyl-(9Z, 12Z)-octadecadienamide were further evaluated by a weight-loaded forced swimming test. Results indicated N-benzyl-(9Z, 12Z)-octadecadienamide supplementation increased the forelimb grip strength of mice and exercising time remaining on the Rota-rod test. Furthermore, significant decreases in pro-inflammatory factors and reactive oxygen species (ROS) contents were observed in mice receiving N-benzyl-(9Z, 12Z)-octadecadienamide treatment after a 30 min swimming test, which was equivalent to that of caffeine. Histological analysis also indicated that N-benzyl-(9Z, 12Z)-octadecadienamide attenuated damage to the liver in mice by up-regulating the expression of heme oxygenase-1 (HO-1) and inhibiting the expression of Interleukin (IL)-1β during exercise. Pearson correlation analysis suggested peripheral fatigue indexes, including energy sources, metabolites were significantly correlated with inflammatory factors and ROS levels. Likewise, central fatigue parameters are also associated, including hippocampal inflammatory response and hypothalamic neurotransmitters. Hence, macamides can be considered to have great potential as a natural drug with high efficiency and low side effects for fatigue management.