Abstract: Objective: To observe the anti-fatigue effect and underlying mechanism of schisantherin A (SCA) in mice. Methods: ICR male mice were divided into four groups: normal control group (CON group; orally given distilled water; sit-in test); chronic fatigue model group (MOD group; orally given distilled water; exhaustive exercise test), SCA (C) group (orally given SCA at 2.5 mg/kg; sit-in test), and SCA (M) group (orally given SCA at 2.5 mg/kg; exhaustive exercise test). All mice were treated once daily for 4 weeks. The effect of SCA on exercise endurance in mice was observed by weight-bearing swimming test and rotarod test. Blood urea nitrogen (BUN), lactic acid (LA), lactate dehydrogenase (LDH), creatine kinase (CK), liver glycogen (LG), muscle glycogen (MG), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in mice were determined by chemical colorimetry, and the level of 8-OHdG was measured with enzyme-linked immunosorbent assay; the expression of Keap1, Nrf2 and HO-1 proteins in liver tissue were measured with Western blot. Results: Compared with the CON and MOD groups, the animals from the SCA (C) and SCA (M) groups showed significantly increased exercise endurance (P < 0.05); the levels of BUN, LA, LDH, CK, MDA and 8-OHdG significantly decreased in the SCA (C) and SCA (M) groups (P < 0.05 or P < 0.01), and the levels of LG, MG, SOD, and GSH-Px significantly increased (P < 0.05 or P < 0.01). In addition, the expression of Keap1 extremely significantly decreased (P < 0.01) and the expression of Nrf2 and HO-1 increased (P < 0.01) in both SCA groups. Conclusion: SCA can improve exercise endurance in chronic fatigue mice, which may be related to increasing energy reserves and antioxidant ability in the blood and regulating the Nrf2/ARE antioxidant pathway in the liver of mice.

Key words: schisantherin A, improvement of exercise endurance, Keap1, Nrf2, HO-1