Mangiferin Alleviates Exercise-Induced Fatigue Through Inhibition of NFκB-Mediated Inflammation and Oxidative Stress Based on Network Pharmacology

Background. Muscle fatigue is defined as a decrease in maximal force or power production in response to contractile activity, which can cause muscle damage and limit athletic performance. A mass of phytochemicals were certified feasibly in relieving exercise-induced fatigue. Mangiferin, a multifactorial pharmacological phytochemical, was a promising candidate in theory; nonetheless, the potential molecular mechanisms of mangiferin on exercise-induced fatigue need to be elucidated. Methods. In this research, a mouse fatigue model was induced by forced swimming 4 weeks, and mangiferin was supplied in 100 mg/kg. The protective effects of mangiferin were illustrated by rotating rod test, serum biochemical indicators (LA, CK, BUN, ALT, and AST), and gastrocnemius morphology. Then, the targets of mangiferin against exercise-induced fatigue were predicted using network pharmacology through a comprehensive search and analysis with STITCH, PharmMapper Serve, STRING, and AutoDock Vina. Furthermore, predicted target genes were verified in gastrocnemius by immunohistochemistry. Results. Mangiferin has a significant antifatigue effect by prolonging the rotating time of the rod test. Serum biochemical indicators were mitigated (LA, CK, BUN, ALT, and AST), and gastrocnemius injury was easing. Network pharmacology was used to find that mangiferin might alleviate exercise-induced fatigue through regulating NFκB, PTGS2, TNF-α, and CCL2, and those aberrant expressions were verified in gastrocnemius. Molecular docking indicated that NFκB may be the most important molecule locking with mangiferin. Furthermore, the levels of IL-1β, TNF-α, IL-6, and MDA were significantly upregulated, while SOD and GSH-PX were downregulated in serum of fatigue mice, which were reversed with mangiferin treatment. Conclusion. Mangiferin is a feasible treatment to mitigate exercise-induced fatigue by anti-inflammation and antioxidative stress, through regulating the expression of NFκB and its downstream molecules.