Gastrodin ameliorates exercise-induced fatigue via modulating Nrf2 pathway and inhibiting inflammation in mice

Gastrodia elata Bl. is traditional Chinese medicine used to alleviate fatigue, but its underlying mechanism is still unclear. This study explored the anti-fatigue mechanism of gastrodin by exercise-induced fatigue model and network pharmacology. This study found that gastrodin (200 mg/kg/day) had significant anti-fatigue effects in C57BL/6J mice based on mouse energy and endurance measurements. Gastrodin could effectively ameliorate biochemical indexes in the fatigue mice. The putative targets of "Gastrodin" and "Fatigue" were obtained by integrating multiple databases, and a virtual network containing 220 interactive targets was constructed by STRING and Cytoscape. Functional annotation analysis of these targets by g:Profiler showed that they mainly contribute to the cellular processes, protein binding, and other functions and participate in metabolic pathways, cancer pathways, PI3K-Akt signaling pathway, etc. We found that oxidation and inflammatory factors played an important role in the virtual network of gastrodin anti-fatigue, which was supported by microarray dataset analysis and a molecular docking prediction. Additionally, real time-quantitative PCR and Western blot analysis indicated that gastrodin could promote the activation of the Nrf2 signal pathway, which could activate HO-1 and NQO1; gastrodin also could down-regulate the expressions of IL-1 beta, TNF-alpha, and IL-6. In summary, gastrodin can ameliorate exercise-induced fatigue by modulating the Nrf2 pathway and inhibiting expressions of inflammatory factors, this provides a new clue for the development of gastrodin-functional foods or anti-fatigue drugs.