Glycyrrhizic Acid Relieves Fatigue Induced by Acute and Chronic Exercise in Mice via Inhibition of the NF‐κB/NLRP3 Signaling Pathway
Xin‐ying Cai, Wen‐jun Li, Cai‐xia Chen, Lu Peng, Li‐chao Yang, Xiao‐ning Lin, Hong‐tao Liu, Jian‐bo Jia, Yan‐chao Jiao, Ying LiABSTRACT
Background
Glycyrrhizic acid (Gly‐A) exhibits anti‐inflammatory and antioxidant effects in various central nervous system disorders. Acute fatigue and chronic fatigue (CF) are associated with serious physical and psychological effects. However, the underlying pathophysiology and effective therapeutic strategies for these conditions remain poorly understood.
Purpose
This study aims to evaluate the therapeutic potential of Gly‐A against fatigue, and to elucidate the underlying mechanisms of its action.
Methods
We established a mouse model of acute exercise‐induced fatigue and evaluated fatigue‐related indices. To identify specific pathways involved in Gly‐A's therapeutic effects, we employed RNA sequencing, network pharmacology, and in vitro oxygen‐deficit models, aiming to clarify the mechanisms. Additionally, we established a mouse model of CF to compare the therapeutic efficacy of Gly‐A with positive control drugs by assessing identical parameters.
Results
Gly‐A significantly improved fatigue‐related indices without affecting body weight. RNA sequencing and network pharmacology analyses showed that Gly‐A modulates oxidative stress responses and targets the NF‐κB (nuclear factor‐kappa B)/NLRP3 (NOD‐like receptor thermal protein domain associated protein 3) signaling and apoptotic pathways. In the CF mouse model, oral administration of Gly‐A significantly increased motor activity, alleviated anxiety and depression, and improved neurocognitive function compared to model mice, exhibiting superior efficacy to positive control drugs. These findings suggest that Gly‐A exerts anti‐inflammatory effects by targeting the NF‐κB/NLRP3 signaling pathway, thereby reducing neuronal apoptosis in CF.
Conclusions
Gly‐A exhibits therapeutic potential against acute exercise‐fatigue and CF, primarily by attenuating apoptosis through the inhibition of the NF‐κB/NLRP3 signaling pathway.