Edible Bird's Nest Attenuates Neuroinflammation and Cognitive Impairment in a Model of Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue with an unclear pathophysiology. Increasing evidence suggests that neuroinflammation plays an important role in the development of CFS; however, the underlying mechanisms remain poorly defined. In this study, we evaluated the effects of edible bird's nest (EBN) in a sleep-deprivation-induced CFS-like mouse model. EBN treatment improved motor and cognitive performance, reduced neuronal necrosis, and preserved synaptic structure in the prefrontal cortex. Blood metabolomic profiling revealed elevated levels of the dipeptide valyl-tryptophan (Val-Trp) following EBN administration. Functional assays showed that Val-Trp attenuates neuroinflammation by suppressing nuclear factor kappa-B signaling, thereby shifting microglia from a pro-inflammatory to a homeostatic state. These findings implicate Val-Trp as a candidate bioactive metabolite associated with the neuroprotective effects of EBN, providing preclinical evidence to support exploration of natural-product-derived interventions for CFS.