Theacrine-rich Jianghua Kucha black tea alleviates depression

Jianghua Kucha black tea (JH), a distinct variety characterized by its high theacrine content, exhibits significant antidepressant potential, however, bridging its systemic metabolic benefits to specific molecular targets remains a major challenge. In this study, we integrated untargeted serum metabolomics with multi-scale computational biology to explore the potential mechanism of action of JH in a chronic unpredictable mild stress (CUMS) mouse model. Rather than acting through a single pathway, metabolomic profiling revealed that JH induced a comprehensive reprogramming of the circulatory metabolic landscape. Specifically, JH attenuated the metabolic perturbations associated with the maladaptive shunting of tryptophan toward the kynurenine pathway, thereby favoring the restoration of serotonin (5-HT) biosynthesis precursors. To elucidate the molecular drivers behind this metabolic shift, integrative network pharmacology and atomistic molecular dynamics (MD) simulations were employed, prioritizing TPH1 as a high potential therapeutic target. The computational models predicted that JH's characteristic bioactives, notably theacrine and theaflavins, could form stable, high-affinity binding conformations with TPH1. Collectively, this study provides a novel "metabolism-target" structural framework, providing theoretical insights into the circulatory mechanisms of JH and highlighting its significant promise as a dietary intervention for mood disorders.