Anti-fatigue mechanism of Dendrobium officinale pseudobulbs from different growth durations against chronic fatigue syndrome in mice and analysis of their active chemical components

To investigate the differential efficacy of Dendrobium officinale pseudobulb alcohol extracts from varying growth durations against chronic fatigue syndrome (CFS) in mice, elucidate the underlying anti-CFS mechanisms, and identify the pharmacologically active components responsible. An ICR mouse model of CFS was established using the forced swimming test (FST). Behavioral characteristics, physiological phenotypes, biochemical parameters, and plasma metabolomics profiles were assessed. Concurrently, untargeted metabolomics and high-performance liquid chromatography (HPLC) were employed to analyze the chemical constituents of D. officinale pseudobulbs from different cultivation periods. Correlation analysis between the identified anti-CFS characteristic metabolites in plasma and the pseudobulb components was performed to predict the potential active ingredients against CFS in D. officinale pseudobulbs. Compared with the one-year-cultivated D. officinale extract (1DOE), the three-year-cultivated D. officinale extract (3DOE) significantly reduced anal temperature, prolonged forced swimming time, decreased liver index and plasma lactate dehydrogenase (LDH) levels, lowered cAMP levels and the cAMP/cGMP ratio, and mitigated renal inflammatory infiltration in model mice. Plasma metabolomic pathway analysis indicated that 3DOE extract alleviated energy metabolism dysregulation by enhancing energy metabolism and promoting oxidative utilization of fatty acids and proteins. Characteristic metabolites included arachidonic acid, L-5-oxoproline, pyroglutamic acid, D-(+)-malic acid, and PC (20:5/22:5). Correlation analysis between key metabolites and pseudobulb bioactive constituents revealed that flavonoids, polyphenols, lignans, terpenoids, and bibenzyls, which are significantly enriched in 3DOE, constitute the pharmacodynamic basis for the anti-CFS efficacy. These findings provide a scientific foundation for applying perennial D. officinale in the management of fatigue-related disorders, including CFS.