Wild ginseng adventitious roots restore sleep homeostasis in sleep-deprived Drosophila melanogaster

Sleep deprivation is increasingly recognized as a major health concern and is associated with impaired physiological and neurological functions. Panax ginseng C. A. Mey. has long been used to improve sleep quality; however, the limited availability and long cultivation cycle of natural ginseng restrict its sustainable utilization. Wild ginseng adventitious roots (ADV), produced via plant tissue culture, provide a renewable source of bioactive ginsenosides, although their potential role in sleep regulation remains poorly understood.

The sleep-promoting effects and safety of ADV were evaluated in a sleep deprivation-induced Drosophila melanogaster model. Sleep parameters, including total sleep duration, sleep latency, deep sleep, and sleep fragmentation, were assessed, together with addiction-like behavioral assays. Transcriptomic analysis was performed to investigate the underlying mechanisms. LC-MS/MS and bioactivity assays were conducted to identify and validate major active ginsenosides.

ADV significantly improved sleep behavior in sleep-deprived flies, increasing total sleep duration and deep sleep while reducing sleep latency and sleep fragmentation, without inducing addiction-like behaviors. Transcriptomic analysis revealed that ADV modulated multiple sleep-related biological processes, particularly stress response pathway, as evidenced by altered expression of Hsp68, Hsp70Aa, Hsp70Ba, Hsp70Bb, and Hsp70Bbb. Combined with LC-MS/MS identification and biological activity comparison, ginsenosides Rc and F2 were preliminarily identified as the principal active metabolites.

In the Drosophila melanogaster sleep-deprivation model, ADV treatment is associated with improvements in sleep-related behavioural parameters alongside altered expression of conserved stress-response-related biological processes. These findings support ADV as a sustainable source of bioactive ginsenosides, though the current experimental design cannot establish a strictly sleep-specific or causal mechanistic relationship.