Sedative-hypnotic effects of an herbal formulation comprising Ganoderma, Gastrodiae Rhizoma, and Chrysanthemi Flos in mice

Background:
The tri-herb formulation GGC, consisting of Ganoderma (GL, the dried fruiting body of Ganoderma lucidum), Gastrodiae Rhizoma (GR, the dried tuber of Gastrodia elata), and Chrysanthemi Flos (CF, the dried flower head of Chrysanthemum morifolium), has shown clinical potential for managing sleep disorders. However, its pharmacological basis remains underexplored.

Purpose:
This study aimed to investigate the sedative-hypnotic effects and underlying mechanisms of an ethanolic GGC extract (GGCE).

Methods:
Mouse models were used to evaluate the sedative-hypnotic effects of GGCE. Mechanistic investigations were performed using RNA sequencing, RT-qPCR, ELISA, and immunoblotting.

Results:
GGCE administration produced dose‐dependent sedative‐hypnotic effects, including reduced locomotor activity, shortened sleep latency, and prolonged sleep duration. RT‐qPCR analysis revealed that GGCE upregulated Gabrd mRNA, which encodes the delta subunit of the GABAA receptor, in brain tissue. Immunoblotting showed increased protein levels of Gabrd, phospho‐PKA C (Thr197), and phospho‐CREB (Ser133) following GGCE treatment. Additionally, ELISA results indicated that GGCE elevated levels of GABA (gamma‐aminobutyric acid), cAMP (cyclic adenosine monophosphate), and BDNF (brain‐derived neurotrophic factor) in brain tissue.

Conclusions:
This study demonstrates for the first time that GGCE exerts sedative-hypnotic effects in mice. These effects are associated with activation of the cAMP/PKA/CREB/BDNF signaling pathway and enhanced GABAergic signaling. These findings provide the first pharmacological justification for the use of GGC in treating insomnia and suggest GGCE’s potential as a modern therapeutic agent for improving sleep.