Insomnia treatment based on the regulation of the GABAergic system: traditional Chinese medicine perspectives and therapeutic approaches

Insomnia is a common clinical manifestation of central nervous system (CNS) dysfunction that may be attributable to the involvement of abnormalities in multiple systems. Dysfunction of the gamma-aminobutyric acid (GABA) system is one of the key pathologic factors responsible for the increased neural excitability. GABA has been regarded as the major inhibitory neurotransmitter in the CNS, which can maintain the dynamic balance of neural networks by regulating neuronal excitability. Traditional Chinese medicine (TCM), with its multi-component, multi-target therapeutic advantages, shows unique potential in regulating the GABAergic system to improve sleep disorders. Accordingly, this review systematically elucidated the underlying mechanisms of TCM in treating insomnia by regulating the GABAergic system. According to the results, the intervention pathways of TCM exhibited multidimensional characteristics. TCM could effectively enhance GABA levels, strengthen GABAergic neural signal transmission, and improve insomnia symptoms by activating GABA receptor expression, upregulating glutamic acid decarboxylase (GAD) expression, and inhibiting GABA transaminase (GABA-T) activity. Furthermore, TCM could regulate the function of the hypothalamic-pituitary-adrenal (HPA) axis, inhibit neuroinflammation, regulate circadian rhythms, and enhance neurotrophic mechanisms, thereby synergizing with the GABAergic system to exert a sedative and sleep-promoting effect. With a systematic elaboration of the mechanisms of the GABAergic system, findings in this study may provide a theoretical basis for establishing a TCM evaluation system for insomnia based on the modulation of the GABAergic system. It can also offer fresh insights into the diagnosis and treatment of insomnia from the perspective of TCM, expand new directions for clinical research, and supply potential reference for future in-depth studies.