Gan-Dan-Liang-Yi-Tang alleviates p-chlorophenylalanine-induced insomnia through modification of the serotonergic and immune system

Abstract

Gan-Dan-Liang-Yi-Tang (GDLYT) is a Traditional Chinese Medicine that has been historically used for the treatment of insomnia. However, investigations into its pharmacological ingredients and the mechanism underlying its sedative and hypnotic effects remain limited. The present study reported the detailed mechanisms underlying the sedative and hypnotic effects of GDLYT. Kunming mice were administered GDLYT at various sub-hypnotic doses, which underwent sodium pentobarbital treatment test, pentetrazole induced convulsant studies and p-chlorophenylalanine (PCPA) induced insomnia model. Potentiated hypnotic and sedative effects in mice was studied, and also the changes in related neurotransmitter and immune factors were evaluated. The results suggested that GDLYT possessed weak sedative effects on pentetrazole-induced convulsive activity in normal mice at a dose of 1.3 mg/kg, with an increase in sleep onset in subhypnotic dose of sodium pentobarbital-treated mice. GDLYT was also able to alleviate insomnia induced by PCPA in the rodent models, and increased 5-hydroxytryptamine levels in the prefrontal cortex, hippocampus, hypothalamus and corpus striatum of PCPA-treated rats. Furthermore, the hypnotic effects of GDLYT were modified, which allowed for PCPA-induced immune system changes, including increased interleukin (IL)-1β, tumor necrosis factor-α and IL-2 expression levels. The results of the present study indicated that GDLYT induced sedative and hypnotic bioactivity by regulating serotonergic activity in the central nervous system and immune system.

Establishment of a rat model with ageing insomnia induced by D‑galactosef and para‑chlorophenylalanine

“…The I-κ/NF-κB signaling pathway is associated with sleep regulation and the immune system and hippocampus play a central role in insomnia ( 60 ). A previous study demonstrated that plasma levels of IL-6 and TNF-α in PCPA-induced insomnia rats were significantly higher compared with the control group ( 25 ). In the current study, the results demonstrated that the serum content of IL-1β, IL-6 and TNF-α and mRNA expression of IL-6, TNF-α and NF-κB in neural tissues in the PCPA+D-gal group were higher compared with control rats.…”

“…The ageing model induced by D-gal has been widely used (21,22) and has been evaluated in behavioral, biochemical and neurochemical aspects (23). The modeling methods of animal models of insomnia mainly include chemical reagent stimulation using intraperitoneal injection of para-chlorophenylalanine (PCPA) (24), the horizontal platform environmental deprivation method (25), the stress stimulation sleep deprivation method (26), the gentle stimulation deprivation method and the forced exercise deprivation method (27). Rat and mouse models can be used; however, rat models are optimal due to model stability in the establishment of the ageing model induced by D-gal (28).…”

Lilium davidii extract alleviates p‑chlorophenylalanine‑induced insomnia in rats through modification of the hypothalamic-related neurotransmitters, melatonin and homeostasis of the hypothalamic-pituitary-adrenal axis

“…To investigate the activity and characteristics of LD extract on alleviating insomnia, the PCPAinduced insomnia test and spontaneous exploration activities were performed. The PCPA-induced insomnia rat model is the most commonly used classic model to study the mechanism of insomnia, which can deplete the 5-HT content in the brain, and is accompanied by dysfunction of the HPA axis (Hu et al 2016).…”

“…The PCPA-induced insomnia rat model is the most commonly used classic model to study the mechanism of insomnia, which can deplete the 5-HT content in the brain, and is accompanied by dysfunction of the HPA axis (Hu et al. 2016 ).…”

Baihe, Dihuang and Baihe Dihuang Tang ameliorates PCPA-Induced Insomnia

“…Sixty male mice were randomly and evenly distributed into ve groups: blank control, PCPA (model, BH, DH and BDT groups. Except for mice in the control group, mice in the rest of the groups were intraperitoneally administrated with PCPA (300 mg/kg) once a day at 8:00 and 9: 00 a.m. for the rst and second day, respectively, to induce insomnia (Hu et al, 2016). Herbal medicines (BH, DH or BDT) were orally administrated 2 days after PCPA injection.…”