Objective:

2

To study the sedative and hypnotic effects and underlying mechanisms of

Polygala tenuifolia

(PT) on treating aged insomnia rats.

Methods:

2

Sixty Sprague-Dawley male rats were divided into 6 groups by a random number table

including control group

model group

diazepam group (0.92 mg/kg)

as well as PT low-

medium- and high-dose groups (0.0875

0.175

0.35 g/kg

respectively)

10 rats in each group. Aged insomnia rat model was established with subcutaneous injection of D-galactose for 42 days and then intraperitoneal injection of para-chlorophenylalanine for 3 days. PT and diazepam were respectively given to aged insomnia rats by intragastric administration for 7 days after model establishment. Then the rats were investigated by body weight

Morris water maze test

pentobarbital test

enzyme-linked immunosorbent assay

and transcriptome sequencing.

Results:

2

Compared with the model group

PT increased the body weight

improved memory ability

and prolonged pentobarbital-induced sleep time of aged insomnia rats (

P

<

0.01 or

P

<

0.05). The medium dose of PT also increased the neurotransmitter levels of 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA)

and decreased the level of Glu in the hippocampus of aged insomnia rats (

P

<

0.05 or

P

<

0.01). Twenty-four differentially expressed genes (DEGs) were overlapped among model group

medium-dose PT group

and diazepam group in transcriptome analysis. Fuom and Pcp2 were down-regulated by the treatment of medium-dose PT (

P

<

0.01 or

P

<

0.05). The metabolic pathways of PT were relatively less than diazepam (91 vs. 104).

Conclusions:

2

The sedative and hypnotic effects of PT in aged insomnia rats might be related to neuro

metabolism pathways

especially through GABAergic signaling pathway. It provided more effective herb choice for the treatment of senile insomnia.