Objective:

2

To explore the therapeutic effects and underlying mechanisms of

Dendrobium officinale

(Tiepi Shihu) extract (DOE) on insomnia.

Methods:

2

Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (

n

=7 per group): normal control

model control

melatonin (MT

40 mg/kg)

and 3-dose DOE (0.25

0.50

and 1.00 g/kg) groups. Rats were raised in a strong-light (10

000 LUX) and -noise (

>

80 db) environment (12 h/d) for 16 weeks to induce insomnia

and from week 10 to week 16

MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment

sucrose preference test

and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure

blood viscosity

blood glucose

and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally

the sleep-related factors gamma-aminobutyric acid (GABA)

glutamate (GA)

5-hydroxytryptamine (5-HT)

and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally

we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry.

Results:

2

DOE significantly improved rats' sleep and mood

increased the sodium pentobarbital-induced sleep time and sucrose preference index

and reduced autonomic activity times (

P

<

0.05 or

P

<

0.01). DOE also had a good effect on metabolic abnormalities

significantly reducing triglyceride

blood glucose

blood pressure

and blood viscosity indicators (

P

<

0.05 or

P

<

0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (

P

<

0.05 or

P

<

0.01). In addition

DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array

and the GABA

A

receptors (Gabra5

Gabra6

Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (

P

<

0.05 or

P

<

0.01).

Conclusion:

2

DOE demonstrated remarkable potential for improving insomnia

which may be through regulating GABA

A

receptors expressions and GA/GABA ratio.