Abstract
Objective
To study the sedative and hypnotic effects and underlying mechanisms of Polygala tenuifolia (PT) on treating aged insomnia rats.
Methods
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
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
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.
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Zhang XP and Ren XJ conceived and supervised the study; Zhang XP and Wang GY designed experiments; Ren XJ and Wang GY performed experiments; Wang QQ analyzed data; Ren XJ wrote the manuscript; Zhang XP made manuscript revisions.
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Supported by the National Natural Science Foundation of China (No. 81960837 and 81560762), Xinjiang Uygur Autonomous Region Healthy Young Medical Science and Technology Talents Special Research Project (No. WJWY-201919), and the 13th Five-Year Plan of Traditional Chinese Medicine Strategic Emerging Key Profession of Xinjiang
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Ren, Xj., Wang, Gy., Zhang, Xp. et al. Sedative and Hypnotic Effects and Transcriptome Analysis of Polygala tenuifolia in Aged Insomnia Rats. Chin. J. Integr. Med. 26, 434–441 (2020). https://doi.org/10.1007/s11655-020-3087-6
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DOI: https://doi.org/10.1007/s11655-020-3087-6