Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying Mechanism
Objective: To investigate the sleep-aiding effect of casein-derived peptide TPTLN and explore its possible mechanism of action. Methods: Thirty mice were divided equally into three groups, an experimental, a positive control and a blank control group, which were gavaged with TPTLN at a dose of 5 mg/...
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China Food Publishing Company
2025-02-01
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| author | DENG Shijie, LIU Ling, HUANG Ju, FENG Fengqin, ZHAO Minjie, DU Juan |
| author_facet | DENG Shijie, LIU Ling, HUANG Ju, FENG Fengqin, ZHAO Minjie, DU Juan |
| author_sort | DENG Shijie, LIU Ling, HUANG Ju, FENG Fengqin, ZHAO Minjie, DU Juan |
| collection | DOAJ |
| description | Objective: To investigate the sleep-aiding effect of casein-derived peptide TPTLN and explore its possible mechanism of action. Methods: Thirty mice were divided equally into three groups, an experimental, a positive control and a blank control group, which were gavaged with TPTLN at a dose of 5 mg/kg mb, intraperitoneally injected with diazepam at a dose of 1 mg/kg mb, and gavaged with sterilized water at a dose of 5 mg/kg mb, respectively. The body mass of all the mice was recorded every day. After 7 days of continuous administration, a sodium pentobarbital-induced sleep test was carried out to evaluate sleep quality. Following 4 more days of administration, the mice were euthanized and dissected to collect blood and tissue samples for analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), 5-hydroxyindoleacetic acid (5-HIAA), glutamate (Glu), β-endorphin (β-EP), cortisol, norepinephrine (NE) in the serum and brain tissue, and the GABA/Glu ratio was evaluated. real-time quantitative polymerase chain reaction (qPCR) was used to detect the effect of TPTLN on the mRNA relative expression levels of γ-aminobutyric acid A receptor α1 (GABAA-α1) and 5-hydroxytryptamine receptor 1A (5-HT1A) in the hypothalamus. Results: Compared with the control group, TPTLN and sodium pentobarbital synergistically increased the sleep onset rate to 100%, significantly shortened the sleep latency by 31.7% (P < 0.05), and extended the sleep duration 2.1 times (P < 0.05); increased the GABA/Glu ratio in the serum and brain tissue by 68.8% and 19.3%, respectively and significantly improved the excitation/inhibition imbalance (P < 0.001, P < 0.000 1) as evidenced by a 49.4% increase in the serum GABA level (P < 0.001), a 7.6% increase in the brain 5-HT level, and a 24.3% and 23.4% decrease in the brain levels of cortisol and NE (P < 0.05); and significantly up-regulated the expression levels of the GABAA-α1 and 5-HT1A genes 1.5 and 1.3 times, respectively (P < 0.01, P < 0.05). Conclusion: Casein-derived peptide TPTLN exhibited a favorable sleep-aiding effect, and the underlying mechanism may be associated with the regulation of GABAA-α1 and 5-HT1A expression levels, as well as the modulation of neurotransmitter contents including GABA, Glu, 5-HT, cortisol and NE in the brain. |
| format | Article |
| id | doaj-art-7f9cc51ad02b44dcb829729c8dd449b4 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-7f9cc51ad02b44dcb829729c8dd449b42025-02-05T09:08:33ZengChina Food Publishing CompanyShipin Kexue1002-66302025-02-0146311912710.7506/spkx1002-6630-20240617-111Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying MechanismDENG Shijie, LIU Ling, HUANG Ju, FENG Fengqin, ZHAO Minjie, DU Juan0(1. Food and Pharmacy College, Zhejiang Ocean University, Zhoushan 316000, China; 2. College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310000, China; 3. Hangzhou Kangyuan Food Technology Co. Ltd., Hangzhou 310003, China)Objective: To investigate the sleep-aiding effect of casein-derived peptide TPTLN and explore its possible mechanism of action. Methods: Thirty mice were divided equally into three groups, an experimental, a positive control and a blank control group, which were gavaged with TPTLN at a dose of 5 mg/kg mb, intraperitoneally injected with diazepam at a dose of 1 mg/kg mb, and gavaged with sterilized water at a dose of 5 mg/kg mb, respectively. The body mass of all the mice was recorded every day. After 7 days of continuous administration, a sodium pentobarbital-induced sleep test was carried out to evaluate sleep quality. Following 4 more days of administration, the mice were euthanized and dissected to collect blood and tissue samples for analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), 5-hydroxyindoleacetic acid (5-HIAA), glutamate (Glu), β-endorphin (β-EP), cortisol, norepinephrine (NE) in the serum and brain tissue, and the GABA/Glu ratio was evaluated. real-time quantitative polymerase chain reaction (qPCR) was used to detect the effect of TPTLN on the mRNA relative expression levels of γ-aminobutyric acid A receptor α1 (GABAA-α1) and 5-hydroxytryptamine receptor 1A (5-HT1A) in the hypothalamus. Results: Compared with the control group, TPTLN and sodium pentobarbital synergistically increased the sleep onset rate to 100%, significantly shortened the sleep latency by 31.7% (P < 0.05), and extended the sleep duration 2.1 times (P < 0.05); increased the GABA/Glu ratio in the serum and brain tissue by 68.8% and 19.3%, respectively and significantly improved the excitation/inhibition imbalance (P < 0.001, P < 0.000 1) as evidenced by a 49.4% increase in the serum GABA level (P < 0.001), a 7.6% increase in the brain 5-HT level, and a 24.3% and 23.4% decrease in the brain levels of cortisol and NE (P < 0.05); and significantly up-regulated the expression levels of the GABAA-α1 and 5-HT1A genes 1.5 and 1.3 times, respectively (P < 0.01, P < 0.05). Conclusion: Casein-derived peptide TPTLN exhibited a favorable sleep-aiding effect, and the underlying mechanism may be associated with the regulation of GABAA-α1 and 5-HT1A expression levels, as well as the modulation of neurotransmitter contents including GABA, Glu, 5-HT, cortisol and NE in the brain.https://www.spkx.net.cn/fileup/1002-6630/PDF/2025-46-3-014.pdfcasein-derived peptide; sleep aid; neurotransmitters; mechanism of action |
| spellingShingle | DENG Shijie, LIU Ling, HUANG Ju, FENG Fengqin, ZHAO Minjie, DU Juan Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying Mechanism Shipin Kexue casein-derived peptide; sleep aid; neurotransmitters; mechanism of action |
| title | Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying Mechanism |
| title_full | Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying Mechanism |
| title_fullStr | Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying Mechanism |
| title_full_unstemmed | Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying Mechanism |
| title_short | Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying Mechanism |
| title_sort | sleep aiding effect of casein derived peptide tptln and its underlying mechanism |
| topic | casein-derived peptide; sleep aid; neurotransmitters; mechanism of action |
| url | https://www.spkx.net.cn/fileup/1002-6630/PDF/2025-46-3-014.pdf |
| work_keys_str_mv | AT dengshijieliulinghuangjufengfengqinzhaominjiedujuan sleepaidingeffectofcaseinderivedpeptidetptlnanditsunderlyingmechanism |