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Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons

Corni fructus, the fruit of Cornus officinalis Sieb. et Zucc., has been used as a tonic for the kidney in China for thousands of years. Loganin is one of the major constituents derived from Corni fructus. In this study, we revealed the sedative and hypnotic activity of loganin and investigated its m...

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Autores principales: Shi, Rui, Han, Yan, Yan, Yu, Qiao, Hao-Yi, He, Jun, Lian, Wen-Wen, Xia, Cong-Yuan, Li, Ting-Li, Zhang, Wei-Ku, Xu, Jie-Kun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491506/
https://www.ncbi.nlm.nih.gov/pubmed/31068813
http://dx.doi.org/10.3389/fphar.2019.00409
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author Shi, Rui
Han, Yan
Yan, Yu
Qiao, Hao-Yi
He, Jun
Lian, Wen-Wen
Xia, Cong-Yuan
Li, Ting-Li
Zhang, Wei-Ku
Xu, Jie-Kun
author_facet Shi, Rui
Han, Yan
Yan, Yu
Qiao, Hao-Yi
He, Jun
Lian, Wen-Wen
Xia, Cong-Yuan
Li, Ting-Li
Zhang, Wei-Ku
Xu, Jie-Kun
author_sort Shi, Rui
collection PubMed
description Corni fructus, the fruit of Cornus officinalis Sieb. et Zucc., has been used as a tonic for the kidney in China for thousands of years. Loganin is one of the major constituents derived from Corni fructus. In this study, we revealed the sedative and hypnotic activity of loganin and investigated its mechanisms for the first time. Pentobarbital-induced sleep test and insomnia mice models [induced by caffeine and p-chlorophenylalanine (PCPA)] were used for the assessment of sedative and hypnotic effects of loganin. It was found that loganin (20–50 mg/kg) exerted sedative effect in normal mice. Loganin exhibited hypnotic effect by increasing sleep onset and sleep duration in pentobarbital-treated mice, recovering PCPA-induced insomnia and exerting synergistic hypnosis effect with 5-HTP. In addition, electroencephalograph (EEG) and electromyography (EMG) recordings of rats showed that loganin (35 mg/kg) prolonged the ratio of non-rapid eye movement (NREM) sleep and shortened wakefulness significantly, further immunohistochemistry showed that loganin (35 mg/kg) increased c-Fos expression in GABAergic neurons of rats in the ventrolateral preoptic nucleus (VLPO). The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite were measured in the hippocampus, prefrontal cortex and striatum of mice, 1 h after loganin (35 mg/kg) treatment. 5-HT, 5-HIAA/5-HT, DA, and DOPAC were decreased significantly in the prefrontal cortex. In conclusion, these results indicated that loganin produced beneficial sedative and hypnotic activity, which might be mainly mediated by modification of the serotonergic system and GABAergic neurons.
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spelling pubmed-64915062019-05-08 Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons Shi, Rui Han, Yan Yan, Yu Qiao, Hao-Yi He, Jun Lian, Wen-Wen Xia, Cong-Yuan Li, Ting-Li Zhang, Wei-Ku Xu, Jie-Kun Front Pharmacol Pharmacology Corni fructus, the fruit of Cornus officinalis Sieb. et Zucc., has been used as a tonic for the kidney in China for thousands of years. Loganin is one of the major constituents derived from Corni fructus. In this study, we revealed the sedative and hypnotic activity of loganin and investigated its mechanisms for the first time. Pentobarbital-induced sleep test and insomnia mice models [induced by caffeine and p-chlorophenylalanine (PCPA)] were used for the assessment of sedative and hypnotic effects of loganin. It was found that loganin (20–50 mg/kg) exerted sedative effect in normal mice. Loganin exhibited hypnotic effect by increasing sleep onset and sleep duration in pentobarbital-treated mice, recovering PCPA-induced insomnia and exerting synergistic hypnosis effect with 5-HTP. In addition, electroencephalograph (EEG) and electromyography (EMG) recordings of rats showed that loganin (35 mg/kg) prolonged the ratio of non-rapid eye movement (NREM) sleep and shortened wakefulness significantly, further immunohistochemistry showed that loganin (35 mg/kg) increased c-Fos expression in GABAergic neurons of rats in the ventrolateral preoptic nucleus (VLPO). The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite were measured in the hippocampus, prefrontal cortex and striatum of mice, 1 h after loganin (35 mg/kg) treatment. 5-HT, 5-HIAA/5-HT, DA, and DOPAC were decreased significantly in the prefrontal cortex. In conclusion, these results indicated that loganin produced beneficial sedative and hypnotic activity, which might be mainly mediated by modification of the serotonergic system and GABAergic neurons. Frontiers Media S.A. 2019-04-24 /pmc/articles/PMC6491506/ /pubmed/31068813 http://dx.doi.org/10.3389/fphar.2019.00409 Text en Copyright © 2019 Shi, Han, Yan, Qiao, He, Lian, Xia, Li, Zhang and Xu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Shi, Rui
Han, Yan
Yan, Yu
Qiao, Hao-Yi
He, Jun
Lian, Wen-Wen
Xia, Cong-Yuan
Li, Ting-Li
Zhang, Wei-Ku
Xu, Jie-Kun
Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons
title Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons
title_full Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons
title_fullStr Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons
title_full_unstemmed Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons
title_short Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons
title_sort loganin exerts sedative and hypnotic effects via modulation of the serotonergic system and gabaergic neurons
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491506/
https://www.ncbi.nlm.nih.gov/pubmed/31068813
http://dx.doi.org/10.3389/fphar.2019.00409
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