Pharmaceuticals
·
2024
·Vol. 17
·期 9
·1161
·
IF 4.3
Luge Chen,Yingwei Liu,Dawei Xu,Na Zhang,Yong Chen,Jin Yang,Lijuan Sun
With the increasing prevalence of insomnia-related diseases, the effective treatment of insomnia has become an important health research topic. Lavender (Lavandula angustifoliaMill.) essential oil (LEO) is a commonly used medicine for the treatment of insomnia and neurological disorders. However, neither the active components nor its sedative–hypnotic mechanism have been fully discovered. This study aimed to screen the main active terpenes and discover the possible mechanism of LEO through network pharmacology in the treatment of insomnia-related diseases, as well as to verify our hypothesis in insomnia mice. The results showed that, in LEO’s 15 potential active ingredients, beta-myrcene had strong sedative–hypnotic effects through the serotonergic synaptic pathway according to the network pharmacological prediction. Further, PCPA(DL-4-chlorophenylalanine)-induced insomnia mice were treated with beta-myrcene for one day or seven days. The quiet state of insomnia mice was increased effectively, and the hypnotic effect was enhanced by anaobarbital sodium by prolonging sleep duration, decreasing sleep latency, and increasing the rate of falling asleep. Beta-myrcene reduced the damage to hypothalamic neuron cells induced by PCPA and increased neurotransmitter levels of GABA, 5-HT, and Glu in the serum and hypothalamus of insomnia mice. Meanwhile, beta-myrcene exerted an improvement in insomnia by upregulating relevant genes and protein expression in the serotonergic synaptic pathway. These results support the merit of the sedative–hypnotic activity of LEO. Beta-myrcene, a terpene in LEO, may be the main source of its sedative–hypnotic properties. It may serve as a good potential compound in future clinical studies on coping with insomnia.
研究领域:
药理学
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神经科学
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医学
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DOI
PubMed
高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2024
·
IF 2.5
Peipei Feng,Jingyi Chen,Xiaolu Chen,Minghui Tang,Ni Song,Lanyue Zhang,Tinggang He
Delayed treatment of insomnia-related symptoms can harm physical health and increase the psychological burden. In addition to oral medications and some physical therapies, aromatherapy can help overcome some treatment-related side effects. Herein, parachlorophenylalanine (PCPA)-induced insomnia was established in Kunming (KM) mice, which were subjected to aromatherapy using five plants ( Jasminum sambac , Magnolia denudata , Rosa rugosa , Aloysia citriodora , and Abies balsamea ) essential oils (EOs). To determine the sleep-inducing effect of the five EOs, the rate of change in body weight, sleep latency, and total sleep time in mice were measured. Specific serum indices were used to evaluate the therapeutic effects of the tested drugs and PCPA modeling. Gas chromatography-mass spectrometry (GC-MS) was employed to identify active components in EOs. The five EOs contained multiple identical constituents and were rich in terpenoids, such as α-farnesene (28.42%), linalool (68.84%), and citronellol (23.78%). The EOs exhibiting varying effects on insomnia-induced weight loss. Nissl staining was used to examine and the number of neurons was elevated in the EO-treated groups when compared with the PCPA-induced group; however, the neuronal number was reduced in the hypothalamic tissues of the R. rugosa EO (RREO)-treated group. All EOs upregulated the expression of 5-HT1A and GABA A Rα1, as demonstrated by immunohistochemistry, western blotting, and reverse transcription-quantitative PCR results. In addition, EOs of A. citriodora and A. balsamea significantly upregulated the expression of 5HT 1A protein, whereas EOs of J. sambac and M. denudata exerted significantly different effects when compared with the model group, as determined by western blotting.
研究领域:
神经科学
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药理学
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植物化学
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2025
·
IF 4.3
Jia Honglin,Liang Zhengting,Yan Deqi,Chen Xu,Liang Ruining,Wu Jinhong,Zhang Xingping
Insomnia is a common sleep disorder worldwide, and oxidative stress and mitochondrial damage are closely related to insomnia. This study aimed to investigate the mechanism by which senegenin exerts neuroprotective effects in regulating oxidative stress and mitochondrial damage in insomnia. In vivo, EEG/EMG analysis confirmed the successful establishment of insomnia rat models; Nissl and HE staining and electron microscopy were used to evaluate the pathological changes of neurons and mitochondria in rat brain tissue. The expression of oxidative stress and sleep factors was assessed. In vitro, an oxidative damage cell model was established to measure oxidative stress–related parameters; the protective concentration of senegenin against oxidative damage was determined using the CCK-8 assay, and the effects of senegenin on the expression of Keap1/Nrf2 and PINK1/Parkin, key signaling pathways involved in oxidative stress and mitochondrial damage, were analyzed. During insomnia, wake is prolonged, and NREM and REM are shortened; learning memory and exploration behavior are impaired, oxidative stress factor expression is changed, and mitochondria are damaged. Brain tissue from insomnia rats showed decreased BDNF, 5-HT1A, GABA-T, and GAD and increased expression of 5-HT2A and Glu. Keap1, PINK1, Parkin, and LC3 expression increased and Nrf2, NQO1, HO-1, and p62 expression decreased in oxidatively injured cells. Senegenin showed a dose–response regulatory effect after the intervention. Senegenin may exert neuroprotective effects in insomnia by improving oxidative stress and mitochondrial damage.
研究领域:
神经生物学
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药理学
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细胞生物学
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睡眠医学
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产品关联
DOI
PubMed
高影响因子
Micromachines
·
2022
·Vol. 13
·期 3
·488
·
IF 3.523
Yun Wang,Mixia Wang,Yuchuan Dai,Yilin Song,Yiding Wang,Botao Lu,Yinghui Li,Xinxia Cai
Research on the intracerebral mechanism of insomnia induced by serotonin (5-HT) deficiency is indispensable. In order to explore the effect of 5-HT deficiency-induced insomnia on brain regions related to memory in rats, we designed and fabricated a microelectrode array that simultaneously detects the electrical activity of the dorsal raphe nucleus (DRN) and hippocampus in normal, insomnia and recovery rats in vivo. In the DRN and hippocampus of insomnia rats, our results showed that the spike amplitudes decreased by 40.16 and 57.92%, the spike repolarization slope decreased by 44.64 and 48.59%, and the spiking rate increased by 66.81 and 63.40%. On a mesoscopic scale, the increased firing rates of individual neurons led to an increased δ wave power. In the DRN and hippocampus of insomnia rats, the δ wave power increased by 57.57 and 67.75%. Furthermore, two segments’ δ wave slopes were also increased in two brain regions of the insomnia rats. Our findings suggest that 5-HT deficiency causes the hyperactivity of neurons in the hippocampus and DRN; the DRN’s firing rate and the hippocampal neuronal amplitude reflect insomnia in rats more effectively. Further studies on alleviating neurons affected by 5-HT deficiency and on achieving a highly effective treatment for insomnia by the microelectrode array are needed.Keywords:microelectrode array;insomnia;electrophysiology;dorsal raphe nucleus;serotonin
研究领域:
神经科学
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电生理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
NEUROMOLECULAR MEDICINE
·
2025
·Vol. 27
·期 1
·1-14
·
IF 3.9
Wang Yiming,Chen Yifei,Yang Jianbo,Sun Wei,Zhang Xiaoning
Post-stroke insomnia (PSI) is a common complication following stroke, which seriously affects patients’ life quality. Electro-acupuncture (EA) is an innovative form of traditional Chinese acupuncture that combines electricity with needles to achieve the prevention and treatment of diseases. However, there is limited understanding regarding the treatment mechanism of EA in PSI. In our study, we aimed to investigate the role of EA on PSI development. Our study findings indicated that the quality of sleep, levels of neurotransmitters 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (γ-GABA), and antioxidant levels showed significant improvement following EA treatment in PSI clinical samples and rat models, while the levels of pro-inflammatory factor interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and astrocyte damage were notably reduced. Furthermore, it was discovered that the levels of sirtuin 1 (Sirt1) were reduced in PSI, a condition that was significantly ameliorated by EA treatment. Additionally, the inhibition of Sirt1 caused a marked elevation in astrocyte apoptosis, inflammatory response, and oxidative stress. Besides, the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway was deactivated in the PSI rat model and Sirt1-silenced cells. However, the suppressive impact was successfully counteracted by EA or estazolam (ES), and the overexpression of Nrf2 partially alleviated the increase in apoptosis, inflammation, and oxidative stress caused by Sirt1 knockdown. Taken together, these findings indicated that EA improved sleep quality and silenced Sirt1-induced apoptosis, inflammation, and oxidative stress in PSI by activating the Nrf2-ARE pathway.
研究领域:
神经科学
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中医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2025
·
IF 3.7
Zhen Zhang,Xinyue Che,Tingyu Feng,Juntao Zou,Guangpei Chen,Wenping Guo,Chunmei Ma,Haozhe Yuan,Jingying Chen,Xiaowu Xu
Objective Jujuboside A (JB-A) is the major component of Semen Ziziphi Spinosae (SZS), a traditional Chinese herbal medicine used to treat sleep with clinical efficacy. This is the first study to investigate the effects of JB-A on mitochondrial structure and function in the prefrontal cortex of the insomnia model mice. Methods Young adult C57BL/6 mice were induced to develop insomnia by P-chlorophenylalanine. After 14 d of JB-A treatment via gavage, anxiety level was assessed using the open field and elevated plus maze tests. Next, the mitochondrial metabolic activity and morphological changes in the prefrontal cortex of each group of mice, as well as their effects on mitochondrial membrane potential, oxidative phosphorylation levels, and cytochrome c (Cyt c) content in neurons were measured. Results In our mouse model, JB-A ameliorated anxiety-like behaviors; up-regulated the membrane potential (Δψm) and had a therapeutic effect on the metabolic activity and damaged microscopic structure of mitochondria in the prefrontal cortex; effectively improved mitochondrial function by increasing the expression of Cyt c oxidase I and IV proteins, ATPase activity, and ATP content; and reduced the accumulation of Cyt c in the neuronal cytoplasm while inhibiting mitochondrial permeability transition pore (mPTP) opening. Conclusions JB-A can improve insomnia by restoring mitochondrial intracellular oxidative phosphorylation, regulating mPTP to maintain mitochondrial homeostasis, and alleviating structural damage, providing a scientific basis for finding new targets for insomnia treatment.
研究领域:
神经科学
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药理学
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传统中医研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2022
·Vol. 45
·期 18
·3431-3442
·
IF 3.614
Zhe Chen,Guangli Yan,Yu Yang,Hui Sun,Aihua Zhang,Ying Han,Shugui Wang,Xijun Wang
Naoling Pian is a prescription composed of 15 herbs, which is mainly used for the treatment of insomnia in clinical practice. However, the chemical constituents in Naoling Pian are numerous and unclear, which hinders the interpretation of its bioactive constituents and the subsequent research on the material basis for pharmacodynamics. The purpose of this study is to develop a rapid method for identifying the chemical constituents of Naoling Pian using high-throughput ultra-performance liquid chromatography quadrupole time of flight coupled with mass spectrometry combined with a software platform for data processing. The whole composition of Naoling Pian was characterized in positive and negative ion modes. In this experiment, an overall total of 201 constituents were identified by using reference standards, online and self-built databases matching, fragmentation rules analysis of mass spectrometry peaks with a software platform. Meanwhile, Naoling Pian was analyzed for the first time using liquid chromatography–mass spectrometry method, the constituents could be identified in a quick and accurate manner, and the results could provide a scientific basis for the follow-up research on the pharmacodynamic material basis and quality control of Naoling Pian.
研究领域:
药理学
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分析化学
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中医药学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Peng Yu,Xu Zhang,Guohui Cheng,Haizhen Guo,Xiaoen Shi,Xinlu Zhang,Jun Zhou,Sheng Wang,Zhenggang Wu,Jin Chang
Insomnia is a severe sleep problem that people in the current society widely face. In clinic, zaleplon is a commonly used drug for insomnia treatment. However, short half-life, poor sleep maintenance effect and low oral utilization rate of zaleplon seriously limit its treatment outcome. Here, we report a nasal gel drug delivery system by using single-walled carbon nanotubes as carriers. Besides the certain neuroprotective effect of single-walled carbon nanotubes, zaleplon loaded on them can effectively improve the drug bioavailability by crossing the blood-brain barrier, appropriately prolonging its effective time and enhance the therapeutic effect. In addition, the carbomer-based gel can extend the residence time of the drug delivery system in the nasal cavity to further enhance absorption efficiency, and its ion responsiveness can prevent nasal obstruction from interfering with normal breathing after sleep. This system improves the shortcomings of zaleplon and increases the effectiveness of the treatment of insomnia by appropriately prolonging the duration of action of the drug. The design of this drug-delivery system provides a new idea for the safe and efficient delivery of insomnia drugs into the brain.
研究领域:
药理学
·
纳米医学
·
神经科学
✓ 已验证
产品关联
DOI
高影响因子
MICROBIOLOGICAL RESEARCH
·
2025
·
IF 6.9
Peifan Li,Ling Yang,Xinyu Shao,Zhi Zou,Hanyu Shi,Yongbing Sun,Xiaoling Wu,Zhonglin Li,Yongli Li,Zuming Li
Insomnia remains a major public health challenge with limited safe treatment options. We demonstrate that mixed probiotics Lactobacillales ( Lactobacillus helveticus L551, Lacticaseibacillus paracasei L578, and Streptococcus thermophilus S709, group P) alleviates insomnia in PCPA-induced mice. P significantly reduced sleep latency and increased sleep duration, while ameliorating anxiety behaviors. The intervention attenuated insomnia-induced colonic structural damage and reactive oxygen species (ROS) accumulation, while restoring hippocampal CA1sp and hypothalamic Nissl body density, as well as normalizing brain glucose metabolism. Crucially, P intervention rebalanced neurotransmitter networks by enhancing serotonin (5-HT) synthesis while suppressing its catabolism, and reducing dopamine (DA) and norepinephrine (NE) levels. The P intervention significantly increased the abundance of Akkermansia and Acinetobacter compared to the insomnia model group (M). Notably, Acinetobacter exhibited significant positive correlations with N-acetylserotonin and gamma-aminobutyric acid (GABA) levels, while showing a significant negative correlation with 5-hydroxyindoleacetic acid (5-HIAA). These findings suggest its potential capacity to modulate tryptophan metabolism. In the M group, Staphylococcus was identified as the signature taxon, showing significant positive correlations with sleep latency and DA levels, and significant negative correlations with sleep duration and serotonin 5-HT levels. P intervention significantly reduced Staphylococcus abundance, concomitant with DA level normalization. In summary, Lactobacillales improve sleep quality and relieve anxiety in insomnia mice via modulating gut microbiota composition, thus regulating tryptophan metabolic pathways and sleep - related neurotransmitters.
研究领域:
微生物学
·
神经科学
·
药理学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Fengjin He,Yanfang Yan,Mei Peng,Ming Gao,Lang Zhou,Faju Chen,Lishou Yang,Liangqun Li,Xiaosheng Yang
BACKGROUND Insomnia, a prevalent sleep disorder, detrimentally affects quality of life and is often challenging to manage with conventional treatments. This study delved into identifying and quantifying the main compounds by employing ultra-performance liquid chromatography–Q-Exactive-Orbitrap mass spectrometry, and further to evaluate the therapeutic potential of Rosa roxburghii folium (RRF) extract, with multiple pharmacological activities. Previous research had hinted at the efficacy of glycosides in influencing the γ -aminobutyric acid (GABAergic) system, which plays a pivotal role in sleep regulation. Utilizing a p -chlorophenylalanine-induced insomnia model in BALB/C mice, this investigation aimed to unravel the effects of various dosages of RRF extract on sleep quality and elucidated its mechanism of action. RESULTS A total of 66 compounds in the RRF extract were analyzed. Behavioral assessments demonstrated notable enhancements in sleep duration and latency. Biochemical analyses further corroborated these findings, revealing modulation in neurotransmitter levels indicative of a potential mechanism through the GABAergic and serotoninergic pathways. Additionally, histological evaluations suggested anti-inflammatory and antioxidant effects of the RRF extract. CONCLUSION The findings from this study underscored the therapeutic efficacy of RRF extract in combating insomnia, particularly highlighting its glycoside components’ role. The extract's significant improvement in sleep duration and latency, alongside its modulation of neurotransmitter levels, showcases its potential as a natural remedy for insomnia. Through its action on the GABAergic and serotoninergic pathways, as well as its anti-inflammatory and antioxidant effects, RRF extract emerges as a promising candidate for insomnia treatment, offering a holistic approach to sleep disorder management. © 2024 Society of Chemical Industry.
研究领域:
药理学
·
神经科学
·
睡眠障碍
·
天然疗法
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Chang Zhou,Yi-fan Hu,Yan Zhang,Cheng-hao Wang,Xue-jing Liao,Fa-feng Cheng,Yan-yan Jiang
Prunella vulgaris L. (P. vulgaris) has great application value and development prospects in improving sleep. In this study, we continued to evaluate the sleep-improvement function and mechanism of P. vulgaris from both chemical characterization and function based on sleep-improvement functional ingredients, rosmarinic acid and salviaflaside, screened out in the previous stage as the index components. The chemical constituents of P. vulgaris and its phenolic acid fraction were characterized by the UPLC-MS n technology. The quality of the sleep-improvement phenolic acid fraction of P. vulgaris was scientifically evaluated by fingerprints combined with quantitative analysis of rosmarinic acid and salviaflaside. The function of phenolic acid parts of P. vulgaris in improving sleep was verified by different insomnia models including the PCPA-induced insomnia model and surface platform sleep deprivation model. HE staining was used to observe the effect of P. vulgaris on the morphology of nerve cells in different brain regions. In vivo experiments and molecular docking explored the sedative-hypnotic effects of functional ingredients of P. vulgaris . All these results investigated the material basis and mechanism of P. vulgaris to improve sleep from multiple perspectives, which contribute to providing a basis for the development of functional food to improve sleep.
研究领域:
药理学
·
化学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Yu Yang,Zhe Chen,Guangli Yan,Ling Kong,Le Yang,Hui Sun,Ying Han,Jie Zhang,Xijun Wang
Insomnia is an accompanying symptom of many diseases and is closely associated with neurodegenerative diseases. Naoling Pian (NLP) is a patented Chinese medicine mainly used to treat insomnia. To evaluate the sedative and hypnotic effects of NLP and its modulatory effects on biological metabolites and metabolic pathways, rats with p-chlorophenylalanine (PCPA)-induced insomnia were given different doses of NLP by oral gavage for seven days. Diazepam (DZP) served as a positive control. Behavior was measured using the open field test, and neurotransmitter levels in the brain tissue related to sleep were measured using ELISA. The metabolic profiles and biomarkers of PCPA-induced insomnia in rats before and after NLP administration were analyzed using UPLC-Q/TOF-MS combined with multivariate data analysis. The results showed that the levels of 5-hydroxytryptamine, gamma-aminobutyric acid, norepinephrine, and dopamine in the brain tissue were significantly recovered in the NLP treatment groups, demonstrating similar or even superior therapeutic effects compared to the DZP group. The behavior of the PCPA-model rats partially recovered to normal levels after seven days of treatment. Metabolomics identified 30 metabolites in the urine as potential biomarkers of insomnia, and NLP significantly altered 25 of these, involving 21 metabolic pathways. NLP has a remarkable effect on insomnia, the therapeutic effects of which may be largely due to the rectification of metabolic disturbances. This is the first study of the sedative and hypnotic effects of NLP from a metabolomic perspective.
研究领域:
药理学
·
神经科学
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代谢组学
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）