Semen Platycladi(SP)is the dried ripe kernel of Platycladus orientalis(L.)Franco,has been used for insomnia treatment for bimillennium in China,which mechanism is not fully understood.The aim of this study was to expl...Semen Platycladi(SP)is the dried ripe kernel of Platycladus orientalis(L.)Franco,has been used for insomnia treatment for bimillennium in China,which mechanism is not fully understood.The aim of this study was to explore the sleep-promoting mechanism of essential oil and saponins from SP.As 2 main bioactive constituents of SP,essential oil(SPO)and saponin(SPS)were extracted,then was given to p-chlorophenylalanine(PCPA)-induced insomnia mice by intragastric administration.Then,the behavioral tests,neurotransmitter receptors,cytokines and hormone in brain were investigated.Behavior test showed that SPO and SPS exhibited sleep-enhancing effect through suppressing depression,shortening the onset time while prolonging the sleep duration in insomnia mice.Also SPO and SPS up-regulated serotonin(5-HT)receptors in serotonergic neurons,increased glutamic acid decarboxylase(GAD)content in GABAergic neurons,and stimulatedγ-aminobutyric acid(GABA)receptors expression to enhance the synaptic inhibition.Moreover,they could down-regulated the cytokines and rebalanced hormone expressions.Although both SPO and SPS exerted sleep-promoting,they had different focusing targets.SPS had stronger effect on neurotransmitter receptors regulation while SPO had better hormone rebalanced ability.Briefly,SPO and SPS exerted sedative-hypnotic effect in insomnia mice through modulating multi-targets in serotonergic and GABAergic system.展开更多
Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess antiinsomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein...Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess antiinsomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine Nmethyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.展开更多
Insomnia affects a large portion of the global population,and the long-term use of conventional hypnotics poses risks such as tolerance and cognitive impairment.As a safer alternative,this study evaluated the hypnotic...Insomnia affects a large portion of the global population,and the long-term use of conventional hypnotics poses risks such as tolerance and cognitive impairment.As a safer alternative,this study evaluated the hypnotic effects and underlying pathways of a standardized Gracilariopsis chorda supplement(SGCS),a red seaweed-derived product developed for functional food use.To investigate these effects,we employed a pentobarbital-induced sleep model and electroencephalogram/electromyogram-based polysomnographic analysis in mice,through which SGCS was found to significantly reduce sleep latency and elevate non-rapid eye movement sleep.Notably,delta activity remained unchanged,suggesting that sleep quality was maintained.Co-administration experiments with receptor-specific antagonists revealed that the hypnotic effects of SGCS were blocked by the adenosine A1 receptor(A1R)antagonist cyclopentyl-1,3-dipropylxanthine,but not by the GABAA receptor antagonist(+)-bicuculline.Subsequent binding and functional assays confirmed SGCS as an A1R agonist with notable affinity(IC_(50)=0.12 mg/mL)and efficacy(EC_(50)=0.0775 mg/mL).Solvent fractionation and total phenolic content(TPC)analysis identified the ethyl acetate fraction as the most potent,with hypnotic activity positively correlating with TPC(R2=0.7436).These findings suggest that SGCS enhances sleep primarily via A1R activation and that polyphenols may be key contributors to its sleep-promoting effect.Altogether,this study highlights the therapeutic potential of red seaweed-derived SGCS as a natural sleep aid and supports its development as a functional food or nutraceutical for managing insomnia and improving sleep quality.展开更多
The first-night effect(FNE)is a prevalent occurrence in sleep monitoring that can impact the accuracy of monitoring results,encompassing both FNE and reverse first-night effect.FNE is characterized by extended sleep o...The first-night effect(FNE)is a prevalent occurrence in sleep monitoring that can impact the accuracy of monitoring results,encompassing both FNE and reverse first-night effect.FNE is characterized by extended sleep onset la-tency,reduced total sleep time,diminished sleep efficiency,prolonged wake-time after sleep onset,among other manifestations.The physiological and psychological mechanisms underlying FNE are primarily linked to acute stress induced by the environment and heightened levels of anxiety,involving the default mode network.FNE exhibits varying manifestations and impacts across individuals of different age groups and genetic predispositions.We also discuss the influence of placebo and sedative-hypnotics on FNE.Under-standing these factors is crucial for guiding clinicians and technologists in standardizing polysomnography(PSG)practices and improving the accuracy of sleep disorder diagnoses.展开更多
基金supported by the National Natural Science Foundation of China(31871778,31801468,and 32072201)Foshan Social Field Technology R&D Special Program(2120001008478)+1 种基金Science and Technology Program of Guangzhou,China(202201011762)State Key Laboratory of Dampness Syndrome of Chinese Medicine,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(SZ2024KF05)。
文摘Semen Platycladi(SP)is the dried ripe kernel of Platycladus orientalis(L.)Franco,has been used for insomnia treatment for bimillennium in China,which mechanism is not fully understood.The aim of this study was to explore the sleep-promoting mechanism of essential oil and saponins from SP.As 2 main bioactive constituents of SP,essential oil(SPO)and saponin(SPS)were extracted,then was given to p-chlorophenylalanine(PCPA)-induced insomnia mice by intragastric administration.Then,the behavioral tests,neurotransmitter receptors,cytokines and hormone in brain were investigated.Behavior test showed that SPO and SPS exhibited sleep-enhancing effect through suppressing depression,shortening the onset time while prolonging the sleep duration in insomnia mice.Also SPO and SPS up-regulated serotonin(5-HT)receptors in serotonergic neurons,increased glutamic acid decarboxylase(GAD)content in GABAergic neurons,and stimulatedγ-aminobutyric acid(GABA)receptors expression to enhance the synaptic inhibition.Moreover,they could down-regulated the cytokines and rebalanced hormone expressions.Although both SPO and SPS exerted sleep-promoting,they had different focusing targets.SPS had stronger effect on neurotransmitter receptors regulation while SPO had better hormone rebalanced ability.Briefly,SPO and SPS exerted sedative-hypnotic effect in insomnia mice through modulating multi-targets in serotonergic and GABAergic system.
基金support from the National Key R&D Program of China(Grant No:2022YFC3401003)the National Natural Science Foundation of China(Grant No:21927808)+2 种基金the National Natural Science Foundation of China(Grant No:22104160)the National Key Research and Development Program of China(Grant No:2017YFC1704006)the Innovation Team of Ethnomedicine of National Ethnic Affairs Commission,China.We thank all the research staff who contributed to the study.
文摘Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess antiinsomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine Nmethyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.
基金supported by Korea Institute of Marine Science&Technology Promotion(KIMST)funded by the Ministry of Oceans and Fisheries,Korea(RS-2022-KS221637).
文摘Insomnia affects a large portion of the global population,and the long-term use of conventional hypnotics poses risks such as tolerance and cognitive impairment.As a safer alternative,this study evaluated the hypnotic effects and underlying pathways of a standardized Gracilariopsis chorda supplement(SGCS),a red seaweed-derived product developed for functional food use.To investigate these effects,we employed a pentobarbital-induced sleep model and electroencephalogram/electromyogram-based polysomnographic analysis in mice,through which SGCS was found to significantly reduce sleep latency and elevate non-rapid eye movement sleep.Notably,delta activity remained unchanged,suggesting that sleep quality was maintained.Co-administration experiments with receptor-specific antagonists revealed that the hypnotic effects of SGCS were blocked by the adenosine A1 receptor(A1R)antagonist cyclopentyl-1,3-dipropylxanthine,but not by the GABAA receptor antagonist(+)-bicuculline.Subsequent binding and functional assays confirmed SGCS as an A1R agonist with notable affinity(IC_(50)=0.12 mg/mL)and efficacy(EC_(50)=0.0775 mg/mL).Solvent fractionation and total phenolic content(TPC)analysis identified the ethyl acetate fraction as the most potent,with hypnotic activity positively correlating with TPC(R2=0.7436).These findings suggest that SGCS enhances sleep primarily via A1R activation and that polyphenols may be key contributors to its sleep-promoting effect.Altogether,this study highlights the therapeutic potential of red seaweed-derived SGCS as a natural sleep aid and supports its development as a functional food or nutraceutical for managing insomnia and improving sleep quality.
文摘The first-night effect(FNE)is a prevalent occurrence in sleep monitoring that can impact the accuracy of monitoring results,encompassing both FNE and reverse first-night effect.FNE is characterized by extended sleep onset la-tency,reduced total sleep time,diminished sleep efficiency,prolonged wake-time after sleep onset,among other manifestations.The physiological and psychological mechanisms underlying FNE are primarily linked to acute stress induced by the environment and heightened levels of anxiety,involving the default mode network.FNE exhibits varying manifestations and impacts across individuals of different age groups and genetic predispositions.We also discuss the influence of placebo and sedative-hypnotics on FNE.Under-standing these factors is crucial for guiding clinicians and technologists in standardizing polysomnography(PSG)practices and improving the accuracy of sleep disorder diagnoses.
