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
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.