Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mou...Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.展开更多
Aims:Shangxia Liangji formula(SXLJF)is a traditional Chinese medicine formula used clinically for the treatment of insomnia.However,the exact mechanism of SXLJF remains unclear.Methods and Results:A mouse insomnia mod...Aims:Shangxia Liangji formula(SXLJF)is a traditional Chinese medicine formula used clinically for the treatment of insomnia.However,the exact mechanism of SXLJF remains unclear.Methods and Results:A mouse insomnia model was established by intra-peritoneal injection of p-chlorophenylalanine.Control,model,low/medium/high-dose SXLJF(9.26,18.72,and 37.44 g/kg/day),and diazepam(2 mg/kg)groups were treated with designated reagents for 7 days.Behavioral changes were assessed via open field and pentobarbital-induced sleep tests.Hippo-campal histopathology was evaluated using HE,Nissl,and TUNEL staining.Levels of serotonin(5-HT),5-HIAA,dopamine(DA),norepinephrine(NE),IL-1β,IL-6,and TNF-αwere measured using ELISA.RT-qPCR and immunoflu-orescence were used to analyze glial fibrillary acidic protein(GFAP),neuronal nuclei(NeuN),and brain-derived neurotrophic factor(BDNF)expression.Behavioral tests showed that SXLJF reduced mouse total distance traveled,average velocity,central distance,and sleep latency but increased sleep duration.It also attenuated expression of IL-1β,IL-6,and TNF-α,modulated levels of the monoamine neurotransmitters 5-HT,5-HIAA,NE,and DA,upre-gulated NeuN and BDNF expression,downregulated GFAP expression,inhibited astrocyte activation,and mitigated neuronal apoptosis.Conclusion:The mechanism underlying SXLJF’s anti-insomnia effect may be related to the regulation of monoamine neurotransmitters,inhibition of astro-cyte activation and inflammatory factors,and suppression of neuronal apoptosis.展开更多
基金Science Foundation of Hunan Province(2021JJ40510)General Guidance Project of Hunan Health Commission(202203074169)+1 种基金Clinical Medical Technology Innovation Guidance Project of Hunan Province(2021SK51901)and Key Guiding Projects of Hunan Health Commission(20201918)for supporting this study.
文摘Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.
基金National Key Clinical Specialty Scientific Research Project,Grant/Award Number:Z2023161。
文摘Aims:Shangxia Liangji formula(SXLJF)is a traditional Chinese medicine formula used clinically for the treatment of insomnia.However,the exact mechanism of SXLJF remains unclear.Methods and Results:A mouse insomnia model was established by intra-peritoneal injection of p-chlorophenylalanine.Control,model,low/medium/high-dose SXLJF(9.26,18.72,and 37.44 g/kg/day),and diazepam(2 mg/kg)groups were treated with designated reagents for 7 days.Behavioral changes were assessed via open field and pentobarbital-induced sleep tests.Hippo-campal histopathology was evaluated using HE,Nissl,and TUNEL staining.Levels of serotonin(5-HT),5-HIAA,dopamine(DA),norepinephrine(NE),IL-1β,IL-6,and TNF-αwere measured using ELISA.RT-qPCR and immunoflu-orescence were used to analyze glial fibrillary acidic protein(GFAP),neuronal nuclei(NeuN),and brain-derived neurotrophic factor(BDNF)expression.Behavioral tests showed that SXLJF reduced mouse total distance traveled,average velocity,central distance,and sleep latency but increased sleep duration.It also attenuated expression of IL-1β,IL-6,and TNF-α,modulated levels of the monoamine neurotransmitters 5-HT,5-HIAA,NE,and DA,upre-gulated NeuN and BDNF expression,downregulated GFAP expression,inhibited astrocyte activation,and mitigated neuronal apoptosis.Conclusion:The mechanism underlying SXLJF’s anti-insomnia effect may be related to the regulation of monoamine neurotransmitters,inhibition of astro-cyte activation and inflammatory factors,and suppression of neuronal apoptosis.
