Lily-Ziziphi Spinosae Semen decoction(LZ)is known for its blood nourishing,mind calming,body sedation,and sleep promoting effects in traditional Chinese medicine.However,its material basis and underlying mechanisms ha...Lily-Ziziphi Spinosae Semen decoction(LZ)is known for its blood nourishing,mind calming,body sedation,and sleep promoting effects in traditional Chinese medicine.However,its material basis and underlying mechanisms have not yet been clearly defined.This study applies liquid chromatography-mass spectrometry,network pharmacology,and animal studies to reveal the material basis and sleep-improving mechanisms of LZ.The mixed decoction(LZ-ME)and single decoction(LZ-SE)were prepared to study their chemical components.Network pharmacology was used to predict the sleep-improving targets and signaling pathways of LZ.ICR mice were intragastrically administered saline(NC),melatonin(positive control group,0.50 mg/kg),low(12.90 g/kg),medium(25.70 g/kg),and high(38.60 g/kg)dose of LZ-ME and LZ-SH for 30 days.The results showed that LZ-ME could prolong the sleep duration and shorten the sleep latency in sodium barbiturate induced mice model.The results of chemical composition showed that total polysaccharides,total flavonoids,total saponins,and total alkaloids in LZ-ME were significantly higher than those in LZ-SE(177.20%,82.34%,30.58%,and 11.66%,respectively).A total of 58 chemical components were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS),and 8 representative difference components of LZ-ME and LZ-SE were found.LZ-ME significantly increased tumor necrosis factor-α(TNF-α)in mice serum and neurotransmitterγ-aminobutyric acid(GABA)levels in mice hippocampus,decreased dopamine(DA)and glutamate(Glu)levels in mice hippocampus(P<0.05).Furthermore,LZ-ME up-regulated the abundance of the beneficial bacteria Lactobacillus and Eubacterium_R,down-regulated the abundance of the harmful bacteria Lachnospiraceae etc.The polysaccharides,flavonoids(spinosin and 6‴-feruloylspinosin)and saponins(jujuboside A and jujuboside B)were the main material bases for the sleep-promoting effects of LZ.These compounds may directly enhance levels of the GABA,reduced levels of Glu and DA and improve TNF-αlevels.And they also may indirectly regulate GABA levels by influencing the relative abundance of Lactobacillus and Eubacterium.展开更多
OBJECTIVE:To elucidate the potential mechanisms and identify bioactive components of Suanzaoren(Ziziphi Spinosae Semen)(ZSS)and it's processed products for insomnia treatment.METHODS:The principal components of ZS...OBJECTIVE:To elucidate the potential mechanisms and identify bioactive components of Suanzaoren(Ziziphi Spinosae Semen)(ZSS)and it's processed products for insomnia treatment.METHODS:The principal components of ZSS and its processed products were analyzed using UltraPerformance liquid chromatography quadrupole time-offlight mass spectrometry(UPLC-Q-TOF-MS).The effects of ZSS on insomnia were assessed in parachlorophenylalanine(PCPA)-induced rats.Additionally,to investigate the mechanisms of action in insomnia,serum and hippocampal non-targeted metabolomics were performed alongside network pharmacology and molecular docking.RESULTS:UPLC-Q-TOF-MS was used to analyze the main components of ZSS and its processed products.In the insomnia rat model induced by PCPA,both ZSS and its processed products demonstrated therapeutic effects,with the processed products showing particularly significant effects,significantly increasing the levels of the Gamma-Aminobutyric Acid and melatonin.Non-targeted metabolomics identified 23 and 10 potential differential metabolites in serum and hippocampus,respectively,involving pathways such as lipid metabolism and amino acid metabolism.Network pharmacology identified three core targets,mainly associated with pathways such as Transient Receptor Potential channel regulation,Advanced Glycation End-products-Receptor for Advanced Glycation End-products signaling pathway,and neuroactive ligand-receptor interaction.Molecular docking confirmed that the main active components of ZSS can stably bind to these core targets,thereby exerting an effect in improving insomnia.CONCLUSIONS:Combining in vivo experiments,metabolomics,and network pharmacology,we have identified potential pharmacological mechanisms by which ZSS and its derivatives mitigate insomnia.These findings provide a theoretical foundation for the further development and utilization of ZSS,supporting the innovation of new therapeutic agents for insomnia treatment.展开更多
[Objectives]To explore the effects of Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound on theβ-secretase activity in mice exposed to aluminum maltolate.[Methods]A total of 60 healthy,clea...[Objectives]To explore the effects of Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound on theβ-secretase activity in mice exposed to aluminum maltolate.[Methods]A total of 60 healthy,clean-grade SPF mice were randomly assigned to four groups based on their body weight,with each group consisting of 15 mice.The groups included a control group,a model group,treatment group 1,and treatment group 2.The control group received an equivalent dose of normal saline,while the model group and treatment groups 1 and 2 were intraperitoneally injected with 0.3 mg/kg of aluminum maltolate solution for 60 d.Additionally,treatment groups 1 and 2 were injected with 0.3 mg/kg of Radix Salviae Miltiorrhizae water extract and 0.3 mg/kg of Semen Ziziphi Spinosae compound,respectively,starting from the 31 st day for a total of 30 d.The cognitive functions of mice,specifically their learning and memory capabilities,were assessed using the Y-shaped water maze test at three distinct time points:prior to,during,and following the experimental procedure.Serum samples were collected for the analysis of various biochemical markers,including hemoglobin(Hb),total cholesterol(TC),triglycerides(TG),total protein(TP),alanine aminotransferase(ALT),and blood urea nitrogen(BUN).Additionally,brain tissues were harvested to evaluate the levels of glutathione peroxidase(GSH-PX)and acetylcholinesterase(AChE)in both serum and brain samples.The expression levels ofα-secretase,β-secretase,andγ-secretase in mouse serum were quantified using enzyme-linked immunosorbent assay(ELISA).[Results]According to the final results of the Y-shaped water maze test,the administration of therapeutic drugs to mice resulted in a gradual reduction in both the swimming time and the distance traveled to reach the platform in treatment groups 1 and 2.Additionally,the number of errors made by these treatment groups was significantly greater than that observed in the control group,with statistically significant differences(P<0.01).Among the three groups subjected to subchronic aluminum exposure,statistically significant differences were observed in the levels of Hb,TC,TG,TP,ALT,BUN,brain GSH-PX,and brain AChE(P<0.05).Furthermore,with the increasing duration of therapeutic drug administration,the levels ofβ-secretase in the brains of mice in both the treatment groups and the model group exhibited a significant decrease,while the levels ofα-secretase showed a significant increase.Additionally,the differences were statistically significant when compared to the control group(P<0.05).[Conclusions]Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound will decrease the expression level ofβ-secretase activity in mice exposed to aluminum maltolate.展开更多
基金supported by the Province Natural Science Foundation of Hunan,China(2022JJ50048)Hunan Agriculture Research System(HARS-11).
文摘Lily-Ziziphi Spinosae Semen decoction(LZ)is known for its blood nourishing,mind calming,body sedation,and sleep promoting effects in traditional Chinese medicine.However,its material basis and underlying mechanisms have not yet been clearly defined.This study applies liquid chromatography-mass spectrometry,network pharmacology,and animal studies to reveal the material basis and sleep-improving mechanisms of LZ.The mixed decoction(LZ-ME)and single decoction(LZ-SE)were prepared to study their chemical components.Network pharmacology was used to predict the sleep-improving targets and signaling pathways of LZ.ICR mice were intragastrically administered saline(NC),melatonin(positive control group,0.50 mg/kg),low(12.90 g/kg),medium(25.70 g/kg),and high(38.60 g/kg)dose of LZ-ME and LZ-SH for 30 days.The results showed that LZ-ME could prolong the sleep duration and shorten the sleep latency in sodium barbiturate induced mice model.The results of chemical composition showed that total polysaccharides,total flavonoids,total saponins,and total alkaloids in LZ-ME were significantly higher than those in LZ-SE(177.20%,82.34%,30.58%,and 11.66%,respectively).A total of 58 chemical components were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS),and 8 representative difference components of LZ-ME and LZ-SE were found.LZ-ME significantly increased tumor necrosis factor-α(TNF-α)in mice serum and neurotransmitterγ-aminobutyric acid(GABA)levels in mice hippocampus,decreased dopamine(DA)and glutamate(Glu)levels in mice hippocampus(P<0.05).Furthermore,LZ-ME up-regulated the abundance of the beneficial bacteria Lactobacillus and Eubacterium_R,down-regulated the abundance of the harmful bacteria Lachnospiraceae etc.The polysaccharides,flavonoids(spinosin and 6‴-feruloylspinosin)and saponins(jujuboside A and jujuboside B)were the main material bases for the sleep-promoting effects of LZ.These compounds may directly enhance levels of the GABA,reduced levels of Glu and DA and improve TNF-αlevels.And they also may indirectly regulate GABA levels by influencing the relative abundance of Lactobacillus and Eubacterium.
文摘OBJECTIVE:To elucidate the potential mechanisms and identify bioactive components of Suanzaoren(Ziziphi Spinosae Semen)(ZSS)and it's processed products for insomnia treatment.METHODS:The principal components of ZSS and its processed products were analyzed using UltraPerformance liquid chromatography quadrupole time-offlight mass spectrometry(UPLC-Q-TOF-MS).The effects of ZSS on insomnia were assessed in parachlorophenylalanine(PCPA)-induced rats.Additionally,to investigate the mechanisms of action in insomnia,serum and hippocampal non-targeted metabolomics were performed alongside network pharmacology and molecular docking.RESULTS:UPLC-Q-TOF-MS was used to analyze the main components of ZSS and its processed products.In the insomnia rat model induced by PCPA,both ZSS and its processed products demonstrated therapeutic effects,with the processed products showing particularly significant effects,significantly increasing the levels of the Gamma-Aminobutyric Acid and melatonin.Non-targeted metabolomics identified 23 and 10 potential differential metabolites in serum and hippocampus,respectively,involving pathways such as lipid metabolism and amino acid metabolism.Network pharmacology identified three core targets,mainly associated with pathways such as Transient Receptor Potential channel regulation,Advanced Glycation End-products-Receptor for Advanced Glycation End-products signaling pathway,and neuroactive ligand-receptor interaction.Molecular docking confirmed that the main active components of ZSS can stably bind to these core targets,thereby exerting an effect in improving insomnia.CONCLUSIONS:Combining in vivo experiments,metabolomics,and network pharmacology,we have identified potential pharmacological mechanisms by which ZSS and its derivatives mitigate insomnia.These findings provide a theoretical foundation for the further development and utilization of ZSS,supporting the innovation of new therapeutic agents for insomnia treatment.
基金Supported by Undergraduate Innovation and Entrepreneurship Training Program(202410599042).
文摘[Objectives]To explore the effects of Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound on theβ-secretase activity in mice exposed to aluminum maltolate.[Methods]A total of 60 healthy,clean-grade SPF mice were randomly assigned to four groups based on their body weight,with each group consisting of 15 mice.The groups included a control group,a model group,treatment group 1,and treatment group 2.The control group received an equivalent dose of normal saline,while the model group and treatment groups 1 and 2 were intraperitoneally injected with 0.3 mg/kg of aluminum maltolate solution for 60 d.Additionally,treatment groups 1 and 2 were injected with 0.3 mg/kg of Radix Salviae Miltiorrhizae water extract and 0.3 mg/kg of Semen Ziziphi Spinosae compound,respectively,starting from the 31 st day for a total of 30 d.The cognitive functions of mice,specifically their learning and memory capabilities,were assessed using the Y-shaped water maze test at three distinct time points:prior to,during,and following the experimental procedure.Serum samples were collected for the analysis of various biochemical markers,including hemoglobin(Hb),total cholesterol(TC),triglycerides(TG),total protein(TP),alanine aminotransferase(ALT),and blood urea nitrogen(BUN).Additionally,brain tissues were harvested to evaluate the levels of glutathione peroxidase(GSH-PX)and acetylcholinesterase(AChE)in both serum and brain samples.The expression levels ofα-secretase,β-secretase,andγ-secretase in mouse serum were quantified using enzyme-linked immunosorbent assay(ELISA).[Results]According to the final results of the Y-shaped water maze test,the administration of therapeutic drugs to mice resulted in a gradual reduction in both the swimming time and the distance traveled to reach the platform in treatment groups 1 and 2.Additionally,the number of errors made by these treatment groups was significantly greater than that observed in the control group,with statistically significant differences(P<0.01).Among the three groups subjected to subchronic aluminum exposure,statistically significant differences were observed in the levels of Hb,TC,TG,TP,ALT,BUN,brain GSH-PX,and brain AChE(P<0.05).Furthermore,with the increasing duration of therapeutic drug administration,the levels ofβ-secretase in the brains of mice in both the treatment groups and the model group exhibited a significant decrease,while the levels ofα-secretase showed a significant increase.Additionally,the differences were statistically significant when compared to the control group(P<0.05).[Conclusions]Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound will decrease the expression level ofβ-secretase activity in mice exposed to aluminum maltolate.
