BACKGROUND Insomnia is closely associated with anxiety and depression,with its pathogenesis involving biological,psychological,and social factors.Sini powder and Suanzaoren decoction are clinically effective tradition...BACKGROUND Insomnia is closely associated with anxiety and depression,with its pathogenesis involving biological,psychological,and social factors.Sini powder and Suanzaoren decoction are clinically effective traditional Chinese medicine formulas for insomnia,demonstrating promising bioactivity.However,the capability of the active components of Sini-Suanzaoren decoction(SNSZRD)to cross the bloodbrain barrier(BBB)and their precise molecular mechanisms,particularly concerning the MT-SIRT1 pathway and mitochondrial function,remain largely unexplored.AIM To elucidate the bioactive components of SNSZRD that are capable of BBB penetration and investigate the therapeutic mechanism of SNSZRD against insomnia.METHODS The chemical components of SNSZRD were analyzed through liquid chromatography-mass spectrometry(LC-MS).Male Sprague-Dawley rats were intraperitoneally injected with DL-4-chlorophenylalanine(PCPA)to establish an insomnia model.Rats were divided into control,model,eszopiclone(positive control),and SNSZRD low-/medium-/high-dose groups.Molecular docking predicted BBBpenetrating components and their binding affinity for SIRT1.Key pathways were analyzed through open-field tests,elevated plus-maze tests,pentobarbital-induced sleep experiments,Haematoxylin and eosin staining,Nissl staining,ELISA,Western blot analysis,quantitative real-time PCR,and immunohistochemistry.RESULTS LC-MS identified 1574 compounds in SNSZRD,of which eight prototype components(e.g.,pachymic acid and senkyunolide G)could cross the BBB.Molecular docking revealed that these components formed stable hydrogen bonds with the SIRT1 protein.SNSZRD treatment significantly ameliorated PCPA-induced anxiety-like behaviors and sleep latency/sleep duration,as well as reduced neuronal degeneration and Nissl body loss in the hypothalamus of treated rats.Additionally,SNSZRD elevated serum melatonin and hypothalamus ATP levels and upregulated the mRNA and protein expression levels of arylalkylamine N-acetyltransferase,SIRT1,PPARγcoactivator-1α,nuclear respiratory factor-1,and mitochondrial transcription factor A in the MT-SIRT1-mitochondrial biogenesis pathway.CONCLUSION SNSZRD might exert its therapeutic effects on insomnia by modulating MT-SIRT1 axis-regulated mitochondrial biogenesis in rats and might serve as an effective therapeutic agent for insomnia.展开更多
Objective:The pharmacokinetics and relative bioavailability of Jiaotai pill self-microemulsion were evaluated by investigating the blood concentration of Berberine,Coptisine,Palmatine and Jatrorrhizine in insomnia rat...Objective:The pharmacokinetics and relative bioavailability of Jiaotai pill self-microemulsion were evaluated by investigating the blood concentration of Berberine,Coptisine,Palmatine and Jatrorrhizine in insomnia rats.Methods:Insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine(PCPA).The model rats were given Jiaotai pill self-microemulsion and Jiaotai pill suspension.The contents of Berberine,Coptisine,Palmatine and Jatrorrhizine in plasma at different times after administration were determined by UPLC-MS/MS,and calculate pharmacokinetic parameters.Results:Under the set chromatographic conditions,the linear relationship of the four components was good,and the precision,accuracy and stability meet the requirements of biological samples.After intragastric administration of Jiaotai pill self-microemulsion,The C_(max) of Berberine,Coptisine,Palmatine and Jatrorrhizine were(412.68±28.45),(68.65±3.92),(34.06±3.13),(40.60±1.22)ng/mL,and AUC_(0-∞)were(672.70±72.55),(146.04±25.01),(71.49±18.67),(72.25±9.54)ng·mL^(-1)·h^(-1),respectively.Compared with Jiaotai pill suspension,the Cmax,AUC_(0-t) and AUC_(0-∞)of the four components in insomnia rats were significantly increased(P<0.01).Conclusion:Jiaotai pill self-microemulsionl can promote the absorption of effective components in insomnia rats and improve its bioavailability.展开更多
基金Supported by the Beijing Natural Science Foundation,No.7232289.
文摘BACKGROUND Insomnia is closely associated with anxiety and depression,with its pathogenesis involving biological,psychological,and social factors.Sini powder and Suanzaoren decoction are clinically effective traditional Chinese medicine formulas for insomnia,demonstrating promising bioactivity.However,the capability of the active components of Sini-Suanzaoren decoction(SNSZRD)to cross the bloodbrain barrier(BBB)and their precise molecular mechanisms,particularly concerning the MT-SIRT1 pathway and mitochondrial function,remain largely unexplored.AIM To elucidate the bioactive components of SNSZRD that are capable of BBB penetration and investigate the therapeutic mechanism of SNSZRD against insomnia.METHODS The chemical components of SNSZRD were analyzed through liquid chromatography-mass spectrometry(LC-MS).Male Sprague-Dawley rats were intraperitoneally injected with DL-4-chlorophenylalanine(PCPA)to establish an insomnia model.Rats were divided into control,model,eszopiclone(positive control),and SNSZRD low-/medium-/high-dose groups.Molecular docking predicted BBBpenetrating components and their binding affinity for SIRT1.Key pathways were analyzed through open-field tests,elevated plus-maze tests,pentobarbital-induced sleep experiments,Haematoxylin and eosin staining,Nissl staining,ELISA,Western blot analysis,quantitative real-time PCR,and immunohistochemistry.RESULTS LC-MS identified 1574 compounds in SNSZRD,of which eight prototype components(e.g.,pachymic acid and senkyunolide G)could cross the BBB.Molecular docking revealed that these components formed stable hydrogen bonds with the SIRT1 protein.SNSZRD treatment significantly ameliorated PCPA-induced anxiety-like behaviors and sleep latency/sleep duration,as well as reduced neuronal degeneration and Nissl body loss in the hypothalamus of treated rats.Additionally,SNSZRD elevated serum melatonin and hypothalamus ATP levels and upregulated the mRNA and protein expression levels of arylalkylamine N-acetyltransferase,SIRT1,PPARγcoactivator-1α,nuclear respiratory factor-1,and mitochondrial transcription factor A in the MT-SIRT1-mitochondrial biogenesis pathway.CONCLUSION SNSZRD might exert its therapeutic effects on insomnia by modulating MT-SIRT1 axis-regulated mitochondrial biogenesis in rats and might serve as an effective therapeutic agent for insomnia.
基金Scientific Research Project of Heilongjiang Provincial Health Commission(No.2018-482)Excellent Discipline Team Project of Jiamusi University(No.JDXKTD-2019005)。
文摘Objective:The pharmacokinetics and relative bioavailability of Jiaotai pill self-microemulsion were evaluated by investigating the blood concentration of Berberine,Coptisine,Palmatine and Jatrorrhizine in insomnia rats.Methods:Insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine(PCPA).The model rats were given Jiaotai pill self-microemulsion and Jiaotai pill suspension.The contents of Berberine,Coptisine,Palmatine and Jatrorrhizine in plasma at different times after administration were determined by UPLC-MS/MS,and calculate pharmacokinetic parameters.Results:Under the set chromatographic conditions,the linear relationship of the four components was good,and the precision,accuracy and stability meet the requirements of biological samples.After intragastric administration of Jiaotai pill self-microemulsion,The C_(max) of Berberine,Coptisine,Palmatine and Jatrorrhizine were(412.68±28.45),(68.65±3.92),(34.06±3.13),(40.60±1.22)ng/mL,and AUC_(0-∞)were(672.70±72.55),(146.04±25.01),(71.49±18.67),(72.25±9.54)ng·mL^(-1)·h^(-1),respectively.Compared with Jiaotai pill suspension,the Cmax,AUC_(0-t) and AUC_(0-∞)of the four components in insomnia rats were significantly increased(P<0.01).Conclusion:Jiaotai pill self-microemulsionl can promote the absorption of effective components in insomnia rats and improve its bioavailability.
