Eight new cyclopyrrolone compounds were synthesized according to the structure activity relationship and action mechanism of Zopiclone, a cyclopyrrolone hypnotic. Their preliminary pharmacodynamics are under investig...Eight new cyclopyrrolone compounds were synthesized according to the structure activity relationship and action mechanism of Zopiclone, a cyclopyrrolone hypnotic. Their preliminary pharmacodynamics are under investigation.展开更多
OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy.According to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investiga...OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy.According to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investigated the anti-inflammatory ingredients of licorice,but for the potency of flavonoid glycoside and their aglycones on inflammation are not evaluated.This study was designed to assess the contributions of licorice flavonoid glycosides and their aglycons to its anti-inflammatory and hypnotic effects.METHODS For the flavonoid aglycone's enrichment,the extract of licorice(EL)was fermented in submerged culture of the edible fungus Grifola frondosa HB0071 mycelia which can produce β-glucosidase and catalyze the flavonoid glycosides to aglycones.EL and fermented extract of licorice(FEL) were used in this study.The anti-inflammation test was carried out in arachidonic acid(AA)-induced ear edema model and the hypnotic test was performed by using electroencephalogram(EEG) analysis method in normal freely moving SD rats.The chemicals constituents were analyzed by HPLC.RESULTS During fermentation,the falvonoid glycosides of licorice were hydrolyzed by the time process.Along with fermentation time,the concentration of the major flavonoid glycosides,liquiritin and isoliquiritin were decreased obviously,and simultaneously their aglycons,liquiritigenin and isoliquiriti.genin were remarkably increased in FEL.Moreover,the content of another major constituent glycyrrhi.zic acid and glycyrrhetinic acid were not changed after the fermentation.In AA-induced mice ear ede.ma test,after topical application,FEL(effective dose range:5-20 μg·ear-1) showed more potent inhibito.ry activity than EL(effective dose range:25-100 μg·ear-1).On the other hand,oral administration of EL and FEL exhibited the same hypnotic potency and both enhanced the total sleep time including rapid eye movement(REM) sleep and non-REM sleep time.CONCLUSION These results suggested that the enrichment of flavonoid aglycons such as liquiritigenin and isoliquiritigenin enhanced the anti-inflam.matory potency of licorice extract,and this potentiation has nothing to do with glycyrrhizic acid or glycyr.rhetinic acid.In addition,enrichment of flavonoid aglycones did not alter the hypnotic effect of licorice.展开更多
On the basis of the Zaleplon structure, novel pyrazolo[l,5-a]pyrimidines were designed and prepared for studies on their hypnotic activity. This paper reported the synthesis of twelve new 5-methyl-7-substituted-pyrazo...On the basis of the Zaleplon structure, novel pyrazolo[l,5-a]pyrimidines were designed and prepared for studies on their hypnotic activity. This paper reported the synthesis of twelve new 5-methyl-7-substituted-pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives by using simple starting materials such as propane dinitrile and triethyl orthoformate. The structures of the derived target compounds were confirmed by their IR and 1H-NMR spectroscopic data. The preliminary pharmacological evaluations indicated that some compounds showed hypnotic activity, while derivative 1c was the most polent one.展开更多
With a small-dose remifentanil, some patients showed no reaction and did not remember it postoperatively. We, therefore, hypothesized that remifentanil may decrease the level of consciousness and/or exhibit amnesic ef...With a small-dose remifentanil, some patients showed no reaction and did not remember it postoperatively. We, therefore, hypothesized that remifentanil may decrease the level of consciousness and/or exhibit amnesic effect when stimulations are avoided. Thirty-patients were divided into two groups: non-stimulation group and stimulation group. Anesthesia was induced with 1 micro-g·kg?1·min?1 of remifentanil using no additional hypnotic agent. In the non-stimulation group, patients were left free from any stimulation except non-invasive blood pressure monitoring. In the stimulation group, patients were asked to follow verbal commands. The level of consciousness was evaluated with electroencephalogram and BIS-value derived from it. In the non-stimulation group, all patients reached the decreased level of consciousness in 5 minutes. In the stimulation group, however, 14 patients were judged to be still conscious. 10 patients could open their mouth at the 5th minute, but 9 of these 10 patients did not remember it postoperatively. In conclusion, remifentanil, with no additional anesthetics, exhibited hypnotic and amnesic effects when stimulations were kept minimal.展开更多
Aim. To statistic the usage of hypnotics and sedatives in outpatient and emergency clinics prescriptions in one day. Method. Check all prescriptions on April 29, 1987 and November 13, 1995 in order to know the quantit...Aim. To statistic the usage of hypnotics and sedatives in outpatient and emergency clinics prescriptions in one day. Method. Check all prescriptions on April 29, 1987 and November 13, 1995 in order to know the quantity, kind and distribution of hypnotics and sedatives in different outpatient departments. Result. There were 1 319 prescriptions on April 29, 1987. Among them, hypnotics and sedatives were 122(9. 24%); in comparing with 2 065 prescriptions on November 13, 1995, hypnotics and sedatives were 141 (6. 82%). Benzodiazepine used more than 80% in all prescriptions. Conclusion. The possibility of long-term low-dosage using benzodiazepine is present. It must strengthen the control and education to avoid the drug-abuse.展开更多
OBJECTIVE: To present a bibliometric analysis of global scientific publications on the nondrug and nonsedative hypnotic treatment of insomnia with regard to influential institutions, publications, countries, research ...OBJECTIVE: To present a bibliometric analysis of global scientific publications on the nondrug and nonsedative hypnotic treatment of insomnia with regard to influential institutions, publications, countries, research hotspots,trends, and frontiers. METHODS: A literature review was conducted by searching the Web of Science Core Collection(Wo SCC) and China National Knowledge Infrastructure(CNKI) databases to identify all publications related to the nondrug and nonsedative hypnotic treatment of insomnia from 2000 to 2021. Eligible publications were reviewed, including annual publication increments, citation analyses, international collaborations, and keyword analyses. The data were analysed using Cite Space(vers5.8.R3, 6.1.R2 and 6.1.6, College of Computing and Informatics, Philadelphia, PA, USA) and virtualized by knowledge maps. RESULTS:In total, 9832 publications were included in this analysis. The results from the WoSCC showed that the United States of America(Count = 2268, 40.33%), Stanford University(Count = 141, 2.51%), and the United States Department of Health and Human Services were the leading country, institute, and funding agency regarding the number of publications, respectively. “Cognitive-behavioural therapy” was the most popular research topic generated from the cocited reference. The most frequently co-occurring keywords were insomnia, cognitive behavioural therapy, disorder, depression, quality of life, Meta-analysis, older adult, sleep, prevalence and efficacy, while keywords including clinical practice guideline, guideline, and Tai Chi remained popular after 2021. Circadian rhythm was the strongest research frontier for 2000-2021. In China, Chengdu University of Traditional Chinese Medicine(Count = 69, 4.79%) was the most productive institute in this field. The most frequently co-occurring keywords from Chinese literature were sleep disorder, sleep quality, acupuncture and moxibustion, Parkinson's disease, transcranial magnetic stimulation, health education, music therapy, chronic insomnia, quality of life, and nonmotor symptoms. Traditional Chinese medicine was the strongest research frontier for 2019-2021. CONCLUSION: This bibliometric study provides an exhaustive mapping encompassing pertinent institute, publications, influential articles, researchers and topics of the global trend of nondrug and nonsedative hypnotic treatment for insomnia. The results show that the research trend has shifted from primary studies on the efficacy and safety of nondrug and nonsedative hypnotic treatment for insomnia to comorbidity studies. Clinical practice guidelines will potentially become the research frontier for this field post-2021. The findings are important for researchers, clinicians, journal editors, and policymakers working in the field of nondrug and nonsedative hypnotic treatment for insomnia to understand the strengths and potentials in the current studies and guide future clinical practice, research, and science policy.展开更多
Objectives This study aimed to investigate the therapeutic effects of Suan Zao Ren(Semen Ziziphi Spinosae,SZS)extract on insomnia induced by p-chlorophenylalanine(PCPA)in rats and its influence on the thioredoxin-inte...Objectives This study aimed to investigate the therapeutic effects of Suan Zao Ren(Semen Ziziphi Spinosae,SZS)extract on insomnia induced by p-chlorophenylalanine(PCPA)in rats and its influence on the thioredoxin-interacting protein(TXNIP)/nucleotide-binding domain Leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3)inflammasome pathway,and to preliminarily explore themechanism by which SZS extract improves insomnia.Methods Fifty male Sprague–Dawley(SD)rats were used,with 8 rats in the blank group and 42 rats in the modeling group.The modeling group was induced by intraperitoneal injection of PCPA at a dose of 500mg·kg^(-1) for six consecutive days,with daily cage exchange.After 6 days,40 successfully modeled rats were randomly divided into five groups:themodel group(equal volume of distilled water),the positive group(0.75 mg·kg^(-1)),and low-,medium-,and high-dose SZS extract groups(1.5,3,and 6 g·kg^(-1),respectively),with 8 rats in each group.Treatments were administered for seven consecutive days.Enzyme-linked immunosorbent assay was used to measure levels of 5-hydroxytryptamine(5-HT)and gamma-aminobutyric acid(GABA)in the rat cerebral cortex.The thiobarbituric acid(TBA)method was used to determine malondialdehyde(MDA)levels,and the hydroxylamine method was used to determine superoxide dismutase(SOD)levels.The 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)method was used to measure total antioxidant capacity(TAOC)in the cerebral cortex.Pathological changes in the cerebral cortex were observed,and Western blot was used to detect the protein expressions of TXNIP,NLRP3,apoptosis-associated speck-like protein containing a Caspase activation and recruitment domain(CARD),and cysteine–aspartate-specific protease 1(Caspase-1)in the cerebral cortex.Results Compared with the blank group,the model group showed a significantly prolonged sleep latency(p<0.001)and a significantly shortened sleep duration(p<0.001).There were no changes in serum MDA and SOD levels.MDA levels in the cerebral cortex were significantly increased(p<0.001),while SOD and TAOC levels were significantly decreased(p<0.001).The 5-HT level was increased(p<0.05),and the GABA level was significantly decreased(p<0.001).SZS extract improved these conditions to varying degrees.Light microscopy showed no significant changes in cortical neurons but transmission electron microscopy revealed intact mitochondrial structures in the blank group,while the model group showed swollen and unclear mitochondria with reduced organelles.After 7 days of treatment,these conditions improved in the SZS extract groups.Compared with the blank group,the expressions of the four proteins in the model group were increased,and the expressions of these proteins were decreased in the SZS extract groups compared with the model group.Conclusion SZS extract may exert an antioxidant effect to treat insomnia by downregulating the expression of TXNIP/NLRP3 proteins and regulating oxidative stress levels in the cerebral cortex.展开更多
文摘Eight new cyclopyrrolone compounds were synthesized according to the structure activity relationship and action mechanism of Zopiclone, a cyclopyrrolone hypnotic. Their preliminary pharmacodynamics are under investigation.
文摘OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy.According to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investigated the anti-inflammatory ingredients of licorice,but for the potency of flavonoid glycoside and their aglycones on inflammation are not evaluated.This study was designed to assess the contributions of licorice flavonoid glycosides and their aglycons to its anti-inflammatory and hypnotic effects.METHODS For the flavonoid aglycone's enrichment,the extract of licorice(EL)was fermented in submerged culture of the edible fungus Grifola frondosa HB0071 mycelia which can produce β-glucosidase and catalyze the flavonoid glycosides to aglycones.EL and fermented extract of licorice(FEL) were used in this study.The anti-inflammation test was carried out in arachidonic acid(AA)-induced ear edema model and the hypnotic test was performed by using electroencephalogram(EEG) analysis method in normal freely moving SD rats.The chemicals constituents were analyzed by HPLC.RESULTS During fermentation,the falvonoid glycosides of licorice were hydrolyzed by the time process.Along with fermentation time,the concentration of the major flavonoid glycosides,liquiritin and isoliquiritin were decreased obviously,and simultaneously their aglycons,liquiritigenin and isoliquiriti.genin were remarkably increased in FEL.Moreover,the content of another major constituent glycyrrhi.zic acid and glycyrrhetinic acid were not changed after the fermentation.In AA-induced mice ear ede.ma test,after topical application,FEL(effective dose range:5-20 μg·ear-1) showed more potent inhibito.ry activity than EL(effective dose range:25-100 μg·ear-1).On the other hand,oral administration of EL and FEL exhibited the same hypnotic potency and both enhanced the total sleep time including rapid eye movement(REM) sleep and non-REM sleep time.CONCLUSION These results suggested that the enrichment of flavonoid aglycons such as liquiritigenin and isoliquiritigenin enhanced the anti-inflam.matory potency of licorice extract,and this potentiation has nothing to do with glycyrrhizic acid or glycyr.rhetinic acid.In addition,enrichment of flavonoid aglycones did not alter the hypnotic effect of licorice.
文摘On the basis of the Zaleplon structure, novel pyrazolo[l,5-a]pyrimidines were designed and prepared for studies on their hypnotic activity. This paper reported the synthesis of twelve new 5-methyl-7-substituted-pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives by using simple starting materials such as propane dinitrile and triethyl orthoformate. The structures of the derived target compounds were confirmed by their IR and 1H-NMR spectroscopic data. The preliminary pharmacological evaluations indicated that some compounds showed hypnotic activity, while derivative 1c was the most polent one.
文摘With a small-dose remifentanil, some patients showed no reaction and did not remember it postoperatively. We, therefore, hypothesized that remifentanil may decrease the level of consciousness and/or exhibit amnesic effect when stimulations are avoided. Thirty-patients were divided into two groups: non-stimulation group and stimulation group. Anesthesia was induced with 1 micro-g·kg?1·min?1 of remifentanil using no additional hypnotic agent. In the non-stimulation group, patients were left free from any stimulation except non-invasive blood pressure monitoring. In the stimulation group, patients were asked to follow verbal commands. The level of consciousness was evaluated with electroencephalogram and BIS-value derived from it. In the non-stimulation group, all patients reached the decreased level of consciousness in 5 minutes. In the stimulation group, however, 14 patients were judged to be still conscious. 10 patients could open their mouth at the 5th minute, but 9 of these 10 patients did not remember it postoperatively. In conclusion, remifentanil, with no additional anesthetics, exhibited hypnotic and amnesic effects when stimulations were kept minimal.
文摘Aim. To statistic the usage of hypnotics and sedatives in outpatient and emergency clinics prescriptions in one day. Method. Check all prescriptions on April 29, 1987 and November 13, 1995 in order to know the quantity, kind and distribution of hypnotics and sedatives in different outpatient departments. Result. There were 1 319 prescriptions on April 29, 1987. Among them, hypnotics and sedatives were 122(9. 24%); in comparing with 2 065 prescriptions on November 13, 1995, hypnotics and sedatives were 141 (6. 82%). Benzodiazepine used more than 80% in all prescriptions. Conclusion. The possibility of long-term low-dosage using benzodiazepine is present. It must strengthen the control and education to avoid the drug-abuse.
基金National Natural Science Foundation of China:Research on Acupoint Sensitization (No. 81590950)Clinical Research on the Phenomena and Patterns of Acupoint Sensitization (No. 81590951)the Key R&D Program of Science and Technology Department of Sichuan Province:Research on the Molecular Mechanism of Specific Acupoint Sensitization in Coronary Heart Disease Angina Pectoris Model Rats Based on Exosome Regulation (No. 20ZDYF1199)。
文摘OBJECTIVE: To present a bibliometric analysis of global scientific publications on the nondrug and nonsedative hypnotic treatment of insomnia with regard to influential institutions, publications, countries, research hotspots,trends, and frontiers. METHODS: A literature review was conducted by searching the Web of Science Core Collection(Wo SCC) and China National Knowledge Infrastructure(CNKI) databases to identify all publications related to the nondrug and nonsedative hypnotic treatment of insomnia from 2000 to 2021. Eligible publications were reviewed, including annual publication increments, citation analyses, international collaborations, and keyword analyses. The data were analysed using Cite Space(vers5.8.R3, 6.1.R2 and 6.1.6, College of Computing and Informatics, Philadelphia, PA, USA) and virtualized by knowledge maps. RESULTS:In total, 9832 publications were included in this analysis. The results from the WoSCC showed that the United States of America(Count = 2268, 40.33%), Stanford University(Count = 141, 2.51%), and the United States Department of Health and Human Services were the leading country, institute, and funding agency regarding the number of publications, respectively. “Cognitive-behavioural therapy” was the most popular research topic generated from the cocited reference. The most frequently co-occurring keywords were insomnia, cognitive behavioural therapy, disorder, depression, quality of life, Meta-analysis, older adult, sleep, prevalence and efficacy, while keywords including clinical practice guideline, guideline, and Tai Chi remained popular after 2021. Circadian rhythm was the strongest research frontier for 2000-2021. In China, Chengdu University of Traditional Chinese Medicine(Count = 69, 4.79%) was the most productive institute in this field. The most frequently co-occurring keywords from Chinese literature were sleep disorder, sleep quality, acupuncture and moxibustion, Parkinson's disease, transcranial magnetic stimulation, health education, music therapy, chronic insomnia, quality of life, and nonmotor symptoms. Traditional Chinese medicine was the strongest research frontier for 2019-2021. CONCLUSION: This bibliometric study provides an exhaustive mapping encompassing pertinent institute, publications, influential articles, researchers and topics of the global trend of nondrug and nonsedative hypnotic treatment for insomnia. The results show that the research trend has shifted from primary studies on the efficacy and safety of nondrug and nonsedative hypnotic treatment for insomnia to comorbidity studies. Clinical practice guidelines will potentially become the research frontier for this field post-2021. The findings are important for researchers, clinicians, journal editors, and policymakers working in the field of nondrug and nonsedative hypnotic treatment for insomnia to understand the strengths and potentials in the current studies and guide future clinical practice, research, and science policy.
基金Research on the Mechanism of Suan Zao Ren’s(SZS)Hypnotic Effect Based on TXNIP/NLRP3 Signaling Pathway(2023-ZXFZJJ-JW-071).
文摘Objectives This study aimed to investigate the therapeutic effects of Suan Zao Ren(Semen Ziziphi Spinosae,SZS)extract on insomnia induced by p-chlorophenylalanine(PCPA)in rats and its influence on the thioredoxin-interacting protein(TXNIP)/nucleotide-binding domain Leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3)inflammasome pathway,and to preliminarily explore themechanism by which SZS extract improves insomnia.Methods Fifty male Sprague–Dawley(SD)rats were used,with 8 rats in the blank group and 42 rats in the modeling group.The modeling group was induced by intraperitoneal injection of PCPA at a dose of 500mg·kg^(-1) for six consecutive days,with daily cage exchange.After 6 days,40 successfully modeled rats were randomly divided into five groups:themodel group(equal volume of distilled water),the positive group(0.75 mg·kg^(-1)),and low-,medium-,and high-dose SZS extract groups(1.5,3,and 6 g·kg^(-1),respectively),with 8 rats in each group.Treatments were administered for seven consecutive days.Enzyme-linked immunosorbent assay was used to measure levels of 5-hydroxytryptamine(5-HT)and gamma-aminobutyric acid(GABA)in the rat cerebral cortex.The thiobarbituric acid(TBA)method was used to determine malondialdehyde(MDA)levels,and the hydroxylamine method was used to determine superoxide dismutase(SOD)levels.The 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)method was used to measure total antioxidant capacity(TAOC)in the cerebral cortex.Pathological changes in the cerebral cortex were observed,and Western blot was used to detect the protein expressions of TXNIP,NLRP3,apoptosis-associated speck-like protein containing a Caspase activation and recruitment domain(CARD),and cysteine–aspartate-specific protease 1(Caspase-1)in the cerebral cortex.Results Compared with the blank group,the model group showed a significantly prolonged sleep latency(p<0.001)and a significantly shortened sleep duration(p<0.001).There were no changes in serum MDA and SOD levels.MDA levels in the cerebral cortex were significantly increased(p<0.001),while SOD and TAOC levels were significantly decreased(p<0.001).The 5-HT level was increased(p<0.05),and the GABA level was significantly decreased(p<0.001).SZS extract improved these conditions to varying degrees.Light microscopy showed no significant changes in cortical neurons but transmission electron microscopy revealed intact mitochondrial structures in the blank group,while the model group showed swollen and unclear mitochondria with reduced organelles.After 7 days of treatment,these conditions improved in the SZS extract groups.Compared with the blank group,the expressions of the four proteins in the model group were increased,and the expressions of these proteins were decreased in the SZS extract groups compared with the model group.Conclusion SZS extract may exert an antioxidant effect to treat insomnia by downregulating the expression of TXNIP/NLRP3 proteins and regulating oxidative stress levels in the cerebral cortex.
