Three new acylated flavonoid C-glycosides,6'''-(-)-phaseoylspinosin(1),6'''-(3'''',4'''',5''''-trimethoxyl)-(E)-cinnamoylspinosin(2),and 6'&#...Three new acylated flavonoid C-glycosides,6'''-(-)-phaseoylspinosin(1),6'''-(3'''',4'''',5''''-trimethoxyl)-(E)-cinnamoylspinosin(2),and 6'''-(4''''-O-β-D-gluco-pyranosyl)-benzoylspinosin(3),were isolated from the seeds of Ziziphus mauritiana(Rhamnaceae).A further 19 known compounds including eight spinosin analogues(4-11)were also isolated.Their structures were elucidated by means of spectroscopic analysis and chemical method.Among spinosin derivatives 1,2,4,7,8,and triterpenoid saponin 14,jujuboside A(14)displayed moderate acetylcholinesterase(AchE)inhibitory activity with an inhibition value of 46.2%at a concentration of 1μM.展开更多
OBJECTIVE:To explore the protective mechanism of spinosin(SPI)on Alzheimer's disease(AD)model cells,Neuro-2a/APP695(N2a/APP695),against H_(2)O_(2)-induced oxidative stress damage,to reflect the influence of oxidat...OBJECTIVE:To explore the protective mechanism of spinosin(SPI)on Alzheimer's disease(AD)model cells,Neuro-2a/APP695(N2a/APP695),against H_(2)O_(2)-induced oxidative stress damage,to reflect the influence of oxidative stress on the development of AD,and to provide a valuable basis for the research and development of therapeutic drug for AD.METHODS:N2a/APP695 cells were exposed to H2O2 and then treated with spinosin.Firstly,the secretion level of amyloidβ(Aβ)1-42 and the production of malondialdehyde(MDA)and lactate dehydrogenase(LDH)were detected by enzyme linked immunosorbent assay kits.Secondly,the oligomerization degree of Aβ1-42 was performed by Thioflavin T staining.Thirdly,the expression levels of p-Tau(Ser199/202/396),synaptophysin(SYP),postsynaptic density protein 95(PSD95),and mitogen-activated protein kinase(MAPK)family-related proteins were detected by Western blot analysis.In addition,FITC-labeled phalloidin was used in cytoskeleton staining to reflect synaptic function.RESULTS:This study showed that H2O2 stimulated N2a/APP695 cells to produce excessive MDA and LDH and secrete a large amount of Aβ,promoted the aggregation of Aβ,induced Tau protein hyperphosphorylation,and led to synaptic dysfunction.Spinosin reversed these changes caused by H2O2 by inactivating p38,which was verified by treatment with the p38 inhibitor BIRB796.CONCLUSION:Spinosin protects N2a/APP695 cells from oxidative stress damage caused by H2O2 through inactivating p38.展开更多
The interaction between advanced glycation end-products(AGEs)and the receptor for advanced glycation end-products(RAGE)triggers oxidative stress and inflammation,both of which are closely associated with impaired inte...The interaction between advanced glycation end-products(AGEs)and the receptor for advanced glycation end-products(RAGE)triggers oxidative stress and inflammation,both of which are closely associated with impaired intestinal health.Spinosin(SPI),a major flavonoid-C-glycoside present in Ziziphus jujuba Mill.var.spinosa,ex-hibits anti-inflammatory and antioxidant properties that may help preserve intestinal integrity by inhibiting the AGEs-RAGE interaction.This study investigates the protective effects of SPI against AGEs-induced damage in Caco-2 cells.A cellular damage model was established using glycolaldehyde and bovine serum albumin-derived AGEs.Cell viability,assessed via the CCK-8 assay,identified 300μg/mL AGEs with 24 h induction as the optimal condition for damage induction.SPI treatment significantly improved cell viability,reduced reactive oxygen species production,and alleviated oxidative stress.Moreover,SPI mitigated AGEs-induced inflammation and apoptosis while promoting the expression of tight junction proteins.qRT-PCR analysis revealed that SPI downregulated the mRNA expression of pro-inflammatory cytokines(TNF-α,IL-6,IL-8,IL-1β)and pro-apoptotic factors(Bax,Caspase-9)while upregulating the expression of anti-apoptotic factor(Bcl-2)and tight junction proteins(ZO-1,Occludin,Claudin-1).Additionally,SPI suppressed RAGE mRNA levels by directly binding to RAGE,thereby inhibiting the MAPK/NF-κB signaling pathway,resulting in decreased inflammation and apoptosis.Molecular docking analysis confirmed the strong binding affinity of SPI to RAGE.These findings suggest that SPI confers protective effects on intestinal cells against AGEs-induced damage by modulating the RAGE/MAPK/NF-κB signaling pathway.This study underscores SPI’s potential for medicinal and dietary ap-plications aimed at promoting intestinal health.展开更多
目的酸枣仁提取物经鼻、经口途径的体内、外入脑行为分析及镇静催眠作用比较。方法建立Calu-3/BMEC和Caco-2/BMEC细胞模型,分别从体外模拟酸枣仁指标成分斯皮诺素经鼻黏膜和经胃肠道吸收入血、入脑过程;考察大鼠经鼻和ig给药,指标成分...目的酸枣仁提取物经鼻、经口途径的体内、外入脑行为分析及镇静催眠作用比较。方法建立Calu-3/BMEC和Caco-2/BMEC细胞模型,分别从体外模拟酸枣仁指标成分斯皮诺素经鼻黏膜和经胃肠道吸收入血、入脑过程;考察大鼠经鼻和ig给药,指标成分在体内的血浆和脑组织分布过程;进一步比较2种给药方式对酸枣仁提取物镇静、催眠作用的影响。结果鼻腔的Calu-3、肠道的Caco-2和血脑屏障的BMEC细胞层对斯皮诺素的跨细胞转运都有阻滞作用,而且模拟体内的多细胞转运过程,进一步加强了阻滞作用;经鼻给药增加斯皮诺素的入血、入脑分布,其药时曲线下面积(area under curve,AUC_(0~t))分别是ig给药的4.8倍(血浆)和5.1倍(脑组织);与ig给药相比,鼻腔给药显著减少了模型小鼠的运动距离(P<0.05),延长了静止时间和睡眠持续时间(P<0.05)。结论经鼻给药可通过直接、间接方式的多种入脑通路增加酸枣仁提取物入脑含量,并增强其镇静催眠作用。展开更多
基金The authors are sincerely grateful to Prof.Huai-Rong Luo for the AChE inhibitory activity bioassay.This work was supported by the 973 Program of Science and Technology of China(2011CB915503)the Fourteenth Candidates of the Young Academic Leaders of Yunnan Province(Min Xu,2011CI044).
文摘Three new acylated flavonoid C-glycosides,6'''-(-)-phaseoylspinosin(1),6'''-(3'''',4'''',5''''-trimethoxyl)-(E)-cinnamoylspinosin(2),and 6'''-(4''''-O-β-D-gluco-pyranosyl)-benzoylspinosin(3),were isolated from the seeds of Ziziphus mauritiana(Rhamnaceae).A further 19 known compounds including eight spinosin analogues(4-11)were also isolated.Their structures were elucidated by means of spectroscopic analysis and chemical method.Among spinosin derivatives 1,2,4,7,8,and triterpenoid saponin 14,jujuboside A(14)displayed moderate acetylcholinesterase(AchE)inhibitory activity with an inhibition value of 46.2%at a concentration of 1μM.
基金National Natural Science Foundation of China:Study on the Basis and Mechanism of Antidepressant Substances in Which Schisandra Chinensis Regulates the Endocannabinoid System in the Body and Participates in"Gut-Brain Dialogue"(No.82173961)National Natural Science Foundation of China:to Investigate the Pharmacological Substance Basis and Mechanism of Suanzaoren Decoction in Improving Depression by Crosstalk Regulating"Gut Microbiota-Gut-Brain"Axis Based on TLR4-NF-κB/NLRP3 and Wnt/β-Catenin Signaling Pathways(No.82003926)+2 种基金the Doctoral Scientific Research Foundation of Liaoning Province:Study on the Mechanism of Antidepressant Action of Schisandra Chinensis Mediated by Intestinal Flora(2019-BS-233)High-Level Innovation and Entrepreneurship Team of Liaoning Province:"Healthy Liaoning"Functional Food Quality and Safety Innovation Team,"Xingliao Talent Plan"High-Level Innovation and Entrepreneurship Team(XLYC2008029)Guizhou Provincial Natural Science Foundation:Probing the Chemical Components and the Detailed Working Mechanisms of Danggui Buxue Tang for Mitigating the Menopausal Syndrome(QKH-J[2020]1Y377)。
文摘OBJECTIVE:To explore the protective mechanism of spinosin(SPI)on Alzheimer's disease(AD)model cells,Neuro-2a/APP695(N2a/APP695),against H_(2)O_(2)-induced oxidative stress damage,to reflect the influence of oxidative stress on the development of AD,and to provide a valuable basis for the research and development of therapeutic drug for AD.METHODS:N2a/APP695 cells were exposed to H2O2 and then treated with spinosin.Firstly,the secretion level of amyloidβ(Aβ)1-42 and the production of malondialdehyde(MDA)and lactate dehydrogenase(LDH)were detected by enzyme linked immunosorbent assay kits.Secondly,the oligomerization degree of Aβ1-42 was performed by Thioflavin T staining.Thirdly,the expression levels of p-Tau(Ser199/202/396),synaptophysin(SYP),postsynaptic density protein 95(PSD95),and mitogen-activated protein kinase(MAPK)family-related proteins were detected by Western blot analysis.In addition,FITC-labeled phalloidin was used in cytoskeleton staining to reflect synaptic function.RESULTS:This study showed that H2O2 stimulated N2a/APP695 cells to produce excessive MDA and LDH and secrete a large amount of Aβ,promoted the aggregation of Aβ,induced Tau protein hyperphosphorylation,and led to synaptic dysfunction.Spinosin reversed these changes caused by H2O2 by inactivating p38,which was verified by treatment with the p38 inhibitor BIRB796.CONCLUSION:Spinosin protects N2a/APP695 cells from oxidative stress damage caused by H2O2 through inactivating p38.
基金supported by the“131”innovative talents training project in Tianjin(Grant No.201927).
文摘The interaction between advanced glycation end-products(AGEs)and the receptor for advanced glycation end-products(RAGE)triggers oxidative stress and inflammation,both of which are closely associated with impaired intestinal health.Spinosin(SPI),a major flavonoid-C-glycoside present in Ziziphus jujuba Mill.var.spinosa,ex-hibits anti-inflammatory and antioxidant properties that may help preserve intestinal integrity by inhibiting the AGEs-RAGE interaction.This study investigates the protective effects of SPI against AGEs-induced damage in Caco-2 cells.A cellular damage model was established using glycolaldehyde and bovine serum albumin-derived AGEs.Cell viability,assessed via the CCK-8 assay,identified 300μg/mL AGEs with 24 h induction as the optimal condition for damage induction.SPI treatment significantly improved cell viability,reduced reactive oxygen species production,and alleviated oxidative stress.Moreover,SPI mitigated AGEs-induced inflammation and apoptosis while promoting the expression of tight junction proteins.qRT-PCR analysis revealed that SPI downregulated the mRNA expression of pro-inflammatory cytokines(TNF-α,IL-6,IL-8,IL-1β)and pro-apoptotic factors(Bax,Caspase-9)while upregulating the expression of anti-apoptotic factor(Bcl-2)and tight junction proteins(ZO-1,Occludin,Claudin-1).Additionally,SPI suppressed RAGE mRNA levels by directly binding to RAGE,thereby inhibiting the MAPK/NF-κB signaling pathway,resulting in decreased inflammation and apoptosis.Molecular docking analysis confirmed the strong binding affinity of SPI to RAGE.These findings suggest that SPI confers protective effects on intestinal cells against AGEs-induced damage by modulating the RAGE/MAPK/NF-κB signaling pathway.This study underscores SPI’s potential for medicinal and dietary ap-plications aimed at promoting intestinal health.
文摘目的酸枣仁提取物经鼻、经口途径的体内、外入脑行为分析及镇静催眠作用比较。方法建立Calu-3/BMEC和Caco-2/BMEC细胞模型,分别从体外模拟酸枣仁指标成分斯皮诺素经鼻黏膜和经胃肠道吸收入血、入脑过程;考察大鼠经鼻和ig给药,指标成分在体内的血浆和脑组织分布过程;进一步比较2种给药方式对酸枣仁提取物镇静、催眠作用的影响。结果鼻腔的Calu-3、肠道的Caco-2和血脑屏障的BMEC细胞层对斯皮诺素的跨细胞转运都有阻滞作用,而且模拟体内的多细胞转运过程,进一步加强了阻滞作用;经鼻给药增加斯皮诺素的入血、入脑分布,其药时曲线下面积(area under curve,AUC_(0~t))分别是ig给药的4.8倍(血浆)和5.1倍(脑组织);与ig给药相比,鼻腔给药显著减少了模型小鼠的运动距离(P<0.05),延长了静止时间和睡眠持续时间(P<0.05)。结论经鼻给药可通过直接、间接方式的多种入脑通路增加酸枣仁提取物入脑含量,并增强其镇静催眠作用。
