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
In this study, the inhibitory effect of jujuboside A (JuA) on a penicillin sodium (Na-PCN) induced hyperactivity model was investigated. Cortical EEG (electroencephalogram) and the concentration of hippocampal Glutama...In this study, the inhibitory effect of jujuboside A (JuA) on a penicillin sodium (Na-PCN) induced hyperactivity model was investigated. Cortical EEG (electroencephalogram) and the concentration of hippocampal Glutamate (Glu) were monitored simultaneously in vivo as indicators of rat’s excitatory state. Power spectral density (PSD) and gravity frequency of PSD were calculated. JuA (0.05 g/L and 0.1 g/L) inhibited the EEG excitation effect caused by Na-PCN by increasing the power of δ1 and δ2 bands (P<0.01 vs model) and lowering the gravity frequency of PSD (P<0.01 vs model). JuA also remarkably reduced the Glu elevation induced by Na-PCN (P<0.05 vs model). Diazepam also depressed Glu concentration and lowered the gravity frequency, but it showed a different EEG pattern in increased β2-activity (P<0.01 vs model). EEG excitation caused by Na-PCN correlated with Glu elevation during the first hour. Neurophysiological inhibitory effects of JuA and diazepam were more persistent than their Glu inhibitoty effects.展开更多
Jujuboside A( JuA) is a main component of Jujubogenin extracted from the seeds of Ziziphus.The authors have not seen report on JuA's direct effect on the neruons of the central nervous system.This study aimed to a...Jujuboside A( JuA) is a main component of Jujubogenin extracted from the seeds of Ziziphus.The authors have not seen report on JuA's direct effect on the neruons of the central nervous system.This study aimed to assess the effect of JuA on paried-pulse responses of dentate gyrus granule cells in urethaneanasesthetized rats,used intracerebroventricular(i.c.v.) JuA to mimic in vitro tath conditions in vivo.Pariedpulse stimuli with 80ms interpulse interval were used to stimulate the perforant pathway.Evoked responses first responses,the slopoes of excitatory postsynaptic potential(EPSP1) and the amplitudes of population spike (PS1) decreased significantly after administration of JuA while the PS1 latencies increased significantly.In the second responses.the EPSP2 slops and PS2 latencies were changed similarly to those of the first ones.but PS2 amplitudes increased.The results showed that JuA may have some inhibitory effect on the granule cell excitability mediated by presynaptic mechanism but may have little effect on the excitability mediated by postsynaptic mechanism since the second evoked N-methyl-D-aspartic mediating paired-pulse facilitation is a postsynaptic mechanism.展开更多
Objective:This study explored the myocardial protection role of Jujuboside A through an ischemia–hypoxia–reperfusion(IHR)model.Materials and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish ...Objective:This study explored the myocardial protection role of Jujuboside A through an ischemia–hypoxia–reperfusion(IHR)model.Materials and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish an aging and IHR model.There are four groups of experiments:Control,IHR,D-gal+IHR,and D-gal+IHR+Jujuboside A.Cells viability,Adenosine triphosphate(ATP),reactive oxygen species(ROS),nicotinamide adenine dinucleotide(NAD+),nicotinamide adenine dinucleotide hydride(NADH)content,and NAD+/NADH ratio were detected using biochemical methods.Inflammatory cytokines level was detected by enzyme-linked immunosorbent assay.The expression of CD38,Recombinant NLR Family,pyrin domain-containing protein 3(NLRP3),and silent mating type information regulation 2homolog 3(SIRT3)protein was detected by Western blotting.Results:Compared to the IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and SIRT3 protein expression decreased,ROS level and inflammatory cytokines increased,and CD38 and NLRP3 proteins raised in the D-gal+IHR group.Compared to the D-gal+IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and expression of SIRT3 protein increased,ROS level and inflammatory cytokines level decreased,and expression of the CD38 and NLRP3proteins decreased in the D-gal+IHR+Jujuboside A group.Conclusions:Jujuboside A inhibited the expression of CD38,improved energy metabolism disorder,and mitochondrial function,and decreased inflammation in D-gal-induced H9c2 cells.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
该文探究了酸枣仁皂苷A(Jujuboside A,JuA)对抑郁模型小鼠行为及神经突触可塑性相关蛋白表达的作用。通过悬尾实验、强迫游泳实验、旷场实验、Morris水迷宫实验评价小鼠的抑郁状态,免疫组织化学染色法检测小鼠海马组织中脑源性神经营养...该文探究了酸枣仁皂苷A(Jujuboside A,JuA)对抑郁模型小鼠行为及神经突触可塑性相关蛋白表达的作用。通过悬尾实验、强迫游泳实验、旷场实验、Morris水迷宫实验评价小鼠的抑郁状态,免疫组织化学染色法检测小鼠海马组织中脑源性神经营养因子(Brain Derived Neurotrophic Factor,BDNF)的表达水平,Western blot实验检测小鼠海马组织酪氨酸激酶受体B(Tyrosine Kinase Receptor B,TrkB)、cAMP反应元件结合蛋白(cAMP Responsive Element Binding,CREB)、突触后密度蛋白95(Postsynaptic Density Protein 95,PSD95)、自噬效应蛋白Beclin1(Autophagy Effector Protein Beclin1,Beclin1)的表达水平。结果表明,JuA显著改善抑郁模型小鼠的抑郁状态。同时,JuA作用后海马组织BDNF、TrkB、CREB、PSD95、Beclin1的表达水平较模型组分别上调了190.23%、137.24%、76.29%、169.32%、82.53%。综上所述,JuA对抑郁模型小鼠具有显著的抗抑郁作用,并能明上调BDNF、TrkB、CREB、PSD95、Beclin1等神经突触可塑性相关蛋白的表达。实验结果为JuA在抑郁症临床治疗方面的应用提供理论依据,并为探究抑郁症药物治疗靶点提供参考。展开更多
Diabetic nephropathy(DN)is one of the most common complications of diabetes mellitus,which is characterized in renal tubulointerstitial fibrosis(TIF).The current study was designed to investigate the protective effect...Diabetic nephropathy(DN)is one of the most common complications of diabetes mellitus,which is characterized in renal tubulointerstitial fibrosis(TIF).The current study was designed to investigate the protective effect of Jujuboside A(Ju A)on TIF in type 2 diabetes(T2DM)mice,and explore its underlying anti-fibrosis mechanism.A mouse T2DM model was established using high fat diet(HFD)feeding combined with intraperitoneal injection of streptozotocin(STZ).Then,diabetic mice were treated with Ju A(10,20 and 40 mg·kg^(−1)·d^(−1),i.g.)for 12 weeks.Results showed that administration of Ju A not only down-regulated fasting blood glucose(FBG)levels,but also improved hyperlipidemia and renal function in diabetic mice.Moreover,the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice,while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition(EMT)of renal tubular epithelial cells(RTECs).Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1(YY1)in the renal cortex of diabetic mice,and reduced the levels of transforming growth factor-β1(TGF-β1)in the serum and renal cortex of Ju A treated mice.According to in vitro studies,the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose(HG)cultured HK-2 cells.Taken together,these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.展开更多
Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy.The present study was aimed to investigate the effects of jujubos...Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy.The present study was aimed to investigate the effects of jujuboside A(JuA)on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells(hUC-MSCs).Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs,while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs.Furthermore,Hoechst 33258 staining,lactate dehydrogenase test,measurement of malondialdehyde,Western blot,high-performance liquid chromatography;and flow cytometry were performed.Our results indicated that JuA(25μmol·L−1)promoted the proliferation of hUC-MSCs,but did not affect the differentiating capability of these cells.JuA pre-treatment inhibited apoptosis,prevented oxidative damage,and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2.In addition,JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs,which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase.In conclusion,our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress,providing a new option for the improvement of hUC-MSCs in the clinical setting.展开更多
The extract from Semen Ziziphi Spinosae(SZS)contains many secondary metabolites(flavonoids,alkaloids,and terpenoids),widely reported for their high medicinal value.In order to know the number and type of flavonoids an...The extract from Semen Ziziphi Spinosae(SZS)contains many secondary metabolites(flavonoids,alkaloids,and terpenoids),widely reported for their high medicinal value.In order to know the number and type of flavonoids and the regulating mechanism of flavonoid biosynthesis during the growth and development of SZS,we identified and analyzed the flavonoid metabolites and genes in SZS using metabolomic and transcriptomic.A total of 13,232 differentially expressed genes and 83 flavonoid metabolites were identified at three different growth and development stages(T1,T2,and T3)of SZS.The main flavonoid metabolic components of SZS were catechin,L-epicatechin,(–)-epigallocatechin,(+)-gallocatechin,spinosin and its derivatives.A total of 53 unigenes encoding 15 enzymes were identified as candidate genes involved in flavonoid biosynthesis in SZS.Among,PAL,C4H,4CL,CHS,CHI,FLS,FNS,ANS,ANR,LAR,and UFGT genes were all downregulated in T3 than in T1.The expression levels of these genes influence the accumulation of flavonoids in SZS.Our results should provide valuable information for flavonoid metabolites and candidate genes involved in flavonoid biosynthesis on SZS .展开更多
Background:To facilitate the preparation of traditional Chinese medicines they are pre-mashed,i.e.,mashed in advance.However,storage conditions for pre-mashed traditional Chinese medicines are based on subjective judg...Background:To facilitate the preparation of traditional Chinese medicines they are pre-mashed,i.e.,mashed in advance.However,storage conditions for pre-mashed traditional Chinese medicines are based on subjective judgments of pharmacists,and the best storage conditions have not generally been determined.Semen Zizyphi Spinosae is a commonly used traditional Chinese medicine,and it is usually used after it is fried.The medicine needs to be mashed in a timely manner to ensure its effectiveness.The Chinese Pharmacopoeia provides a limit for its aflatoxin content.Methods:The orthogonal experimental design method optimizes the best plan for pre-mashed fried Semen Zizyphi Spinosae.Experimental conditions were defined using the L^(9)(3^(4))orthogonal design table.Four factors and three levels were used to study storage conditions.The four factors and three levels are as follows:storage temperature(10°C,20°C,and 30°C),storage humidity(45%,60%,and 75%),storage times(10,20 and 30 days),and particle sizes for the powder(coarsest,coarse and medium powders).The contents of jujuboside A,spinosin,aflatoxin B1,total aflatoxins(aflatoxins B1,B2,G1,and G2),moisture,total ash,acid value,and saponification values were measured.Results:The results demonstrated that the highest jujuboside A and spinosin contents were obtained using a storage temperature of 20°C,a storage humidity of 75%,a storage time of 10 days,and with a coarse powder particle size.Aflatoxin B1 and total aflatoxins(aflatoxins B1,B2,G1 and G2)were not detected under these conditions.Conclusion:There is no requirement for traditional Chinese medicines to be pre-mashed.This study evaluated various storage conditions for pre-mashed fried Semen Zizyphi Spinosae,and considered the influence of four factors on the contents of jujuboside A,spinolin and aflatoxin for quality control to provide a reference for other pre-mashed traditional Chinese medicines.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Project supported by the National Natural Science Foundation ofChina (No. 30170275) and the Key Laboratory for Biomedical En-gineering of the Ministry of Education of China and Science andTechnology Department of Zhejiang Province (No. 011106239)
文摘In this study, the inhibitory effect of jujuboside A (JuA) on a penicillin sodium (Na-PCN) induced hyperactivity model was investigated. Cortical EEG (electroencephalogram) and the concentration of hippocampal Glutamate (Glu) were monitored simultaneously in vivo as indicators of rat’s excitatory state. Power spectral density (PSD) and gravity frequency of PSD were calculated. JuA (0.05 g/L and 0.1 g/L) inhibited the EEG excitation effect caused by Na-PCN by increasing the power of δ1 and δ2 bands (P<0.01 vs model) and lowering the gravity frequency of PSD (P<0.01 vs model). JuA also remarkably reduced the Glu elevation induced by Na-PCN (P<0.05 vs model). Diazepam also depressed Glu concentration and lowered the gravity frequency, but it showed a different EEG pattern in increased β2-activity (P<0.01 vs model). EEG excitation caused by Na-PCN correlated with Glu elevation during the first hour. Neurophysiological inhibitory effects of JuA and diazepam were more persistent than their Glu inhibitoty effects.
文摘Jujuboside A( JuA) is a main component of Jujubogenin extracted from the seeds of Ziziphus.The authors have not seen report on JuA's direct effect on the neruons of the central nervous system.This study aimed to assess the effect of JuA on paried-pulse responses of dentate gyrus granule cells in urethaneanasesthetized rats,used intracerebroventricular(i.c.v.) JuA to mimic in vitro tath conditions in vivo.Pariedpulse stimuli with 80ms interpulse interval were used to stimulate the perforant pathway.Evoked responses first responses,the slopoes of excitatory postsynaptic potential(EPSP1) and the amplitudes of population spike (PS1) decreased significantly after administration of JuA while the PS1 latencies increased significantly.In the second responses.the EPSP2 slops and PS2 latencies were changed similarly to those of the first ones.but PS2 amplitudes increased.The results showed that JuA may have some inhibitory effect on the granule cell excitability mediated by presynaptic mechanism but may have little effect on the excitability mediated by postsynaptic mechanism since the second evoked N-methyl-D-aspartic mediating paired-pulse facilitation is a postsynaptic mechanism.
基金Construction of atrial fibrillation-specific disease database(shdc2020cr6012-003)3 years action plan of Shanghai Shenkang Medical Development Center(shdc2020cr1053b)+1 种基金Science and technology support project of Shanghai Municipal Commission of Science and Technology(18401932800)Shanghai Shenkang medical development center emerging frontier technology joint research project(shdc12018125)。
文摘Objective:This study explored the myocardial protection role of Jujuboside A through an ischemia–hypoxia–reperfusion(IHR)model.Materials and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish an aging and IHR model.There are four groups of experiments:Control,IHR,D-gal+IHR,and D-gal+IHR+Jujuboside A.Cells viability,Adenosine triphosphate(ATP),reactive oxygen species(ROS),nicotinamide adenine dinucleotide(NAD+),nicotinamide adenine dinucleotide hydride(NADH)content,and NAD+/NADH ratio were detected using biochemical methods.Inflammatory cytokines level was detected by enzyme-linked immunosorbent assay.The expression of CD38,Recombinant NLR Family,pyrin domain-containing protein 3(NLRP3),and silent mating type information regulation 2homolog 3(SIRT3)protein was detected by Western blotting.Results:Compared to the IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and SIRT3 protein expression decreased,ROS level and inflammatory cytokines increased,and CD38 and NLRP3 proteins raised in the D-gal+IHR group.Compared to the D-gal+IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and expression of SIRT3 protein increased,ROS level and inflammatory cytokines level decreased,and expression of the CD38 and NLRP3proteins decreased in the D-gal+IHR+Jujuboside A group.Conclusions:Jujuboside A inhibited the expression of CD38,improved energy metabolism disorder,and mitochondrial function,and decreased inflammation in D-gal-induced H9c2 cells.
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.
文摘该文探究了酸枣仁皂苷A(Jujuboside A,JuA)对抑郁模型小鼠行为及神经突触可塑性相关蛋白表达的作用。通过悬尾实验、强迫游泳实验、旷场实验、Morris水迷宫实验评价小鼠的抑郁状态,免疫组织化学染色法检测小鼠海马组织中脑源性神经营养因子(Brain Derived Neurotrophic Factor,BDNF)的表达水平,Western blot实验检测小鼠海马组织酪氨酸激酶受体B(Tyrosine Kinase Receptor B,TrkB)、cAMP反应元件结合蛋白(cAMP Responsive Element Binding,CREB)、突触后密度蛋白95(Postsynaptic Density Protein 95,PSD95)、自噬效应蛋白Beclin1(Autophagy Effector Protein Beclin1,Beclin1)的表达水平。结果表明,JuA显著改善抑郁模型小鼠的抑郁状态。同时,JuA作用后海马组织BDNF、TrkB、CREB、PSD95、Beclin1的表达水平较模型组分别上调了190.23%、137.24%、76.29%、169.32%、82.53%。综上所述,JuA对抑郁模型小鼠具有显著的抗抑郁作用,并能明上调BDNF、TrkB、CREB、PSD95、Beclin1等神经突触可塑性相关蛋白的表达。实验结果为JuA在抑郁症临床治疗方面的应用提供理论依据,并为探究抑郁症药物治疗靶点提供参考。
基金supported by the National Natural Science Foundation of China(Nos.81973377,81903689 and 82073906)the Key Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.19KJB350006 and 19KJA460008)+3 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Initializing Fund of Xuzhou Medical University(No.D2018011)the Postgraduate Research Practice Innovation Program of Jiangsu Province(Nos.KYCX21-2733,KYCX21-2735 and KYCX21-2736)the Undergraduate Innovation and Entrepreneurship Training Program of Jiangsu Province(No.201910313018Z).
文摘Diabetic nephropathy(DN)is one of the most common complications of diabetes mellitus,which is characterized in renal tubulointerstitial fibrosis(TIF).The current study was designed to investigate the protective effect of Jujuboside A(Ju A)on TIF in type 2 diabetes(T2DM)mice,and explore its underlying anti-fibrosis mechanism.A mouse T2DM model was established using high fat diet(HFD)feeding combined with intraperitoneal injection of streptozotocin(STZ).Then,diabetic mice were treated with Ju A(10,20 and 40 mg·kg^(−1)·d^(−1),i.g.)for 12 weeks.Results showed that administration of Ju A not only down-regulated fasting blood glucose(FBG)levels,but also improved hyperlipidemia and renal function in diabetic mice.Moreover,the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice,while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition(EMT)of renal tubular epithelial cells(RTECs).Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1(YY1)in the renal cortex of diabetic mice,and reduced the levels of transforming growth factor-β1(TGF-β1)in the serum and renal cortex of Ju A treated mice.According to in vitro studies,the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose(HG)cultured HK-2 cells.Taken together,these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.
基金supported by the Educational Department of Liaoning Province(Nos.L201945,L202036).
文摘Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy.The present study was aimed to investigate the effects of jujuboside A(JuA)on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells(hUC-MSCs).Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs,while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs.Furthermore,Hoechst 33258 staining,lactate dehydrogenase test,measurement of malondialdehyde,Western blot,high-performance liquid chromatography;and flow cytometry were performed.Our results indicated that JuA(25μmol·L−1)promoted the proliferation of hUC-MSCs,but did not affect the differentiating capability of these cells.JuA pre-treatment inhibited apoptosis,prevented oxidative damage,and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2.In addition,JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs,which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase.In conclusion,our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress,providing a new option for the improvement of hUC-MSCs in the clinical setting.
基金supported by Hebei Province Key Research and Development Program Special Project(22326301D)Ministry of Science and Technology Project(2017YFC1700702)+2 种基金HAAFS Agriculture Science and Technology Innovation Project(2022KJCXZX-JZS-4)Technical System of Traditional Chinese Medicine Industry in Hebei Province(HBCT2018060203)State Key Laboratory of Research&Development of Characteristic Qin Medicine Resources(Cultivation),No.QY202102.
文摘The extract from Semen Ziziphi Spinosae(SZS)contains many secondary metabolites(flavonoids,alkaloids,and terpenoids),widely reported for their high medicinal value.In order to know the number and type of flavonoids and the regulating mechanism of flavonoid biosynthesis during the growth and development of SZS,we identified and analyzed the flavonoid metabolites and genes in SZS using metabolomic and transcriptomic.A total of 13,232 differentially expressed genes and 83 flavonoid metabolites were identified at three different growth and development stages(T1,T2,and T3)of SZS.The main flavonoid metabolic components of SZS were catechin,L-epicatechin,(–)-epigallocatechin,(+)-gallocatechin,spinosin and its derivatives.A total of 53 unigenes encoding 15 enzymes were identified as candidate genes involved in flavonoid biosynthesis in SZS.Among,PAL,C4H,4CL,CHS,CHI,FLS,FNS,ANS,ANR,LAR,and UFGT genes were all downregulated in T3 than in T1.The expression levels of these genes influence the accumulation of flavonoids in SZS.Our results should provide valuable information for flavonoid metabolites and candidate genes involved in flavonoid biosynthesis on SZS .
基金This work was supported by the Shanghai Municipal Commission of Health and Family Planning(No.20174Y0034)the Third batch of specialized subject construction of traditional Chinese medicine in Jiading District-Traditional Chinese Medicine(No.2020-JDZYYZDXK-01).
文摘Background:To facilitate the preparation of traditional Chinese medicines they are pre-mashed,i.e.,mashed in advance.However,storage conditions for pre-mashed traditional Chinese medicines are based on subjective judgments of pharmacists,and the best storage conditions have not generally been determined.Semen Zizyphi Spinosae is a commonly used traditional Chinese medicine,and it is usually used after it is fried.The medicine needs to be mashed in a timely manner to ensure its effectiveness.The Chinese Pharmacopoeia provides a limit for its aflatoxin content.Methods:The orthogonal experimental design method optimizes the best plan for pre-mashed fried Semen Zizyphi Spinosae.Experimental conditions were defined using the L^(9)(3^(4))orthogonal design table.Four factors and three levels were used to study storage conditions.The four factors and three levels are as follows:storage temperature(10°C,20°C,and 30°C),storage humidity(45%,60%,and 75%),storage times(10,20 and 30 days),and particle sizes for the powder(coarsest,coarse and medium powders).The contents of jujuboside A,spinosin,aflatoxin B1,total aflatoxins(aflatoxins B1,B2,G1,and G2),moisture,total ash,acid value,and saponification values were measured.Results:The results demonstrated that the highest jujuboside A and spinosin contents were obtained using a storage temperature of 20°C,a storage humidity of 75%,a storage time of 10 days,and with a coarse powder particle size.Aflatoxin B1 and total aflatoxins(aflatoxins B1,B2,G1 and G2)were not detected under these conditions.Conclusion:There is no requirement for traditional Chinese medicines to be pre-mashed.This study evaluated various storage conditions for pre-mashed fried Semen Zizyphi Spinosae,and considered the influence of four factors on the contents of jujuboside A,spinolin and aflatoxin for quality control to provide a reference for other pre-mashed traditional Chinese medicines.