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jujuboside a ameliorates tubulointerstitial fibrosis in diabetic mice through down-regulating the YY1/TGF-β1 signaling pathway

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Chinese Journal of Natural Medicines 2022年第9期20卷 656-668页

作者： LIU Yang-Yang LI Lin JI Bei HAO Shi-Long KUANG Xiao-Feng CAO Xin-Yun YUAN Jia-Yu JIANG Zhen-Zhou QIAN Si-Tong WEI Chu-Jing XU Jing YIN Xiao-Xing LU Qian YANG Ting-Ting Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing 210009China

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 *** showed that administration of Ju A not only down-regulated fasting blood glucose(FBG)levels,but also improved hyperlipidemia and renal function in diabetic ***,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 *** to in vitro studies,the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose(HG)cultured HK-2 *** together,these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.

关键词： Diabetic nephropathy jujuboside a Tubulointerstitial fibrosis Extracellular matrix YY1/TGF-β1 signaling pathway

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jujuboside a inhibits oxidative stress damage and enhances immun-omodulatory capacity of human umbilical cord mesenchymal stem cells through up-regulating IDO expression

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Chinese Journal of Natural Medicines 2022年第7期20卷 494-505页

作者： CHEN Ji-Cong XIAO Hong-He ZHANG Qiang KONG Liang WANG Tian-Min TIAN Yu ZHAO Yu-Meng LI He TIAN Jin-Ming WANG Cui YANG Jing-Xian School of Pharmacy Liaoning University of Traditional Chinese MedicineDalian 116600China Department of Neurology Dalian Municipal Central Hospital Affiliated to Dalian Medical UniversityDalian 116033China

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation *** 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 ***,Hoechst 33258 staining,lactate dehydrogenase test,measurement of malondialdehyde,Western blot,high-performance liquid chromatography;and flow cytometry were *** results indicated that JuA(25μmol·L−1)promoted the proliferation of hUC-MSCs,but did not affect the differentiating capability of these *** 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 *** 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,*** 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.

关键词： Human umbilical cord mesenchymal stem cells jujuboside a Immunomodulation Oxidative stress Indoleamine 2,3-dioxygenase

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jujuboside a Improved Energy Metabolism in Senescent H9c2 Cells Injured by Ischemia, Hypoxia, and Reperfusion through the CD38/Silent Mating Type Information Regulation 2 Homolog 3 Signaling Pathway

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World Journal of Traditional Chinese Medicine 2023年第3期9卷 322-329页

作者： Yi-Ran Hu Hui-Yan Qu Jia-Ying Guo Tao Yang Hua Zhou Shuguang Hospital Shanghai University of Traditional Chinese MedicineShanghaiChina Institute of Cardiovascular Disease Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina Institute of Cardiovascular Disease Shanghai Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western MedicineShanghaiChina

Objective:This study explored the myocardial protection role of jujuboside a through an ischemia–hypoxia–reperfusion(IHR)*** and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish an aging and IHR *** are four groups of experiments:Control,IHR,D-gal+IHR,and D-gal+IHR+jujuboside *** 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 *** cytokines level was detected by enzyme-linked immunosorbent *** 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 ***: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 *** 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 ***:jujuboside a inhibited the expression of CD38,improved energy metabolism disorder,and mitochondrial function,and decreased inflammation in D-gal-induced H9c2 cells.

关键词： CD38 D-galactose ischemia hypoxia and reperfusion jujuboside a nicotinamide adenine dinucleotide

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Upregulation of Mark3 and Rpgripl mRNA expression by jujuboside a in mouse hippocampus

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Acta Pharmacologica Sinica 2007年第3期 334-338页

作者： Cheng WANG Zi-li YOU~2 Qing XIA Tao XIONG Yang XIA De-zhong YAO School of Life Science and Technology University of Electronic Science and Technology of China,Chengdu 610054,China

Aim:To investigate the effect of jujuboside a(JuA)on modulating gene expres-sion in the ***:The spontaneous activity of mice wasmonitored,and the differential display polymerase chain reaction was adapted toscreen differentially-expressed genes modulated by JuA in the mouse ***:JuA significantly decreased the total activity intensity(P<0.01 vs control)at a dosage of 80 mg/kg,and the genes MAP/microtubule affinity-regulatingkinase3(Mark3)and retinitis pigmentosa GTPase regulator interacting protein l(Rpgripl)were upregulated by JuA in the mouse ***:JuAhad an inhibitory effect on the spontaneous activity of the mice,and JuA regu-lated the transcription of Mark3 and Rpgripl in the mouse hippocampus.

关键词： jujuboside a hippocampus DD-PCR Mark3 Rpgrip1

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New spinosin derivatives from the seeds of Ziziphus mauritiana

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Natural Products and Bioprospecting 2013年第3期3卷 93-98页

作者： Bin WANG Hong-Tao ZHU Dong WANG Chong-Ren YANG Min XU Ying-Jun ZHANG State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China

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 *** structures were elucidated by means of spectroscopic analysis and chemical *** 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.

关键词： Ziziphus mauritiana Rhamnaceae seeds spinosin derivatives jujuboside a acetylcholinesterase inhibitory

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A study of storage conditions for pre-mashed fried Semen Zizyphi Spinosae using a multi-factor orthogonal design

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Traditional Medicine Research 2021年第6期6卷 52-58页

作者： Duo Liu Ze-Xian Yu Mei Sang Hui-Jun Pan Yong Peng Xiao-Qian Ren Yan Gao Yan Gu Fang Qian Jiading Hospital of Traditional Chinese Medicine Shanghai 201800China Shanghai Skin Disease Hospital Shanghai 200443China Skin Disease Hospital of Tongji University Shanghai 200443China

Background:To facilitate the preparation of traditional Chinese medicines they are pre-mashed,i.e.,mashed in ***,storage conditions for pre-mashed traditional Chinese medicines are based on subjective judgments of pharmacists,and the best storage conditions have not generally been *** Zizyphi Spinosae is a commonly used traditional Chinese medicine,and it is usually used after it is *** medicine needs to be mashed in a timely manner to ensure its *** Chinese Pharmacopoeia provides a limit for its aflatoxin ***:The orthogonal experimental design method optimizes the best plan for pre-mashed fried Semen Zizyphi *** conditions were defined using the L^(9)(3^(4))orthogonal design *** factors and three levels were used to study storage *** 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 ***: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 *** B1 and total aflatoxins(aflatoxins B1,B2,G1 and G2)were not detected under these ***:There is no requirement for traditional Chinese medicines to be *** 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.

关键词： Semen Zizyphi Spinosae orthogonal experimental design pre-mashed jujuboside a spinosin aflatoxin

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Sleep deprivation: a major risk factor for early progression of Alzheimer's disease

Sleep deprivation: a major risk factor for early progression...

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中国神经科学学会第十二届全国学术会议

作者： Sidra Tabassum Afzal Ali Misrani Li Yang Cheng Long School of Life Sciences South China Normal University School of Psychology and Center for Studies of Psychological Application South China Normal University Institute of Brain Science and Rehabilitation Medicine South China Normal University

Alzheimer’s disease(AD) is a neurodegenerative disorder characterized by progressive cognitive impairment that is a current and growing public health crisis but only has minimally effective treatments. Age is the greatest risk factor for AD, however the progression to cognitive impairment likely results from genetic(e.g., ApoE4 or mutations in APP, PS1 or PS2) and environmental(e.g., exercise, diet, and sleep) factors that influence AD pathology. The relationship between sleep and AD has important implications for the optimal clinical management and potential treatment strategies in patients with AD. Sleep disturbances are prevalent in AD patients and may play a significant role in the advancement of pathology and disease progression. However, the mechanisms underlying poor sleep and disturbed circadian rhythms in AD are poorly understood. The aim of this study was to explore the effects of disrupted sleep in AD prone mouse model. APP/PS1 mice at 3 months of age were sleep deprived for 72 hours using automated treadmill method and compare with age matched non-sleep deprived APP/PS1 mice as control. Open field test and morris water maze(MWM) were used to assess neurobehavioral symptoms in sleep deprived and control mice, which showed an increase in anxiety like behavior, a decrease in locomotor activity and significant decrease in learning and memory. To further explore the molecular mechanism underlying these behavioral alterations, major excitatory and inhibitory protein levels(GluR1, GluR2, NMDAR, GS, GABA α1, GABAB1, GABA) were analyzed by western blot. Results showed a significant increase in Glu R1 and decrease in GABAAα1 in prefrontal cortex while same trend was observed in hippocampus. These findings suggest altered coordination between excitatory and inhibitory neurons in sleep deprived AD mouse model. Treatment with jujoboside A, a widely used hypnotic-sedative component of semen ziziphi, normalized Glu R1 levels and improved learning and memory behavior in

关键词： memory anxiety behavior sleep deprivation Alzheimer’s disease jujuboside a

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