Inhibitory effects of jujuboside A on EEG and hippocampal glutamate in hyperactive rat

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.

The effect of Jujuboside A on the evoked field potentials of Granule cells in dentate gyrus

Jujuboside A (JuA) is a main component of Jujubogenin extracted from the seeds of Ziziphus. The authors have not seen any report on JuA's direct effect on the neurons of the central nervous system. This study aimed to assess the effect of JuA on paired pulse responses of dentate gyrus granule cells in urethane anaesthetized rats, used intracerebroventricular (i.c.v.) JuA to mimic in vitro bath conditions in vivo. Paired pulse stimuli with 80ms interpulse interval were used to stimulate the perforant pathway. Evoked responses were recorded in the dentate gyrus cell layer after i.c.v. administration of 0.9% normal saline or JuA. In the first responses, the slopes 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 slopes 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.

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

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.

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

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.

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

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.

New spinosin derivatives from the seeds of Ziziphus mauritiana

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.

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

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.

Primary Study of Novel Method for Determination of Saponin in Ziziphi Spinosae Semen (<i>Suan-Zao-Ren</i>) by Digitally Scanning the Photo of the HPTLC Image without Configuration of TLC Scanner Facility

Conventional quantity determination of Chinese herbal medicines by High-Performance Thin-Layer Chromatography (HPTLC) must be carried out on a TLC scanner for measuring the marker component on the HPTLC plate. Generally the HPTLC image of the herbal drug always takes the photograph as the permanent visual document. Considering the photo of the HPTLC image preserving all the visual quality-related parameters, there might be an alternative cost/effective approach worth studying. It would be presumably applicable to use the exclusively developed software as a virtual scanner instead of the TLC Scanner instrument to do digital scanning, integrating and calculating target components in the photo of the HPTLC image. It means digitally scanning the photo of the HPTLC image solely with software does the same thing as the instrumental scanner does. Based on this protocol, we primarily conducted the assay of the contents of the major saponins, jujuboside a and jujuboside b, in Ziziphi Spinosae Semen (Suan-Zao-Ren). Using home-developed software “digiscan” for acquiring the raw data and integrating the peaks area of the target components with “Origin Pro”, the contents of jujuboside a and jujuboside b can then be calculated respectively. The primary investigated experiment results were well compatible with official HPLC-ELSD method in Chinese Pharmacopoeia. The methodology validation and comparative analysis with HPLC confirmed that the unprecedented method is acceptable. The advantage of the recommended approach is far more simple, flexible and cost/effective than the conventional method, and it can be done at anytime and anywhere once only if the high quality HPTLC image photo is available. There would be a bright perspective for application to other herbal medicines. And the one-stop software for merging digital scanning, integration and calculation together is in progress.

Mimetic Preparation of Analogues of Territrem B, A Potent Acetylcholinesterase Inhibitor

A mimetic synthesis of a potent acetylcholinesterase inhibitor, Territrem B, was carried out from the naturally occurring jujubosides. The anti-AChE activity of the product, which possesses the 2-en-1-one pharmacophore and the aromatic ring, was measured. The aromatic ring moiety seemed to be less influencing when comparing with the 2-en-1-one moiety.