Potential drug targets on insomnia and intervention effects of Jujuboside A through metabolic pathway analysis as revealed by UPLC/ESI-SYNAPT-HDMS coupled with pattern recognition approach

Wang, Xijun; Yang, Bo; Zhang, Aihua; Sun, Hui; Ge, Yan

doi:10.1016/j.jprot.2011.11.011

Cited by 94 publications

(63 citation statements)

References 43 publications

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“…[13][14][15] Recent studies have revealed that the ethanol extract of EZJ and its constituents produce hypnotic effects through the modulation of neurotransmitter systems including serotonergic and γ-aminobutyric acid (GABA)ergic systems. [16][17][18][19][20] Further, numerous brain pathology models have indicated memory-enhancing effects of EZJ. 21,22) These findings demonstrated that EZJ can modulate brain function and may show anti-AD actions.…”

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confidence: 99%

The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

Kwon

Jung

Jing

et al. 2017

Biological & Pharmaceutical Bulletin

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Ziziphus jujuba is a plant, which bears fruits and seeds that are used for medicinal purposes in Traditional oriental medicine. The seed of Zizyphus jujuba var. spinosa (EZJ) has been also traditionally used for psychiatric disorders in Chinese and Korean medicines. Recent findings have indicated that EZJ improves memory impairment, a common symptom of various neurological diseases. However, the effects of EZJ on amyloid β (Aβ) toxicity, which is a main cause of Alzheimer's disease (AD), remain to be elucidated. To illuminate the potential anti-AD effect and mechanism in the mouse hippocampal tissue, we examined the effect of standardized EZJ on Aβ-induced synaptic long-term potentiation (LTP) deficit in the hippocampal tissue. EZJ blocked Aβ-induced LTP deficits in a concentration-dependent manner. Moreover, EZJ increased brain-derived neurotrophic factor (BDNF) level in naïve hippocampal slices. The finding that the blockade of BDNF receptor reduced the effect of EZJ suggests that EZJ ameliorates the Aβ-induced LTP deficit through BDNF/topomyosin receptor kinase B (TrkB) signaling. However, transcription or translation inhibitors failed to block the effect of EZJ, suggesting that BDNF synthesis is not required for the action of EZJ on LTP. Finally, we found that EZJ stimulates plasmin activity. In contrast, plasmin inhibitor blocked the effect of EZJ on the Aβ-induced LTP deficit. Our findings indicate that EZJ ameliorates Aβ-induced LTP deficits through BDNF/TrkB signaling. This phenomenon is induced by a regulatory effect of EZJ on the post-translation modification of BDNF.Key words Zizyphus jujuba var. spinosa; amyloid β (Aβ); long-term potentiation; brain-derived neurotrophic factor (BDNF); plasmin Alzheimer's disease (AD) is a typical neurodegenerative disorder showing progressive memory decline. Learning and memory deficits and the loss of higher cognitive function are observed in the early stage of AD. 1) AD is characterized by the amyloid plaques and neurofibrillary tangles accumulation in the brain. Although the specific initiators of AD still remain unknown, mounting evidence suggests that amyloid β (Aβ) plays an important role in the progress of the AD pathology. Extensive research revealed that soluble Aβ oligomers block hippocampal long-term potentiation (LTP), the cellular model of learning and memory.2,3) These indicated that hippocampal LTP could be a target for developing an anti-AD drug.Brain-derived neurotrophic factor (BDNF) is an endogenous neurotrophin family important for the structural and functional plasticity of the brain. 4,5) In AD patients, BDNF level is decreased in the several brain regions even in pre-clinical stages (very earl time) of AD.6,7) Because BDNF is critical for neuronal survival, neuronal function, synaptic plasticity, and cognition, BDNF deficiency may result from AD pathology.8-10) Recent findings have shown that BDNF has protective effects against the toxic effects of Aβ peptides. 11) Therefore, BDNF and its signaling activators are being investigated for applicat...

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confidence: 99%

The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

Kwon

Jung

Jing

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Metabolomics has recently demonstrated significant potential in many fields, including disease diagnosis, investigations of toxicological mechanisms, and determination of the mechanism of drug intervention. To explain the action mechanism of drugs, metabolomics methodology has been widely used (Wang et al, 2012a, b). NBP is the most common urological diagnosis in men under 50 years of age and is the third common urologic diagnosis in men over 50 years of age.…”

Section: Discussionmentioning

confidence: 99%

Berberine Ameliorates Nonbacterial Prostatitis via Multi-Target Metabolic Network Regulation

Sun

Wang

Zhang

et al. 2015

OMICS: A Journal of Integrative Biology

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Metabolomics has been increasingly applied to discovering biomarkers and identifying perturbed pathways. Berberine has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties, but its mechanisms for treating nonbacterial prostatitis (NBP) remain unclear completely. We developed the untargeted metabolomics approach based on UPLC-Q-TOF-HDMS to profile the metabolite changes in urine samples in order to discover novel potential biomarkers to clarify mechanisms of berberine in treating a rat model of capsaicin-induced nonbacterial prostatitis (NBP). The changes in metabolic profiling were restored to their base-line values after berberine treatment according to the principal component analysis (PCA) score plots. Fourteen different potential biomarkers and five acutely perturbed metabolic pathways contributing to the treatment of NBP were discovered and identified. Specifically, the berberine-treated rats are located closer to the normal group, indicating that the NBP-induced disturbances to the metabolic profile were partially reversed by berberine treatment. After treatment with berberine, the relative contents of 12 potential biomarkers were effectively regulated, which suggested that the therapeutic effects of berberine on NBP may involve regulating disturbances to the metabolism. Our results show that the protective effect of berberine occurs in part through a reversal of the NBP-caused disturbances.

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“…In the present study, a different method for embryonic evaluation, the MS, was applied. Mass Spectrometry allied with PLS-DA model has been successfully employed in biomarker identification in other areas than reproduction (Duan et al, 2011;Wang et al, 2012a;Wang et al, 2012b;Yang et al, 2012). Recently, our group also applied an embryo viability prediction (Cortezzi et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Prediction of Blastocyst Formation by Day Three Embryo Culture Medium Mass Spectrometry Lipid Fingerprinting

Braga

Setti

Cabral

et al. 2015

JBRA Assisted Reproduction

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Objective: To identify lipid markers of blastocyst formation by day three culture medium mass spectrometry (MS) fingerprinting. Methods: For this study, 50 embryo samples from culture media were harvested on day three, from patients undergoing embryo transfers on day five. Samples were split into groups based on their degree of expansion and hatching status on day five n=25 and No-Blastocyst, n=25) and its secretomes were analysed by MS. Mass spectra fingerprinting was acquired using a Q-Tof spectrometer (LC-MS, Agilent 6550 iFunnel Q-TOF) equipped with an automated injector. The data was analysed using the principal component analysis (PCA) followed by a partial least square discrimination analysis (PLS-DA), combined with variable influence in the projection (VIP) scores. Results: In total, there were 1,657 ions found, in which 165 ions were differently expressed between groups, with a fold chance ≥ 4x and P<0.001, in the t-test. PLS-DA showed a clear separation between the groups and among 15 VIPs selected by the program, 13 of them were highly expressed in the Complete-Blastocyst Group and two were expressed in the No-Blastocyts Group. Besides embryo status on day five, the PLS-DA was also able to classify samples according to patients' age. Lipids supposedly highly expressed in the Complete-Blastocyst Group included: isoprenoids, diacylglycerols, sterols, fatty esters, secosteroids, phosphosphingolipids, glycerophosphates and diacylglycerophosphates, while fatty amides were suggested to be highly expressed in the No-Blastocysts Group. Conclusions: Day three culture medium MS is a promising approach for the identification of embryos that should be cultured until day five.

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Potential drug targets on insomnia and intervention effects of Jujuboside A through metabolic pathway analysis as revealed by UPLC/ESI-SYNAPT-HDMS coupled with pattern recognition approach

Cited by 94 publications

References 43 publications

The Seed of <i>Zizyphus jujuba</i> var. <i>spinosa</i> Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

The Seed of <i>Zizyphus jujuba</i> var. <i>spinosa</i> Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

Berberine Ameliorates Nonbacterial Prostatitis via Multi-Target Metabolic Network Regulation

Non-Invasive Prediction of Blastocyst Formation by Day Three Embryo Culture Medium Mass Spectrometry Lipid Fingerprinting

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