Frontiers in Pharmacology
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2021
·
IF 5.811
Bian Zhenhua,Zhang Wenming,Tang Jingyue,Fei Qianqian,Hu Minmin,Chen Xiaowei,Su Lianlin,Fei Chenghao,Ji De,Mao Chunqin,Tong Huangjin,Yuan Xiaohang,Lu Tulin
Purpose: This study aimed to investigate the potential mechanisms and related bioactive components of ZSS for the treatment of insomnia.Method: The insomnia model of rat induced by PCPA was established. After oral administration of ZSS extract, the general morphological observation, pentobarbital sodium-induced sleep test and histopathological evaluation were carried out. Network pharmacology, assisted by UHPLC-Q-Exactive-MS/MS analysis, was developed to identify the targets of ZSS in the treatment of insomnia, as well as the corresponding signaling pathways. In addition, we validated the identified targets and pathways by RT-qPCR and immunohistochemical analysis.Results: The pentobarbital sodium-induced sleep test, determination of 5-HT and GABA levles in hypothalamic tissues and HE staining showed that ZSS extract was an effective treatment for insomnia. Network pharmacology analysis identified a total of 19 candidate bioactive ingredients in ZSS extract, along with 433 potentially related targets. Next, we performed protein-protein interaction (PPI), MCODE clustering analysis, GO functional enrichment analysis, KEGG pathway enrichment analysis, and ingredient-target-pathway (I-T-P) sub-networks analysis. These methods allowed us to investigate the synergistic therapeutic effects of crucial pathways, including the serotonergic and GABAergic synapse pathways. Our analyses revealed that palmitic acid, coclaurine, jujuboside A, N-nornuciferine, caaverine, magnoflorine, jujuboside B, and betulinic acid, all played key roles in the regulation of these crucial pathways. Finally, we used the PCPA-induced insomnia in rats to validate the data generated by network pharmacology; these in vivo experiments clearly showed that pathways associated with the serotonergic and GABAergic system were activated in the rats model. Furthermore, ZSS treatment significantly suppressed high levels of HTR1A, GABRA1, and GABRG2 expression in the hypothalamus and reduced the expression levels of HTR2A.Conclusion: Based on the combination of comprehensive network pharmacology and in vivo experiments, we successfully identified the potential pharmacological mechanisms underlying the action of ZSS in the treatment of insomnia. The results provide a theoretical basis for further development and utilization of ZSS, and also provide support for the development of innovative drugs for the treatment of insomnia.
研究领域:
药理学
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神经科学
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中医药
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DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2023
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IF 6
Xiaoxia Xia,Fuhua Li,Huan Ran,Jichun Zhao,Xiaojuan Lei,Lin Lei,Jing Wen,Gengsheng Xiao,Kaifang Zeng,Jian Ming
Jujube powder is of high nutritional value, but it is easy to absorb moisture and agglomerate, leading to the deterioration of jujube powder quality. Therefore, it is necessary to decrease the hygroscopicity of jujube powder. In this study, the effect of jujube kernel powder on the moisture absorption performance of jujube powder was studied by adding different contents of jujube kernel powder and measuring the moisture absorption performance at different humidity levels. The results showed that the addition of jujube kernel powder could effectively reduce the color difference change of jujube powder during moisture absorption, and reduce the hardness and stickiness of jujube powder during agglomeration. The addition of jujube kernel powder into jujube powder effectively reduced the moisture content of jujube powder, and therefore significantly decreased the caking degree of jujube powder, and the higher content of jujube kernel powder added in jujube powder, the lower the balanced dry basis moisture content of jujube powder. Such a hygroscopic behavior could be well fitted by the Peleg model, and the goodness of fit was 0.9899. Adding jujube kernel powder into jujube powder is a suitable way to positively affect the quality of jujube powder.
研究领域:
食品科学
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营养学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
·
IF 4.784
Zhen Wu,Hong Li,Yongde Wang,Dajian Yang,Hongjun Tan,Yong Zhan,Yong Yang,Yang Luo,Gang Chen
As a discarded byproduct of jujube ( Z . jujuba ), its seeds contain various biological components. Response surface methodology was used to optimize ultrasound-assisted heating extraction conditions of polysaccharides from Z . jujuba cv . Ruoqiangzao seeds (ZJSPs). The optimal parameters were as follows: temperature 83.1 °C, time 100 min, ultrasonic power 140 W, and water-material ratio 33.5 mL/g, allowed a maximum yield of 1.97%. One main fraction (ZJSPs-1) was successfully purified by ion-exchange and gel-permeation chromatography. With a molecular weight of 342 kDa, ZJSPs-1 was composed of arabinose, glucose, xylose, galactose and rhamnose. The presence of pyranose-form sugars as well as both α- and β-configurations was validated by FT-IR and 1 H NMR. TG/DSC indicated that ZJSPs-1 has a favorable thermal stability. XRD suggested that ZJSPs-1 exhibited both crystalline and amorphous portions. ZJSPs-1 was in aggregates of homogenous-dense honeycomb like structures observed by SEM and AFM. ZJSPs-1 possessed antitumor activities against HeLa cells in a dose- and time-dependent manner at 24 and 48 h with IC 50 of 164.6 and 87.1 μg/mL, respectively. Fluorescent microscopic and flow cytometry revealed that ZJSPs-1 inhibited the proliferation of HeLa cells through apoptosis. Z . jujuba seeds are good sources for antitumor polysaccharides in pharmaceutical and food industries.
研究领域:
食品科学
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药学
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生物化学
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DOI
PubMed
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
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2023
·Vol. 57
·期 5
·712-724
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IF 0.9
Li Danqi,Li Weihong,Shi Wenhao,Wu XiaoJing,Liu Xuegui,Gao Pinyi
Depression is a common mental health disease, with the characteristics of significant and persistent low mood. Traditionally, Ziziphus jujuba Mill . was used to treat depression. However, its chemical pharmacologic profiles remain to be elucidated. The present study was aimed to explore the potential targets and mechanisms of Z. jujuba in the treatment of depression using network pharmacology and in vitro neuroprotective experiment. In this study, 11 compounds of Z. jujuba were obtained by multiple column chromatography. Based on the network pharmacology, the C-T network was established by the results of molecular docking. The information on target proteins was enriched via DAVID database, followed by the analysis of GO and KEGG. The results indicated that 10 compounds, 5 target proteins and 3 signaling pathways played important roles in treating depression. Based on the predicted result of network pharmacology, compounds 1 , 9 and 10 were identified with significant neuroprotective effects by in vitro cell experiments with human neuroblastoma cell line SH-SY5Y. This study was the first to investigate the mechanisms of Z. jujuba action in the treatment of depression from the system level, and could provide the basis of the mechanism with action of compounds for the in-depth utilization of Z. jujuba.
研究领域:
中药学
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神经科学
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生物信息学
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DOI
高影响因子
BRAIN RESEARCH BULLETIN
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2025
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IF 3.7
Zhen Zhang,Xinyue Che,Tingyu Feng,Juntao Zou,Guangpei Chen,Wenping Guo,Chunmei Ma,Haozhe Yuan,Jingying Chen,Xiaowu Xu
Objective Jujuboside A (JB-A) is the major component of Semen Ziziphi Spinosae (SZS), a traditional Chinese herbal medicine used to treat sleep with clinical efficacy. This is the first study to investigate the effects of JB-A on mitochondrial structure and function in the prefrontal cortex of the insomnia model mice. Methods Young adult C57BL/6 mice were induced to develop insomnia by P-chlorophenylalanine. After 14 d of JB-A treatment via gavage, anxiety level was assessed using the open field and elevated plus maze tests. Next, the mitochondrial metabolic activity and morphological changes in the prefrontal cortex of each group of mice, as well as their effects on mitochondrial membrane potential, oxidative phosphorylation levels, and cytochrome c (Cyt c) content in neurons were measured. Results In our mouse model, JB-A ameliorated anxiety-like behaviors; up-regulated the membrane potential (Δψm) and had a therapeutic effect on the metabolic activity and damaged microscopic structure of mitochondria in the prefrontal cortex; effectively improved mitochondrial function by increasing the expression of Cyt c oxidase I and IV proteins, ATPase activity, and ATP content; and reduced the accumulation of Cyt c in the neuronal cytoplasm while inhibiting mitochondrial permeability transition pore (mPTP) opening. Conclusions JB-A can improve insomnia by restoring mitochondrial intracellular oxidative phosphorylation, regulating mPTP to maintain mitochondrial homeostasis, and alleviating structural damage, providing a scientific basis for finding new targets for insomnia treatment.
研究领域:
神经科学
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药理学
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传统中医研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2016
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IF 3.138
Li Zhang,Xinquan Liu,Yongjie Wang,Guangpu Liu,Zhen Zhang,Zhongxi Zhao,Huiling Cheng
Zizyphus jujuba has been used as a traditional Chinese medicinal herb since ancient time. Polysaccharides have been found to be important bioactive compounds in the jujube. This work was designed to investigate the physicochemical characteristics and bioactivities of polysaccharides purified from Zizyphus jujuba cv. Muzao . Water-soluble polysaccharides were extracted using an ultrasonically assisted extraction method. The purified polysaccharides (HJP) were obtained by deproteinization and decoloration. Three main fractions (HJP1, HJP2 and HJP3) were isolated using DEAE-Sepharose fast flow ion-exchange chromatography. The purified polysaccharides were found to consist of mannose, rhamnose, galactose, galacturonic acid, glucose and arabinose at various levels for different fractions. The HJP and its three main fractions displayed DPPH radical scavenging activities as well as relatively strong reducing power and HJP had stronger activities than homogeneous compositions. Moreover, the results from in vitro immunological activities studies indicated that HJP could improve the phagocytosis activity of THP-l cells and had effect on the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In conclusion, the polysaccharides from Zizyphus jujuba cv. Muzao were discovered to have antioxidative and immunological activities.
研究领域:
药理学
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生物化学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 9
·8259-8272
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IF 4.171
Shuhua Shan,Yue Xie,Chengying Zhang,Bin Jia,Hanqing Li,Zhuoyu Li
Homology of medicine and food-zizyphi spinosi semen (ZSS) exhibits abundant pharmacological activities, such as sedation, hypnosis and anti-depression. In the present study, the water soluble polyphenols extracted from ZSS via the acid digestion method were named ZSSP, and exhibited significant anti-colorectal cancer (CRC) activity, characterized by restraining cell proliferation, promoting cell apoptosis and increasing chemo-sensitivity of CRC cells. The potential of ZSSP in vivo was further evaluated in an AOM/DSS-induced colitis-associated carcinogenesis (CAC) mouse model. Intriguingly, ZSSP diminished the number and volume of CAC polyps in mice in a dose-dependent manner, and effectively limited the damage of mice organs induced by AOM/DSS. The immunohistochemistry result showed that the elevated CRC early markers in CAC mice, such as COX-II, EMR1, and Ki67, were potently prevented by the ZSSP treatment. Further, the component in ZSSP with the anti-CRC activity was identified as spinosin by the macroporous resin of SP207 and RP-HPLC-MS/MS. Interestingly, during the extraction process, sodium ions were introduced forming spinosin·Na+, which had better water solubility and more remarkable anti-CRC activity than the spinosin. This study provides a new pharmacological property of spinosin derived from ZSS, inhibiting the growth of human CRC cells and colitis-associated CRC in mice, which indicates its potential use as a natural agent against CRC.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2024
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IF 5.3
Remah Sobhy,Jianing Zhang,Zhihua Li,Xiaobo Zou,Asad Nawaz,Noman Walayat,Salim Manoharadas,Yangyang Jia,Mahmoud Salah
We aimed at tabulating and characterizing a flavan-3-ol isolated from date seeds into date seed pills (DSP) as a commercial healthcare pill, and deeply studying their anti-glycoxidation impacts on bovine serum albumin using multi-dimensional approaches SDS-PAGE/NBT, UPLC-ESI-Q-TOF-MS, antiradical via Fenton-type reaction, multispectral, and molecular docking. Results showed that DSP were successfully tabulated (an encapsulation efficiency of 98.78 %) with high antioxidant values via noncovalently binding with whey proteins supported by FTIR and lib-dock results. DSP dose-dependently decayed fluorescent-AGEs by 16.77, 5.32, and 37.41 % in DSP500-BSA-G/MGO/GO models, respectively, later confirmed by SDS-PAGE and initial precursors mitigation results. The docking results confirmed that DSP could bind with glycoxidation sites of BSA-subunits, namely Lys431, Arg458, and Arg196 via H-bonds. DSP trapped both di-carbonyls and reduced CML-level, where new adducts such as epicatechin-mono/MGO-GO, were identified. 500 µg mL −1 DSP reduced OH-induced fluorescence intensity of AGEs by 43.32 % in BSA-G/Fe 2+ /H 2 O 2 . Our results open a new direction for upcycling by-products as effective glycoxidation inhibitors in a type of healthcare pills in protein-rich models.
研究领域:
药学
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生物化学
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营养保健品
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食品科学
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产品关联
DOI
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2023
·Vol. 75
·期 7
·886-897
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IF 3.3
Du Jianhao,Zhang Fugui,Chen Min,Xiao Yifei,Zhang Li,Dong Linlin,Dong Dong,Wu Baojian
ObjectiveDelirium (acute brain syndrome) is a common and serious neuropsychiatric disorder characterized by an acute decline in cognitive function. However, there is no effective treatment clinically. Here we investigated the potential effect of jujuboside A (JuA, a natural triterpenoid saponin) on cognitive impairment in delirium.MethodsDelirium models of mice were established by injecting lipopolysaccharide (LPS) plus midazolam and implementing a jet lag protocol. Novel object recognition test and Y maze test were used to evaluate the effects of JuA on delirium-associated cognitive impairment. The mRNA and protein levels of relevant clock factors and inflammatory factors were measured by qPCR and Western blotting. Hippocampal Iba1+ intensity was determined by immunofluorescence staining.Key findingsJuA ameliorated delirium (particularly delirium-associated cognitive impairment) in mice, which was proved by the behavioural tests, including a preference for new objects, an increase of spontaneous alternation and improvement of locomotor activity. Furthermore, JuA inhibited the expression of ERK1/2, p-p65, TNFα and IL-1β in hippocampus, and repressed microglial activation in delirious mice. This was attributed to the increased expression of E4BP4 (a negative regulator of ERK1/2 cascade and microglial activation). Moreover, loss of E4bp4 in mice abrogated the effects of JuA on delirium as well as on ERK1/2 cascade and microglial activation in the hippocampus of delirious mice. Additionally, JuA treatment increased the expression of E4BP4 and decreased the expression of p-p65, TNFα and IL-1β in LPS-stimulated BV2 cells, supporting a protective effect of JuA on delirium.ConclusionsJuA protects against delirium-associated cognitive impairment through promoting hippocampal E4BP4 in mice. Our findings are of great significance to the drug development of JuA against delirium and related disorders.
研究领域:
神经科学
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药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Haiqin Ren,Xiangpeng Kong,Yue Zhang,Fanying Deng,Jianli Li,Fuxia Zhao,Pei Li,Ke Pei,Jinyan Tan,Yangang Cheng,Yan Wang,Lu Zhang,Yingli Wang,Xuliang Hao
Ethnopharmacological relevance Ziziphi Spinosae Semen and Polygalae Radix (ZSS-PR) constitute a traditional Chinese herbal combination with notable applications in clinical and experimental settings due to their evident sedative and calming effects. Aligned with traditional Chinese medicine principles, Ziziphi Spinosae Semen supports cardiovascular health, nourishes the liver, and induces mental tranquillity. Simultaneously, Polygalae Radix elicits calming effects, fosters clear thinking, and reinstates proper coordination between the heart and kidneys. ZSS-PR is commonly employed as a therapeutic intervention for various insomnia types, demonstrating distinct clinical efficacy. Our previous study findings provide evidence that ZSS-PR administration significantly reduces sleep onset latency, increases overall sleep duration, and improves abnormal neurotransmitter levels in a murine insomnia model. Aim of study This investigation aimed to scrutinize the intrinsic regulatory mechanism of ZSS-PR in managing insomnia using gut microbiota and serum metabolomics techniques. Materials and methods Mice were given DL-4-Chlorophenylalanine to induce insomnia and then treated with ZSS-PR. The open-field test assessed the animals' spontaneous activity. Concentrations of neurotransmitters, endocrine hormones, and cytokines in the duodenum were measured using enzyme linked immunosorbent assay, and brain histopathology was evaluated with H&E staining. The impact of ZSS-PR on the metabolic profile was examined by liquid chromatography couped to high resolution mass spectrometry, and 16S rDNA sequencing was used to study the influence of ZSS-PR on the gut microbiota. Additionally, the content of short-chain fatty acids (SCFAs) was analyzed by GC-MS. Finally, correlation analysis investigated relationships between biochemical markers, metabolites, SCFAs, and gut microbiota. Results ZSS-PR treatment significantly increased movement time and distance in mice with insomnia and improved pathological impairments in the cerebral cortex and hippocampus. It also restored abnormal levels of biochemical markers in the gut of insomnia-afflicted mice, including 5-hydroxytryptamine , dopamine, gastrin, melatonin, tumour necrosis factor-α, and interleukin-1β. Metabolomics findings showed that ZSS-PR had a significant restorative effect on 15 endogenous metabolites in mice with insomnia. Furthermore, ZSS-PR primarily influenced five metabolic pathways, such as phenylalanine, tyrosine, and tryptophan biosynthesis, glutamine, and glutamate metabolism. Additionally, gut microbiota analysis revealed notable alterations in both diversity and microbial composition after ZSS-PR treatment. These changes were primarily attributed to the relative abundances of microbiota, including Firmicutes, Bacteroidota, Fusobacteriota, Muribaculaceae_unclassified , and Ligilactobacillus . The results of SCFAs analysis demonstrated that ZSS-PR effectively restored abnormal levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid in insomniac mice. Subsequent correlation analysis revealed that microbiota show obvious correlations with both biochemical markers and metabolites. Conclusions The results provide compelling evidence that ZSS-PR effectively mitigates abnormal activity, reduces cerebral pathological changes, and restores abnormal levels of neurotransmitters, endocrine hormones, and cytokines in mice with insomnia. The underlying mechanism is intricately linked to the modulation of gut microbiota and endogenous metabolic pathways.
研究领域:
药理学
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神经科学
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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2019
·
IF 1.773
Yan YAN,Qiang LI,Hui-Zhi DU,Chen-Xi SHEN,Ai-Ping LI,Xiang-Ping PEI,Chen-Hui DU,Xue-Mei QIN
ABSTRACT Ziziphi Spinosae Semen (ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin (5-HT), glutamic acid (Glu), γ -aminobutyric acid (GABA), noradrenaline (NE) and dopamine (DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESI- MS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring (MRM) and the procedure was completed in less than 10 min. The method showed a good linearity ( R 2 > 0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower ( P < 0.01) in para -chlorophenylalanine (PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group ( P < 0.01). Treatment with ZSS aqueous extract (4 or 8 g·kg –1 ·d –1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.
研究领域:
药理学
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神经科学
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中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Neuroscience
·
2024
·
IF 3.2
Hongxiong Zhang,Taixiang Gao,Zhao,Nan Wang,Zhixuan Li,Xuemei Qin,Ying Liu,Rui Wang
Insomnia and depression are psychiatric disorders linked to substantial health burdens. The gut microbiome and metabolomic pathways are increasingly recognized as key contributors to these conditions’ pathophysiology. Suanzaoren Decoction (SZRD), a traditional Chinese herbal formulation, has demonstrated significant therapeutic benefits for both insomnia and depression. This study aims to elucidate the mechanistic effects of SZRD on insomnia and depression by integrating gut microbiome and metabolomic analyses and to assess the differential impacts of SZRD dosages. Using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC–MS), we identified 66 chemical constituents within SZRD. Behavioral assays indicated that low-dose SZRD (LSZRD) significantly ameliorated insomnia symptoms in rat models, whereas high-dose SZRD (HSZRD) markedly improved depressive behaviors. 16S rRNA sequencing revealed that SZRD modulated gut microbiome dysbiosis induced by insomnia and depression, characterized by an increased abundance of short-chain fatty acid (SCFA)-producing genera. Metabolomic profiling demonstrated reduced plasma amino acid metabolites and disrupted γ-aminobutyric acid (GABA) and L-glutamic acid metabolism in the hippocampus of affected rats. SZRD administration restored fecal SCFA levels and ameliorated metabolic imbalances in both plasma and hippocampal tissues. These findings underscore the pivotal role of gut microbiome modulation and metabolic regulation in the therapeutic effects of SZRD, providing a scientific basis for its use in treating insomnia and depression.
研究领域:
药理学
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神经科学
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微生物学
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代谢组学
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中医
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）