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
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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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
Frontiers in Neuroscience
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2024
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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
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DOI
PubMed
高影响因子
Reproductive Sciences
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2024
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IF 2.6
Zhou Nan,Lv Wenqiang,Chen Linna,Chen Kexin,He Qing,Xie Guangyan,Ma Jiachen,Cao Yijuan,Zhang Bei,Zhou Xueyan
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. This study aimed to investigate the therapeutic effects and mechanism of Jujuboside A on PCOS using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Estrogen and androgen homeostasis was evaluated in serum from both clinical samples and PCOS mice. The stages of the estrous cycle were determined based on vaginal cytology. The ovarian morphology was observed by stained with hematoxylin and eosin. Moreover, we analyzed protein expression of cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AhR) in ovary and KGN cells. Molecular docking, immunofluorescence, and luciferase assay were performed to confirm the activation of AhR by Jujuboside A. Jujuboside A effectively alleviated the disturbance of estrogen homeostasis and restored ovarian function, leading to an improvement in the occurrence and progression of PCOS. Furthermore, the protective effect of JuA against PCOS was dependent on increased CYP1A2 levels regulated by AhR. Our findings suggest that Jujuboside A improves estrogen disorders and may be a potential therapeutic agent for the treatment of PCOS. Graphical Abstract
研究领域:
内分泌学
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药理学
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生殖生物学
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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 FOOD SCIENCE AND TECHNOLOGY-MYSORE
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2024
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IF 2.6
Zhu Jie,Zhang Hua-nan,Wu Jia-kai,Li Fei-fei,Liu Yu-qing,Ning Er-juan,Yu Li-qin,Liang Shen
Camelina sativa oil (CSO) and Semen Ziziphi Spinosae oil (SZSO) are functional oils that have beneficial effects on brain health. This study evaluated the sedative and hypnotic effects of vegetable oils with various n − 6/n − 3 polyunsaturated fatty acids (PUFA) ratios and ɑ-linolenic acid (ALA) contents to mice. The n − 6/n − 3 PUFA ratios of CSO (CSO:SZSO = 1:0, 1.8 g/kg), SZSO (CSO:SZSO = 0:1, 1.8 g/kg), CSO-SZSO-L (CSO:SZSO = 1:1, 1.8 g/kg), and CSO-SZSO-H (CSO:SZSO = 1:1, 3.6 g/kg) were 0.51, 140, 1.69, and 1.69, respectively. The doses of ALA administered to mice with p-chlorophenylalanine-induced insomnia were approximately 0.64, 50 × 10 –4 , 0.32, and 0.64 g/kg, respectively. The mice were administered CSO, SZSO, and a low-dose combination of CSO and SZSO for seven days with no obvious hypnotic effects. However, the administration of a high-dose combination of CSO and SZSO significantly prolonged sleep duration in mice with induced insomnia and inhibited the serum levels of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol. Interestingly, there were no significant effects on the structure and function of the hippocampal tissue. The results indicated that the anti-insomnia effects of these vegetable oils were positively correlated with a low n − 6/n − 3 PUFA ratio and the absolute amount of ALA.
研究领域:
营养学
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神经科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）