BIOMEDICAL CHROMATOGRAPHY
·
2021
·Vol. 35
·期 6
·e5084
·
IF 1.902
Jian-Sha Li,Hong-mei Qiu,Qing-song Jiang,Yong-hong Liu,Jing Zhang,Tao Gong,Xin-hui Jiang
Emerging evidence suggests that amino acid (AA) neurotransmitters play important roles in the pathophysiological processes of cerebral ischemia. In this work, an HPLC with fluorescence detection (HPLC-FLR) method was developed for the simultaneous determination of 18 AAs in the cortex and plasma after cerebral ischemia in mice. The ischemia model was prepared by bilateral common carotid artery occlusion, and then the cortex and plasma of the sham, ischemia, and naringenin groups were collected. Based on the protein precipitation method, a simple and effective sample preparation method was developed. The treated sample contained minimal proteins and lipids. The analysis of the sample was performed by the proposed HPLC-FLR method in combination with o -phthalaldehyde. The results showed a statistically significant increase in excitatory AAs (aspartic acid and glutamic acid), inhibitory AAs (glycine and 4-aminobutyric acid), phenylalanine, citrulline, isoleucine, and leucine levels, and a decrease of glutathione and phenylalanine levels when compared with the sham group in the cortex. Besides, the administration of naringenin had significant effects on excitatory AAs, inhibitory AA (glycine), glutamine, tyrosine, phenylalanine, and leucine levels when compared with the sham group in the cortex. These findings could be utilized in studying and clarifying the mechanisms of ischemia.
研究领域:
神经科学
·
生物化学
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PubMed
高影响因子
CELL PROLIFERATION
·
2025
·Vol. 58
·期 10
·e70057
·
IF 5.6
Yiyang Wang,Xinyi Du,Chenxi Duan,Miaomiao Wang,Ying Zhu,Lihua Wang,Jun Hu,Yanhong Sun
Effective treatment of depression poses a major clinical challenge, accompanied by considerable social and emotional burdens. Electroacupuncture, a non-pharmacological modality derived from traditional Chinese medicine, offers a promising alternative for depression treatment due to its safety and efficacy. However, its underlying molecular mechanisms remain unclear. In this study, a corticosterone-induced depression model in C57BL/6 mice was employed and electroacupuncture was applied to stimulate at Zusanli (ST36) acupoint. The results demonstrated that electroacupuncture effectively alleviated depression-like symptoms and restored the structural morphology and plasticity of neurons in the hippocampal CA1 region. Further analysis revealed a significant upregulation of brain-derived neurotrophic factor (BDNF) and β-type calmodulin-dependent protein kinase II (CaMKIIβ), which are associated with neuronal plasticity regulatory pathways. This study elucidates the potential molecular mechanisms by which electroacupuncture alleviates depression through the regulation of neuroplasticity, providing an experimental basis for its clinical application.
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PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2018
·Vol. 34
·期 2
·141-149
·
IF 2.491
Xia Wang,Baida Kong,Bingnan He,Lai Wei,Jianbo Zhu,Yuanxiang Jin,Yudong Shan,Weitao Wang,Chunqiang Pan,Zhengwei Fu
8:2 Fluorotelomer alcohol (8:2 FTOH) is widely used in houseware and industrial goods and is ubiquitous in the surrounding environment. 8:2 FTOH has been linked to hepatoxicity, nephrotoxicity, and reproductive toxicity, as well as endocrine-disrupting effects. However, as of yet, the research regarding immunotoxicity of 8:2 FTOH remains largely limited. In the present study, adult male C57BL/6 mice were administered with 10, 30, and 100 mg/kg/d 8:2 FTOH by gavage for 28 days to investigate its immunotoxicity in vivo. The results showed that exposure to 8:2 FTOH caused increases in liver weight and histological changes in the liver, including vacuolation, cell swelling, immune cell infiltration, karyopyknosis and nuclear swelling. No histological change in either the spleen or the thymus was observed after administration of 8:2 FTOH. In addition, exposure to 8:2 FTOH reduced the concentration of IL-1β in serum, and mRNA levels of IL-1β, IL-6 , and TNF-α in both the thymus and spleen. CXCL-1 mRNA expression was downregulated in both the liver and thymus after 8:2 FTOH administration, while only IL-1β mRNA expression was upregulated in the liver. Moreover, the exposure of primary cultured splenocytes to 8:2 FTOH inhibited the ConA-stimulated proliferation of splenocytes at concentrations of 30 and 100 μM, and the LPS-stimulated proliferation of splenocytes at 100 μM. Furthermore, 8:2 FTOH inhibited the level of secreted IFN-γ in ConA-stimulated splenocytes. The results obtained in the study demonstrated that 8:2 FTOH posed potential immunotoxicity and liver injury in mice. Our findings will provide novel data for the health risk assessment of 8:2 FTOH.
研究领域:
毒理学
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免疫学
·
环境健康
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PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2021
·Vol. 43
·期 1
·146-156
·
IF 6.15
Yao Xin-peng,Jiao Ting-ying,Jiang Yi-ming,Fan Shi-cheng,Zhao Ying-yuan,Yang Xiao,Gao Yue,Li Fei,Zhou Yan-ying,Chen Pan-pan,Huang Min,Bi Hui-chang
Mifepristone (Mif), an effective synthetic steroidal antiprogesterone drug, is widely used for medical abortion and pregnancy prevention. Due to its anti-glucocorticoid effect, high-dose Mif is also used to treat Cushing’s syndrome. Mif was reported to active pregnane X receptor (PXR) in vitro and PXR can induce hepatomegaly via activation and interaction with yes-associated protein (YAP) pathway. High-dose Mif was reported to induce hepatomegaly in rats and mice, but the underlying mechanism remains unclear. Here, the role of PXR was studied in Mif-induced hepatomegaly in C57BL/6 mice and Pxr -knockout mice. The results demonstrated that high-dose Mif (100 mg · kg −1 · d −1 , i.p .) treatment for 5 days significantly induced hepatomegaly with enlarged hepatocytes and promoted proliferation, but low dose of Mif (5 mg · kg −1 · d −1 , i.p .) cannot induce hepatomegaly. The dual-luciferase reporter gene assays showed that Mif can activate human PXR in a concentration-dependent manner. In addition, Mif could promote nuclear translocation of PXR and YAP, and significantly induced the expression of PXR, YAP, and their target proteins such as CYP3A11, CYP2B10, UGT1A1, ANKRD, and CTGF. However, Mif (100 mg · kg −1 · d −1 , i.p .) failed to induce hepatomegaly in Pxr -knockout mice, as well as hepatocyte enlargement and proliferation, further indicating that Mif-induced hepatomegaly is PXR-dependent. In summary, this study demonstrated that PXR-mediated Mif-induced hepatomegaly in mice probably via activation of YAP pathway. This study provides new insights in Mif-induced hepatomegaly, and provides novel evidence on the crucial function of PXR in liver enlargement and regeneration.
研究领域:
药理学
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毒理学
·
分子生物学
·
肝病学
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PubMed
高影响因子
Drug Discoveries and Therapeutics
·
2023
·Vol. 17
·期 4
·294-298
·
IF 3.1
Jing Li,Fangzhou Dou,Shasha Hu,Jianjun Gao
Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disorder. Pharmacotherapy serves as the main treatment strategy for IBD; however, the current medications have certain limitations, such as inefficacy and a tendency to induce tolerance, thereby requiring the development of innovative drugs to fulfill therapeutic requirements. A model of acute colitis induced with a solution of approx. 3% dextran sulfate sodium (DSS) has been widely used in preclinical drug development. Nevertheless, this model has some drawbacks, including rapid disease progression leading to mortality in some mice and disparities between the inflammatory characteristics of mice and the pathological features of human IBD. The current study found that mice freely consuming a lower concentration of a DSS solution (1-1.5%) for 10-15 days exhibited milder colitis symptoms. Continued consumption of the DSS solution for 15-20 days resulted in chronic inflammation in colon tissue, accompanied by a significant increase in the proportion of Th1 cells, indicating the involvement of adaptive immune responses. Subsequently, mice were treated with mesalazine or Centella triterpenes while concurrently consuming the DSS solution for 10 days. The treated mice had significant improvements in body weight and colon length compared to the control group. The advantages of this subacute model include minimal mortality among experimental mice and the fact that intestinal mucosal inflammation in mice resembles the pathological features of human IBD, enabling the assessment of drug efficacy against IBD.
研究领域:
免疫学
·
药理学
·
消化病学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Suwen Liu,Xuedong Chang,Jincheng Yu,Weifeng Xu
This study aimed to determine the anti-obesity effects and mechanisms of Cerasus humilis polyphenol (CHP) in C57BL/6 obese mice and 3T3-L1 cells. High-performance liquid chromatography–electrospray ionization-tandem mass spectrometry was used for the qualitative and quantitative identification of CHP components. The obese mice, induced by feeding high-fat diet (HFD), were treated with CHP (250 mg/kg/day) by gavage for 12 weeks. Orlistat was gavaged at 15.6 mg/kg bw/day, as a positive control group. The analysis revealed that the main components of CHP were procyanidin B2, cyanidin-3-glucoside, and pelargonidin-3-glucoside. CHP dietary supplementation significantly reduced body weight and improved blood lipid measurements in HFD-fed mice (p < 0.01). Moreover, it inhibited mRNA expression of miR-122, Srebp-1c, and Cpt1a (p < 0.01) and reduced hepatic lipid deposition, as seen by hematoxylin and eosin staining. CHP downregulated the protein expression of PPARγ and C/EBPα in HFD-induced obese mice and inhibited adipocyte differentiation (p < 0.01). Compared with the HFD group, CHP supplementation had an obvious anti-inflammatory effect (decreased protein expression, such as TNF-α, IL-6, and MCP1), reducing leptin levels and TNF-α secretion in serum and cells (p < 0.01). CHP significantly inhibited the expression of miR-27a/b (53.3 and 29.9%, p < 0.01) in mice retroperitoneal white adipocytes, enhancing the expression of the target gene Prdm16 and significantly upregulating Sirt1 (105.5%, p < 0.01) compared with the HFD group. Moreover, CHP supplementation effectively improved oxidative stress (ROS, T-AOC, SOD, CAT, and GSH-Px) induced by HFD in obese mice (p < 0.01). Thus, CHP mitigates adipocyte differentiation, browning of white adipocytes, and reduction of inflammation and antioxidant activity to reduce obesity. Consequently, these results provide novel insights into the anti-obesity roles of CHP in HFD-induced obesity.
研究领域:
营养学
·
药理学
·
分子生物学
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2022
·
IF 1.555
Zhang Jing,Yang Junqing,Luo Ying,Li Jiansha,Gong Tao,Huang Suqiong,Xiong Yan,Jiang Xinhui
Using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as a pre-column derivatization reagent, optimized derivatization and chromatography parameters, a simple high-performance liquid chromatography fluorescence detector (HPLC–FLD) method was developed and validated to determine 23 related amines in plasma and cortex of C57BL/6 mice with cerebral ischemia–reperfusion injury. The prepared samples were separated on a ZORBAX SB-C18 column (4.6 mm × 250 mm, 5 μm) with 60% acetonitrile (ACN) and 20 mM sodium acetate solution (pH adjusted to 5.0 by phosphoric acid). All analytes achieved good separation within 1.2 h at a flow rate of 1 mL/min. The limits of detection and limits of detection quantitation of the method were ranged from (0.1–9.2) to (0.3–30.6) ng/mL, respectively. The analytical method was apt for simultaneously determining 23 amino acids in plasma and cortex. Our results revealed that the relevant amino acids were significantly altered (P < 0.05) in C57BL/6 mice.
研究领域:
分析化学
·
神经生物学
·
医学
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PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2015
·Vol. 2015
·期 1
·239749
·
IF 1.88
Zhiping Wang,Junbiao Wu,Qun Zhou,Yifei Wang,Tongsheng Chen
Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D- α -tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.
研究领域:
药剂学
·
药理学
·
分子药理学
·
药物递送系统
·
糖尿病研究
·
药物代谢
·
纳米医学
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DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Xueru Wang,Waseem Ali,Kanglei Zhang,Yonggang Ma,Hui Zou,Xishuai Tong,Jiaqiao Zhu,Ruilong Song,Hongyan Zhao,Zongping Liu,Wenxuan Dong
Cadmium (Cd) has adverse effects on organisms. Serine is an essential nutritional factor and its nutritional value is extremely high for body. To explore the effects of serine on spleen toxicity induced by Cd in mice, cadmium chloride (CdCl 2 , 50 mg/L) and serine (50 g/L) were individually administered or co-administrated in drinking water of mice for 18 weeks. Results demonstrated that Cd exposure induced splenic toxicity and serine against the toxicity damage caused by Cd in mice. Under Cd stress, trace element homeostasis was disturbed, the mice's body weight and spleen index were increased, and splenic morphology and ultrastructure were altered. Furthermore, Cd exposure led to the cell populations disorder, which in turn triggers cell death. Notably, Cd treatment induced oxidative stress and inflammation, increased M1/M2 (iNOS, CD68) and Th1/Th2 (T-bet, CD4) levels, decreased M1/M2 (Arg1) and Th1/Th2 (GATA3) levels, while disrupted the macrophages and lymphocytes homeostasis, which trigged apoptosis and pyroptosis in spleen. In contrast, serine supplementation changed the levels of Cd and other elements, weakened Cd-induced tissue damage and inflammation, enhanced antioxidant capacity, significantly restored cell homeostasis, and effectively inhibited Cd-induced apoptosis and pyroptosis in the spleen. Shortly, the results verified that serine had an ameliorating toxicity effect and restored the M1/M2 and Th1/Th2 balance, restrained apoptosis and pyroptosis induced by Cd.
研究领域:
毒理学
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免疫学
·
营养科学
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PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Yan Wang,Yudi Zhang,Xiao Hu,Yunjie Shi
Effective anesthesia is crucial for ensuring the validity and reliability of animal experiments. In recent years, tribromoethanol has been widely used for small animal anesthesia. However, direct injection poses risks of overdose, anesthesia instability, and organ damage, affecting experimental reliability and animal welfare. Therefore, developing a safer and more stable delivery system for tribromoethanol is essential. In this study, we first synthesized two complexes using a solvothermal method. Then, we modified the traditional biopolymer PEG to synthesize an amphiphilic block copolymer, Cyanine 7-PEG-DDAT, which was used to coat CP1 and load tribromoethanol (TBE) for structural characterization. We then conducted biological tests on Cyanine 7-PEG-DDAT-CP1@TBE and compared its anesthetic effects in C57BL/6 mice with those of direct tribromoethanol injection. The results provide a reference for the application of tribromoethanol in mouse models and surgeries.
研究领域:
药学
·
材料科学
·
生物医学工程
·
动物实验
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高影响因子
ACTA PHARMACOLOGICA SINICA
·
2022
·Vol. 44
·期 1
·169-177
·
IF 7.169
Zhang Yi-fei,Gao Yue,Yang Jie,Jiang Yi-ming,Huang Min,Fan Shi-cheng,Bi Hui-chang
Pregnane X receptor (PXR) is highly expressed in the liver and plays a pivotal role in xenobiotic and endobiotic metabolism. We previously reported that PXR activation by its specific mouse agonist pregnenolone 16α-carbonitrile (PCN) significantly induces liver enlargement and lipid accumulation. However, the effect of long-term PCN treatment on PXR and mouse liver is still unknown. This study aimed to explore the influence of long-term administration of PCN on mouse liver and hepatic lipid homeostasis. Male C57BL/6 mice were injected intraperitoneally with PCN (100 mg/kg once a week) for 42 weeks. Serum and liver samples were collected for biochemical and histological analysis. PXR activation was investigated by Western blot. Ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS)-based lipidomics analysis was performed to explore the change in different lipid categories. The results showed that long-term treatment with PCN significantly promoted hepatomegaly without hepatocyte proliferation and enlargement. Long-term treatment with PCN did not upregulate PXR target proteins in mice, and there was no significant upregulation of CYP3A11, CYP2B10, UGT1A1, MRP2, or MRP4. Lipidomics analysis showed obvious hepatic lipid accumulation in the PCN-treated mice, and the most significant change was found in triglycerides (TGs). Additionally, long-term treatment with PCN had no risk for carcinogenesis. These findings demonstrated that long-term PCN treatment induces hepatomegaly and lipid accumulation without hepatocyte proliferation or enlargement.
研究领域:
药理学
·
毒理学
·
肝病学
·
脂质代谢
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Shengli Quan,Jinhua Li,Shuxian Ding,Xingjie Zhuo,Yuanxiao Yang,Qin Li
Background Parkinson's disease is a progressive neurodegenerative disorder of the brain, that commonly leads to motor dysfunction and dementia. Artemether is a semi - synthetic derivative of artemisinin, which is extracted from the traditional Chinese herb Artemisia annua. And it is widely used in the treatment of malaria. Recent studies have shown that it exhibits significant neuroprotective effects and holds potential for the treatment of neurodegenerative diseases. However, its effects and mechanisms in the context of Parkinson 's disease remain unclear. Objective To explore Artemether's neuroprotective effects and mechanisms in 6-OHDA-induced PD models. Methods Network pharmacology and molecular docking were used to predict potential pathways and targets of Artemether against Parkinson's disease. PD models were established using 6-OHDA-induced PC12 cells and C57BL/6 mice to assess Artemether's effects and mechanisms. Results Through network pharmacological analysis and molecular docking verification, it was found that Artemether against Parkinson 's disease was related to apoptosis-related signaling pathways, and Artemether had good spontaneous binding activity with key targets PI3K, Akt, GSK-3β, and Bcl-2. Furthermore, the related experimental results showed that Artemether could increase the cell viability of PC12 cells induced by 6-OHDA, reduce intracellular ROS level, increase mitochondrial membrane potential and decrease apoptosis. In addition, Artemether improved motor dysfunction and cognitive dysfunction in Parkinson 's disease mice, and increased the expression of dopamine neurons in both the Substantia Nigra and Striatum. Conclusion Artemether exerted neuroprotective effects in Parkinson 's disease models in vitro and in vivo induced by 6-OHDA through the PI3K/Akt/GSK-3β signaling pathway.
研究领域:
神经科学
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药理学
·
分子生物学
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PubMed
高影响因子
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