Oncotarget
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2017
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IF 5.168
Yan Lou,Wenqi Qiu,Zhe Wu,Qian Wang,Yunqing Qiu,Su Zeng
We previously showed that BZG is a novel multitarget kinase inhibitor, which inhibited hepatocellular carcinoma in vivo and in vitro . In the present study, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize BZG and its metabolites generated in vivo . The probable metabolic mechanism was further confirmed by analysis of Phase I and Phase II metabolism in liver microsomes and with recombinant enzymes. In addition, the binding affinities of BZG metabolites to vascular endothelial growth factor receptor 2 (VEGFR2) were predicted using electronic high throughput screening (eHiTS). The results showed that BZG underwent phase I and phase II metabolism. We detected 11 BZG metabolites and identified hydroxylation, glucuronation, acetylation, sulfonation and degradation as the major metabolic processes in vivo and in vitro . Five of the eleven metabolites showed highly favorable eHiTS energy scores that were lower than sorafenib. Knowledge of the in vivo metabolic pathways of BZG and its binding affinities to VEGFR2 will be beneficial for further clinical development of BZG.
研究领域:
药理学
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癌症研究
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药物代谢
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Junling Ren,Xia Wang,Yuran Sun,Le Yang,Hui Sun,Ye Sun,Ling Kong,Guangli Yan,Ying Han,Xijun Wang
Background Danggui Sini Decoction (DGSND) is a classic prescription for treating primary dysmenorrhea (PD), while, the ameliorating effects of DGSND on PD and its mechanisms are not yet fully understood. Purpose The present study is devoted to investigate the protective effect of DGSND against PD and the possible mechanism from the perspective of metabolomics as well as lipidomics. Methods DGSND was characterized by UPLC-Q-TOF/MS. The PD rat model was induced by estradiol benzoate and oxytocin, and traditional pharmacology, including writhing times, latency time, biochemical index, organ index, and histopathology were performed to evaluated the efficacy of DGSND on PD. Urine metabolomics strategy combined with functional analysis was adopted to delineate the therapeutic effect of DGSND on PD rats and anchor the crucial pathway, and lipidomics analysis was further performed with the uterine tissue as the research object to elucidate the protective mechanism of DGSND from the perspective of lipid homeostasis. Finally, western blot analysis was used to validate the expression of key metabolic enzymes in lipid metabolism. Results DGSND was effective in ameliorating writhing times, latency time, the value of prostaglandin F 2α (PGF 2α )/PGE 2 , uterus index, and morphological changes of PD rats. Metabolic signature of PD rats was primarily characterized by the disturbance of steroid hormone metabolism, amino acid metabolism, and lipid metabolism. Functional analysis revealed the urine biomarkers of PD were most related with lipid abnormality. Further lipidomics analysis indicated DGSND exerted anti-PD effects by remodeling lipid homeostasis, which might be due to the significant correlations between different kinds of lipids, especially the extremely high correlation of phosphatidylethanolamine, phosphatidylcholine, and fatty acids. Moreover, the key metabolic enzymes expression of CK, PLA 2 , LPCAT3, COX-2, and 5-LOX can be greatly downregulated by DGSND. Conclusion Our findings demonstrated a novel protective mechanism of DGSND against PD by regulating lipid homeostasis.
研究领域:
药理学
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代谢组学
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脂质组学
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中医
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动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2022
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IF 6.656
Lu Zhang,Ling-Ling Wang,Hao Zeng,Bin Li,Hua Yang,Guang-Ji Wang,Ping Li
Background Mild and systematically improving multiple metabolic disorders was a focused view for Compound Danshen Dripping Pills playing synergistic effects through multiple components and multiple targets. The difference in overall therapeutic effects and endogenous metabolic regulation between short- and long-term administration was still unclear. Purpose This study aimed to explore the difference in endogenous metabolic regulation between short- and long-term Compound Danshen Dripping Pills (CDDP) administration against acute myocardial infarction (AMI). Methods The model of AMI was induced by ligating the left anterior descending coronary artery . The cardiac protection effects of CDDP were investigated by echocardiography , 1- or 2-week were defined as short- and long-term based on desirable efficacy variability. The entire metabolic changes between short- and long-term administration of CDDP were profiled by UPLC-Q-TOF-MS. In addition, the metabolic regulatory network of CDDP administration against myocardial infarction rats was also compared with those of a typical chemical drug isosorbide 5-mononitrate (ISMN). Results After 1- or 2-week continuous oral administration , CDDP could significantly alleviate AMI-induced cardiac dysfunction. By using LC-MS-based metabolomics analyses, we systematically investigated the metabolic profiles of plasma and heart tissue samples at fixed exposure time-points (2 h, 24 h) from AMI rats with CDDP treatment . Most interestingly, global endogenous metabolic changes were observed in cardiac samples collected at different stages post consecutive CDDP administration, fluctuating at 2 and 24 h after 1 week but stabilizing after 2 weeks. The disrupted metabolic pathways such as glycerophospholipid , amino acids , fatty acids, and arachidonic acid metabolism were reconstructed after both short- and long-term CDDP treatment, while taurine and hypotaurine metabolism and purine metabolism contributed to the whole efficacy after long-term CDDP administration. Conclusion Long-term CDDP treatment plays prolonged and stable efficacy against AMI compared with short-term treatment by specifically regulating purine and taurine and hypotaurine metabolism and systematically redressing metabolic disorders.
研究领域:
药理学
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心脏病学
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代谢组学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS
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2018
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IF 3.468
Chuanchuan Liu,Qiang Yao
The thermal degradation of resorcinol bis(diphenyl phosphate) (RDP) and bisphenol A bis(diphenyl phosphate) (BDP) has been studied by 31 P NMR, Q-TOF, and GPC at normal and extreme heating conditions. The thermal degradation begins with the elimination reaction that generates reactive monomers and arynes. The aryne-bisphosphate adducts or their decomposition products were identified through Q-TOF analysis. Through the intertwined condensations, transesterifications, and elimination reactions, the reactive acid phosphates are formed and eventually convert the bisphosphates into volatile triphenyl phosphate, oligomeric aryl/acid polyphosphates, and non-volatile polyphosphoric acid. It is these reactions and products that provide the bisphosphates effective pathways for entry into the vapor phase or action in the condensed phase. The facility of these reactions, particularly the elimination reaction that is the initiation step, to occur is critical for the high efficiency of flame retardancy displayed by the bisphosphates. A thermal Melvin rearrangement of the bisphosphates to arylphosphonates has also been established.
研究领域:
材料科学
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化学
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高分子科学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）