Frontiers in Pharmacology
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2024
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IF 4.4
Chu Simeng,Yang Wei,Lu Yujie,Li Junjie,Peng Jiamin,Liu Wenjuan,Jiang Min,Bai Gang
Introduction: Tetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro.Methods: The diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats.Results: Tet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis.Discussion: This study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.
研究领域:
药理学
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化学生物学
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心血管研究
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分子生物学
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DOI
PubMed
高影响因子
Reviews in Cardiovascular Medicine
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2025
·Vol. 26
·期 4
·27001
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IF 1.3
Yipin Yu,Qiong Yi,Chenglong Yang,Xudong Song,Duoting Tan,Qinghua Peng,Xiang Sun,Hao Liang
Background:Diuretic resistance (DR) is characterized by insufficient fluid and sodium excretion enhancement despite maximum loop diuretic doses, indicating a phenotype of refractory heart failure (HF). Recently, metabolomics has emerged as a crucial tool for diagnosing and understanding the pathogenesis of various diseases. This study aimed to differentiate diuretic-resistant patients from non-resistant HF to identify biomarkers linked to the emergence of DR.Methods:Serum samples from HF patients, both with and without DR, were subjected to non-targeted metabolomic analysis using liquid chromatography-tandem mass spectrometry. Metabolite variations between groups were identified using principal component analysis and orthogonal partial least-square discriminant analysis. Metabolic pathways were assessed through the Kyoto Encyclopedia of Genes and Genomes database enrichment analysis, and potential biomarkers were determined using receiver operating characteristic curves (ROCs).Results:In total, 192 metabolites exhibited significant differences across the two sample groups. Among these, up-regulation was observed in 164 metabolites, while 28 metabolites were down-regulated. A total of 28 pathways involving neuroactive ligand-receptor interaction and amino acid biosynthesis were affected. The top five metabolites identified by ROC analysis as potential DR biomarkers were hydroxykynurenine, perillic acid, adrenic acid, 5-acetamidovalerate, and adipic acid.Conclusions:Significant differences in metabolite profiles were observed between the diuretic-resistant and non-diuretic-resistant groups among patients with HF. The top five differentially expressed endogenous metabolites were hydroxykynurenine, perillic acid, adrenic acid, 5-acetamidovalerate, and adipic acid. The metabolic primary pathways implicated in DR were noted as amino acid, energy, and nucleotide metabolism.Clinical Trial Registration:This study was registered with the China Clinical Trials Registry (https://www.chictr.org.cn/hvshowproject.html?id=197183&v=1.7, ChiCTR2100053587).
研究领域:
医学
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代谢组学
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心血管病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
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2025
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IF 4.6
Yalin Xie,Rui Tan,Min Hu,Xiaojun Luo,Xiaojun Deng,Yuanyuan Li
Certain diuretics have been identified as potential contaminants in pharmaceutical and food products, posing a risk to food safety and public health. In this study, a surface-enhanced Raman spectroscopy (SERS) detection method based on Silver nanostars (Ag NSs) was developed for the detection of motion-prohibited diuretics in food and biological samples. Ag NSs synthesized via a simple solution-based method exhibited a star-like morphology with high-density "hot spot", achieving an enhancement factor of 1.0 × 10 5 —3 orders of magnitude higher than that of traditional spherical silver nanoparticles. A highly sensitive SERS detection system was established for bumetanide (limit of detection: 7.08 × 10 −9 g/mL), triamterene (1.13 × 10⁻⁸ g/mL), and dorzolamide (1.04 × 10⁻⁸ g/mL) for the first time. Characteristic fingerprint peaks enabled accurate molecular identification. The method was validated in milk and urine with recoveries of 94.2 %–104.9 %, and relative standard deviation (RSD) < 7 %. Results were consistent with those obtained by HPLC-HRMS/MS, confirming the method's reliability. The proposed system offers advantages of rapid detection (<10 min), low cost, and minimal matrix interference, enabling efficient multi-residue analysis in complex samples. This work provides a promising tool for food safety monitoring and anti-doping surveillance, contributing to effective regulatory enforcement.
研究领域:
分析化学
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纳米技术
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食品安全
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药物分析
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生物分析
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DOI
高影响因子
CHEMOSPHERE
·
2022
·
IF 8.943
Nan Zhang,Yan Gao,Kangjia Sheng,Xianliang Xu,Wanghui Jing,Tao Bao,Sicen Wang
Herein, corncob waste was used as a scaffold for the fabrication of effective adsorbents. Porphyrinic zirconium metal-organic frameworks (MOFs) PCN-223 and PCN-224 constructed by different numbers of Zr6 cluster nodes were grown on the surface of the corncob. Fe (Ш) ions were implanted in the porphyrin ring by post-synthesis modification. The results showed that the extraction capacity of diuretics on [email protected] containing suitable pore size was larger than that of [email protected] The adsorption of diuretics was further enhanced because of the electrostatic effect caused by implantation of Fe (Ш) ions. [email protected] was recyclable and selective for the extraction of furosemide (Fur) and bumetanide (Bum). Coupled in-syringe solid phase extraction (IS-SPE) with ultra-performance liquid chromatography (UPLC), an efficient, sensitive, and stable method was established. With a sensitivity between 0.6 and 1.0 μg/L and a recovery between 83.2% and 119.2%, it is used for the analysis of trace amounts of Fur and Bum in weight loss products and environmental water. The functionalized corncob has potential application for the adsorption of diuretics, and the metal ions implantation in MOFs provides a promising strategy for enhancing extraction capacity.
研究领域:
材料科学
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环境化学
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分析化学
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废物管理
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产品关联
DOI
PubMed
高影响因子
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