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从L.种子中体外和计算机模拟鉴定及验证尿素转运蛋白B抑制剂

Identification and Validation of Urea Transporter B Inhibitor from L. Seeds In Vitro and In Silico.

作者信息

Chen Guanzhong, Li Xin, Pan Xinhui, Guo Li, Wei Wei, Sun Xiaoying, Wei Hongtao, Qin Xue, Zhang Ke, Zhang Wei, Wei Lili, Sun Pinghua, Yang Xiaoda

机构信息

School of Pharmacy, Key Laboratory of Xinjiang Phytomedicine Resource and Utilization Ministry of Education/Institute for Safflower Industry Research, Shihezi University, Shihezi 8320002, China.

Stake Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology at School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

出版信息

Molecules. 2025 Mar 30;30(7):1540. doi: 10.3390/molecules30071540.

DOI:10.3390/molecules30071540
PMID:40286206
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11990171/
Abstract

Celery ( L.) seeds are rich in carbohydrates and protein, and they are widely used in diuretic drugs among Uyghur doctors. However, the diuretic mechanism is still unclear. To explore the possible diuretic mechanism of celery seeds, urea transporters, a potential diuresis-related target, are used in this study. Urea transporters (UTs) play a key role of urine concentration. Selective knockout of UTs can concentrate urea without affecting water and electrolytes, resulting in selective diuresis, which is a promising new diuretic target. In the present study, we obtained different polar fractions by extracting and separating celery seed extract, characterized its polar fractions using UPLC-TOF-MS, and verified its action using an erythrocyte lysis model in vitro. Then, it was found that the isovaleric acid -tolylester exhibited moderate activity (IC = 80.34 μM). Finally, its inhibitory effect on UT-B was investigated by using molecular docking, a pharmacophore model, and molecular dynamics simulations. This study provides a new approach to developing novel diuretics.

摘要

芹菜（L.）种子富含碳水化合物和蛋白质，在维吾尔族医生中被广泛用于利尿药物。然而，其利尿机制仍不清楚。为了探究芹菜种子可能的利尿机制，本研究使用了尿素转运蛋白这一潜在的与利尿相关的靶点。尿素转运蛋白（UTs）在尿液浓缩中起关键作用。选择性敲除UTs可使尿素浓缩而不影响水和电解质，从而导致选择性利尿，这是一个有前景的新利尿靶点。在本研究中，我们通过提取和分离芹菜籽提取物获得了不同极性的馏分，使用超高效液相色谱-飞行时间质谱对其极性馏分进行了表征，并在体外使用红细胞裂解模型验证了其作用。然后，发现异戊酸对甲苯酯表现出中等活性（IC = 80.34 μM）。最后，通过分子对接、药效团模型和分子动力学模拟研究了其对UT-B的抑制作用。本研究为开发新型利尿剂提供了一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/fb698ee6d54f/molecules-30-01540-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/185fc02709aa/molecules-30-01540-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/1c1533e226d9/molecules-30-01540-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/fb698ee6d54f/molecules-30-01540-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/185fc02709aa/molecules-30-01540-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/49db599ca0db/molecules-30-01540-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/822dc8c6c354/molecules-30-01540-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/96587f3d5bae/molecules-30-01540-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/e606298b974f/molecules-30-01540-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/11990171/fb698ee6d54f/molecules-30-01540-g011.jpg

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Urea Transporter Inhibitor 25a Reduces Ascites in Cirrhotic Rats.尿素转运体抑制剂25a可减轻肝硬化大鼠的腹水。
Biomedicines. 2023 Feb 17;11(2):607. doi: 10.3390/biomedicines11020607.
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Safety evaluation and biochemical efficacy of celery seed extract (Apium Graveolens) capsules in hypertensive patients: a randomized, triple-blind, placebo-controlled, cross-over, clinical trial.芹菜籽提取物（Apium Graveolens）胶囊治疗高血压患者的安全性评价及生化功效：一项随机、三盲、安慰剂对照、交叉临床试验。
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