College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Dongqingnan Road, Huaxi District, 550025 Guiyang, Guizhou, PR China.
College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Dongqingnan Road, Huaxi District, 550025 Guiyang, Guizhou, PR China.
Ann Pharm Fr. 2024 Jan;82(1):44-52. doi: 10.1016/j.pharma.2023.07.002. Epub 2023 Jul 6.
Hydrochlorothiazide, a diuretic commonly used for the treatment of hypertension, is often associated with serious metabolic side effects. Pyrrosia petiolosa (Christ) Ching is a traditional Chinese medicine that possesses diuretic properties, without any obvious side effects.
To evaluate the diuretic effect of P. petiolosa (Christ) Ching and to elucidate its underlying mechanism of action.
Extracts obtained from different polar components of P. petiolosa (Christ) Ching were analyzed for toxicity in a Kunming mouse model. The diuretic effects of the extracts were compared to that of hydrochlorothiazide in rats. In addition, compound isolation procedures, cell assays of Na-Cl cotransporter inhibition and rat diuretic test of monomeric compounds were conducted to identify the active ingredients in the extract. Subsequently, homology modeling and molecular docking were performed to explain the reason behind the diuretic activity observed. Finally, LC-MS analysis was used to elucidate the underlying mechanism of action of P. petiolosa (Christ) Ching.
No toxicity was observed in mice administered P. petiolosa (Christ) Ching extracts. The ethyl acetate fraction showed the most significant diuretic effect. Similar results were obtained during the analysis for Na content in rat urine. Further separation of P. petiolosa (Christ) Ching components led to the isolation of methyl chlorogenate, 2',3'-dihydroxy propyl pentadecanoate, and β-carotene. Results from cell assays showed that the Na-Cl cotransporter inhibitory activity of methyl chlorogenate was greater than that of hydrochlorothiazide. This result was again confirmed by the diuresis tests of monomeric compounds in rats. The molecular simulations explain the stronger interactions between the methyl chlorogenate and Na-Cl cotransporter. Of the compounds determined using LC-MS analysis, 185 were identified to be mostly organic acids.
P. petiolosa possesses significant diuretic activities without any obvious toxicity, with least two possible mechanisms of action. Further study on this herb is warranted.
氢氯噻嗪是一种常用于治疗高血压的利尿剂，常伴有严重的代谢副作用。贯众是一种具有利尿作用的中药，没有明显的副作用。
评价贯众的利尿作用，并阐明其作用机制。
分析贯众不同极性部位提取物在昆明种小鼠模型中的毒性。比较提取物与氢氯噻嗪在大鼠中的利尿作用。此外，通过化合物分离、Na-Cl 共转运蛋白抑制细胞试验和单体化合物大鼠利尿试验，鉴定提取物中的活性成分。随后，进行同源建模和分子对接，以解释观察到的利尿活性的原因。最后，通过 LC-MS 分析阐明贯众的作用机制。
给予贯众提取物的小鼠未观察到毒性。乙酸乙酯部分显示出最显著的利尿作用。在大鼠尿液中 Na 含量分析中也得到了类似的结果。进一步分离贯众成分得到甲基绿原酸、2',3'-二羟基丙基十五烷酸酯和β-胡萝卜素。细胞试验结果表明，甲基绿原酸对 Na-Cl 共转运蛋白的抑制活性大于氢氯噻嗪。这一结果在大鼠单体化合物利尿试验中再次得到证实。分子模拟解释了甲基绿原酸与 Na-Cl 共转运蛋白之间更强的相互作用。通过 LC-MS 分析确定的化合物中，有 185 种被鉴定为主要是有机酸。
贯众具有显著的利尿作用而无明显毒性，可能有两种作用机制。有必要对这种草药进行进一步研究。
