通过抑制醛固酮合成酶发挥海柯吉宁和醋酸海柯吉宁的利尿作用

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Saudi Pharmaceutical Journal Pub Date : 2024-05-16 DOI:10.1016/j.jsps.2024.102105
Abdulmohsin J. Alamoudi , Maria Nazeer , Nabi Shah , Saif Ullah , Meshal Alshamrani , Waleed Y. Rizg , Osama M. Ashour , Ashraf B. Abdel-naim , Abdul Jabbar Shah
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引用次数: 0

摘要

橙皮苷(HEC)是一种甾体皂甙,存在于许多植物物种中,是甾体药物的前体。HEC 及其衍生物乙酸橙皮苷(HA)的利尿作用在很大程度上仍未得到研究。本研究旨在探讨 HEC 和 HA 与呋塞米(FUR)和螺内酯(SPIR)相比的潜在利尿作用。此外,本研究还旨在探索其潜在机制,特别是关注醛固酮合成酶基因的表达。54 只 Sprague-Dawley 大鼠被分为九组(1-9 组)。第 1 组(对照组)接受载体,第 2 组接受 10 毫克/千克的 FUR,第 3、4 和 5 组接受 HEC,而第 6、7 和 8 组接受 HA,剂量分别为 5、10 和 25 毫克/千克。第 9 组静脉注射 SPIR,剂量为 25 毫克/千克。在给药后 1、2、3、4、5、6 和 24 小时监测尿量、利尿指数和利尿活性。每天治疗一次,连续七天。之后,大鼠被处死,采血测定血清电解质。解剖肾上腺进行基因表达研究。研究结果表明,在给药剂量下,HEC 和 HA 能显著增加尿液和电解质的排泄量,且呈剂量依赖性。这些结果主要是在每种化合物的剂量为 25 毫克/千克时观察到的。基因表达研究表明,醛固酮合成酶基因表达的减少与剂量有关,这表明抑制醛固酮合成是这两种化合物具有利尿活性的潜在机制。值得注意的是,HA 的利尿作用比 HEC 更明显。HA 的这种增强的利尿活性可归因于其对醛固酮合成酶更强的抑制作用。这些发现为了解 HEC 和 HA 的利尿作用及其潜在的分子机制提供了宝贵的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Diuretic effects of Hecogenin and Hecogenin acetate via aldosterone synthase inhibition

Hecogenin (HEC) is a steroidal saponin found in many plant species and serves as a precursor for steroidal drugs. The diuretic effects of HEC and its derivative, hecogenin acetate (HA), remain largely unexplored. The present study aimed to explore the potential diuretic effects of HEC and HA compared to furosemide (FUR) and spironolactone (SPIR). Additionally, the study aimed to explore the underlying mechanism particularly focusing on aldosterone synthase gene expression. Fifty-four Sprague-Dawley rats were allocated into nine groups (Group 1–9). Group 1 (control) received the vehicle, Groups 2 received FUR 10 mg/kg, Group 3, 4, and 5 were given HEC, while Groups 6, 7 and 8 received HA i.p at doses of 5, 10, and 25 mg/kg, respectively. Group 9 received SPIR i.p at the dose of 25 mg/kg. Urine volume, diuretic index and diuretic activity were monitored at 1, 2, 3, 4, 5, 6, and 24 h post-administration. Treatment was given daily for seven days. After that, rats were sacrificed and blood was collected for serum electrolytes determination. Adrenal glands were dissected out for gene expression studies. The results revealed that HEC and HA at the administered doses significantly and dose-dependently increased urine and electrolyte excretion. These results were primarily observed at 25 mg/kg of each compound. Gene expression studies demonstrated a dose-dependent reduction in aldosterone synthase gene expression, suggesting aldosterone synthesis inhibition as a potential mechanism for their diuretic activity. Notably, HA exhibited more pronounced diuretic effects surpassing those of HEC. This enhanced diuretic activity of HA can be attributed to its stronger impact on aldosterone synthase inhibition. These findings offer valuable insights into the diuretic effects of both HEC and HA along with their underlying molecular mechanisms.

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来源期刊
Saudi Pharmaceutical Journal
Saudi Pharmaceutical Journal PHARMACOLOGY & PHARMACY-
CiteScore
6.10
自引率
2.40%
发文量
194
审稿时长
67 days
期刊介绍: The Saudi Pharmaceutical Journal (SPJ) is the official journal of the Saudi Pharmaceutical Society (SPS) publishing high quality clinically oriented submissions which encompass the various disciplines of pharmaceutical sciences and related subjects. SPJ publishes 8 issues per year by the Saudi Pharmaceutical Society, with the cooperation of the College of Pharmacy, King Saud University.
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