白细胞介素-1受体1型拮抗剂和野刺叶乙酸乙酯部分对κ-卡拉胶致大鼠静脉血栓形成的潜在治疗作用

Q3 Pharmacology, Toxicology and Pharmaceutics

Phytomedicine Plus Pub Date : 2025-03-31 DOI:10.1016/j.phyplu.2025.100795

Asmaa F. Aboul Naser , Wessam M. Aziz , Amal M. El-Feky , Marwa M. Elbatanony , Noha N. Nasr , Yomna R. Ahmed , Sylvia E. Shaker , Wagdy K.B. Khalil , Manal A. Hamed

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引用次数: 0

摘要

血栓形成是心血管疾病、脑缺血、缺氧、组织软化和坏死的主要原因。κ-卡拉胶诱导大鼠静脉尾血栓形成模型是评价抗血栓和溶栓药物的最佳模型之一。目的通过拮抗剂IL-1RA1阻断白细胞介素-1受体1型（IL-1R1）对静脉血栓形成的治疗作用，并与香叶乙酸乙酯部位（EAF）的治疗作用进行比较。研究设计：利用HPLC和LC-ESI-MS/MS对其主要活性成分进行了鉴定，并通过UV、IR、MS、1HNMR和13CNMR对其进行了分离。大鼠经κ-角菜胶诱导24 h后，进行治疗并通过测定血凝指数（凝血酶时间（TT）、凝血酶原时间（PT）、纤维蛋白原）、IL-1R1、白细胞介素-1β (IL-1β)、血管细胞粘附分子-1 （VCAM-1）、丙二醛（MDH）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、天冬氨酸和丙氨酸转氨酶(AST&；ALT)、碱性磷酸酶（ALP）、总蛋白、尿素、肌酐、肾损伤分子-1 （KIM-1）及尾组织病理分析。结果HPLC鉴定出11种酚酸和7种黄酮类化合物。hplc - esi - ms共检测到62个化合物，分离到4个化合物，分别为：百里氏醇4′-葡萄糖苷(1)、对香豆酸(2)、双花蒿素(3)和5,7 -二羟基-3,6-二甲氧基-3′，4′-亚甲二氧黄酮(4)。结果表明，IL-1RA1和野刺草叶EAF通过减轻所研究的生化参数，表现出抗血栓形成的作用。结论il - 1ra1和EAF可作为抗血栓、溶栓和抗炎药物，可能成为疾病治疗的良好候选药物。

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$Potential therapeutic effects of interleukin-1 receptor type 1 antagonist and the ethyl acetate fraction of Murraya exotica leaves against κ-carrageenan induced vein thrombosis in rats$

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Potential therapeutic effects of interleukin-1 receptor type 1 antagonist and the ethyl acetate fraction of Murraya exotica leaves against κ-carrageenan induced vein thrombosis in rats

Background

Thrombosis is the primary cause of cardiovascular diseases, cerebral ischemia, hypoxia, tissue softening, and necrosis. One of the best models used to assess antithrombotic and thrombolytic drugs is the κ-carrageenan induced vein tail thrombosis rats model.

Purpose

The purpose of this study is to evaluate the treatment of vein thrombosis by blocking intrelukin-1 receptor type 1 (IL-1R1) via its antagonist (IL-1RA1) comparing with the treatment role of the ethyl acetate fraction (EAF) of Murraya exotica L. leaves.

Study design

The major bioactive compounds from the EAF were identified by HPLC and LC-ESI-MS/MS analyses, while, isolation achieved via UV, IR, MS, ¹HNMR , and ¹³CNMR . After 24 h of κ-carrageenan induction to rats, treatments occurred and the evaluation was done through measuring hemagglutination index (thrombin time (TT), prothrombin time (PT), and fibrinogen), genes expression of IL-1R1, interleukin-1 beta (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), malondialdehyde (MDH), glutathione (GSH) and superoxide dismutase (SOD), aspartate and alanine aminotransferase (AST& ALT), alkaline phosphatase (ALP), total protein, urea, creatinine, kidney injury molecule-1 (KIM-1) and the histopathological analysis of tail tissues.

Results

The HPLC analysis led to characterization of 11 phenolic acids and 7 flavonoids. LC-ESI-MS data detected 62 compounds while, 4 compounds were isolated: Cirsiliol 4′-glucoside (1), p-coumaric acid (2), bismurrangatin (3) and 5, 7-dihydroxy-3,6-dimethoxy-3′,4′-methylenedioxyflavone (4). The results revealed that treatment with IL-1RA1 and the EAF of M. exotica leaves manifested anti-thrombosis effects by alleviating all the biochemical parameters under investigation.

Conclusion

IL-1RA1 and the EAF could be considered as antithrombotic, thrombolytic and anti-inflammatory agents that may be served as good candidates for disease treatment.

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