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

Abstract

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.

Keywords

• Vein thrombosis
• κ-carrageenan
• IL-1receptor antagonist
• Murraya exotica, Gene expression
• Inflammation