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

• Sixty-two compounds were identified from the EAF of M. exotica leaves by LC-MS. • Seven compounds were identified as novelty from the analytical data. • Vein thrombosis is a systematic harmful disease. • IL-1RA1 and M. exotica leaves mitigated the selected biochemical and genetic alterations. • IL-1RA1 and the EAF of M. exotica leaves are considered as thrombolytic agents. 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. 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. The major bioactive compounds from the EAF were identified by HPLC and LC-ESI-MS/MS analyses, while, isolation achieved via UV, IR, MS, 1 HNMR , and 13 CNMR . 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. 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. 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.