Metabolomic Profiling of <i>Aegle marmelos</i> Leaves Butanol Fraction and TNF‐α Receptor‐2 Antagonist in Treatment of Venous Thrombosis via Receptor Blockade and Gene Expression Modulation

Abstract Venous thrombosis (VT) leads to erythema, cardiovascular collapse and thromboembolism. This study aimed to treat vein thrombosis by targeting tumor necrosis factor‐ alpha receptor type 2 (TNF‐αR2) comparing with the butanol fraction (BF) of Aegle marmelos leaves. Leaves were extracted with methanol and n‐butanol, phytochemically screened, and the major bioactive compounds were isolated and identified by variable techniques. κ‐carrageenan was intraperitoneally injected to rats at a single dose of 20mg/kg body weight. After 24 h, treatments occurred with TNF‐α receptor type 2 antagonist (TNF‐αR2A), BF of the leaves extract and the reference drug; Dipyridamole. The biochemical evaluation was done through measuring hemagglutination index, TNF‐αR2genes expression, TNF‐α level, vascular cell adhesion molecule‐1 (VCAM‐1), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), aspartate and alanine aminotransferase (AST&amp; ALT), alkaline phosphatase (ALP), total protein, urea, creatinine and kidney injury molecule‐1 (KIM‐1). The HPLC analysis indicated the highest phenolic and flavonoid compounds in the butanol fraction. The LC/MS analysis identified 47 compounds (phenolic acids, flavonoids, coumarins, and alkaloids). Treatment with TNF‐αR2A and the leaves extract mitigated the drastic changes in the biochemical parameters. In conclusion, the BF of A. marmelos leaves and TNF‐αR2A manifested anti‐thrombosis and anti‐inflammatory effects and could be acted as nutraceutical agents.