In vivo anti-inflammatory, analgesic, and hepatoprotective potencies and acute toxicity of chrysanthenone and thymol
DOI:
https://doi.org/10.69998/d0s2s839Keywords:
Chrysanthenone, thymol, lipoxygenase, cyclooxygenase, hepatoprotective activity, Molecular dockingAbstract
Thymol and chrysanthenone are two bioactive compounds primarily found in the essential oils of Thymus algeriensis and Artemisia herba-alba, respectively. This study aimed to evaluate the anti-inflammatory, analgesic, and hepatoprotective potential of thymol and chrysanthenone, individually and in combination, and assess their acute toxicity. Anti-inflammatory activity was evaluated by measuring the severity of hind paw edema in rats following carrageenan injection, a standard inflammation model. Analgesic activity was assessed using the writhing test, which measures the number of abdominal constrictions. In silico evaluations of anti-inflammatory and analgesic activities were performed using the Maestro 12.5 software from the Schrödinger suite. Hepatoprotective effects were tested against carbon tetrachloride (CCl₄)-induced hepatotoxicity in albino rats. Additionally, serum levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were measured, and liver tissue from treated animals was histologically examined. The results demonstrated that the oral administration of the thymol/chrysanthenone combination at a dose of 150 mg/kg significantly reduced inflammation, outperforming 1% Diclofenac with maximum edema reductions of 97 ± 3.7% and 88.6 ± 0.81%, respectively. In the writhing test, rats treated with the combination exhibited significantly fewer abdominal contractions (40 ± 0.40) compared to those treated with the serotonin–norepinephrine reuptake inhibitor Tramadol (42.00 ± 2.70), a drug commonly used to manage moderate to severe pain. Molecular docking studies revealed that thymol exhibited strong binding affinities in the active sites of lipoxygenase and cyclooxygenase, with docking scores of –4.805 kcal/mol and –7.821 kcal/mol, respectively. Chrysanthenone also demonstrated favorable binding, with scores of –4.082 kcal/mol and –6.938 kcal/mol at the same targets. The thymol/chrysanthenone combination showed marked hepatoprotective effects, evidenced by the normalization of ASAT and ALAT levels and the prevention of histological liver damage following CCl₄ intoxication. Acute toxicity testing revealed no signs of toxicity, with an LD₅₀ greater than 150 mg/kg.
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