imad ed- dahmani ¹ Mohamed El fadili ^1* ghizlane Nouiria ¹ fahd kandsi ² yassine El Atki ³ Hatem A. Abuelizz ⁴ raffael conte ⁵ Fatima Zahra Lafdil ² Abdeslam Taleb ⁶ abdelfatah abdellaoui ¹ Mustapha Taleb ¹

• ¹ Sidi Mohamed Ben Abdellah University, Fes, Morocco
• ² Mohamed Premier University, Oujda, Morocco
• ³ Higher Institutes of Nursing and Health Technology Professions (ISPITS), Casablanca, Morocco
• ⁴ King Saud University, Riyadh, Riyadh, Saudi Arabia
• ⁵ Fondazione IRET ONLUS, Bologna, Emilia-Romagna, Italy
• ⁶ University of Hassan II Casablanca, Casablanca, Casablanca-Settat, Morocco

Ferula communis has demonstrated an abundance of pharmacological and antioxidative qualities. Methods: This study investigates the antioxidant activity of F. communis leaf aqueous extract, total polyphenol, flavonoid concentration, and UHPLC composition, then evaluates the toxicity of the plant's leaves in vitro and in silico. The major compound of the studied extract, namely p-hydroxybenzoic was chosen for molecular docking technique to discover the inhibition mechanism towards antioxidant protein. In addition, a detailed molecular dynamics simulation was carried out to examine the thermodynamic stability of the produced intermolecular interactions. The antioxidant capacity of the extracts of F. communis has been evaluated using 2,2-Diphenylpicryl hydroxyl radical (DPPH), and Ferric reducing antioxidant power (FRAP) procedures. Acute toxicity was tested on albino mice at doses of 200, 300, and 400 mg/kg. Results: The results show that the polyphenol and flavonoid contents of the extract are significant (0.257 ± 0.003 mg Eq AG/mg and 0.32 ± 0.04 mg Eq Q/mg, respectively). The antioxidant activity illustrates that the extracts have notable activity in DPPH and FRAP assays.The toxicity study revealed that mice's behavior, body weight, and organ weights (liver, kidneys) were unaffected by Ferula communis leaf extract administration compared with controls. UHPLC-MS/MS analysis of the extract highlights the presence of 11 compounds, the most abundant of which is p-hydroxybenzoic, representing 53.65%. The predicted pharmacokinetic characteristics of ADMET (Absorption, distribution, metabolism, and excretion) attest to the well-absorbed nature of the isolated compounds, with human intestinal absorption (HIA) varying from 42% for Arbutin (M3) to 100% for Ursolic acid (M4).In conclusion, the leaves of Ferula communis are a good source of natural antioxidants and phenolic compounds. Thus, this study demonstrates that this plant has a wide range of applications, including natural food preservatives, pharmaceuticals, and cosmetics, as evidenced by ongoing research.