Flavonoid-enriched fractions of Pimpinella anisum and Coriandrum sativum: antioxidant, hepatoprotective, and antimutagenic activities supported by in vivo and dynamics simulation studies

Pimpinella anisum and Coriandrum sativum, members of the Apiaceae family, have long been used in traditional medicine, yet comprehensive phytochemical and pharmacological profiling of their aerial parts remains scarce. This study aimed to investigate the flavonoid composition, hepatoprotective, antimutagenic, and antioxidant potentials of their flavonoid-enriched fractions, supported by in vivo assessments and molecular docking studies. LC–ESI–MS analysis revealed that P. anisum contained 11 phenolic acids and 29 flavonoids, while C. sativum comprised 13 phenolic acids and 28 flavonoids. The flavonoid-rich extracts demonstrated significant antioxidant activities, with P. anisum showing strong DPPH inhibition (83.72–86.22%) and C. sativum exhibiting comparable effects (86.43–88.18%) to ascorbic acid. In vivo studies confirmed the hepatoprotective effect of both extracts in thioacetamide-induced hepatic fibrosis in rats, as evidenced by reduced serum transaminases, nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α), along with enhanced total antioxidant capacity (TAC) and MMP-9 levels. Histological examinations supported the biochemical findings. Antimutagenic studies further revealed a reduction in chromosomal aberrations, DNA damage, and sperm abnormalities. Molecular docking identified six flavonoid compounds—apigenin 6-C-glucoside, apigenin 7-O-glucoside, myricetin 3-O-β-D-glucopyranoside, luteolin, kaempferol, and chrysin—as potent ligands for TNF-α, MMP-9, SOD, and GPx. ADMET predictions indicated high oral bioavailability, drug-likeness, and minimal toxicity. Additionally, Molecular dynamics simulations were used to evaluate the binding energetics and stability of GPx1, MMP-9, and TNF complexes with specific flavonoids. Trajectory analyses demonstrated that GPx1 and MMP-9 rapidly form structurally compact, highly stable, and tightly anchored interactions. The flavonoid-enriched fractions of P. anisum and C. sativum exhibit potent antioxidant, hepatoprotective, and antimutagenic activities, likely mediated through modulation of oxidative stress and inflammatory pathways. The identified flavonoids represent promising candidates for the development of multi-target hepatoprotective therapeutics with favorable safety and pharmacokinetic profiles.