Bioinformatics Study of Arctigenin from Jatropha curcas as a KEAP1-Nrf2 Modulator for Antioxidant Activity
DOI:
https://doi.org/10.35473/ijpnp.v9i1.4625Keywords:
Arctigenin, Keap1-Nrf2, molecular docking, antioxidant, Jatropha curcas leavesAbstract
Oxidative stress is a major contributor to metabolic disorders, making the Keap1–Nrf2 pathway a key therapeutic target for antioxidant interventions. This study aimed to evaluate the therapeutic potential of Arctigenin, a lignan from Jatropha curcas leaves, as a natural Keap1 antagonist using an in silico bioinformatics approach. Molecular docking with YASARA Structure was used to determine bond affinity and interaction dynamics, followed by 50-ns molecular dynamics simulations to assess the stability of the complex. ADMET and drug-likeness predictions were performed to evaluate pharmacokinetic properties and safety. Arctigenin demonstrated strong binding affinity (-8.73 kcal/mol) and formed six hydrogen bonds with key Kelch residues (Arg415, Ser508, Val604, Leu365, Ala510, Val463), along with stable hydrophobic and π interactions involving Arg415, Ala556, Leu557, and Tyr572. Molecular dynamics confirmed complex stability, indicated by low RMSD values for Cα and backbone (1.6–1.8 Å), minimal residue fluctuations, stable radius of gyration (17.7–18.1 Å), and consistent SASA. ADMET predictions showed excellent intestinal absorption (94.416%), low blood-brain barrier permeability, and favorable safety profile (AMES-negative, non-hepatotoxic). Overall, Arctigenin exhibits strong potential as a natural Keap1 inhibitor for the development of antioxidant, antihypertensive, or antidiabetic drugs.
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