Tangeretin obtained from Citrus limonum L. represents the key secondary metabolite amongst other citrus derived polymethoxyflavones eliciting a comprehensive bioactive potential establishing versatility in abating neurodegenerative disorders.
The present study was aimed to decipher additional targets and interacting mechanisms for tangeretin in elucidating the neuro-inflammatory profiles through computer aided drug designing and deciphering potential molecular mechanisms.
Pharmacokinetic evaluation waswill be performed for ADMET properties comprising Liver Toxicity, Metabolism, blood brain barrier permeability, cardiotoxicity, mitochondrial toxicity, mutagenicity by vNN web server and SWISS-ADME for drug likeliness deriving medicinal properties of tangeretin, comparatively. Polar surface area-based drug assimilatory profiles were catalogued using Molinspiration toolkit for confirming the tangeretin’s bioavailibility and solubility. Extra-precision flexible molecular docking studies was preceded using Glide XP incorporated in Schrödinger, LLC, New York, NY, 2021 for protein (5-Beta-reductase, PLA2, IRAK4, COX-1, COX-2, 5-LOX, NIK) – ligand (tangeretin) interaction assessment. Phylogenetic analysis of the selected protein targets in docking experiments were assessed for closely relatedness by maximum likelihood iterations using MEGA 10.2.6. Further tangeretin-gene targets-interaction assessment was cross-verified in STITCH and SWISSTARGET prediction data for affirming putative drug targets.
Pharmaokinetic assessment revealed the tangeretin’s role in safety, efficacy and druglike properties based on chemi-informatic profiles. Further selected proteins utilized for flexible docking corresponds to 3KK6, 1CX2 (Cyclooxygenases family), 2B03 (Phospholipase A2), 4IDV (NF-KB-inducing kinase), 6O9D (Interleukin-1 receptor-associated kinase domain) and 3BV7 (steroid 5beta-reductase) that were assessed for binding affinity patterns revealed the efficacy in the order of 5-Beta-reductase > PLA2 > IRAK4 > COX-1 > COX-2 > 5-LOX > NIK. Phylogenetic relatedness proved that 3BV7 posed the ancestral node for rest of the selected proteins emphasizing cascade mechanisms in absorption potentiating additional protein-protein interaction and crosstalk. Comparative gene target analysis revealed two putative potential targets namely AKT1 and CYP1A1.
Pharmacokinetic based docking assessment and network pharmacology studies pertaining neuro-inflammatory protection are coerced with confirmation of putative targets aiding the safety, efficacy, and efficiency of tangeretin.