5-Fluorouracil (5-FU) is widely used in chemotherapy but poses serious risks of cardiotoxicity, which can significantly affect treatment outcomes. Identifying interventions that can prevent these adverse effects without undermining anticancer efficacy is crucial. This study investigates the efficacy of Thymoquinone (TQ) and Hesperidin (HESP) in preventing cardiotoxicity induced by 5-FU in Wistar rats and elucidates the molecular interactions through docking studies. We employed an experimental design involving multiple groups of Wistar rats exposed to 5-FU, with and without the concurrent administration of TQ and HESP. Cardiac function markers, oxidative stress indicators, and inflammatory markers were assessed. Additionally, molecular docking was used to analyze the interaction of TQ and HESP with key inflammatory proteins. Treatment with TQ and HESP not only lowered levels of cardiac enzymes but also improved antioxidant capacity and reduced inflammation in cardiac tissues. Notably, the combination of TQ and HESP provided more significant protective effects than either agent alone. Molecular docking supported these findings, showing effective binding of TQ and HESP to inflammatory targets. TQ and HESP demonstrate potential as protective agents against cardiotoxicity in 5-FU-treated rats, with their combined use offering enhanced protection. These findings suggest a viable strategy for reducing cardiac risks associated with 5-FU chemotherapy.

Objective: Mucuna pruriens (Velvet beans) is a leguminous plant recognised in Vedic therapy as an anti-Parkinsonism agent. The plant is known as the natural reservoir for levodopa. The study aims to evaluate the multitarget inhibitory potency of active constituents present in Mucuna pruriens using in silico tools. Methods: The phytoconstituents present in Mucuna pruriens were retrieved from the IMPPAT database. The physicochemical and toxicity parameters of phytoconstituents were evaluated using Qikprop and ProTox-3. The inhibitory potential of phytoconstituents on the enzymes Monoamine Oxidase-B (MAO-B), Acetylcholinesterase (AChE), and Catechol-O-Methyltransferase (COMT) was evaluated using in silico techniques, including molecular docking, pharmacophore modelling, and molecular dynamics simulations, conducted with Schrödinger software programs. Results: The active constituents comply with Lipinski’s rule for drug-likeness. Further, the molecular docking studies revealed the phytoconstituent luteolin and acacetin showed promising multitargeted inhibitory properties. Especially luteolin (-11.504 kcal/mol) and acacetin (-10.620 kcal/mol) have obtained excellent docking scores with MAO-B, whereas the known drug levodopa showed a docking score of-8.501 kcal/mol. The pharmacophore modelling revealed that donor, acceptor, and aromatic features present in luteolin and acacetin are the essential pharmacophoric features accountable for biological activity. The simulation study generated the stability of the protein-ligand complex and found that luteolin showed a stable complex with MAO-B. Conclusion: Based on these findings, the result of the current study can be used to develop a novel luteolin-based drug for treating Parkinson’s disease with preferred structural modification. However, additional and more comprehensive research is required on this compound.

Objective: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder involving oxidative stress, protein aggregation, and neurotransmitter imbalance. This study aimed to evaluate the neuroprotective potential of Drynaria quercifolia (DQ) phytoconstituents, particularly DQ5 (naringin), using in silico, in vitro, and pharmacological analyses for multitargeted AD therapy. Methods: Phytocompounds from DQ were analysed through molecular docking to assess binding affinities with AD-related targets, including acetylcholinesterase (AChE), monoamine oxidase-B (MAO-B), and peroxiredoxin-5 (Prdx-5). DQ5 (naringin) was further evaluated using molecular dynamics (MD) simulations and pharmacophore modelling. Density Functional Theory (DFT) was employed to assess molecular stability and reactivity. In vitro assays measured AChE, MAO-B, tyrosinase inhibition, and hydrogen peroxide scavenging. Neuroprotective effects were evaluated using MTT assay on SH-SY5Y neuroblastoma cells. Results: Molecular docking showed strong binding of DQ5 to AChE (-14.182 kcal/mol) and MAO-B (-13.393 kcal/mol). MD simulations confirmed complex stability. DQ5 (naringin) exhibits high stability in its gas-phase optimised structure, and its small HOMO-LUMO gap indicates it may be quite reactive, which could contribute to its biological activity. DQ5 inhibited AChE (IC₅₀ = 8.05±1.02 µg/ml) and 90% SH-SY5Y cell viability. Pharmacokinetic predictions supported favourable drug-likeness and safety profiles. Conclusion: DQ5 (naringin), a key metabolite from DQ, exhibits significant multitarget activity against AD-related enzymes and oxidative stress. The compound's pharmacological properties and neuroprotective effects highlight its promise as a natural therapeutic candidate for addressing multiple pathways involved in AD pathogenesis.

Objective: Zingiber officinalis (ginger) rhizomes are widely recognised for their health benefits, but the leaves, primarily used as flavouring agents, have not been explored for therapeutic potential. This study investigates the antiphlogistic properties of Z. Officinalis leaf constituents through molecular docking and dynamic simulation of 24 bioactive molecules identified via Gas Chromatography-Mass Spectroscopy (GC-MS), with a focus on pro-inflammatory gene suppression and inflammatory cell apoptosis induction. Methods: Docking studies were conducted using Schrödinger software (version 2023-1) on secondary metabolites from aqueous and methanolic extracts of Z. officinalis leaves against Cyclooxygenase-2 (COX-2), Interleukin-1 receptor-associated kinase-4 (IRAK-4), Phospholipase A2 (PLA2), and NF-kB-inducing kinase (NF-kB) targets. Physicochemical and pharmacokinetic properties were assessed with the QikProp module. MMGBSA simulations evaluated protein-ligand interactions, and molecular dynamics assessed protein adaptation under physiological conditions. Results: Compound Pterin-6-carboxylic acid exhibited an excellent docking score with the target NF-kB compared to standard Diclofenac. Compounds such as Cyclopropane pentanoic acid 2-undecyl and 14-pentyl bicyclohexyl-4-carbonamide showed docking scores of-8.586 kcal/mol and-7.759 kcal/mol, respectively, against COX-2 and IRAK-4. Cyclopropane pentanoic acid 2-undecyl also demonstrated a score of-7.279 kcal/mol against IRAK-4. MMGBSA showed consistent binding free energies, and pharmacokinetic properties were within acceptable limits. The simulation study generated the stability of the protein-ligand complex and found that Pterin-6-carboxylic acid showed a stable complex with 4UY1. Conclusion: Pterin-6-carboxylic acid and Cyclopropane pentanoic acid 2-undecyl demonstrate significant anti-inflammatory potential. These findings suggest their promise for developing anti-inflammatory drugs, though further in vitro and in vivo studies are required to confirm their therapeutic viability.