Shareefa Alghamdi

Erucic acid is a single unsaturated fatty acid that falls under the omega‐9 fatty acid family. It was suggested to treat Wistar rats with lipopolysaccharide (LPS)‐induced memory impairment and minimize cognitive impairment. A total of 30 animals were randomized: group I was normally treated group, group II was administered with LPS, group III was treated with LPS along with erucic acid at the dose of 10 mg kg –1 p.o. –1 , group IV was treated with LPS along with erucic acid at 20 mg kg –1 p.o. –1 and group V was the erucic acid per se group provided at the dose of 20 mg kg –1 p.o. –1 per se. Behavioral tests were evaluated by using the Morris water maze and Y‐maze. Biochemical analysis including acetylcholine esterase (AChE), choline acetyltransferase (ChAT), glutathione (GSH), catalase activity (CAT), superoxide dismutase (SOD), and nitric oxide (NO) along with proinflammatory mediators tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), caspase 3, and neuroinflammatory biomarker (nuclear factor kappa B‐NF‐κB) were measured. Erucic acid produced substantial behavioral improvement in the Y‐maze test, including spontaneous alterations and reduced latency time during acquisition, and a longer duration of time in the consolidation phase undergoing the MWM test. Furthermore, erucic acid improved the AChE, proinflammatory markers, and oxidative stress as well as restoring endogenous antioxidant levels, ChAT, caspase 3, and NF‐κB levels. Erucic acid may be a therapeutic component for conditions related to memory disorders such as memory impairment, enhances memory functioning, and protects against neuronal damage.

The second leading cause of death in the world is cancer. Mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK) 1 and 2 (MEK1/2) stand out among the different anticancer therapeutic targets. Many MEK1/2 inhibitors are approved and widely used as anticancer drugs. The class of natural compounds known as flavonoids is well-known for their therapeutic potential. In this study, we focus on discovering novel inhibitors of MEK2 from flavonoids using virtual screening, molecular docking analyses, pharmacokinetic prediction, and molecular dynamics (MD) simulations. A library of drug-like flavonoids containing 1289 chemical compounds prepared in-house was screened against the MEK2 allosteric site using molecular docking. The ten highest-scoring compounds based on docking binding affinity (highest score: −11.3 kcal/mol) were selected for further analysis. Lipinski’s rule of five was used to test their drug-likeness, followed by ADMET predictions to study their pharmacokinetic properties. The stability of the best-docked flavonoid complex with MEK2 was examined for a 150 ns MD simulation. The proposed flavonoids are suggested as potential inhibitors of MEK2 and drug candidates for cancer therapy.