TARGETING YIN-YANG 1 INFLAMMATORY PATHWAY AS AN ALTERNATIVE TO MITIGATE THE SYMPTOMS OF MDD

Abstract

Major Depressive Disorder (MDD) poses a substantial burden on global health and calls for innovative therapeutic approaches. MDD is associated with disruptions in inflammatory pathways, making it a promising target for alternative treatments to antidepressants (I. Bin Kim et al., 2022). For decades the main goal of antidepressant therapy has traditionally been to increase levels of monoamine neurotransmitters in the synaptic cleft. However, this approach is not effective for all patients, as depressive symptoms can return after discontinuing antidepressants (Smit et al., 2023). Research has evaluated that 25% of patients with MDD experience neuroinflammation, which is associated with resistance to treatment and decreased quality of life(Smit et al., 2023). This in-silico study explores a novel approach to MDD treatment by targeting the YY1-NF-KB inflammatory pathway, which is involved in the pathophysiology of neuroinflammation linked MDD. The molecular docking study of fifteen candidate compounds with YIN-YANG 1((YY1) reveals a stable and favourable interaction with almost six of them, namely Turgorin , Flavylium , Kaempferol , Sitosterol , Luteolin and Sulindac suggesting , they may directly bind to the YY1 transcription factor in the inflammatory pathway in order to further control the casting of interleukin-13 (IL-1f3) and interleukin-6 (IL-6), two important pro-inflammatory cytokines involved in inflammation-mediated depression, ADMET analysis further explored the potential of these compounds as way outs for treating depression wherein Flavylium, an anthocyanin ,emerges as a potential drug and presents a novel therapeutic approach over antidepressants for treating Major Depressive Disorder. This discussion marks the theoretical foundations, potential advantages over traditional antidepressants, and the need for further research to fully understand the therapeutic potential of targeting the YY1- NF-KB inflammatory pathway in MDD treatment.