COMPUTATIONAL ANALYSIS OF FERULIC ACID’s ANTIDEPRESSANT ACTION TARGETING THE YY1 PATHWAY IN MAJOR DEPRESSIVE DISORDER

Abstract

Major Depressive Disorder (MDD) significantly increases global burden of major public health challenge ,highlighting the need of novel therapeutic strategies for successful treatment.MDD is linked with disrupted inflammatory signalling, suggesting it as a promising goal for the development of novel treatment strategies as compared to traditional antidepressants.Historically, the main goal of antidepressant development has been on increasing monoamine neurotransmitters levels in the synaptic space.However, this monoaminergic approach is ineffective for substantial portion of patients. In some patients, antidepressant discontinuation leads to a recurrence of depressive symptoms.Research suggests that 1 out of 4 patients of Major Depressive Disorder experiences neuroinflammation and is associated with treatment resistance and diminished quality of life.Traditional antidepressant medications, the mainstay of treatment for depression, are believed to primarily influence neurotransmitter levels in the brain. The effectiveness of traditional antidepressants is not universal.Research suggests that approximately 40% of patients may experience inadequate response to current medications. Limited effectiveness of existing antidepressants has spurred exploration of alternative treatment options.This research investigates a promising new approach for MDD treatment.This approach targets the (YY1)-NF-𝜅B-IL-1β PATHWAY, which is implicated in pathophysiology of MDD. Ferulic acid is an organic compound found in variety of plants.Early research suggests that Ferulic acid might reduces inflammation and oxidative stress,both are associated with MDD.Previous studies showed Ferulic acid as an effective antidepressant in depression treatment in non-human disease models. Preclinical models of depression in mice treated with Ferulic acid exhibited major improvement in depressive symptoms ,suggesting its significant value for the treatment of MDD.Simulations of Yin-Yang 1 i.e YY1 (1UBD) docking with Ferulic acid suggests a strong, stable and favourable interaction.This research suggests that Ferulic acid may inhibit the activity of YY1,a protein involved in regulation of inflammation,by directly bind to the YY1 transcription factor.This inhibition of YY1 by Ferulic acid could potentially inhibit the production of interleukin-1β (IL-1β) and interleukin-6(IL-6).which are major pro-inflammatory cytokines and plays an essential role in inflammation. v Targeting YY1 with Ferulic acid has emerged as a potential target for Major Depressive Disorder treatment (MDD) treatmeBlocking YY1 activity represents a novel therapeutic approach for MDD.ADMET analysis which includes studies on absorption,bioavailability,metabolism and toxicity investigated Ferulic acid’s potential as a treatment for MDD. To validate these findings,further exploration through experimental validation and clinical studies is necessary. While this initial research is promising,more studies are required to solidify Ferulic acid’s effectiveness in treatment of Major Depressive Disorder (MDD).