Yury Nascimento Abreu¹, Laura Beatriz de Souza Martins¹, Camila Nogueira dos Santos¹, Gerllanny Mara de Souza Lopes¹, Quezia Damaris Jones Severino Vasconcelos², Gislei Frota Aragão^1,2

Autism spectrum disorder (ASD) involves neurological alterations resulting from a complex combination of factors, often associated with inflammatory processes, increased oxidative stress in the central nervous system, and synaptic dysfunctions. Honokiol, a polyphenol extracted from the bark of the stem of Magnolia officinalis, has shown promising neuroprotective and anti-inflammatory effects in in vivo studies with animal models of neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Amyotrophic Lateral Sclerosis. This work proposes a predictive in silico approach, based on differential proteomics data from animal models of ASD, with the aim of identifying potential molecular targets of honokiol. Differentially expressed proteins, those with distinct expression levels between the ASD-induced group and the control group, will be analyzed using public data from brains of models induced by valproic acid. The interactions between these proteins and honokiol will be evaluated through molecular docking and pathway analysis, using databases such as SFARI, UniProt, PubChem, SwissDock, and STRING. The proposal aims to explore the applicability of honokiol as a potential therapeutic modulator in ASD, contributing to the identification of biomarkers and relevant pharmacological targets. As a result of molecular docking, the honokiol–Asap2 and honokiol–Phb complexes showed weak interactions, with Asap2 approaching the threshold for moderate affinity (ΔG ≈ –5 kcal/mol). In contrast, the complexes with Stx1a and Upf3b exhibited binding energies consistent with moderate to strong interactions (ΔG between –5 and –7 kcal/mol), suggesting greater modulation potential by honokiol. Pathway analysis indicated relevant interactions among the proteins, with a PPI enrichment value (p = 0.000362), representing only a 0.036% chance of the network occurring by chance. The high degree of statistical reliability (TFP < 0.01) reinforces the functional importance of these proteins, whose dysregulation may negatively impact the organism in ASD-related contexts. Finally, honokiol demonstrated modulatory potential over proteins associated with the disorder, particularly those related to the synaptic region. Although direct functional effects were not evaluated, the results indicate a possible therapeutic relevance of these interactions.

Agradecimentos: The authors acknowledge the National Council for Scientific and Technological Development (CNPq), the Study Group on Neuroinflammation and Neurotoxicology (GENIT/UECE), and the Laboratory of Clinical and Toxicological Analyses (LabTox-UNIFAC/UFC).