ArticleInternational journal of molecular sciences2024
Computational Analysis and Experimental Data Exploring the Role of Hesperetin in Ameliorating ADHD and SIRT1/Nrf2/Keap1/OH-1 Signaling.
Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- The SIRT-1/Nrf-2/HO-1 antioxidant defense axis in adult attention-deficit/hyperactivity disorder.Metabolic brain disease · 2026Article
- Investigation of the Theranekron Ameliorative Effect on Sepsis-Induced Hepatotoxicity via Inflammation and Oxidative Stress Pathways.Cell biochemistry and biophysics · 2025Article
- A tardive dyskinesia drug target VMAT-2 participates in neuronal process elongation.Scientific reports · 2025Article
- Molecular Docking, Bioinformatic Analysis, and Experimental Verification for the Effect of Naringin on ADHD: Possible Inhibition of GSK-3β and HSP90.Pharmaceuticals (Basel, Switzerland) · 2024Article
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Abstract
Attention deficit hyperactivity disorder (ADHD) manifests as poor attention, hyperactivity, as well as impulsive behaviors. Hesperetin (HSP) is a citrus flavanone with strong antioxidant and anti-inflammatory activities. The present study aimed to test hesperetin efficacy in alleviating experimental ADHD in mice and its influence on hippocampal neuron integrity and sirtuin 1 (SIRT1) signaling. An in silico study was performed to test the related proteins. Groups of mice were assigned as control, ADHD model, ADHD/HSP (25 mg/kg), and ADHD/HSP (50 mg/kg). ADHD was induced by feeding with monosodium glutamate (0.4 g/kg, for 8 weeks) and assessed by measuring the motor and attentive behaviors (open filed test, Y-maze test, and marble burying test), histopathological examination of the whole brain tissues, and estimation of inflammatory markers. The in-silico results indicated the putative effects of hesperetin on ADHD by allowing the integration and analysis of large-scale genomic, transcriptomic, and proteomic data. The in vivo results showed that ADHD model mice displayed motor hyperactivity and poor attention in the behavioral tasks and shrank neurons at various hippocampal regions. Further, there was a decline in the mRNA expression and protein levels for SIRT1, the erythroid 2-related factor-2 (Nrf2), kelch like ECH associated protein 1 (Keap1) and hemeoxygenase-1 (OH-1) proteins. Treatment with HSP normalized the motor and attentive behaviors, prevented hippocampal neuron shrinkage, and upregulated SIRT1/Nrf2/Keap1/OH-1 proteins. Taken together, HSP mainly acts by its antioxidant potential. However, therapeutic interventions with hesperetin or a hesperetin-rich diet can be suggested as a complementary treatment in ADHD patients but cannot be suggested as an ADHD treatment per se as it is a heterogeneous and complex disease.
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