Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorder: an integrated study combining meta-analysis, network pharmacology, and computational biology.

This study looked at whether sulforaphane (a natural compound found in broccoli and other vegetables) helps children with autism. Researchers combined results from six studies involving 333 people and found that taking sulforaphane for 4-10 weeks improved social skills scores compared to placebo pills. No serious side effects were reported. The researchers also used computer modeling to understand how sulforaphane might work in the brain and body.

This comprehensive study combined meta-analysis of six randomized controlled trials (333 participants) with computational approaches to evaluate sulforaphane supplementation for autism spectrum disorder. Results showed significant improvements in Social Responsiveness Scale scores after both 4-5 weeks and 8-10 weeks of treatment compared to placebo, with no increased adverse events. Network pharmacology identified 10 core molecular targets and pathways including PI3K-Akt, MAPK, and inflammatory signaling. Computational analyses suggested sulforaphane works through anti-oxidant, anti-inflammatory, and autophagy-modulating mechanisms.

The study provides both clinical evidence for efficacy and molecular insights into potential mechanisms of action.

Sulforaphane shows promise as a safe adjunctive therapy for autism with potential social benefits. However, larger, longer-term studies are needed to establish optimal dosing, duration, and clinical significance. The identified molecular mechanisms warrant further investigation to understand individual response variability.

Small number of included trials (6 studies) and participants (333 total). Computational analyses provide theoretical mechanisms but require experimental validation. Duration of studies limited to 10 weeks maximum. Effect sizes and clinical significance thresholds not reported.

Sulforaphane, a natural antioxidant rich in cruciferous vegetables, has emerged as a promising dietary supplement for autism spectrum disorder (ASD). However, its therapeutic efficacy remains controversial, and the pharmacological mechanisms are not fully elucidated. Eligible randomized controlled trials were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. Review Manager 5.4 was used for meta-analysis and bias risk assessment.

Network pharmacology, Mendelian randomization, GEO data analyses, molecular docking, and molecular dynamics simulation were employed to explore the mechanisms of sulforaphane in ASD. Six trials involving 333 participants were included in the meta-analysis. Pooled results demonstrated that both 4-5 weeks and 8-10 weeks of sulforaphane supplementation significantly decreased the scores on the Social Responsiveness Scale compared to placebo controls. No significant difference was observed in the incidence of adverse events.

Network pharmacology identified 10 core targets of sulforaphane in ASD, including AKT1, EGFR, HSP90AA1, SRC, CASP3, STAT1, MAPK1, MMP9, MAPK8, and JAK2. These targets were implicated in the PI3K-Akt signaling pathway, MAPK signaling pathway, Chemokine signaling pathway, Chemical carcinogenesis - reactive oxygen species, TNF signaling pathway, Th17 cell differentiation, mTOR signaling pathway, and IL-17 signaling pathway. Mendelian randomization further revealed an inverse association between STAT1 levels and ASD risk. GEO transcriptomic data provided independent validation for the network pharmacology predictions.

The binding energies between sulforaphane and the top 10 core targets are all ≤ -4.0 kcal/mol. Molecular dynamics simulations further validated the stable interaction between MMP-9 and sulforaphane. Sulforaphane may serve as an efficacious and safe adjunctive therapy for ASD, mediated by its anti-oxidant and anti-inflammatory effects along with the modulation of autophagy. CRD42025635045.