The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model

Objective

To evaluate the effects of honeysuckle extract and its active component, luteolin, on the autistic-like behaviors and neuroinflammatory responses in NDE1-deficient autism spectrum disorder (ASD) zebrafish models. Also, to assess whether differences exist in their behavioral improvement effects and impacts on brain inflammatory factor expression levels.

Methods

Behavioral phenotyping (hyperactivity, stereotypic back-and-forth swimming, and 1VS6 social preference/grouping tests) and molecular analyses (quantification of NF-κB, IL6, TNFα, and IL1β) were performed on NDE1-deficient zebrafish treated with honeysuckle extract or luteolin.

Results

Honeysuckle extract improved two core symptoms of ASD, small circling repetitive stereotyped behavior and 1VS6 social preference behavior. While luteolin enhanced one core symptom, shoaling behavior, and one comorbid symptom, hyperactive locomotor activity. Molecularly, honeysuckle extract normalized IL6 levels, and luteolin reduced IL1β overexpression; their effects on brain inflammation in the NDE1-deficient autism model differed.

Conclusion

Both honeysuckle extract and luteolin demonstrated behavioral rescue and anti-neuroinflammatory effects in NDE1-deficient ASD zebrafish models. The ameliorating effects of luteolin on ASD-related behaviors and neuroinflammation are supported by literature, while the beneficial effects of honeysuckle on ASD-related behaviors represent a novel finding of this study, highlighting medicinal plants and plant-derived compounds as potential ASD therapeutics. Given honeysuckle's traditional Chinese medicinal and food uses, established safety, and superior improvement of core ASD symptoms compared to luteolin, it may offer a safer autism treatment option than luteolin-based small-molecule medication.