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 ef...

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Main Authors: Qi Zhang, Shenglan Gou, Jia Lin, Yinglan Zhang, Qiang Li
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-06-01
Series:Journal of Holistic Integrative Pharmacy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2707368825000287
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author Qi Zhang
Shenglan Gou
Jia Lin
Yinglan Zhang
Qiang Li
author_facet Qi Zhang
Shenglan Gou
Jia Lin
Yinglan Zhang
Qiang Li
author_sort Qi Zhang
collection DOAJ
description 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.
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spelling doaj-art-5a36c68b41ea411ba12522bffeecc8e72025-08-20T03:58:14ZengKeAi Communications Co., Ltd.Journal of Holistic Integrative Pharmacy2707-36882025-06-016219520310.1016/j.jhip.2025.06.007The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency modelQi Zhang0Shenglan Gou1Jia Lin2Yinglan Zhang3Qiang Li4Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 210013, ChinaTranslational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 210013, ChinaTranslational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 210013, ChinaTranslational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 210013, ChinaCorresponding author.; Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 210013, ChinaObjective: 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.http://www.sciencedirect.com/science/article/pii/S2707368825000287AutismNeuroinflammationBehaviorZebrafishHoneysuckle (Lonicera japonica thunb.)Luteolin
spellingShingle Qi Zhang
Shenglan Gou
Jia Lin
Yinglan Zhang
Qiang Li
The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model
Journal of Holistic Integrative Pharmacy
Autism
Neuroinflammation
Behavior
Zebrafish
Honeysuckle (Lonicera japonica thunb.)
Luteolin
title The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model
title_full The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model
title_fullStr The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model
title_full_unstemmed The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model
title_short The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model
title_sort ameliorative effects of honeysuckle extract and its major component luteolin on autism like behaviors in the nde1 deficiency model
topic Autism
Neuroinflammation
Behavior
Zebrafish
Honeysuckle (Lonicera japonica thunb.)
Luteolin
url http://www.sciencedirect.com/science/article/pii/S2707368825000287
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