Potential therapeutic effects of Ferula gummosa Boiss. Extract on Autistic-like behaviors in maternally separated mice: Role of NMDA receptor gene
Background and objective: Autism spectrum disorder (ASD) is a neurodevelopmental condition that manifests in early childhood. NMDA receptors are crucial in the functioning of the brain, especially in memory and learning, and have been implicated in the development of ASD. Ferula gummosa Boiss. is on...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025013386 |
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| Summary: | Background and objective: Autism spectrum disorder (ASD) is a neurodevelopmental condition that manifests in early childhood. NMDA receptors are crucial in the functioning of the brain, especially in memory and learning, and have been implicated in the development of ASD. Ferula gummosa Boiss. is one of the most valuable medicinal plants used since ancient times for several symptomatic conditions such as vomiting and diarrhea. The current interest has pointed out anti-inflammatory, antipyretic, and anticonvulsant actions. Thus, the present work aims to evaluate the hydroalcoholic extract from F. gummosa in mouse autism-like behavior caused by early maternal separation and its possible action by the involvement of the NMDA receptors. Methods: Hydroalcoholic extract of F. gummosa was prepared using the maceration method. LC-MS analysis was performed to identify the extract's phenolic and flavonoid compounds. The autism-like behaviors were induced using a maternal separation model. Forty male NMRI mice were randomly divided into five groups: a non-stressed control group, an MS group that received normal saline, and three MS groups treated with the hydroalcoholic extract of F. gummosa at doses of 50, 100, and 150 mg/kg. Intraperitoneal injections were administered 14 days (postnatal days 50–64). Immediately after assessing autism-like behaviors, the mice were euthanized under deep anesthesia, and Real-Time PCR studied the expression of Nr2a and Nr2b genes in the hippocampus. Results: Inducing autism-like behaviors using the MS method significantly decreased the secondary latency to enter the dark compartment in the Shuttle box test, reduced the social interaction index in the Three-chamber test, increased the number of buried marbles in the Marble-burying test, and elevated the expression of Nr2a and Nr2b genes in the hippocampus compared to the control group (p < 0.05). Treatment with the hydroalcoholic extract of F. gummosa at doses of 100 and 150 mg/kg significantly increased the social interaction index, the secondary latency to enter the dark compartment, and also reduced the number of buried marbles compared to the MS group received saline (p < 0.05). Additionally, these doses significantly decreased the expression of Nr2a and Nr2b genes compared to the MS group that received saline (p < 0.05). LC-MS analysis revealed that the main components of the extract included gallic acid, caffeic acid, ferulic acid, naringenin, and kaempferol, all of which have neuroprotective and anti-inflammatory effects reported in previous studies. Conclusion: F. gummosa hydroalcoholic extract has great potential for reducing MS-induced autism-like symptoms in mice, possibly through modulations on the NMDA receptor gene expression. The identified active compounds explain the possible mechanisms of action of the extract. These results support further investigation of F. gummosa as a natural therapeutic option for ASD. |
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| ISSN: | 2405-8440 |