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Saffron and crocin ameliorate prenatal valproic acid-induced autistic-like behaviors and brain oxidative stress in the male offspring rats

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Abstract

Autism is a neurobehavioral disease that induces cognitive and behavioral alterations, usually accompanied by oxidative stress in the brain. Crocus sativus (saffron) and its active ingredient, crocin, have potent antioxidative effects that may benefit autistic behaviors. This study aimed to determine the effects of saffron extract and crocin against brain oxidative stress and behavioral, motor, and cognitive deficits in an animal model of autism in male offspring rats. 14 female rats were randomly divided into the saline and valproic acid (VPA) groups. Then, they were placed with mature male rats to mate and produce offspring. VPA (500 mg/kg, i.p.) was injected on day 12.5 of pregnancy (gestational day, GD 12.5) to induce an experimental model of autism. 48 male pups were left undisturbed for 29 days. First-round behavioral tests (before treatments) were performed on 30–33 post-natal days (PND), followed by 28 days of treatment (PND 34–61) with saffron (30 mg/kg, IP), crocin (15 or 30 mg/kg, i.p.), or saline (2 ml/kg, i.p.). The second round of behavioral tests (after treatments) was performed on PND 62–65 to assess the effects of the treatments on behavioral and cognitive features. In the end, animals were sacrificed under deep anesthesia, and their brains were dissected to evaluate the brain oxidative stress parameters, including malondialdehyde (MDA), glutathione (GSH), and catalase (CAT). VPA injection into female rats increased anxiety-like behaviors, enhanced pain threshold, impaired motor functions, disturbed balance power, increased MDA, and decreased GSH and CAT in their male offspring. 28 days of treatment with saffron or crocin significantly ameliorated behavioral abnormalities, reduced MDA, and increased GSH and CAT levels. Brain oxidative stress has been implicated in the pathophysiology of autistic-like behaviors. Saffron and crocin ameliorate anxiety-like behaviors, pain responses, motor functions, and brain oxidative stress parameters in an experimental model of autism. Saffron and crocin may hold promise as herbal-based pharmacological treatments for individuals with autism. However, further histological evidence is needed to confirm their efficacy.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the Vice-chancellor of Research and Technology at the Semnan University of Medical Sciences for providing financial support (grant number 1462).

Funding

This study was supported by grants from the Semnan University of Medical Sciences (Semnan, Iran, 1462).

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Authors and Affiliations

  1. Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran

    Seyed Ali Seyedinia, Parnia Tarahomi, Davood Abbarin, Katayoun Sedaghat, Ali Rashidy-Pour, Habib Yaribeygi, Abbas Ali Vafaei & Payman Raise-Abdullahi

  2. Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Katayoun Sedaghat, Ali Rashidy-Pour & Abbas Ali Vafaei

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  1. Seyed Ali Seyedinia
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  2. Parnia Tarahomi
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  3. Davood Abbarin
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  4. Katayoun Sedaghat
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  5. Ali Rashidy-Pour
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  6. Habib Yaribeygi
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  7. Abbas Ali Vafaei
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Contributions

A.A.V. and A.R.P. designed the experiment. S.A.S., P.T., D.A., K.S., H.Y., P.R.A., and A.A.V. conducted the research, collected data, and carried out the lab work. A.A.V., H.Y., and A.R.P. carried out the statistical analysis and mostly drafted the manuscript. A.A.V., A.R.P., and P.R.A. coordinated and supervised the study. All authors approved the manuscript.

Corresponding authors

Correspondence to Abbas Ali Vafaei or Payman Raise-Abdullahi.

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All the authors have approved this paper's contents and agreed to the “Metabolic Brain Disease” journal publication policies.

Ethical considerations

The Ethical Review Board of Semnan University of Medical Sciences, Semnan, Iran approved the experimental protocol. All experiments were completed in agreement with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. (NO: IR.SEMUMS.REC.1397.144).

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This research involved non-human subjects (Rats).

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This research involved non-human subjects (Rats).

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Seyedinia, S.A., Tarahomi, P., Abbarin, D. et al. Saffron and crocin ameliorate prenatal valproic acid-induced autistic-like behaviors and brain oxidative stress in the male offspring rats. Metab Brain Dis 38, 2231–2241 (2023). https://doi.org/10.1007/s11011-023-01275-7

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