Saffron (Crocus sativus L.): A multi-target phytochemical with potential therapeutic relevance for autism spectrum disorder - A review of pharmacological mechanisms and future perspectives.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Saffron (Crocus sativus L.) has a long history of use in traditional medicine practices across Persia/the Middle East, India, and the Mediterranean region. Traditionally, it has been regarded for its potential to regulate mood, support cognition, and promote sleep. This paper explores saffron's potential applications and mechanisms of action in autism spectrum disorder (ASD) and related comorbidities (such as anxiety, sleep disorders, and cognitive impairments) from an ethnopharmacological perspective. It integrates pharmacological evidence from saffron's primary constituents-crocins, crocetin, picrocrocin, and safranal-emphasizing the convergence of traditional medicinal knowledge with modern scientific evidence. AIM OF THE STUDY: This review aims to systematically evaluate the therapeutic potential of saffron (Crocus sativus L.) and its bioactive constituents (crocins, crocetin, picrocrocin, safranal) in ASD, its comorbid conditions, and related neurodegenerative diseases. The goal is to synthesize current evidence on saffron's mechanisms of action and translational prospects for ASD management. MATERIALS AND METHODS: A comprehensive literature search was conducted across PubMed, Web of Science and Science Direct databases up to May 2025. Search terms included combinations of keywords such as "saffron," "crocetin," "autism," "anxiety," "depression," "Alzheimer's disease," and "Parkinson's," to identify relevant preclinical and clinical studies on saffron's neuroprotective effects and therapeutic applications. RESULTS: Saffron exhibits pleiotropic neuroprotective effects by modulating multiple key pathways involved in ASD and neurodegeneration, including inhibition of neuroinflammatory signaling pathways such as NF-κB/NLRP3, activation of antioxidant responses via the Nrf2/ARE pathway, and restoring balance between GABAergic and glutamatergic neurotransmission. These mechanisms support saffron's potential to reestablish neurodevelopmental homeostasis and alleviate core ASD symptoms, along with associated comorbidities such as anxiety and cognitive impairments. CONCLUSION: Saffron is a promising natural multi-target agent with significant translational potential for ASD and related disorders. Its ability to modulate neuroinflammatory, oxidative, and neurotransmission pathways underscores its potential as an adjunctive or alternative therapy. Future research should focus on elucidating precise mechanisms, conducting rigorous clinical validations, and optimizing formulations to facilitate evidence-based integration of saffron into ASD treatment strategies.

Key Findings

• Saffron and its constituents exhibit neuroprotective effects relevant to autism spectrum disorder and related neurodegenerative diseases.
• Mechanisms include inhibition of neuroinflammatory pathways such as NF-κB/NLRP3 and activation of antioxidant responses via the Nrf2/ARE pathway.
• Saffron helps restore balance between GABAergic and glutamatergic neurotransmission, which is important for neurodevelopmental regulation.

Clinical Significance

Citation

Wei Mengzhen, Zhang Qiong, Zhao Zhigaoet al.. Saffron (Crocus sativus L.): A multi-target phytochemical with potential therapeutic relevance for autism spectrum disorder - A review of pharmacological mechanisms and future perspectives. Journal of ethnopharmacology. 2026-Apr-24.