Crocin as a multimodal therapy for multiple sclerosis: Recent breakthroughs in immunomodulation and neuroprotection

Background: Multiple sclerosis (MS) is a disabling neurological disorder characterized by the existence of demyelinating lesions and affects more than 2.5 million people globally. The current approaches for patients with MS are mainly based on ameliorating symptoms and decreasing acute attacks, and so far, they have not been successful in providing effective neurological regeneration. Recently, natural-based therapies, like crocin, in light of their pharmacological and biological benefits, have acquired much attention in the treatment of neurological diseases like MS. Hence, this study attempts to answer the question of whether crocin therapy can be a suitable approach for MS with a mechanistic insight. Methods: In this narrative literature review, all related articles (in press and published) in English were searched and assessed using electronic databases, including Web of Science, PubMed, and Google Scholar, up to April 1, 2025. The search keywords in the title and/or abstract of articles were: "Crocin" or "Crocus Sativus" and "Multiple Sclerosis" or "MS". Results: Experimental evidence has revealed the ability of crocin to alleviate reflexive motor behavior-related tests, cognitive indices, depressive-like behavior, tail flick latency, the conduction velocity of the motor and sensory nerve, antioxidant factors, and to attenuate inflammatory factors. Besides improving some mental factors, such as anxiety, clinical outcomes indicated that crocin could modulate oxidative stress and inflammation-associated markers. Conclusion: The current preclinical and clinical studies have provided convincing evidence showing that crocin therapy can be a suitable candidate for MS cases; however, larger and more in-depth clinical trials are warranted to support these results.