Neuroprotective potential of saffron metabolites in Parkinson's disease

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. Although current pharmaceutical treatments mitigate symptoms, these frequently induce adverse effects and may not prevent disease progression, highlighting the need for safer neuroprotective alternatives. Natural products like saffron (Crocus sativus L.) have emerged as promising candidates due to their pharmacological and nutritional properties. While prior studies have investigated saffron and its extracts in the context of PD, no review has comprehensively analyzed the specific roles of its major secondary metabolites. Saffron’s bioactive compounds, particularly crocetin, crocins, and safranal, have demonstrated significant therapeutic potential across in vitro, in vivo, and clinical studies. Crocetin has been shown to inhibit α-synuclein aggregation and preserve mitochondrial integrity. Crocins exhibit neuroprotective effects, including inhibition of amyloid fibril formation, protection of dopaminergic neurons, and enhancement of synaptic plasticity through pathways such as PI3K/Akt/mTOR. Notably, picrocrocin remains unstudied mainly, representing a significant research gap. Safranal has shown efficacy in preclinical PD models, with promising effects on dopaminergic neuron preservation, motor function improvement, and apoptosis regulation. However, clinical trials are warranted to validate its therapeutic potential further. This review highlights existing findings, critically examines the literature, and identifies underexplored mechanisms, including neurotrophic and mitochondrial pathways, as promising targets for future research, ultimately paving the way for innovative therapeutic strategies in PD management.