Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 24 3 2021 03 01 Prospects of Saffron and its Derivatives in Alzheimer’s Disease 233 252 10.34172/aim.2021.35 EN Nadia Zandi Benyamin Pazoki Nazanin Momeni Roudsari Naser-Aldin Lashgari Vahid Jamshidi Saeideh Momtaz Amir Hossein Abdolghaffari Shahin Akhondzadeh REVIEW 10.34172/aim.2021.35 2019 09 17 2020 10 04 Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the old age population, making it a worldwide concern. Unfortunately, few drugs have been presented for treatment of mild and moderate AD. To meet this need, more effective anti-AD agents are emerging. Accumulating evidence supports the beneficial roles of natural-based products in brain function, neurotransmission, neurogenesis, synaptogenesis, and the prevention of amyloid fibrillation and neuronal injury. Several in vitro, preclinical, and clinical studies suggest that saffron (its bioactive compounds) is a potential nutraceutical with antioxidant, radical scavenging, anti-inflammatory, hypolipidemic, hypotensive, neuroendocrine, and neuroprotective effects. It has also been proposed that saffron may delay the onset of AD, prevent its progression or help to attenuate the symptoms of the disease. Therefore, we performed a comprehensive search on this plant and its derivatives for AD treatment. Saffron and its active constituents interfere with AD by improving learning behavior, spatial memory, and cognitive function; protecting against neuronal loss; inhibiting beta-amyloid aggregation and neurotoxicity; preventing senile plaques and neurofibrillary tangle (NFT) formation; suppressing the acetylcholinesterase (AChE) activity; and reducing neuroinflammation. Given conclusive scientific findings, saffron and its derivatives might counter neurodegenerative diseases through multiple pathways. Further clinical trials are expected to confirm the neuroprotective properties of this herb and also to translate such findings to improve patients’ outcomes.