Crocin, the main active saffron (Crocus sativus L.) constituent, as a potential candidate to prevent anxiety and depressive-like behaviors induced by unpredictable chronic mild stress

Introduction: Saffron, the dried stigmas of Crocus sativus L. is a famous and high-value agricultural product of Iran exclusively used for cooking purpose and well known to treat mood and cognition disorder with antioxidant and anti-inflammatory activities. However, the majority of medicinal properties of saffron are associated with its main component named Crocin. Several evidence-based studies confirmed the strong positive correlation be-tween stress hormones, and depression. The main aim of the present study is to determine the potential anti-depressant effects of crocin, saffron's constitute, in unpredictable chronic mild stress (UCMS) induced anxiety and depression in rats. Materials and methods: The rats were treated as 1) Vehicle with saline, 2) UCMS, 3-5) UCMS-Crocin 10, 20, and 30 mg/kg by oral gavage, 6) Vehicle with Crocin 30 mg/kg by oral gavage. Male Wistar Rats were subjected to UCMS for a total of 4 weeks. During 4 weeks, they received seven training trials. After behavioral tests, the rat brain sections were collected to examine inflammation and oxidative stress damage criteria. Results: Serum corticosterone levels, cortical malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were increased in rats exposed to UCMS, while UCMS decreased IL-10 superoxide dismutase (SOD), Catalase (CAT, and thiol. In addition, UCMS decreased brain-derived neurotrophic factor (BDNF) level in cortical tissues. Crocin improved the behaviors of the UCMS rats in the open field (OF, elevated plus maze (EPM), and forced swimming (FS) tests and reversed the effects of UCMS in all measured parameters. Conclusion: Crocin improved UCMS-induced anxiety and depression through decreasing brain oxidative stress, inflammatory mediators, and corticosterone serum levels.