Memory enhancement and protective effects of crocin against D-galactose aging model in the hippocampus of Wistar rats

Objective(s): The neurodegeneration and loss of memory function are common consequences of aging. Medicinal plants have potent protective effects against chronic neurodegenerative diseases. The aim of this study was to investigate the beneficial effects and molecular mechanisms of crocin on brain function in D-galactose (D-gal)-induced aging model in rats. Materials and Methods: Male Wistar rats weighing 220 ± 20 g were randomly divided into six groups: control, D-gal (400 mg/kg, SC), D-gal (400 mg/kg) plus crocin (7.5, 15, 30 mg/kg, IP) and crocin alone at dose of 30 mg/kg for 8 weeks. The neuroprotective effects of crocin were evaluated by Morris water maze, determination of malondialdehyde (MDA) levels and Western blot analysis. Results: Crocin significantly inhibited the neurotoxic effects of D-gal through improvement of spatial learning and memory functions as well as the reduction of MDA levels. It was also found that administration of crocin up-regulated pAkt/Akt and pErk/Erk ratio which were decreased by chronic D-gal treatment. In addition, the elevated level of carboxymethyl lysine (CML), as an advance glycation product (AGE), NF-κB p65, TNFα and IL1β significantly decreased in crocin treated rats compared to D-gal group. Conclusion: These findings suggest that crocin is able to enhance memory function in D-gal aging model through anti-glycative and anti-oxidative properties which finally can suppress brain inflammatory mediators (IL-1, TNF and NF-κB) formations and increase PI3K/Akt and Erk/MAPK pathways activity. Therefore, crocin can be considered as healthcare product to prevent age-related brain diseases such as Alzheimer.