Crocin suppresses inflammation-induced apoptosis in rmTBI mouse model via modulation of Nrf2 transcriptional activity

Repetitive mild traumatic brain injury (rmTBI) has been considered a serious health issue. Crocin, a bioactive carotenoid in Crocus sativus (saffron) is well known for its anti-inflammatory and anti-oxidant properties. The aim of this study is to investigate the neuroprotective role of crocin in a repetitive mild traumatic brain injury (rmTBI) mouse model and thus fits the pharmacological scope of pharmanutrition. Balb c mice were divided into four groups, sham, crocin sham, TBI and crocin TBI. Injured groups received seven multiple closed brain injuries. Treated groups were injected with crocin (30 mg/kg) 30 min before each hit. Brain cortices were extracted 24 h post the last injury for molecular analysis. Brain cytokine levels of IL-6 and IL-10 were measured using ELISA. Also, using RT-PCR, the expression levels of the following genes, Bcl-2, caspase3, Bax, P53, NF-κB, Nrf2, HO-1 and NQO1 were assessed. There was a significant increase in the level of the inflammatory cytokine Il-6. Crocin administration induced a decrease in IL-6 accompanied with elevation in the anti-apoptotic cytokine IL-10. Crocin induced a decrease in the gene expression of the apoptotic factors caspase3, Bax and P53 in injured mice and enhanced the mRNA levels of the anti-apoptotic Bcl-2. Also, crocin enhanced the gene expression levels of transcription factor Nrf2 and the antioxidant enzymes HO-1 and NQO-1 whereas reduced the expression of NF-κB. Crocin exerted its neuroprotective effect following rmTBI. Crocin proves to play a prospect role in conferring protection against concussions. [Display omitted] •Repetitive mild traumatic brain injury poses serious public health burdens.•Crocin has for long manifested its anti-oxidant and anti-inflammatory properties.•Crocin administration to injured mice induced a decrease in inflammation.•A boost of the anti-oxidative mechanism was observed in injured treated mice.•Crocin-treated mice exhibited a decrease in apoptotic factors.