Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease

Abstract

Due to its complex pathogenesis, the prevention and therapization of Alzheimer’s disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including anti-apoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In l-glutamate-damaged HT22 cells, 3-h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase-3 and increased the expression levels of B-cell lymphoma-extra large, phosphorylated (P-) protein kinase B and P-mammalian target of rapamycin compared with untreated cells. In mice with AD induced by d-galactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the Aβ1-42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced Aβ1-42 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stress-associated apoptosis signaling pathway.

Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease

“…The brain sections were prepared as in our previous study [ 26 ]. The sections were incubated with primary antibodies against Aβ (dilution ratio 1:1000; ab2539), p-tau (p-s396; dilution ratio 1:4000; ab109390), 4-hydroxynonenal (4-HNE; dilution ratio 1:200; ab46545; Abcam, Cambridge, MA, USA), glial fibrillary acidic protein (GFAP; dilution ratio 1:200; bs-0199R), and ionized calcium-binding adapter molecule 1 (Iba1; dilution ratio 1:200; bs-1363R; Bioss Inc., Beijing, China) at 4 °C overnight.…”

Antioxidant Therapies for Neuroprotection—A Review

“…Moreover, the co-administration of astaxanthin and fucoxanthin exhibited neuroprotective effects on pheochromocytoma neuronal cells for the treatment of Alzheimer’s disease [165]. Another carotenoid with antioxidant properties, crocin, has been administered for the therapy of Alzheimer’s and Parkinson’s diseases with the results proving its potential in the treatment of neurodegeneration [166,167,168]. Furthermore, one studied investigated the potential of β-carotene for the treatment of acute spinal cord injury with the results showing the reduced progression of secondary injury events by preventing the nuclear factor–κB pathway [169].…”

Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease

“…The brain sections were prepared as our previous study [25]. The sections were incubated with the primary antibody against Aβ (Dilution ratio 1:1000) (ab2539), p-Tau (phospho S396) (Dilution ratio 1:4000) (ab109390) and 4-hydroxynonenal (4-HNE) (Dilution ratio 1:200) (ab46545) (Abcam, Cambridge, MA, USA), glial brillary acidic protein (GFAP) (Dilution ratio 1:200) (bs-0199R) and ionized calcium binding adapter molecule 1 (Iba1) (Dilution ratio 1:200) (bs-1363R) (Bioss Inc., Beijing, China) at 4 °C overnight.…”