Crocin molecular signaling pathways at a glance: A comprehensive review

Abstract

Crocin is a hydrophilic carotenoid that is synthesized in the flowers of the Crocus genus. Numerous in vitro and in vivo research projects have been published about the biological and pharmacological properties and toxicity of crocin. Crocin acts as a memory enhancer, anxiolytic, aphrodisiac, antidepressant, neuroprotective, and so on. Here, we introduce an updated and comprehensive review of crocin molecular mechanisms based on previously examined and mentioned in the literature. Different studies confirmed the significant effect of crocin to control pathological conditions, including oxidative stress, inflammation, metabolic disorders, neurodegenerative disorders, and cancer. The neuroprotective effect of crocin could be related to the activation of phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT)/mammalian target of rapamycin (mTOR), Notch, and cyclic‐AMP response element‐binding protein signaling pathways. The crocin also protects the cardiovascular system through the inhibitory effect on toll‐like receptors. The regulatory effect of crocin on PI3K/AKT/mTOR, AMP‐activated protein kinase, mitogen‐activated protein kinases (MAPK), and peroxisome proliferator‐activated receptor pathways can play an effective role in the treatment of metabolic disorders. The crocin has anticancer activity through the PI3K/AKT/mTOR, MAPK, vascular endothelial growth factor, Wnt/β‐catenin, and Janus kinases‐signal transducer and activator of transcription suppression. Also, the nuclear factor‐erythroid factor 2‐related factor 2 and p53 signaling pathway activation may be effective in the anticancer effect of crocin. Finally, among signaling pathways regulated by crocin, the most important ones seem to be those related to the regulatory effect on the PI3K/AKT/mTOR pathway.

Protective effect of crocin on peroxidation‐induced oxidative stress and apoptosis in IPEC‐J2 cells

“…Additionally, the PI3K-AKT pathway is an intracellular signal transduction pathway that promotes metabolism, proliferation, cell survival, growth, and angiogenesis in response to extracellular signals. 23 Data from studies on neuroprotection and anticancer treatments indicate that crocin restores normal function through the PI3K/ AKT pathway. 23,24 These results provide an explanation for our findings that crocin may influence intestinal cells and intestinal barrier function by regulating the AGE-RAGE and PI3K/AKT pathways.…”

“…23 Data from studies on neuroprotection and anticancer treatments indicate that crocin restores normal function through the PI3K/ AKT pathway. 23,24 These results provide an explanation for our findings that crocin may influence intestinal cells and intestinal barrier function by regulating the AGE-RAGE and PI3K/AKT pathways.…”

“…Our study's enrichment of the AGE‐RAGE pathway aligns with these findings, suggesting that crocin effectively alleviates damage to intestinal cells through the AGE‐RAGE signaling pathway. Additionally, the PI3K‐AKT pathway is an intracellular signal transduction pathway that promotes metabolism, proliferation, cell survival, growth, and angiogenesis in response to extracellular signals 23 . Data from studies on neuroprotection and anticancer treatments indicate that crocin restores normal function through the PI3K/AKT pathway 23,24 .…”

Crocus sativus updated

“…Ein wichtiger Signalweg, der durch Safran induziert wird, ist der über den nuclear factor erythroid 2-related factor 2 (Nrf2)/2/HO-1/Keap1 21 . Die Beeinflussung anderer Sigalwege ist im Review von Boozari et al 5 zusammengefasst.…”

Therapeutic implications of crocin in Parkinson's disease: A review of preclinical research

“…Furthermore, saffron's antioxidant impact has been linked to its memory and learning-boosting qualities in screening models involving animals (Amin & Hosseinzadeh, 2015;Papandreou et al, 2006Papandreou et al, , 2011. Crocin, one of saffron's active components, is well-known as an effective antioxidant and has numerous therapeutic applications (Boozari & Hosseinzadeh, 2022;Bukhari et al, 2018;Vakili et al, 2014).…”