The Protection of Crocin Against Ulcerative Colitis and Colorectal Cancer via Suppression of NF-κB-Mediated Inflammation

Abstract

Background: In China, the incidence of ulcerative colitis (UC) is increasing every year, but the etiology of UC remains unclear. UC is known to increase the risk of colorectal cancer (CRC). The aim of this study was to investigate the protective effects of crocin against UC and CRC in mouse models.Methods: Crocin was used to treat the dextran sodium sulfate (DSS)-induced UC mice for 3 weeks, and ApcMinC/Gpt mice with colorectal cancer for 8 weeks. Proteomics screening was used to detect changes in the protein profiles of colon tissues of UC mice. Enzyme-linked immunosorbent assays and western blot were used to verify these changes.Results: Crocin strongly reduced the disease activity index scores of UC mice, and improved the pathological symptoms of the colonic epithelium. The anti-inflammatory effects of crocin were indicated by its regulation of the activity of various cytokines, such as interleukins, via the modulation of nuclear factor kappa-B (NF-κB) signaling. Crocin significantly suppressed tumor growth in ApcMinC/Gpt mice and ameliorated pathological alterations in the colon and liver, but had no effects on spleen and kidney. Additionally, crocin significantly decreased the concentrations of interleukins and tumor necrosis factor-α in the sera and colon tissues, suggesting its anti-inflammatory effects related to NF-κB signaling. Finally, 12-h incubation of SW480 cells with crocin caused cell cycle arrest, enhanced the apoptotic rate, promoted the dissipation of mitochondrial membrane potential, and the over-accumulation of reactive oxygen species. From the theoretical analyses, phosphorylated residues on S536 may enhance the protein-protein interactions which may influence the conformational changes in the secondary structure of NF-κB.Conclusion: The protective effects of crocin on UC and CRC were due to its suppression of NF-κB-mediated inflammation.

Anti-Epileptic Effect of Crocin on Experimental Temporal Lobe Epilepsy in Mice

“…One possible explanation is that crocin has been reported to have multiple acting targets including anti-inflammation, BDNF, and apoptosis etc. ( Hosseinzadeh and Talebzadeh, 2005 ; He et al, 2016 ; Mazumder et al, 2017 ; Rana and Musto, 2018 ; Teng et al, 2021 ). Due to the multiple targets, different treatment doses may activate different targets and pathways, which may cause the anti-epileptic effect of crocin lacks significant dose-dependence.…”

“…Crocin is considered as one of the main effective components of saffron with a low toxicity ( Bostan et al, 2017 ). Extensive preclinical and clinical studies about its traditional use have been reported, such as anti-inflammation ( Teng et al, 2021 ), anti-tumor ( Mousavi et al, 2009 ), sedation and hypnosis ( Masaki et al, 2012 ), anti-depression ( Amin et al, 2015 ), anti-anxiety ( Pitsikas et al, 2008 ) and anti-Parkinson’s disease ( Rao et al, 2016 ). Several papers also reported its anti-epileptic activity in experimental epilepsy.…”

Saffron Pre-Treatment Promotes Reduction in Tissue Inflammatory Profiles and Alters Microbiome Composition in Experimental Colitis Mice

“…This effect of saffron may be achieved by the virtue of its antioxidant property. NF-κB, being a redox-sensitive transcription factor, is activated by various inflammatory insults and translocate to the nucleus to induce proinflammatory cytokines during inflammation [ 16 , 17 ]. Saffron pre-treatment inhibited the nuclear translocation of p65 NF-κB in mice colonic tissue samples, which corresponds to inhibition of the secretion of IL-6, IL-1β, and TNF-α.…”

“…Saffron, by virtue of its potent antioxidant property, showed a significant decrease in lipoprotein oxidation susceptibility (LOS) in human subjects and was evaluated as a promising anti-obesity drug [ 16 ]. Crocin, a biologically active carotenoid constituent of saffron, was demonstrated to protect against DSS-induced colitis in C57BL/6 J mice and suppressed tumor growth in ApcMinC/Gpt mice by suppressing NF-κB-mediated inflammation [ 17 ]. NF-κB, an oxidative stress sensitive transcription factor, is associated with tissue induction of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β [ 18 , 19 ].…”

Protection against ulcerative colitis and colorectal cancer by evodiamine via anti‑inflammatory effects

“…The disease activity index (dai) is a comprehensive score of weight loss, stool consistency and rectal bleeding that is used extensively to evaluate the clinical progress of patients with colitis (21,22). dai values were calculated according to a previously described method (23).…”