Crocetin exerts its anti-inflammatory property in LPS-induced RAW264.7 cells. - GreenMedInfo Summary
Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-B/iNOS Pathway and Nrf2/HO-1 Pathway.
Oxid Med Cell Longev. 2021 ;2021:6631929. Epub 2021 Sep 10. PMID: 34545298
Crocetin is a main bioactive component with a carotenoid skeleton in, a typical traditional Chinese medicine with a long history in Southeast Asia. Crocetin is being commonly consumed as spices, dyes, and food colorants. Recent pharmacological studies had implied that crocetin may possess potent anti-inflammatory properties; however, the underlying molecular mechanism is not fully elucidated. In the present study, the regulatory effect of crocetin on redox balance was systematically investigated in lipopolysaccharide- (LPS-) stimulated RAW264.7 cells. The results showed that crocetin dose-dependently inhibited LPS-induced nitric oxide production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells. Molecular data revealed that crocetin exerted its anti-inflammatory property by inhibiting the MEK1/JNK/NF-B/iNOS pathway and activating the Nrf2/HO-1 pathway. The shRNA-knockdown (KD) of MEK1 and ERK1 confirmed that the activation of MEK1 and inhibition of JNK mediated the anti-inflammatory effect of crocetin. Moreover, the pull-down assay and computational molecule docking showed that crocetin could directly bind to MEK1 and JNK1/2. It is noticed that both KD and knockout (KO) ofgene blocked this action. More detailed data have shown that-KO blocked the inhibition of p-IB-by crocetin. These data indicated that crocetin exerted its anti-inflammatory property via modulating the crosstalk between the MEK1/JNK/NF-B/iNOS pathway and the Nrf2/HO-1 pathway, highlighting HO-1 as a major player. Therefore, the present study reveals that crocetin can act as a potential candidate for redox-balancing modulation in charge of its anti-inflammatory and chemopreventive effect, which strengthens its potency in the subsequent clinic application in the near future.