ReferenceID 4979

Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF- κ B/iNOS Pathway and Nrf2/HO-1 Pathway

Oxid Med Cell Longev

Crocetin is a main bioactive component with a carotenoid skeleton in Gardenia jasminoides, a typical traditional Chinese medicine with a long history in Southeast Asia. Crocetin is being commonly consumed as spices, dyes

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Reference Id
4979
Evidence Id
21569
Core Evidence Id
21569
Source Reference Id
3209
Herb2 Reference Id
HBREF004006
Subject Paper Key
HBIN021703_34545298
Pubmed Id
34545298
Doi
10.1155/2021/6631929
Paper Title
Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF- κ B/iNOS Pathway and Nrf2/HO-1 Pathway
Paper Abstract
Crocetin is a main bioactive component with a carotenoid skeleton in Gardenia jasminoides, 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-kappaB/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) of HO-1 gene blocked this action. More detailed data have shown that HO-1-KO blocked the inhibition of p-IkappaB-alpha by crocetin. These data indicated that crocetin exerted its anti-inflammatory property via modulating the crosstalk between the MEK1/JNK/NF-kappaB/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.
Journal
Oxid Med Cell Longev
Publish Year
2021
Experiment Subject
lipopolysaccharide- (lps-) stimulated raw264.7 cells; raw264.7 cells
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF- κ B/iNOS Pathway and Nrf2/HO-1 Pathway
Bilingual Status
semi_complete