The Regulation of the NF-κB p65 and Nrf2/HO-1 Signaling Pathways by Fucoxanthin in Human THP-1 Monocyte Macrophages Under a Lipopolysaccharide-Induced Inflammation Model

在脂多糖诱导的炎症模型中,岩藻黄素对人THP-1单核细胞巨噬细胞中NF-κB p65和Nrf2/HO-1信号通路的调控

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Abstract

Fucoxanthin (Fx), a natural carotenoid predominantly found in brown algae and certain microalgae, has garnered significant attention in recent years for its potent antioxidant and anti-inflammatory properties. As inflammation and oxidative stress represent fundamental physiological responses that play pivotal roles in disease pathogenesis, their intricate interplay has become a focus of scientific investigation. This study employed an LPS-induced THP-1 cell inflammation model to elucidate the anti-inflammatory mechanisms of fucoxanthin and its interaction with oxidative stress pathways. Our findings demonstrate that fucoxanthin effectively suppresses the LPS-induced secretion of pro-inflammatory mediators, including IL-1β, IL-6, iNOS, COX-2, and TNF-α, in THP-1 cells. Mechanistically, this effect is achieved through the inhibition of IκB-α phosphorylation, thereby blocking the activation of the NF-κB p65 signaling pathway. Concurrently, fucoxanthin exhibits robust antioxidant activity, as evidenced by enhanced catalase (CAT) and superoxide dismutase (SOD) activities coupled with reduced malondialdehyde (MDA) production. Furthermore, fucoxanthin activates the Nrf2 signaling pathway, leading to upregulated heme oxygenase-1 (HO-1) expression and the consequent attenuation of reactive oxygen species (ROS) generation. These results collectively indicate that fucoxanthin exerts dual protective effects through anti-inflammatory action mediated by NF-κB pathway inhibition and antioxidant activity via Nrf2/HO-1 pathway activation. The observed crosstalk between these pathways suggests that fucoxanthin's therapeutic potential stems from its ability to simultaneously modulate interconnected inflammatory and oxidative stress responses. Our study provides compelling evidence that fucoxanthin's antioxidant and anti-inflammatory activities are functionally interrelated, with the Nrf2 signaling pathway serving as a critical node in this protective mechanism against LPS-induced cellular damage.

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