Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis

Abstract

Acute lung injury (ALI) is a critical clinical condition with a high mortality rate. It is believed that the inflammatory storm is a critical contributor to the occurrence of ALI. Fucoxanthin is a natural extract from marine seaweed with remarkable biological properties, including antioxidant, anti-tumor, and anti-obesity. However, the anti-inflammatory activity of Fucoxanthin has not been extensively studied. The current study aimed to elucidate the effects and the molecular mechanism of Fucoxanthin on lipopolysaccharide-induced acute lung injury. In this study, Fucoxanthin efficiently reduced the mRNA expression of pro-inflammatory factors, including IL-10, IL-6, iNOS, and Cox-2, and down-regulated the NF-κB signaling pathway in Raw264.7 macrophages. Furthermore, based on the network pharmacological analysis, our results showed that anti-inflammation signaling pathways were screened as fundamental action mechanisms of Fucoxanthin on ALI. Fucoxanthin also significantly ameliorated the inflammatory responses in LPS-induced ALI mice. Interestingly, our results revealed that Fucoxanthin prevented the expression of TLR4/MyD88 in Raw264.7 macrophages. We further validated Fucoxanthin binds to the TLR4 pocket using molecular docking simulations. Altogether, these results suggest that Fucoxanthin suppresses the TLR4/MyD88 signaling axis by targeting TLR4, which inhibits LPS-induced ALI, and fucoxanthin inhibition may provide a novel strategy for controlling the initiation and progression of ALI.

Fucoxanthin Attenuates Oxidative Damage by Activating the Sirt1/Nrf2/HO-1 Signaling Pathway to Protect the Kidney from Ischemia-Reperfusion Injury

“…In terms of antioxidant capacity, fucoxanthin contains a unique chemical structure (Supplementary Figure S1) including a propadiene bond and 5,6-monocyclic oxides with an enhanced antioxidant capacity [37]. Published studies have shown that fucoxanthin has unique advantages in the treatment of several oxidative stress-related diseases, such as ischemic stroke, subarachnoid hemorrhage, acute lung injury, and atherosclerotic cardiovascular disease [38][39][40][41]. In addition, as an edible carotenoid, fucoxanthin has a good safety profile.…”

Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids

“…According to these findings, this carotenoid (200 mg/kg) improved LPS-induced depressive and anxiety-like behaviors via suppression of NF-κB and its proinflammatory target genes iNOS, COX-2, IL-1β, IL-6, and TNF-α, as well as activation of AMPK [292]. In addition, FX treatment demonstrated antifibrotic actions in bleomycin-induced pulmonary fibrosis in mice [293], as well as antiasthmatic effects in an ovalbumin-induced asthma mouse model [294,295].…”

Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways

“…Acute lung injury (ALI) is a series of clinical syndromes caused by damage to alveolar epithelial cells and capillary endothelial cells, which mainly manifest as diffuse alveolar parenchymal injury and refractory hypoxemia, while some severe cases may develop into acute respiratory distress syndrome (ARDS). [1][2][3] ALI is typically characterized by increased respiratory rate, pulmonary edema, progressive hypoxemia, and respiratory distress, and is associated with high mortality rates. 4 ALI has been reported in clinical cases with severe acute respiratory syndrome (SARS), 5 which is prevalent in 2003, and in the current global outbreak of coronavirus disease (COVID-19), 6 manifesting as diffuse alveolar damage, hyaline membrane formation, and interstitial thickening, with severe cases resulting in pulmonary fibrosis and ARDS.…”