Abstract
Myricitrin, a naturally occurring polyphenol hydroxy flavonoid, has been reported to possess anti-inflammatory properties. However, the precise molecular mechanism of myricitrin's effects on LPS-induced inflammation is unclear. In the present study, myricitrin significantly alleviated acute lung injury in mice. Myricitrin also markedly suppressed the production of NO, TNF-α, IL-6, and MCP-1 in RAW264.7 macrophage cells. The inhibition of NO was concomitant with a decrease in the protein and mRNA levels of iNOS. The phosphorylation of JAKs and STAT-1 was abrogated by myricitrin. Furthermore, myricitrin inhibited the nuclear transfer and DNA binding activity of STAT1. The JAK-specific inhibitor ruxolitinib simulated the anti-inflammatory effect of myricitrin. However, myricitrin had no impact on the MAPK signalling pathway. Myricitrin attenuated the generation of intracellular ROS by inhibiting the assembly of components of the gp91phox and p47phox. Suppression of ROS generation using NAC or apocynin or by silencing gp91phox and p47phox all demonstrated that decreasing the level of ROS inhibited the LPS-induced inflammatory response. Collectively, these results confirmed that myricitrin exhibited anti-inflammatory activity by blocking the activation of JAKs and the downstream transcription factor STAT1, which may result from the downregulation of NOX2-dependent ROS production mediated by myricitrin.
Highlights
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) refers to a variety of conditions characterized by acute, progressive, hypoxic respiratory failure primarily caused by an inflammatory response rather than cardiogenic factors
Clinical studies indicate that the mortality rate from Acute Lung Injury (ALI) and the more severe form, ARDS, of patients in China varies from 30% to 67.7%, and it is positively correlated with pulmonary inflammation and colloid osmotic pressure in the body [1,2,3]
To evaluate the anti-inflammatory effects of myricitrin, we first measured the production of NO and prostaglandin E2 (PGE2) in RAW264.7 cells following LPS treatment
Summary
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) refers to a variety of conditions characterized by acute, progressive, hypoxic respiratory failure primarily caused by an inflammatory response rather than cardiogenic factors. Endotoxaemia caused by a severe gram-negative bacterial infection leads to acute lung injury. Exposure of macrophages to LPS rapidly induces the secretion of proinflammatory mediators, such as NO, prostaglandin E2 (PGE2), ROS, and proinflammatory cytokines, including IL-6, TNF-α, and MCP-1. These cytokines further aggravate asthmatic pathological alterations and lung inflammatory responses [4]
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