Abstract
2′-O-galloylhyperin, a major compound of Pyrola incarnata Fisch., possesses a variety of biological and pharmacological activities, including anti-oxidative and anti-inflammatory activities. Nevertheless, the underlying molecular mechanisms of 2′-O-GH in microbial infection and sepsis are not clear. In this study, we investigated the anti-inflammatory effects of 2′-O-GH. We found that 2′-O-GH significantly reduced the production of TNF-α, IL-6, and nitric oxide (NO), suppressed the expression levels of iNOS, blocked the translocation of NF-κB from the cytosol to nucleus, and decreased the MAPK activation in LPS-activated RAW 264.7 cells. 2′-O-GH also enhanced the nuclear translocation of Nrf2 and up-regulated the expression of heme oxygenase-1 (HO-1) and SIRT1. In addition, the administration of 2′-O-GH attenuated the TNF-α and IL-6 production in the serum, infiltration of inflammatory cells, liver tissue damage, and the mortality rate of LPS-challenged mice. Moreover, 2′-O-GH significantly upregulated Nrf2 and SIRT1 expression and inhibited the inflammatory responses in the liver of septic mice. The collective data indicate that 2′-O-GH could potentially be a novel functional food candidate in the treatment of sepsis.
Highlights
Inflammation has been recognized as a complex physiological process that eliminates injurious stimuli and initiates the healing process regulated by the immune defensive system
Pretreatment with Mitogen-activated protein kinase (MAPK) inhibitors (U0126, SP600125, and SB203580) suppressed the production of nitric oxide (NO) (Supplementary Figure S1). These results indicated that 2 -2 -O-galloylhyperin (O-GH) effectively inhibited the activation of both nuclear factor-κB (NF-κB) and MAPK in LPS-induced macrophages
Our results showed that NAC significantly blocked LPS-induced SIRT1 down-regulation in RAW 264.7 cells, whereas treatment with 10 mM NAC alone did not affect the expression of SIRT1 compared with the normal group (Figure 4B)
Summary
Inflammation has been recognized as a complex physiological process that eliminates injurious stimuli and initiates the healing process regulated by the immune defensive system. LPS, a complex glycolipid in the Abbreviations: 2 -O-GH, 2 -O-galloylhyperin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; DEX, dexamethasone; DMEM, Dulbecco’s Modified Eagel Medium; FBS, Fetal bovine serum; GSH, glutathione; H&E, hematoxylin and eosin; IL-6, interleukin 6; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; MAPK, Mitogen-activated protein kinase; NAC, N-acetyl-L-cysteine; NF-κB, nuclear factor-κB; Nrf, nuclear transcription factor erythroid 2-related factor; ROS, reactive oxygen species; SIRT1, silent mating type information regulation 2 homolog 1; SOD, superoxide dismutase; TNF-α, tumor necrosis factor α. 2 -O-Galloylhyperin Attenuates LPS-Induced Inflammation outer membrane of Gram-negative bacteria, can innate immune system, because it binds the CD14/TLR4/MD2 receptor complex in many cell types, especially in monocytes and macrophages, which modulates cytokine networks by producing pro-inflammatory cytokines such as TNF-α, IL-6, and proinflammatory mediators including nitric oxide (NO) (Mo et al, 2014; Wu et al, 2017). The reduction of inflammatory mediators and ROS in macrophages provides a useful therapeutic approach against various inflammatory diseases
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