Abstract
Sepsis-associated liver dysfunction presents a significant public health problem. 6-Shogaol is the key bioactive component in dry ginger, which has antioxidant and anti-inflammation capacity. The present study aims to investigate the preventive effect of 6-shogaol on sepsis-induced liver injury. 6-Shogaol was administered to mice for 7 consecutive days before being intraperitoneally injected with lipopolysaccharide (LPS). After 24 h, mice were sacrificed, and biochemical and transcriptomic analyses were performed. Our results demonstrated that 6-shogaol prevented LPS-induced impairment in antioxidant enzymes and elevation in malondialdehyde level in the liver. The hepatic inflammatory response was significantly suppressed by 6-shogaol through suppressing the MAPK/NFκB pathway. RNA-sequencing data analysis revealed that 41 overlapped genes between the LPS vs. control group and 6-shogaol vs. LPS group were identified, among which 36 genes were upregulated, and 5 genes were downregulated for the LPS vs. control group. These overlapped genes are enriched in inflammation-related pathways, e.g., TNF and NFκB. The mRNA expression of the overlapped genes was also verified in the LPS-induced BRL-3A cell model. In summary, 6-shogaol shows great potential as a natural chemopreventive agent to treat sepsis-associated hepatic disorders.
Highlights
Sepsis is a systematic inflammatory response caused mainly by bacteria
Primary antibodies against β-actin, IκBα, phosphoIκBα(Ser32), p65, phospho-p65(Ser536), and secondary antibody horseradish peroxidase (HRP)-linked anti-rabbit antibody were purchased from Cell Signaling Technology (Danvers, MA, USA)
MAPK by significantly elevating the phosphorylation of JNK and ERK, thereby caused degradation of IκBα and triggered the phosphorylation of p65 (p < 0.01). All these changes were markedly reversed by treatment with 6-shogaol (p < 0.05 and p < 0.01). These results indicate that 6-shogaol regulated hepatic inflammation through MAPK/NFκB pathway
Summary
Sepsis is a systematic inflammatory response caused mainly by bacteria. It is one of the most life-threatening illnesses among intensive care patients worldwide [1]. It has been demonstrated that patients with sepsis and early liver dysfunction exhibited significantly elevated mortality and poor prognosis [8]. 6-Shogaol attenuates neuroinflammation and cognitive deficits in animal models of dementia [15]. It has been reported as the most potent anti-inflammatory and anti-oxidant component in ginger [18]. We hope that this study will provide candidate targets for treating endotoxin-related hepatic disorders, as well as evidence for the therapeutic application of 6-shogaol for inflammatory liver diseases in the future
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