epidermal-growth-factor and gingerol

Sepsis is a major cause of death for ICU patients. Sepsis development depends heavily on the presence of mature IL-1β cytokine. This study evaluates the potential therapeutic properties of a bioactive compound known as 6-gingerol on sepsis. This compound has previously been demonstrated to possess anti-inflammatory properties both in vivo and in vitro.. C57BL/6 mice was used to establish models of sepsis by means of cecal ligation and puncture (CLP). Upon treatment with 6-gingerol, we assessed the survival rate of mice and measured the levels of key pro-inflammatory cytokines in serum and colon tissues. Sepsis pathogenesis was further explored using the RAW264.7 cell line and bone marrow-derived macrophages (BMDMs) treated with ATP and lipopolysaccharide (LPS). The impact of 6-gingerol on pyroptosis was also examined. In addition, we assessed the role of MAPK signaling in 6-gingerol-induced effects in BMDMs and RAW264.7 cells.. In CLP mice, 6-gingerol significantly ameliorated sepsis development, which was associated with the reduction of serum IL-1β. In BMDMs and RAW264.7 cells, 6-gingerol strongly attenuated pyroptosis as well as the release of caspase-1p20, HMGB1, mature IL-1β, IL-18 in response to ATP and LPS treatment. 6-Gingerol conferred these effects by blocking MAPK activation. Exposure to an ERK agonist (EGF) reversed effects of 6-gingerol, causing pyroptosis, LDH and caspase-1p20 release.. By targeting MAPK signaling, 6-gingerol significantly suppressed secretion of pro-inflammatory cytokines and inhibited macrophage cells pyroptosis resulting in overall inhibition of sepsis development.

Topics: Adenosine Triphosphate; Animals; Caspase 1; Catechols; Cytokines; Disease Models, Animal; Epidermal Growth Factor; Fatty Alcohols; HMGB1 Protein; Interleukin-18; Interleukin-1beta; Lipopolysaccharides; Macrophages; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Prognosis; Pyroptosis; RAW 264.7 Cells; Sepsis

Many spices, including plants of the ginger family, possess anticarcinogenic activity. However, the molecular mechanisms by which they exert their antitumorigenic effects are unknown. Activator protein 1 (AP-1) has a critical role in tumor promotion, and blocking of tumor promoter-induced activation of AP-1 inhibits neoplastic transformation. Epidermal growth factor induces cell transformation and AP-1 activity. The purpose of this study was to investigate the effect of two structurally related compounds of the ginger family, [6]-gingerol and [6]-paradol, on EGF-induced cell transformation and AP-1 activation. Our results provide the first evidence that both block EGF-induced cell transformation but act by different mechanisms.

Topics: Animals; Anticarcinogenic Agents; Catechols; Cell Death; Cell Line; Cell Transformation, Neoplastic; DNA; Enzyme Induction; Epidermal Cells; Epidermal Growth Factor; Epidermis; Fatty Alcohols; Guaiacol; Ketones; Mice; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Plants, Medicinal; Transcription Factor AP-1