Abstract
Inflammation is a serious health issue worldwide that induces many diseases such as sepsis. There has been a vast search for potentially effective drugs to decrease mortality from sepsis. Pheophytin a is a chlorophyll-related compound derived from green tea. We found that pre-treatment with pheophytin a suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-1β in RAW 264.7 macrophages. NO synthase-2 (NOS2) and cyclooxygenase-2 (COX-2) expression levels were repressed by pre-treatment with pheophytin a at both the transcriptional and translational levels. Pheophytin a inhibited NOS2 promoter activity, but not its mRNA stability, through extracellular signal-regulated kinase (ERK1/2). This suppression was reversed by ERK1/2 inhibitor (U0126). Pheophytin a reduced signal transducers and activators of transcription 1 (STAT-1) activation, without an obvious influence on activator protein-1 (AP-1) and nuclear factor κB (NF-κB). These results suggest that pheophytin a functions by down-regulating the transcriptional levels of inflammatory mediators and blocking the ERK and STAT-1 pathways.
Highlights
Sepsis is a critical syndrome associated with microorganism infection that has a high mortality rate [1]. the “germ theory” was proposed several decades ago, host immune factors have recently been considered to have a more important role in the progression of sepsis [2]
Production was quantified as described in the Section 3.7; (B) RAW 264.7 cells were pre-treated with the indicated concentrations of pheophytin a for 30 min followed by LPS
Tubulin was used as a control gene; (C) RAW 264.7 cells were pre-treated with the indicated concentrations of pheophytin a for 30 min followed by LPS (100 ng/mL) for 6 h
Summary
Sepsis is a critical syndrome associated with microorganism infection that has a high mortality rate [1]. The LPS-induced activation of transcription factors such as NF-κB and signal transducer and activator of transcription-1 (STAT-1) play pivotal roles in the expression of genes such as iNOS, COX-2 and inflammatory cytokines [15]. Pheophytin a (C55H74N4O5), a chlorophyll-related compound [16], is an important component of green tea It has anti-inflammatory [17], anti-oxidant, and anti-chemotactic properties in human polymorphonuclear neutrophils [18], and anti-hepatitis C activity and functions in anti-tumor promotion. Because sepsis is a dysregulated inflammatory response, drugs that could modulate the production of inflammatory mediators might be useful to treat inflammatory diseases and endotoxin shock These results have led us to hypothesize that pheophytin a might modulate NO, PGE2, and IL-1β production and the migration of macrophages during LPS-induced sepsis, and these issues are addressed in the present study. The findings here might lead to the further development of new potential therapeutic or prophylactic agents for sepsis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
