Abstract
Piperine is a phytochemical present in black pepper (Piper nigrum Linn) and other related herbs, possessing a wide array of pharmacological activities including anti-inflammatory effects. Previously, we demonstrated that piperine has therapeutic effects on bacterial sepsis in mice, but the underlying mechanism has not been fully elucidated. In this study, we aimed to investigate the influences of piperine on pyroptosis in murine macrophages. The results showed that piperine dose-dependently inhibited ATP-induced pyroptosis, thereby suppressing interleukin-1β (IL-1β) or high mobility group box-1 protein (HMGB1) release in LPS-primed bone marrow-derived macrophages and J774A.1 cells. Accompanying this, ATP-induced AMP-activated protein kinase (AMPK) activation was greatly suppressed by piperine, whereas AMPK agonist metformin counteracted piperine’s inhibitory effects on pyroptosis. Moreover, piperine administration greatly reduced both peritoneal and serum IL-1β levels in the mouse model intraperitoneally infected with Escherichia coli, suggestive of suppressing systemic inflammation and pyroptosis. Our data indicated that piperine could protect macrophages from pyroptosis and reduced IL-1β and HMGB1 release by suppressing ATP-induced AMPK activation, suggesting that piperine may become a potential therapeutic agent against bacterial sepsis.
Highlights
Piperine is an alkaloid present in black pepper (Piper nigrum Linn) and other related herbs (Wattanathorn et al, 2008)
By using in vitro cell models where mouse bone marrow-derived macrophages (BMDMs) and J774A.1 cells were primed with LPS followed by triggering with extracellular adenosine triphosphate (ATP) [a damage-associated molecular patterns (DAMPs) released by hosts or bacteria (Mempin et al, 2013; Ren et al, 2014; Wegiel et al, 2014)], we found that piperine treatment significantly suppressed ATP-induced pyroptosis, which was associated with suppression of AMPK activity
As pyroptosis has been reported being causative of sepsis-induced organ damages, we explored whether piperine could suppress pyroptosis in LPS-primed macrophages upon ATP triggering
Summary
Piperine is an alkaloid present in black pepper (Piper nigrum Linn) and other related herbs (Wattanathorn et al, 2008). This alkaloid has been reported to possess a broad spectrum of pharmacological activities. It is well known for its anti-depressive and anti-epileptic activities (Pal et al, 2011; Mao et al, 2014). It is known as a booster for promoting bioavailability of other drugs enhancing their pharmacological effects (Johnson et al, 2011; Di et al, 2015). Piperine may be generally regarded as an anti-inflammatory agent against various inflammatory disorders as a consequence of bacterial infections or autoimmune responses
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