Piperine ameliorated lupus nephritis by targeting AMPK-mediated activation of NLRP3 inflammasome

Programmed Cell Death Pathways in the Pathogenesis of Systemic Lupus Erythematosus

“…It is characterized by gasdermin family-mediated pore formation on the plasma membrane, cell swelling, and eventual lysis, followed by release of cellular contents, especially inflammatory mediators IL-1 β and IL-18 [83]. Although pyroptosis was first described in macrophage infected with Shigella flexneri in 1992 [84], it can also occur in monocytes, dendritic cells, CD4 + T cells, hepatocytes, vascular endothelial cells (VECs), tubular epithelial cells, and many other cell types [85–89]. To date, three pathways have been reported to participate in pyroptosis, including the caspase-1-dependent canonical pathway, the noncanonical pathway involving caspase-4,5 (for human) or caspase-11 (for mouse), and the newly discovered caspase-3-dependent pathway.…”

“…Renal tubular cell pyroptosis can be induced by the miR-155/FoxO3a pathway [118]. Importantly, an animal experiment has demonstrated that piperine significantly reduced the pyroptosis of tubular epithelial cells, leading to the suppression of LN development in pristane-induced lupus mice [89]. Interestingly, vascular endothelial cells can also be induced to undergo pyroptosis through the miR-125a-5p/TET2 pathway, perhaps explaining one kind of mechanisms in tissue damage in SLE [119].…”

Mechanical regulation of macrophage function - cyclic tensile force inhibits NLRP3 inflammasome-dependent IL-1β secretion in murine macrophages

“…Phosphorylation of AMPK activates the NLRP3 inflammasome and promotes IL-1β secretion and pyroptosis, and suppression of AMPK phosphorylation inhibits the NLRP3 inflammasome [61]. Piperine (an alkaloid contained in black pepper) inhibits AMPK phosphorylation, which accompanies extracellular ATP stimulation in mouse macrophages J774A.1 and human proximal tubular cell line HK-2 cells, and suppresses NLRP3 inflammasome activation [62, 63]. In addition, in mice placed on a ketogenic diet, reduction of AMPK phosphorylation in the retina and concomitant suppression of NLRP3 inflammasome are observed [64].…”

Piperine protects against pyroptosis in myocardial ischaemia/reperfusion injury by regulating the miR‐383/RP105/AKT signalling pathway

“…Previous studies have reported that PIP exerts pharmacological effects possible via miRNA‐dependent manners 16,17 . Recently, the effects of PIP on the modulation of pyroptosis and I/R insults have attracted much attention 18‐21 . However, the exacted effects of PIP via the miRNA‐related ways in MIRI are not clear, and possible pathogenetic mechanism associated with pyroptosis remains unknown.…”