piperine and Acute-Disease

Acute pancreatitis was a common acute abdominal disease characterized by pancreatic acinar cell death and inflammation. Endoplasmic reticulum autophagy (ER-phagy) coud maintain cell homeostasis by degrading redundant and disordered endoplasmic reticulum and FAM134B and CCPG1 was main ER-phagy receptors. As a natural alkaloid, piperin is found in black pepper and has anti-inflammatory properties, whose effect on ER-phagy in pancreatitis has not been studied.. The objective of this study was to demonstrate the pivotal role of FAM134B and CCPG1 dependent ER-phagy for alleviating acute pancreatitis and explore the molecular mechanism of piperine in alleviating acute pancreatitis.. In this study we investigated the role of ER-phagy in acute pancreatitis and whether piperine could alleviate pancreatitis through ER-phagy regulation. We first detected endoplasmic reticulum stress (ER-stress) and ER-phagy in different degrees of acute pancreatitis. Then we used ER-stress and autophagy regulators to explore the relationship between ER-stress and ER-phagy in acute pancreatitis and their regulation of cell death. Through using FAM134B. In this study, we confirmed that with the progression of acute pancreatitis, the pancreatic endoplasmic reticulum stress increased continuously, but the ER-phagy increased first and then was inhibited. Meanwhile, in acute pancreatitis, ER-stress and ER-phagy interacted: endoplasmic reticulum stress can induce ER-phagy, but serious ER-stress would inhibit ER-phagy; and ER-phagy could alleviate ER-stress. Next, we found that piperine reduced ER-stress by enhancing FAM134B and CCPG1 dependent ER-phagy, thereby alleviating pancreatic injury.. Impaired ER-phagy was both a cause and a consequence of ER-stress in AP mice, which contributed to the transition from AP to SAP. Piperine targeting ER-phagy provided a new insight into the pharmacological mechanism of piperine in treating AP.

Topics: Acute Disease; Alkaloids; Animals; Autophagy; Benzodioxoles; Endoplasmic Reticulum Stress; Mice; Pancreatitis; Piperidines; Polyunsaturated Alkamides

Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation.

Topics: Acute Disease; Alkaloids; Animals; Benzodioxoles; Capsules; Colitis; Dendritic Cells; Dextran Sulfate; Dose-Response Relationship, Drug; Drug Stability; Inflammation; Interleukin-6; Intestinal Diseases; Lipopolysaccharides; Liposomes; Mice; Peptidoglycan; Piperidines; Polyphenols; Polyunsaturated Alkamides; Quercetin; Tumor Necrosis Factor-alpha