Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation and fibrosis. Currently, there are no drugs for the treatment of pancreatic fibrosis associated with CP. Piperine, a natural alkaloid found in black pepper, has been reported to show anti‑inflammatory, anti‑oxidative, and antitumor activities. Although piperine exhibits numerous properties in regards to the regulation of diverse diseases, the effects of piperine on CP have not been established. To investigate the effects of piperine on CP in vivo, we induced CP in mice through the repetitive administration of cerulein (50 µg/kg) six times at 1‑h intervals, 5 times per week, for a total of 3 weeks. In the pre‑treatment groups, piperine (1, 5, or 10 mg/kg) or corn oil were administrated orally at 1 h before the first cerulein injection, once a day, 5 times a week, for a total of 3 weeks. In the post‑treatment groups, piperine (10 mg/kg) or corn oil was administered orally at 1 or 2 week after the first cerulein injection. Pancreases were collected for histological analysis. In addition, pancreatic stellate cells (PSCs) were isolated to examine the anti‑fibrogenic effects and regulatory mechanisms of piperine. Piperine treatment significantly inhibited histological damage in the pancreas, increased the pancreatic acinar cell survival, reduced collagen deposition and reduced pro‑inflammatory cytokines and chemokines. In addition, piperine treatment reduced the expression of fibrotic mediators, such as α‑smooth muscle actin (α‑SMA), collagen, and fibronectin 1 in the pancreas and PSCs. Moreover, piperine treatment reduced the production of transforming growth factor (TGF)‑β in the pancreas and PSCs. Furthermore, piperine treatment inhibited TGF‑β‑induced pSMAD2/3 activation but not pSMAD1/5 in the PSCs. These findings suggest that piperine treatment ameliorates pancreatic fibrosis by inhibiting TGF‑β/SMAD2/3 signaling during CP.
Retinoic Acid Ameliorates Pancreatic Fibrosis and Inhibits the Activation of Pancreatic Stellate Cells in Mice With Experimental Chronic Pancreatitis via Suppressing the Wnt/β-Catenin Signaling PathwayW Xiao et al. PLoS One 10 (11), e0141462. PMID 26556479.Pancreatic fibrosis, a prominent feature of chronic pancreatitis (CP), induces persistent and permanent damage in the pancreas. Pancreatic stellate cells (PSCs) provide a …
Bone Morphogenetic Protein Signaling Protects Against Cerulein-Induced Pancreatic FibrosisX Gao et al. PLoS One 9 (2), e89114. PMID 24586530.Bone morphogenetic proteins (BMPs) have an anti-fibrogenic function in the kidney, lung, and liver. However, their role in chronic pancreatitis (CP) is unknown. The aim o …
BMP2 Inhibits TGF-β-induced Pancreatic Stellate Cell Activation and Extracellular Matrix FormationX Gao et al. Am J Physiol Gastrointest Liver Physiol 304 (9), G804-13. PMID 23429583.Activation of pancreatic stellate cells (PSCs) by transforming growth factor (TGF)-β is the key step in the development of pancreatic fibrosis, a common pathological feat …
Roles of Pancreatic Stellate Cells in Pancreatic Inflammation and FibrosisA Masamune et al. Clin Gastroenterol Hepatol 7 (11 Suppl), S48-54. PMID 19896099. - ReviewOver a decade, there is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic fibrosis. In response t …
Signal Transduction in Pancreatic Stellate CellsA Masamune et al. J Gastroenterol 44 (4), 249-60. PMID 19271115. - ReviewPancreatic fibrosis is a characteristic feature of chronic pancreatitis and of desmoplastic reaction associated with pancreatic cancer. For over a decade, there has been …
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Docosahexaenoic Acid Inhibits Expression of Fibrotic Mediators in Mice With Chronic PancreatitisS Lee et al. J Cancer Prev 24 (4), 233-239. PMID 31950023.DHA may be beneficial in preventing CP by suppressing pancreatic expression of fibrotic mediators.