Emodin attenuated severe acute pancreatitis via the P2X ligand‑gated ion channel 7/NOD‑like receptor protein 3 signaling pathway.

Abstract

Acute pancreatitis (AP) is an aseptic inflammation characterized with an annual incidence rate, and ~20% patients progressing to severe AP (SAP) with a high mortality rate. Although Qingyi decoction has been frequently used for SAP treatment over the past 3 decades in clinic, the actual mechanism of its protective effects remains unknown. As the major active ingredient of Qingyi decoction, emodin was selected in the present study to investigate the effect of emodin against severe acute pancreatitis (SAP) in rats through NOD‑like receptor protein 3 (NLRP3) inflammasomes. The rats were randomly divided into a sham operation group, an SAP model group induced by a standard retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct, and low‑dose (30 mg/kg) and high‑dose (60 mg/kg) emodin‑treated groups. At 12 h after the event, the plasma amylase, lipase, interleukin (IL)‑1β, IL‑18 and myeloperoxidase (MPO) activities were examined. Furthermore, the pathological scores of pancreases were evaluated by hematoxylin and eosin staining. The expression levels of P2X ligand‑gated ion channel 7 (P2X7), NLRP3, apoptosis‑associated speck‑like protein containing a C‑terminal caspase recruitment domain and caspase‑1 were also analyzed by western blot analysis. The data demonstrated that, compared with the SAP group, emodin could significantly relieve the pancreatic histopathology and acinar cellular structure injury, and notably downregulate the plasma amylase and lipase levels, as well as the MPO activities in pancreatic tissues, in a dose‑dependent manner. Furthermore, emodin inhibited the P2X7/NLRP3 signaling pathway followed by the decrease of pro‑inflammatory factors, and the latter is beneficial for the recovery of SAP. Collectively, the data indicated that emodin may be an efficient candidate natural product for SAP treatment.

• Authors: Qingkai Zhang, Xufeng Tao, Shilin Xia, Jialin Qu, Huiyi Song, Jianjun Liu, Hailong Li, Dong Shang
• Journal: Oncology reports (Oncol Rep) Vol. 41 Issue 1 Pg. 270-278 (Jan 2019) ISSN: 1791-2431 [Electronic] Greece
• PMID: 30542707 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• P2RX7 protein, human
• Plant Extracts
• Protective Agents
• Receptors, Purinergic P2X7
• dachengqi decoction
• qingyi
• Taurocholic Acid
• MPO protein, human
• Peroxidase
• Emodin

Topics

• Animals
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Emodin (pharmacology, therapeutic use)
• Humans
• Male
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Pancreatitis (chemically induced, diagnosis, drug therapy, pathology)
• Peroxidase (metabolism)
• Plant Extracts (pharmacology, therapeutic use)
• Protective Agents (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Purinergic P2X7 (metabolism)
• Rheum (chemistry)
• Severity of Illness Index
• Signal Transduction (drug effects)
• Taurocholic Acid (toxicity)
• Treatment Outcome