Emodin and baicalein inhibit sodium taurocholate-induced vacuole formation in pancreatic acinar cells

World J Gastroenterol. 2018 Jan 7;24(1):35-45. doi: 10.3748/wjg.v24.i1.35.

Abstract

Aim: To investigate the effects of combined use of emodin and baicalein (CEB) at the cellular and organism levels in severe acute pancreatitis (SAP) and explore the underlying mechanism.

Methods: SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol (1,4,5)-trisphosphate receptor (IP3R) expression were investigated to assess the mechanism of CEB.

Results: Pancreatic histopathology score (2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05) and serum amylase activity (2866.2 ± 617.7 vs 5241.3 ± 1410.0, P < 0.05) were significantly decreased in the CEB (three doses) treatment group compared with the SAP group (2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory cytokines IL-6 (466.82 ± 48.55 vs 603.50 ± 75.53, P < 0.05) and TNF-α (108.04 ± 16.10 vs 215.56 ± 74.67, P < 0.05) and increased the level of the anti-inflammatory cytokine IL-10 (200.96 ± 50.76 vs 54.18 ± 6.07, P < 0.05) compared with those in the SAP group. CEB increased cell viability, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 mRNA expression compared with those in the SAP group (P < 0.05). There was a trend towards decreased IP3R protein in the CEB treatment group; however, it did not reach statistical significance (P > 0.05).

Conclusion: These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.

Keywords: Baicalein; Calcium overload; Emodin; Inositol (1,4,5)-trisphosphate receptor; Pancreatic acinar cell; Severe acute pancreatitis.

MeSH terms

  • Acinar Cells / drug effects*
  • Acinar Cells / metabolism
  • Acinar Cells / pathology
  • Acute Disease
  • Animals
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Emodin / pharmacology*
  • Flavanones / pharmacology*
  • Inflammation Mediators / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / drug effects
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy*
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Taurocholic Acid*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Vacuoles / drug effects*
  • Vacuoles / metabolism
  • Vacuoles / pathology

Substances

  • Flavanones
  • Inflammation Mediators
  • Inositol 1,4,5-Trisphosphate Receptors
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • baicalein
  • Taurocholic Acid
  • Emodin
  • Calcium