Protective effects of Panax notoginseng saponins ina rat model of severe acute pancreatitis occur through regulation ofinflammatory pathway signaling by upregulation of miR-181b

摘要

Panax notoginseng saponins are extracted from Chinese ginseng—Panax notoginseng Ledeb—and are known to have therapeutic anti-inflammatory effects. However, the precise mechanism behind their anti-inflammatory effects remains relatively unknown. To better understand how Panax notoginseng saponins exert their therapeutic benefit, we tested them in a rat model of severe acute pancreatitis (SAP). Rats received a tail vein injection of Panax notoginseng saponins and were administered 5% sodium taurocholate 2 h later. Pancreatic tissue was then harvested and levels of miR-181b, FSTL1, TREM1, TLR4, TRAF6, IRAK1, p-Akt, p-p38MAPK, NF-κBp65, and p-IκB-α were determined using Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assays were used to determine serum levels of tumor necrosis factor-α (TNF-α), TREM1, interleukin (IL)-6, ACAM-1, IL-8, and IL-12 and DNA-bound levels of NF-KB65 and TLR4 in pancreatic and ileum tissue. Serum levels of lipase and amylase, pancreatic myeloperoxidase (MPO) activity, and pancreatic water content were also measured. Hematoxylin and eosin staining was used for all histological analyses. Results indicated upregulation of miR-181b,but negligible levels of FSTL1, p-p38MAPK, TLR4, TRAF6, p-Akt, IRAK1, TREM1,p-NF-κBp65, and p-IκB-α, as well as negligible DNA-bound levels of NF-KB65 andTLR4. We also observed lower levels of IL-8, IL-6, ACAM-1, TNF-α, MPO, and IL-12in the Panax notoginseng saponin–treated group when comparedwith controls. In addition, Panax notoginseng saponin–treatedrats had significantly reduced serum levels of lipase and amylase. Histologicalanalyses confirmed that Panax notoginseng saponin treatmentsignificantly reduced taurocholate-induced pancreatic inflammation.Collectively, our results suggest that Panax notoginsengsaponin treatment attenuated acute pancreatitis and pancreatic inflammation byincreasing miR-181b signaling. These findings suggest that Panaxnotoginseng saponins have therapeutic potential in the treatment oftaurocholate-induced SAP.