scholarly journals Protective effects of Panax notoginseng saponins in a rat model of severe acute pancreatitis occur through regulation of inflammatory pathway signaling by upregulation of miR-181b

2018 ◽  
Vol 32 ◽  
pp. 205873841881863
Author(s):  
Ming-wei Liu ◽  
Yun-qiao Huang ◽  
Ya-ping Qu ◽  
Dong-mei Wang ◽  
Deng-yun Tang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Rat Model ◽  
Therapeutic Potential ◽  
Sodium Taurocholate ◽  
Panax Notoginseng ◽  
Serum Levels ◽  
Panax Notoginseng Saponins ◽  
Tnf Α ◽  
Anti Inflammatory

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 and TLR4. We also observed lower levels of IL-8, IL-6, ACAM-1, TNF-α, MPO, and IL-12 in the Panax notoginseng saponin–treated group when compared with controls. In addition, Panax notoginseng saponin–treated rats had significantly reduced serum levels of lipase and amylase. Histological analyses confirmed that Panax notoginseng saponin treatment significantly reduced taurocholate-induced pancreatic inflammation. Collectively, our results suggest that Panax notoginseng saponin treatment attenuated acute pancreatitis and pancreatic inflammation by increasing miR-181b signaling. These findings suggest that Panax notoginseng saponins have therapeutic potential in the treatment of taurocholate-induced SAP.

Effects of Acupuncture at St25 on Inflammatory Mediators and Nuclear Factor κB Activation in a Rat Model of Severe Acute Pancreatitis

2015 ◽  
Vol 33 (4) ◽  
pp. 299-304 ◽  
Author(s):  
Qi-Ming Xue ◽  
Hui Pan ◽  
Lu Huang ◽  
Ning Li
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Inflammatory Mediators ◽  
Morphological Changes ◽  
Sodium Taurocholate ◽  
Serum Levels ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Sprague Dawley ◽  
Tnf Α

Objective To observe the effect of electroacupuncture (EA) and manual acupuncture (MA) at ST25 on inflammatory mediators and nuclear factor κ-B (NF-κB) activation in rats with sodium taurocholate-induced severe acute pancreatitis (SAP). Methods Eighty-eight male Sprague–Dawley rats were randomly divided into four groups: control (sham-operated), SAP, SAP+EA and SAP+MA (n=22 each). A SAP model was established by injecting 3.5% sodium taurocholate 1 mL/kg into the pancreatic duct. In each group, animals were killed at t=3 h (n=7), 6 h (n=7) and 12 h (n=8) after the procedure. Pancreatic expression of NF-κB was examined by immunohistochemical staining. The levels of tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) in serum were determined by ELISA. Pathological changes in the pancreas were examined microscopically. Results Serum levels of TNF-α and IL-6 increased and morphological changes consistent with tissue damage were observed in the pancreas of SAP rats. NF-κB p65 expression was significantly higher in the SAP group than in the sham-operated group (p<0.05). Treatment with acupuncture at ST25 attenuated morphological damage and reduced levels of TNF-α and IL-6 in serum. NF-κB p65 expression was also significantly reduced by acupuncture at ST25 in the pancreas at 6 and 12 h after the procedure (p<0.05). There were no significant differences between the SAP+EA and SAP+MA groups. Conclusions Acupuncture at ST25 might have a therapeutic effect on rats with SAP through inhibition of NF-κB expression and a reduction in the release of pro-inflammatory cytokines.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

scholarly journals Comparative study of the therapeutic potential of octreotide versus trimetazidine and their combination on acute pancreatitis in male rats

2018 ◽  
Vol 4 (4) ◽  
Keyword(s):  
Acute Pancreatitis ◽  
Therapeutic Potential ◽  
Serum Levels ◽  
Male Rats ◽  
Combination Group ◽  
Mortality And Morbidity ◽  
Tnf Α ◽  
Total Antioxidant ◽  
Factor Α ◽  
Necrosis Factor

Objective Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are stillvery limited. Various theories have been suggested regarding the pathophysiology of acute pancreatitis, lot of research into differentmedical treatments for the treatment of acute pancreatitis, but it is not clear what benefits each treatment has, or indeed if any medicaltreatment is beneficial apart from supportive treatment.Aim To clarify the potential therapeutic effect of octreotide, trimetazidine, and their combination in acute pancreatitis.Methods Acute pancreatitis was induced by L-arginine and treated with octreotide subcutaneously, trimetazidine intraperitoneally andcombination therapy by octreotide and trimetazidine. The rats were followed for 24 h. At the 24th hour we determined serum levels oftumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total antioxidant capacity (TAC), lipase, and amylase, and the pancreatic tissues wereanalyzed histopathologically.Results TNF-α (P < 0.001), IL-1β (P < 0.001), TAC (P < 0.001), lipase (P < 0.001), and amylase (P < 0.001) serum levels and scores ofhistopathological changes (P < 0.05) were significantly lower in combination group as compared with both octreotide and trimetazidinegroups.Conclusion Combination treatment markedly decreases biochemical and histopathological changes in acute pancreatitis, thus amelioratepancreatic injury in l-arginine induced acute pancreatitis.

scholarly journals Ulinastatin in combination with glutamine dipeptide reduces serum levels of TNF-α, endotoxin and IL-6 in patients with severe acute pancreatitis

2011 ◽  
Vol 19 (18) ◽  
pp. 1946
Author(s):  
Dao-Pang Lin ◽  
Zhi-Yun Deng ◽  
Xiao-Dong He ◽  
Quan Cui ◽  
Xiao-Lei Zhao ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Serum Levels ◽  
Tnf Α

scholarly journals Picroside II Improves Severe Acute Pancreatitis-Induced Intestinal Barrier Injury by Inactivating Oxidative and Inflammatory TLR4-Dependent PI3K/AKT/NF-κB Signaling and Improving Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xuehua Piao ◽  
Baohai Liu ◽  
Xiaodan Sui ◽  
Shuangdi Li ◽  
Wei Niu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Gut Microbiota ◽  
Severe Acute Pancreatitis ◽  
Rat Model ◽  
Intestinal Barrier ◽  
Oxidative Stress Marker ◽  
Inflammatory Signaling ◽  
Picroside Ii ◽  
Anti Inflammatory

Background. Picroside II exerts anti-inflammatory and antidiarrheal effects for treating the diseases associated with oxidative injury. However, its function on pancreatitis-induced intestinal barrier injury remains unclear. Hypothesis/Purpose. We hypothesized that picroside II will have protective effects against pancreatitis-induced intestinal barrier injury by affecting oxidative and inflammatory signaling (Toll-like receptor 4- (TLR4-) dependent phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and nuclear factor kappa B (NF-κB)). Study Design and Methods. A Sprague-Dawley (SD) rat model with severe acute pancreatitis (SAP) was induced via the injection of sodium taurocholate (4% wt/vol; 1 mL/kg). All rats were divided into 3 groups: sham (CG), SAP-induced intestinal barrier injury (MG), and picroside II (PG) groups. Intestinal barrier injury was assessed by scanning electron microscopy (SEM), hematoxylin and eosin staining, and pathological scores. We measured the levels of pancreatitis biomarkers (amylase and lipase), oxidative and inflammatory signaling (TLR4-dependent PI3K/AKT/NF-κB), oxidative stress marker (superoxidase dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx), and malondialdehyde), and inflammatory markers (tumor necrosis factor α (TNFα), interleukin- (IL-) 1, IL-6, and IL-10) in serum and/or gut tissues. Gut microbiota composition in feces was measured by using 16S rRNA sequencing. Results. SEM showed that intestinal barrier injury was caused with the loss of intestinal villi and mitochondria destruction, and pathological scores were increased in the MG group. The levels of amylase, lipase, malondialdehyde, TNFα, IL-1, IL-6, TLR4, PI3K, AKT, and NF-κB were increased, and the levels of SOD, GPx, CAT, and IL-10 was reduced in the MG group when compared with CG group (P<0.05). Picroside II treatment inhibited the symptoms in the MG group and showed antioxidant and anti-inflammatory activities. The serum levels of picroside II had strong correlation with the levels of inflammatory and oxidative stress biomarkers (P<0.05). Picroside II treatment increased the proportion of Lactobacillus and Prevotella and decreased the proportion of Helicobacter and Escherichia_Shigella in the model. Conclusions. Picroside II improved the SAP-induced intestinal barrier injury in the rat model by inactivating oxidant and inflammatory signaling and improving gut microbiota.

scholarly journals Qingyi decoction attenuates severe acute pancreatitis in rats via inhibition of inflammation and protection of the intestinal barrier

2019 ◽  
Vol 47 (5) ◽  
pp. 2215-2227 ◽  
Author(s):  
Song Su ◽  
Tiancheng Liang ◽  
Xiang Zhou ◽  
Kai He ◽  
Bo Li ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Sodium Taurocholate ◽  
Intestinal Barrier ◽  
Pancreatic Tissue ◽  
Small Intestinal Mucosa ◽  
Barrier Dysfunction ◽  
Ileal Mucosa ◽  
Inflammatory Infiltration ◽  
Tnf Α

Objective Qingyi decoction (QYD) has beneficial effects in severe acute pancreatitis (SAP). We assessed the therapeutic effect and mechanisms of QYD in SAP. Methods A rat model of SAP was induced by pancreatic ductal injection of sodium taurocholate. QYD was administered intragastrically immediately postoperatively and once every 12 hours. Serum amylase, endotoxin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-lactate levels were measured at 12, 24, and 48 hours. Histological changes in the pancreas and ileum were analyzed. Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. Results Pancreatic tissue showed extracellular space expansion, inflammatory infiltration, vessels with necrotic walls, and hemorrhage. Ileal tissue showed hemorrhage, inflammatory infiltration, and ileal mucosa destruction. These histological features were dramatically improved by QYD. Increased serum levels of amylase, endotoxin, TNF-α, IL-6, and D-lactic acid were significantly decreased by QYD administration. Increased expression of NF-κB p65 and TLR4 and decreased expression of ZO-1 in the ileal mucosa were also restored to normal levels by QYD treatment. Conclusion QYD alleviates SAP by reducing intestinal barrier dysfunction, inhibiting intestinal bacteria and endotoxin translocation, and preventing NF-κB activation.

scholarly journals Pro-inflammatory cytokine-driven PI3K/Akt/Sp1 signalling and H2S production facilitates the pathogenesis of severe acute pancreatitis

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Ying Liu ◽  
Ribin Liao ◽  
Zhanrong Qiang ◽  
Cheng Zhang
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Rat Model ◽  
Intestinal Motility ◽  
Inhibitory Effect ◽  
Vital Role ◽  
Signalling Pathway ◽  
Pi3k Inhibitor Ly294002 ◽  
Tnf Α ◽  
Bowel Movements

Severe acute pancreatitis (SAP) is a disease usually associated with systemic organ dysfunction or pancreatic necrosis. Most patients with SAP suffer from defective intestinal motility in the early phase of the disease. Additionally, SAP-induced inflammation produces hydrogen sulphide (H2S) that impairs the gastrointestinal (GI) system. However, the exact mechanism of H2S in the regulation of SAP is yet to be elucidated. In the present paper, we used a rat model of SAP to evaluate the role of H2S on intestinal motility by counting the number of bowel movements and investigating the effect of H2S on inflammation. We treated colonic muscle cells (CMCs) with SAP plasma, tumour necrosis factor-α (TNF-α) or interleukin-6 (IL-6) and measured the expressions of H2S-producing enzymes cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS) and Sp1 and PI3K/Akt by using quantitative PCR, Western blotting and immunohistochemical detection. We used the PI3K inhibitor LY294002 and the siRNA si-Sp1 to suppress the activity of the PI3K/Akt/Sp1 signalling pathway. We found that, in the SAP rat model, H2S facilitated an inhibitory effect on intestinal motility and enhanced the inflammatory response caused by SAP (P<0.05). The expressions of CSE and CBS in CMCs were significantly increased after treatment with TNF-α or IL-6 (P<0.05). Blocking the PI3K/Akt/Sp1 pathway remarkably inhibited the synthesis of CSE and CBS. Our data demonstrated that H2S plays a vital role in the pathogenesis of SAP and that SAP is modulated by inflammation driven by the PI3K/Akt/Sp1 signalling pathway.

Protective Effect of Hippophae rhamnoides Polysaccharide Against Kidney Injury in Rats with Severe Acute Pancreatitis

2020 ◽  
Vol 19 (3) ◽  
pp. 303-307
Author(s):  
Changfei Cen ◽  
Jiping Hu ◽  
Yanping Fu ◽  
Shuhui Li ◽  
Daliang Yu
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Caspase 3 ◽  
Inflammatory Cell ◽  
Sodium Taurocholate ◽  
Kidney Injury ◽  
Serum Levels ◽  
Hippophae Rhamnoides ◽  
Hippophaë Rhamnoides ◽  
Liver Injuries

In the traditional Chinese medicine, polysaccharide of Hippophae rhamnoides (also known as sea buckthorn) has been widely used for the treatment of liver injuries or cardiovascular problems. The effect of the polysaccharide of H. rhamnoides on kidney injury in rats with severe acute pancreatitis induced by biliopancreatic duct injection with sodium taurocholate was examined. The rats with severe acute pancreatitis showed series of degenerative changes in pancreas and kidney including inflammatory cell infiltration, edema, and necrosis that were diminished following treatment with the polysaccharide of Hippophae rhamnoides. Furthermore, sodium taurocholate injection also aggravated renal function with enhanced levels of proinflammatory cytokines, blood urea nitrogen, serum creatinine, and serum levels of amylase and lipase that were ameliorated by the polysaccharide. There was an upregulation of cleaved caspase-3 and Bax, as well as downregulation of Bcl-2, in the rats model with SAP that diminished following polysaccharide treatment. Lastly, there was an activation of MAPK/NF-κB pathway in the rats exhibiting severe acute pancreatitis that was repressed by the polysaccharide of Hippophae rhamnoides.

Sign in / Sign up

Export Citation Format

Share Document