Efficacy of Agmatine Treatment in Experimental Acute Pancreatitis Rat Model.

BACKGROUND/AIMS: Acute pancreatitis which is characterized by pancreatic inflammation can sometimes be difficult to treat because of limited therapeutic options. The purpose of the study was to assess the effects of agmatine in the acute pancreatitis experimental rat model. MATERIALS AND METHODS: An acute pancreatitis model was created with the administration of cerulein in 40 female Sprague-Dawley rats. Agmatine was administered as a protective agent at 5 mg/kg (low dose) and 10 mg/kg (high dose). The rats were divided into 5 groups, each with 8 rats: group 1 (acute pancreatitis); group 2 (acute pancreatitis+low-dose agmatine 5 mg/kg); group 3 (acute pancreatitis+high-dose agmatine 10 mg/kg); group 4 (placebo, acute pancreatitis+saline); and group 5 (sham and saline infusion). All rats were sacrificed 24 hours after the last injection, and the levels of superoxide dismutase, interleukin-1 beta, and tumor necrosis factor-alpha were assessed in blood samples collected via cardiac puncture. Histopathological examination was performed by a pathologist, who was blind to the groups, according to the Schoenberg's pancreatitis scoring index. RESULTS: The amylase (16.67 and 37.89 U/L), glutathione peroxidase (13.62 and 18.44 ng/mL), tumor necrosis factor-α (39.68 and 64 ng/mL), interleukin-1 (484.73 and 561.83 pg/mL), and transforming growth factor-ß (110.52 and 126.34 ng/L) levels were significantly lower and superoxide dismutase (1.29 and 0.98 ng/L) and malondialdehyde (0.99 and 0.96 nmol/mL) levels were significantly higher in group 3 compared to group 1 (P < .05). Moreover glutathione peroxidase, tumor necrosis factor-α, and transforming growth factor-ß levels were lower, and malondialdehyde levels were higher in the group 3 compared to group 2 (P < .05). Although the Schoenberg's pancreatitis scoring index was not significantly different between the high- and low-dose treatment groups, rats who received high-dose treatment had significantly lower scores compared to those with acute pancreatitis group. CONCLUSION: This is the first study that evaluated the efficacy of agmatine in an experimental model of acute pancreatitis. Agmatine, an anti-inflammatory and antioxidant agent, had a protective effect in an experimental rat model of acute pancreatitis.

Decreased inflammatory gene expression accompanies the improvement of liver enzyme and lipid profile following aerobic training and vitamin D supplementation in T2DM patients.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is one of the health issues causing untoward low-grade systemic inflammation. Aerobic Training (AT) and Vitamin D (Vit D) supplementation are among the approaches that improve lipid profile and liver enzymes in T2DM. However, the mechanisms responsible for these improvements are not fully elucidated. OBJECTIVES: This study aimed to evaluate the effects of AT and Vit D supplementation on lipid profile, liver enzymes, Interleukin-6 (IL-6), Interleukin-10 (IL-10), Cluster of differentiation 27 (CD27), Chemokine (C-X-C motif) Ligand 13 (CXCL13), Interferon-Gamma (IFN-γ) and Transforming Growth Factor-Beta 1 (TGF-ß1) gene expressions in patients with T2DM. METHODS: In this study, 40 male T2DM patients aged 35-50 years were randomly selected and assigned into four groups (n = 10 for each); AT+vitamin D supplementation (AT+Vit D), AT+placebo (AT), Vit D supplementation (Vit D), and control+placebo (C). The intervention consisted of 8 weeks of 20-40 minutes AT protocol at 60-75% HRmax 3 sessions/week and taking 50,000 IU of Vit D supplement once a week. Serum levels of lipid profile and liver enzymes and gene expression of IL-6, IL-10, CD27, CXCL13, IFN-γ, and TGF-ß1 in Peripheral Blood Mononuclear Cells (PBMCs) were measured. One-way analysis of variance (ANOVA), Tukey's post hoc, and paired sample t-test at P-values less than 0.05 were used to analyze the data using SPSS software. RESULTS: AT+Vit D, AT, and Vit D significantly decreased TC, TG, LDL, AST, ALT, and GGT while increased HDL after 8 weeks in favor of AT+Vit D. Also, gene expressions of IL-6, IL-10, CD27, CXCL13, IFN-γ, and TGF-ß1 were downregulated significantly in AT+Vit D, AT, and Vit D, while upregulated in C. Furthermore, compared to individual AT or Vit D, AT+Vit D significantly downregulated IL-6 (P = 0.013; P = 0.025), IL-10 (P = 0.012; P = 0.026), CD27 (P = 0.023; P = 0.041), CXCL13 (P = 0.014; P = 0.025), IFN-γ (P = 0.017; P = 0.026), and TGF-ß1 (P = 0.001; P = 0.028). CONCLUSION: In comparison to individual AT or Vit D, AT+Vit D may enhance lipid profile, and liver enzymes and drive the balance to favor inhibition of inflammation by downregulating gene expression of inflammation-related factors. As a result, AT+Vit D may be considered appropriate therapy for managing T2DM.

Celastrus orbiculatus Extract Inhibits the Epithelial-Mesenchymal Transition Process by Transforming Growth Factor-ß Signaling Pathway in Gastric Cancer.

BACKGROUND: Gastric cancer is the fifth most common tumor and has the third-highest mortality rate among various malignant tumors, and the survival rate of patients is low. Celastrus orbiculatus extract (COE) has been shown to inhibit the activity of a variety of tumors. In this study, we examined the inhibition of the epithelial-mesenchymal transition (EMT) process in gastric cancer cells by COE through the transforming growth factor-ß (TGF-ß) signaling pathway. METHODS: COE was first diluted to various concentrations and then used to treat SGC-7901, BGC-823, MGC-803, and AGS cells. Cell proliferation was assessed by an MTT (thiazole blue) assay. Transwell assays were used to assess cell invasion and migration. The high-content imaging technology was used to further observe the effects of the drug on cell invasion and migration. Western blotting was used to assess the effects of the drug on the expression of EMT and Smad2/3 signaling pathway-related proteins. RESULTS: We found that COE inhibited the migration and invasion of AGS gastric cancer cells in a dose-dependent manner. Consequently, COE decreased the expression of EMT-related proteins and proteins related to the Smad2/3 signaling pathway in gastric cancer cells, inhibiting the migration and invasion of gastric cancer cells, and this effect occurred through the TGF-ß signaling pathway. CONCLUSION: We investigated that COE could inhibit the proliferation of gastric cancer cells and inhibit invasion and metastasis by inhibiting the EMT process at the molecular level and its effect on the TGF-ß signaling pathway.