The aim of this study was to explore the possible mechanisms of Ficus carica leaf (FCL) extract in suppressing hepatic gluconeogenesis in diabetic mice. Diabetic mice (streptozotocin-induced) received 1 g/kg of FCL extract twice a day for 6 weeks. Fasting blood glucose levels were measured and a 2-h oral glucose tolerance test was conducted. AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) expression was examined. HepG2 hepatocytes were treated with FCL extract and an AMPK inhibitor (compound C) or agonist (AICAR), and PEPCK, G6pase, PGC-1α, AMPK, forkhead transcription factor O1 (FOXO1), and hepatic nuclear factor 4α (HNF4α) expression was determined. The results showed that FCL extract inhibited the expression of PEPCK and G6Pase in the liver of diabetic mice and HepG2 hepatocytes. FCL extract activated AMPK and decreased PGC-1α, HNF4α, and FOXO1 expression. The AMPK inhibitor attenuated those effects through inhibiting gluconeogenesis, while the AMPK agonist partially enhanced gluconeogenesis. In conclusion, FCL extract inhibits hepatic gluconeogenesis via activation of AMPK and down-regulation of gluconeogenic enzymes.
The aim of this study was to explore the inhibitory effects of Ficus carica leaves (FCL) extract on AMPK/JNK/caspase3 signaling pathway and antioxidation in pancreatic β-cells. H&E staining, insulin immunohistochemistry, and TUNEL methods were used to investigate the effects of FCL on pancreatic histopathology in type 1 diabetic mice. The expression levels of caspase-3, AMPK, and JNK protein in the pancreatic tissue and MIN6 cells [induced by palmitic acid (PA) and hydrogen peroxide] were determined. Flow cytometry was used to detect the effects of FCL on apoptosis and ROS production of MIN6 cells. FCL (2 g/kg, continuous gavage for 6 weeks) significantly improved the pancreatic tissue injury in type 1 diabetic mice and reduced the expression levels of apoptosis-related proteins such as FasL, caspase8, Bax/Bcl-2, Cyt-C, caspase-3, p-AMPK, and p-JNK. FCL inhibited cell apoptosis induced by PA and the protein expression levels of caspase-3, p-AMPK, and p-JNK. The AMPK agonist AICAR could reverse the protective effects of FCL on MIN6 cells. The AMPK inhibitor compound C had a similar effect on MIN6 cells as that of FCL. FCL could inhibit cell apoptosis induced by hydrogen peroxide and reduced the production of ROS. In conclusion, FCL could inhibit pancreatic β-cell apoptosis by inhibiting the AMPK/JNK/caspase-3 signaling pathway and by antioxidation properties.
This study aimed to evaluate the role of the clinical pharmacist in the rational use of proton pump inhibitors (PPIs) in a general surgery department. All enrolled patients had attended the general surgery department of a tertiary hospital. This single-center prospective study compared differences in the overall rate of rational PPI use, proportion of unindicated PPI use, utilization rate, average defined daily dose (DDD), drug costs, PPI costs, and cost-effectiveness of clinical pharmacist intervention between the intervention (538 cases) and control (536 cases) groups. In the intervention group, Pareto and fishbone diagram analyses were combined with the Plan-Do-Check-Act cycle; Statistical Package for the Social Sciences was used for analyzing all data. The overall rate of rational PPI use was significantly higher in the intervention group than in the control group (p < 0.01). The proportion of unindicated PPI use, utilization rate, average DDD, drug costs, and PPI costs were significantly lower in the intervention group than in the control group (p < 0.05). Cost-effectiveness analysis for the overall rate of rational PPI use indicated a positive impact of intervention, with economic benefits in the intervention group. Clinical pharmacist intervention for rational use of PPIs in general surgery departments could significantly increase the overall rate of rational PPI use; it could also reduce the proportion of unindicated PPI use, utilization rates, average DDDs, drug costs, and PPIs costs. Pharmacist intervention also offers economic benefits by improving the overall rate of rational PPI use.
1 April 2023 in Diabetes, Metabolic Syndrome and Obesity
Purpose: To evaluate the dichloromethane extract of Ficus carica leaves (FCL) had a hypoglycemic impact in diabetic mice, as well as to identify the bioactive components in the extract and analyze their anti-hyperglycemia potential in HepG2 cells. Material and Methods: The antidiabetic activity of dichloromethane extract of Ficus carica leaves was evaluated in diabetic mice induced by streptozotocin (STZ,100 mg/kg) combined with high-fat diet. The fasting blood glucose (FBG), blood lipids, oral glucose tolerance, glycated hemoglobin (HbA1c), and pathological change effects of the extract were measured after administering two doses of the extract (500 and 1000 mg/kg). On the other hand, we used column chromatography to isolate the dichloromethane extract, and we structurally identified the compounds based on 1H NMR and 3C NMR spectra. The hypoglycemic activity of isolated compounds was investigated in palmitic acid (PA)-induced HepG2 cells. Results: FCL extract lowers blood glucose and improves blood lipids and the pancreatic β-cell also tend to recover whether the psoralen is removed or not. Meanwhile, three coumarins except psoralen were isolated from dichloromethane extract: 3,4-dihydropsoralen, umbelliferone and 7-hydroxyl-6-methylcoumarin. Psoralen and umbelliferone promoted glucose uptake in HepG2 cells. Discussion and Conclusion: In vivo experiments, dichloromethane extract of FCL has potential antidiabetic activity, mainly by lowering blood glucose, improving blood lipids, glucose tolerance and repairing pancreatic islet damage, which justifies its use in the treatment of diabetes in Spanish folklore. Additionally, in vitro experiments, psoralen and umbelliferone demonstrated substantial glucose-lowering activity. Graphical Abstract:
19 January 2023 in Asia-Pacific Journal of Clinical Oncology