Epigallocatechin gallate attenuated high glucose-induced pancreatic beta cell dysfunction by modulating DRP1-mediated mitochondrial apoptosis pathways.

Long-term exposure to hyperglycemic conditions leads to ß-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of ß-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus.

In vitro PCR verification that lysozyme inhibits nucleic acid replication and transcription.

Lysozyme can kill bacteria by its enzymatic activity or through a mechanism involving its cationic nature, which can facilitate electrostatic interactions with the viral capsid, the negatively charged parts of nucleic acids, and polymerase, so binding to nucleic acids may be another biological function of lysozyme. Here, PCR was used as a research tool to detect the effects of lysozyme on the replication and transcription of nucleic acids after treatment in different ways. We found that lysozyme and its hydrolysate can enter cells and inhibit PCR to varying degrees in vitro, and degraded lysozyme inhibited nucleic acid replication more effectively than intact lysozyme. The inhibition of lysozyme may be related to polymerase binding, and the sensitivity of different polymerases to lysozyme is inconsistent. Our findings provide a theoretical basis for further explaining the pharmacological effects of lysozyme, such as antibacterial, antiviral, anticancer, and immune regulatory activities, and directions for the development of new pharmacological effects of lysozyme and its metabolites.

EGCG Upregulates UCP3 Levels to Protect MIN6 Pancreatic Islet Cells from Interleukin-1ß-Induced Apoptosis.

OBJECTIVE: The protective effects of epigallocatechin gallate (EGCG) on interleukin-1ß (IL-1ß)-induced apoptosis were investigated in murine MIN6 pancreatic ß-cells. The role of uncoupling protein-3 (UCP3) signaling in this process was also explored. METHODS: After treatment with IL-1ß and EGCG, cells were collected and analyzed. Cell viability was measured using the CCK8 assay and the function of ß-cells was evaluated by analyzing insulin secretion. Detection of mitochondrial function in cells was performed by measuring mitochondrial membrane potential, the concentration of ATP and activity of ROS. Apoptosis was analyzed by Hochest33258 staining and flow cytometry. Expression levels of UCP3 were interrogated using immunohistochemistry, RT-PCR and Western blotting. RESULTS: Compared with the control group, IL-1ß treatment (20nM) for 24 h significantly decreased cell viability and insulin secretion, damaged mitochondrial function and increased ROS activity. Results also showed increased apoptosis and a decrease in UCP3 expression levels (p<0.01). However, treatment with low (1mM) or high (5mM) concentrations of EGCG significantly decreased IL-1ß-induced apoptosis (p<0.01), restored mitochondrial function and subsequently increased UCP3 levels in IL-1ß-induced ß-cells (p<0.01). CONCLUSION: These results suggest that EGCG protects against IL-1ß-induced mitochondrial injury and apoptosis in ß-cells through the up-regulation of UCP3.