Background and Objective: Anthocyanins are associated with aging and longevity. However, the mechanism involving the pure anthocyanin compounds in aging remains elusive. To investigate the possible mechanism of action of the different anthocyanin compounds towards aging-associated enzymes, the lead-likeness, binding affinity, and binding interactions were evaluated. Methodology: The different anthocyanin compounds such as cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin were assessed for lead-likeness following the criteria of Lipinski's rule of five (Ro5). These same compounds were virtually docked to different aging-related enzymes involved in MAPK, AMPK, and insulin signaling pathways. The top binding anthocyanins for each enzyme were visualized and compared to the enzyme inhibitors. Results: The different anthocyanin compounds abide with Ro5 denoting its potential as a lead compound. For each enzyme, there were different top-binding anthocyanins. The crystal structures of the docked anthocyanins reveal that there were different substructures involved during the non-covalent interaction. Some substructures, particularly the hydroxy groups, have different roles during the H-bond formation. These findings suggest that the various anthocyanin compounds may have a distinct mechanism of action towards a specific enzyme. Conclusion Taken together, these results suggest that the anthocyanin compounds may have varying effects in aging enzymes, which may be due to the differences in their substructures. Nonetheless, further investigations are needed to understand these findings using cells and animal models.
Insulin ; AMP-Activated Protein Kinases ; Anthocyanins ; Insulin, Regular, Human ; Computer Simulation

Allergic reaction to insulin is mediated by several mechanisms; differences in amino acid sequence of animal and human insulin, altered tertiary structure of insulin and the presence of non-insulin protein contaminants or pharmaceutical additives. Anaphylactic reactions to insulin only occur in 0.1 to 2% of patients who stopped insulin therapy and have then resumed treatment. We report a diabetic patient who suffered severe anaphylactic reactions to human recombinant insulin, successfully treated by desensitization. A 19-year-old man with type 1 diabetes receiving Insulatard HM(R) developed generalized urticaria and angioedema with progression to dyspnea, dizziness and syncope. Skin prick test to all kinds of human recombinant insulin products revealed immediate type hypersensitivity and the titer of insulin IgE was increased in serum. The desensitization trial with Velosulin HM(R) using modified desensitization method was performed. Six months after the desensitization he was taking Velosulin HM(R) as well as Insulatard HM(R) without any evidence of systemic allergic reactions.
Amino Acid Sequence ; Anaphylaxis* ; Angioedema ; Animals ; Dizziness ; Dyspnea ; Humans* ; Hypersensitivity ; Immunoglobulin E ; Insulin* ; Insulin, Regular, Pork ; Skin ; Syncope ; Urticaria ; Young Adult ; Isophane Insulin, Human

OBJECTIVE: To investigate the effect of oral administration of insulin on insulitis beta cell apoptosis and diabetes in non-obese diabetic (NOD) mice, and to explore the mechanism of immune tolerance induced by insulin. METHODS: Eighty-six female NOD mice were randomly divided into an insulin group (n=43) and a phosphate buffered saline (PBS) group (n=43). From 4 weeks of age, the recombinant human insulin (Humulin R) 1 mg (70 microL) was administrated in the oral insulin group and 70 microL PBS in the control group respectively, twice per week before 12 weeks of age and then once weekly until 30 weeks. Insulitis and beta cell apoptosis of islets were observed at 12 weeks. IL-4 and IFN-gamma in the sera were measured by enzyme linked immunosorbent assay (ELISA). The expression levels of I-Abeta(g7), IL-4, IFN-gamma, IL-1beta, Fas and TGF-beta mRNA of islets, and IL-4, IFN-gamma, TGF-beta mRNA of Peyer's patch were measured by reverse transcription-polymerase chain reaction (RT-PCR) at 12 weeks. RESULTS: The incidences in the insulin group were significantly lower than those in the PBS group (55.6% vs 85.7% at 30 weeks, 70.4% vs 96.4% at 52 weeks, P<0.05). The insulitis scores in the insulin group were lower than those in the PBS group, but there was no statistical significance. Fas expression on islets and apoptotic beta cell rates in the insulin group were lower than those in the PBS group (P<0.05). In the insulin group, serum IL-4 levels were higher, and IFN-gamma levels were lower than those in the PBS group (P<0.05). The levels of I-Abeta(g7), IFN-gamma, IL-1beta and Fas mRNA transcription in islets and IFN-gamma mRNA transcription in Peyer's patch were both lower in the insulin group, and IL-4, TGF-beta mRNA levels were higher than those in the PBS group (P<0.05). CONCLUSION The specific autoantigen insulin may induce the immune tolerance and prevent the diabetes in NOD mice, but it cannot block the progression of insulitis. Oral administration of insulin can induce the regulatory T cells, and make Th1 to Th2 cytokine shifts in the system and islets, thus preventing the Fas-mediated beta-cell apoptosis and diabetes.
Administration, Oral ; Animals ; Apoptosis ; drug effects ; Cytokines ; metabolism ; Diabetes Mellitus, Type 1 ; drug therapy ; pathology ; Female ; Insulin, Regular, Human ; administration & dosage ; pharmacology ; Islets of Langerhans ; cytology ; drug effects ; Mice ; Mice, Inbred NOD ; Th1-Th2 Balance ; fas Receptor ; metabolism