Pharmacological advantages of melatonin in immunosenescence by improving activity of T lymphocytes

Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models. Splenocytes, CD4＋, and naive CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation （CD28 and p21） and the melatonin receptor （MT1A and MT1B） were assessed. The T cell activation- related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT 1 A, and MT 1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4＋ T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4＋ T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.

In vitro,in vivo and in silico anti-hyperglycemic inhibition by sinigrin

Objective:To evaluate the anti-hyperglycemic potential of sinigrin using in ritro.in silico and in riro streptozotocin(STZ) induced hyperglycemic zebrafish model.Methods:The in vitro enzyme inhibition assay was carried out to determine the IC_(50) value against α-glucosidase and α-amylase.in silico molecular docking was performed against both enzymes with PyRx tool and simulations were performed using GROMACS tool.Hyperglycemia was induced in zebrafishes using three intraperitoneal injections on alternating days for one week at 350mg/kg of STZ.Hyperglycemic fishes were treated intraperitoncally with 50.100 and 150 mg of sinigrin/kg of body weight for 24 h and glucose levels were measured.Results:The sinigrin showed very strong inhibition against α-glucosidase and α-amylase with 0.248 and0.00124 μM while reference drug acarbose showed IC_(50) value of 73.0700 and 0.0017 μM against α-glucosidase and α-amylase,respectively.Kinetic analysis revealed that sinigrin has the mixed type mode of inhibition against α-glucosidase.Molecular docking results revealed its strong binding affinity with α-glucosidase(-10.00 Kcal/mol) and α-amylase(-8.10 Kcal/mol).Simulations graphs confirmed its stability against both enzymes.Furthermore.in hyperglycemic zebrafishes most significant(P<0.001) reduction of glucose was occurred at150 mg/kg.moderate significant reduction of glucose was observed at 100 mg/kg and no any significant reduction of glucose was measured at 50 mg/kg.Conclusions:It can be evident from the present results that sinigrin has potent anti-hyperglycemic activity and it may prove to be effective treatment for the hyperglycemia.