The anorexigenic neuropeptide prolactin-releasing peptide (PrRP) is involved in the regulation of food intake and energy expenditure. Lipidization of PrRP stabilizes the peptide, facilitates central effect after peripheral administration and increases its affinity for its receptor, GPR10, and for the neuropeptide FF (NPFF) receptor NPFF-R2. The two most potent palmitoylated analogs with anorectic effects in mice, palm11-PrRP31 and palm-PrRP31, were studied in vitro to determine their agonist/antagonist properties and mechanism of action on GPR10, NPFF-R2 and other potential off-target receptors related to energy homeostasis. Palmitoylation of both PrRP31 analogs increased the binding properties of PrRP31 to anorexigenic receptors GPR10 and NPFF-R2 and resulted in a high affinity for another NPFF receptor, NPFF-R1. Moreover, in CHO-K1 cells expressing GPR10, NPFF-R2 or NPFF-R1, palm11-PrRP and palm-PrRP significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt) and cAMP-responsive element-binding protein (CREB). Palm11-PrRP31, unlike palm-PrRP31, did not activate either c-Jun N-terminal kinase (JNK), p38, c-Jun, c-Fos or CREB pathways in cells expressing NPFF-1R. Palm-PrRP31 also has higher binding affinities for off-target receptors, namely, the ghrelin, opioid (KOR, MOR, DOR and OPR-L1) and neuropeptide Y (Y1, Y2 and Y5) receptors. Palm11-PrRP31 exhibited fewer off-target activities; therefore, it has a higher potential to be used as an anti-obesity drug with anorectic effects.

The present study aims to investigate the antidiabetic as well as the effect on lipid peroxidation of three different doses (50, 100, and 200 mg/kg) of Cleome droserifolia aerial parts methanolic extract in comparison with glibenclamide in alloxan-induced diabetic rats.Forty-two rats (35 diabetic and 7 normal) were included in this study. Oral administration of 100 and 200 mg/kg of the methanolic extract for 3 weeks significantly (P < 0.05) restored the blood glucose level, plasma malondialdehyde and urine sugar to near the physiological values whereas the effect of 50 mg/kg was not significant.Furthermore, from the HPLC chromatograms, we identified the presence of three flavonoids (quercetin, kaempferol, and isorhamnetin) together with three phenolic acids (sinapinic acid, ferulic acid and 4-coumaric acid) which may explain at least in part some of the antidiabetic and antioxidative properties observed in this study.

The purpose of the study was to monitor the antioxidative effect of morine in alloxan-induced diabetes mellitus in laboratory rat. The animals were divided by random selection into two groups (n = 7). The treated group was given morine in oral doses of 10 mg/kg -1 in 0.5% solution of Methocel E5 once a day; the control diabetic group was given only the solution of Methocel E5. Once a week, selected laboratory indices were determined in all animals (glucose, urea and cholesterol levels in serum, total glucose and protein losses through urine); diuresis as well as antioxidative enzymes (superoxiddismutase, glutathione peroxidase); total antioxidative capacity and malondialdehyde level in the blood. On the 20 th day the animals were exsanguinated and kidney tissue and pancreas samples were taken for histopathological analysis.We found a significant increase (p ≤ 0.05) of the glutathione peroxidase catalytic activity in the treated group compared to control diabetic group. There was also a highly significant increase (p ≤ 0.01) of total antioxidative capacity in the treated group compared to control diabetic group. A significant decrease (p ≤ 0.05) of malondialdehyde level was identified in the treated group compared to the control diabetic group. The superoxiddismutase catalytic activity involved nonsignificant changes. A significant decrease (p ≤ 0.05) of cholesterol level in serum was identified in the treated group compared to control diabetic group. Other examined laboratory parameters did not exhibit significant changes.Biochemical indices followed in this study indicated a protective antioxidative effect of morine. However, the results of histopathological examination did not correlate with them.

The most important risk factor for the development of sporadic Alzheimer's disease (AD) is ageing. Senescence accelerated mouse prone 8 (SAMP8) is a model of sporadic AD, with senescence accelerated resistant mouse (SAMR1) as a control. In this study, we aimed to determine the onset of senescence-induced neurodegeneration and the related potential therapeutic window using behavioral experiments, immunohistochemistry and western blotting in SAMP8 and SAMR1 mice at 3, 6 and 9 months of age. The Y-maze revealed significantly impaired working spatial memory of SAMP8 mice from the 6 th month. With ageing, increasing plasma concentrations of proinflammatory cytokines in SAMP8 mice were detected as well as significantly increased astrocytosis in the cortex and microgliosis in the brainstem. Moreover, from the 3 rd month, SAMP8 mice displayed a decreased number of neurons and neurogenesis in the hippocampus. From the 6 th month, increased pathological phosphorylation of tau protein at Thr231 and Ser214 was observed in the hippocampi of SAMP8 mice. In conclusion, changes specific for neurodegenerative processes were observed between the 3 rd and 6 th month of age in SAMP8 mice; thus, potential neuroprotective interventions could be applied between these ages.