Steroidal alkaloids efficient aromatase inhibitors with potential for the treatment of postmenopausal breast cancer.

Plant-derived natural products are of great interest due to their diversity in modern drug discovery. Sarcococca saligna has been used for the treatment of different diseases. The present study was aimed at isolating phytochemical constituents including Alkaloid-C (a), Dictyophlebine (b), Sarcovagine-D (c) and Saracodine (d) Holaphylline (e) from Sarcococca saligna to investigate the anticancer effect of these compounds. These compounds were evaluated for inhibition of aromatase enzyme of breast cancer in assistance by molecular docking simulations to understand molecular interaction between the enzyme and ligands. The IC50 values of compound 1 and 5 were found 138.27 ± 0.01 µl and 12.91 ± 0.01 µl, respectively, and both were found active due to their bulky structures in comparison to the active site of aromatase enzyme. The standard drug exemestane showed potent activity in comparison with the test compounds, having IC50 values of 0.052 ± 0.01 µl. Both compounds showed favorable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds was the limiting factor in their inhibitory effects. New lead compounds could be generated after extensive modifications guided by computational and experimental tools as a possible anticancer agents by targeting aromatase enzyme.

Hypoglycemic potential of herbal product dolabi compared with pioglitazone in streptozotocin-induced diabetic rats.

OBJECTIVES: To investigate and compare the hypoglycemic potential of commonly used polyherbal formulation dolabi with pioglitazone in streptozotocin-induced diabetic rats. METHODS: A total of 24 adult male Wistar rats were randomized into diabetic control group, diabetic group receiving dolabi (17.6 mg kg-1 day-1), diabetic group receiving dolabi (35.2 mg kg-1 day-1) and diabetic group receiving pioglitazone (2.7 mg kg-1 day-1), with 6 rats in each group. The study was conducted for 4 weeks. Blood samples were collected for fructosamine estimation, fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) were measured at different time points. RESULTS: Compared with baseline, the groups receiving dolabi (35.2 mg kg-1 day-1) and pioglitazone showed signififi cant reductions (P<0.05) in fructosamine levels at the end point and same was the case for FPG and OGTT with pioglitazone showing greater hypoglycemic potential. However, the group receiving dolabi (17.6 mg kg-1 day-1) showed significant reduction (P<0.05) only in FPG level and failed to achieve significant changes either in fructosamine level or OGTT. Moreover, signififi cant differences (P<0.05) in FPG and fructosamine levels were observed between groups receiving dolabi (17.6 mg kg-1 day-1) and pioglitazone at the end point. CONCLUSIONS: These results showed sluggish hypoglycemic effects of dolabi at manufacturer's recommended doses. At a higher dose however, good glycemic control was achieved with dolabi and the results were comparable to pioglitazone. The shorter duration of study (4 weeks) might be the reason of poor glycemic control associated with dolabi at a normal dose.

Liraglutide in diabetes mellitus: More facts and findings.

Liraglutide exert favorable effects on most of the diabetes associated cardiovascular (CV) risk factors and this study was designed to further explore the benefits of liraglutide by observing its effect on plasma sialic acid (PSA) in diabetic rats. A total of 30 streptozotocin induced (50 mg/Kg; i.p.) diabetic rats were randomized into vehicle treated (1 ml/Kg s.c, twice daily) group I, liraglutide treated groups II and III (30 µg/Kg and 150 µg/Kg, twice daily respectively) and studied for 6 weeks. Liraglutide treated groups showed significant reductions in fructosamine levels (p≤0.05) from baseline. Between groups comparison revealed significant difference (p≤.05) at the end point. Similarly, at week 6, liraglutide treated groups showed significantly low levels of PSA compared to baseline (p<0.03 and p<0.005 for group II and III respectively) and control group I (p<0.002 and p<0.001 for group II and III respectively). However, the difference was non-significant between groups II and III (p<0.09). Other parameters including glucose tolerance, fasting plasma glucose (FPG), blood lipids, systolic blood pressure (SBP) and body weight also improved by liraglutide with the group III showing greater improvement. The study concludes that liraglutide produce favourable effects on PSA and may bea useful choice in protecting against diabetes associated CV complications.

A comparison of the effect of glitazones on serum sialic acid in patients with type 2 diabetes.

Although management of hyperglycaemia represents one of the principal treatment goals of diabetes therapy, the high incidence of cardiovascular (CV) complications in diabetes also needs effective management. Therefore, the present study was designed to determine and compare the effect of glitazones on serum sialic acid (SSA), a known risk marker for CV disease, along with fasting plasma glucose (FPG), glycohaemoglobin (HbA1-c) and blood lipids, in overweight, previously only diet-treated patients with type 2 diabetes (n=60). The study was conducted for a period of 12 months. Significant improvement in FPG and HbA1-c were shown by both rosiglitazone (p<0.003 and p<0.001, respectively) and pioglitazone (p<0.005 and p<0.001, respectively), compared with baseline, and pioglitazone showed greater beneficial effects on other parameters monitored, significantly reducing total cholesterol (TC) (p≤0.05). Both the drugs showed a decrease in SSA and no significant differences were observed between the groups. However, the decrease was significant only in the pioglitazone-treated group at month 12 (p≤0.05), compared with baseline. A significant decrease in SSA by pioglitazone indicates its greater cardioprotective effect compared with rosiglitazone.