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Diabetes mellitus is characterized by hyperglycemia that makes insulin more prone to glycation and form advanced glycation end products (AGEs). Here, we report the effect of glyoxal (GO) on the formation of AGEs using human insulin as model protein and their structural modifications. The present investigation also reports the anti-AGE potential of Heliotropium bacciferum (Leaf) extracts. The phytochemical analysis of H. bacciferum revealed that free phenolic extract contains higher amount of total phenolic (3901.58 ± 17.06 mg GAE/100 g) and total flavonoid content (30.41 ± 0.32 mg QE/100 g) when compared to bound phenolic extract. Naringin and caffeic acid were identified as the major phenolic ingredients by UPLC-PAD method. Furthermore, bound phenolics extract showed significantly higher DPPH and superoxide radicals scavenging activity (IC50 17.53 ± 0.36 µg/mL and 0.306 ± 0.038 mg/ mL, respectively) (p ≤ 0.05). Besides, the bound phenolics extract also showed significant (p ≤ 0.05) chelating power (IC50 0.063) compared to free phenolic extract. In addition, bound phenolic extract could efficiently trap GO under physiological conditions. Spectroscopic investigation of GO-modified insulin illustrated changes in the tertiary structure of insulin and formation of AGEs. On the other hand, no significant alteration in secondary structure was observed by far UV-CD measurement. Furthermore, H. bacciferum extract inhibited α-glucosidase activity and AGEs formation implicated in diabetes. Molecular docking analysis depicted that GO bind with human insulin in both chains and forms a stable complex with TYR A: 14, LEU A:13, ASN B:3, SER A:12 amino acid residues with binding energy of - 2.53 kcal/mol. However, caffeic acid binds to ASN A:18 and GLU A:17 residues of insulin with lower binding energy of -4.67 kcal/mol, suggesting its higher affinity towards human insulin compared to GO. Our finding showed promising activity of H. bacciferum against AGEs and its complications. The major phenolics like caffeic acid, naringin and their derivatives could be exploited for the drug development for management of AGEs in diabetes.

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The present investigation was performed to study the effects of Acacia nilotica Delile (Fabaceae) fruit extract on serum concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and glucose in control and alloxan-induced diabetic rats. The rats were divided into four groups: Normal Control Rats (NC), normal control rats administered A. nilotica (NC + AN), Diabetic Control rats (DC) and diabetic rats administered A. nilotica (DC + AN). Each group comprised 10 to 14 rats. The methanolic extract A. nilotica fruit was orally administered at a concentration of 200 mg kg(-1) b.wt. for 5 consecutive weeks. The A. nilotica fruit extract significantly (p < 0.005) decreased serum glucose levels in control rats after the third week. The serum glucose concentrations of diabetic rats following A. nilotica fruit extract administration did not change significantly. The A. nilotica extract showed a strong hypolipidemic effect on diabetic rats and significantly decreased serum levels of triglycerides and low-density lipoprotein cholesterol (p < 0.02 and p < 0.001, respectively). The present findings suggest that hypolipidemic effects following oral administration ofA. nilotica fruit extract could be beneficial for treatment of diabetes related-complications and

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The present study aimed to examine the effect of pumpkin (Cucurbita pepo L.) seeds supplementation on atherogenic diet-induced atherosclerosis. Rat were divided into two main groups , normal control and atherogenic control rats , each group composed of three subgroups one of them supplemented with 2% arginine in drinking water and the other supplemented with pumpkin seeds in diet at a concentration equivalent to 2% arginine. Supplementation continued for 37 days. Atherogenic rats supplemented with pumpkin seeds showed a significant decrease (p<0.001) in their serum concentrations of total cholesterol and LDL - C as they dropped from 4.89 mmol / L to 2.55 mmol /L and from 3.33 mmol / L to 0.70 mmol / L respectively. Serum concentrations of HDL-C were also significantly elevated in the same group. Although, atherogenic rats supplemented with 2% arginine showed significant increase in serum concentration of HDL-C, no significant changes were observed in their serum concentrations of total cholesterol and LDL-C. Our results showed that treatment of atherogenic rats with pumpkin seeds significantly decreased serum concentrations of TC and LDL-C. Our findings suggest that pumpkin seeds supplementation has a protective effect against atherogenic rats and this protective effect was not attributed to the high arginine concentrations in pumpkin seeds.

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The aim of the present investigation was to examine the effect of Flax Seeds (FS) and Date Palm Leaves (DPL) extracts on the concentration of serum glucose and lipids in alloxan diabetic rats. Rats were divided into six groups, normal control rats (without treatment with either FS or DPL), normal control rats treated with either FS or DPL extract for four weeks, diabetic control rats and diabetic rats treated with either FS or DPL extract for four weeks. The concentration of glucose in diabetic rats treated with FS (D+FS) for four weeks was significantly decreased from 17.20 +/- 2.33 to 8.14 +/- 0.54 mmol L(-1) (p < 0.001). Serum total cholesterol concentration (TC) of diabetic rats treated with either FS or DPL extract showed significant decrease by 40 and 31% respectively in the fourth week. Also, serum low density lipoprotein cholesterol (LDL-C) concentration was significantly decreased after two weeks of treatment (p < 0.001 and p < 0.01, respectively). However, no significant changes were obtained in serum high density lipoprotein cholesterol (HDL-C) concentration. Results of the present study showed that FS extract has a hypoglycaemic effect against alloxan diabetic rats. Present findings also showed that treatment of alloxan diabetic rats with either FS or DPL extract significantly decreased serum concentration of TC and LDL-C. Present findings suggest that both of FS and DPL extracts could have a protective effect against diabetes complications as well as against hyperlipidemia through improvement of lipid profile.

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OBJECTIVE: To examine whether the vaccination with low density lipoprotein (LDL) antibodies could have a protective effect on rats developed atherosclerosis through the action of atherogenic diet. METHODS: Four groups of rats (ranged 8 and 14) were treated for 8 weeks (13 January 2007 to 9 March 2007) at the animal house, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia, with normal control diet (NC), normal control diet+LDL-Ab (NC +I), atherogenic diet (AT), and atherogenic diet + LDL-Ab (AT+I). Lipid concentrations and other different parameters were measured in serum. RESULTS: The concentrations of total cholesterol in atherogenic rats treated with LDL-Ab (AT+I) (n=9) were significantly decreased from 5.72 +/- 0.21 mmol/l to 1.81 +/- 0.08 mmol/l (p<0.001). Low density lipoprotein-cholesterol concentrations were also significantly decreased in AT+I group (p<0.001), as it dropped by 73% from 3.06 +/- 0.09 mmol/l to 0.84 +/- 0.04 mmol/l. Phospholipids concentrations were also decreased in AT+I group (p<0.01). The concentrations of both HDL-cholesterol and triacylglycerol were not significantly different from their matched groups. CONCLUSION: Results of the present study showed that treatment of atherogenic rats with LDL-Ab significantly decreased the serum concentrations of TC and LDL-C. Our findings suggest that immunization with LDL-Ab has a protective effect on artherogenic rats.

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