Ameen M Rezq

Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy

BackgroundCurcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1.Materials and methodsRats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied.ResultsNCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin.

Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study)

BackgroundDiabetes mellitus type 1 is an autoimmune disorder caused by lymphocytic infiltration and beta cells destruction. Curcumin has been identified as a potent inducer of heme-oxygenase-1 (HO-1), a redoxsensitive inducible protein that provides protection against various forms of stress. A novel water soluble curcumin derivative (NCD) has been developed to overcome low in vivo bioavailability of curcumin. The aim of the present work is to evaluate the anti diabetic effects of the “NCD” and its effects on diabetes-induced ROS generation and lipid peroxidation in experimental type- 1 diabetes mellitus. We also examine whether the up regulation of HO-1 accompanied by increased HO activity mediates these antidiabetic and anti oxidant actions.Materials and methodsRats were divided into control group, control group receiving curcumin derivative, diabetic group, diabetic group receiving curcumin derivative and diabetic group receiving curcumin derivative and HO inhibitor ZnPP. Type-1 diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin derivative was given orally for 45 days. At the planned sacrification time (after 45 days), fasting blood samples were withdrawn for estimation of plasma glucose, plasma insulin and lipid profile . Animals were sacrificed; pancreas, aorta and liver were excised for the heme oxygenase - 1 expression, activity and malondialdehyde estimation.ResultsNCD supplementation to diabetic rats significantly lowered the plasma glucose by 27.5% and increased plasma insulin by 66.67%. On the other hand, the mean plasma glucose level in the control group showed no significant difference compared to the control group receiving the oral NCD whereas, NCD supplementation to the control rats significantly increased the plasma insulin by 47.13% compared to the control. NCD decreased total cholesterol, triglycerides, LDL cholesterol and increased HDL cholesterol levels. Also, it decreased lipid peroxides (malondialdehyde) in the pancreas, aorta and liver.ConclusionThe (NCD) by its small dose possesses antidiabetic actions and that heme oxygenase induction seems to play an important role in its anti-diabetic effects. NCD also improves the lipid profile and oxidative status directly, proved by decreasing lipid peroxides (malondialdehyde) in pancreas, liver & aorta. The new water soluble curcumin derivative still retains the essential potencies of natural curcumin.

Effects of a Water‐Soluble Curcumin Protein Conjugate vs. Pure Curcumin in a Diabetic Model of Erectile Dysfunction

INTRODUCTION Curcumin is involved in erectile signaling via elevation of cyclic guanosine monophosphate (cGMP). AIM Assessment of the effects of water-soluble curcumin in erectile dysfunction (ED). METHODS One hundred twenty male white albino rats were divided into: 1st and 2nd control groups with or without administration of Zinc protoporphyrin (ZnPP), 3rd and 4th diabetic groups with or without ZnPP, 5th diabetic group on single oral dose of pure curcumin, 6th diabetic group on pure curcumin administered daily for 12 weeks, 7th and 8th diabetic groups on single dose of water-soluble curcumin administered with or without ZnPP, 9th and 10th diabetic groups on water-soluble curcumin administered daily for 12 weeks with or without ZnPP. All curcumin dosage schedules were administered after induction of diabetes. MAIN OUTCOME MEASURES Quantitative gene expression of endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid2 (Nrf2), NF-Кβ, and p38. Cavernous tissue levels of HO and NOS enzyme activities, cGMP and intracavernosal pressure (ICP). RESULTS Twelve weeks after induction of diabetes, ED was confirmed by the significant decrease in ICP. There was a significant decrease in cGMP, NOS, HO enzymes, a significant decrease in eNOS, nNOS, HO-1 genes and a significant elevation of NF-Кβ, p38, iNOS genes. Administration of pure curcumin or its water-soluble conjugate led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in eNOS, nNOS, HO-1, and Nrf2 genes, and a significant decrease in NF-Кβ, p38, and iNOS genes. Water-soluble curcumin showed significant superiority and more prolonged duration of action. Repeated doses regimens were superior to single dose regimen. Administration of ZnPP significantly reduced HO enzyme, cGMP, ICP/ mean arterial pressure (MAP), HO-1 genes in diabetic groups. CONCLUSION Water-soluble curcumin could enhance erectile function with more effectiveness and with more prolonged duration of action.

The effect of a novel curcumin derivative on pancreatic islet regeneration in experimental type-1 diabetes in rats (long term study)

BackgroundSeveral studies highlight curcumin’s benefit as a hypoglycemic agent, however; a limited number of reports present the importance of curcumin in improvement of pancreatic islets in diabetes. The aim of the present study is to evaluate the antidiabetic effect of a novel curcumin derivative and its effect on pancreatic islet regeneration in type I diabetes-induced by STZ.Materials and methodsRats were divided into diabetic rats and diabetic rats treated orally with the novel curcumin derivative (NCD) for 40 days. Fasting blood samples were withdrawn periodically from all rats to estimate plasma glucose, insulin and C-peptide for 10 months. Histopathology was performed to allow the assessment of pancreatic islet morphology. Insulin and CD105 were detected immunohistochemically.ResultsIn diabetic rats, the plasma glucose, insulin and C-peptide levels remained within the diabetic range for about 4 months, after which a gradual decrease in glucose and increase in insulin and C-peptide was observed, which reached almost normal levels after 10 months. NCD treated diabetic rats showed significantly lowered plasma glucose and increased plasma insulin and C-peptide levels. This was followed by a further significant decrease in plasma glucose and increase in plasma insulin and C-peptide after two months from oral administration of the NCD. The plasma insulin and C-peptide continued to increase for ten months reaching levels significantly higher than the basal level. Histopathological examination of diabetic rat pancreas revealed absence of islets of Langerhans, minimal adipose tissue infiltration and localized lymphocytic infiltrates. However, after 6 months of induction of diabetes, rat pancreas showed the appearance of small well formed islets and positive insulin cells but no CD105 positive cells. NCD treated rats showed the appearance of primitive cell collections, large insulin positive cells and CD105 positive cells in the adipose tissue infiltrating the pancreatic tissues. This was followed by the gradual appearance of insulin positive cells in the islets while, CD 105 positive cells remained in the adipose tissue. After 5 and 10 months from the onset of diabetes, rat pancreas showed, well developed larger sized islets with disappearance of primitive cell collections and CD 105 positive cells. Also, insulin positive islets of variable size with disappearance of insulin positive cells in adipose tissue were detected.ConclusionThe NCD possesses antidiabetic actions and enhanced pancreatic islets regeneration.

Novel Water‐soluble Curcumin Derivative Mediating Erectile Signaling

INTRODUCTION Curcumin is an inducer of heme oxygenase enzyme-1 (HO-1) that is involved in erectile signaling via elevating cyclic guanosine monophosphate (cGMP)levels. AIM To assess the effect of oral administration of a water-soluble long-acting curcumin derivative on erectile signaling. METHODS Two hundred and thirty six male white albino rats were divided into four groups; group 1 (N = 20) includes control. Group 2 (N = 72) was equally divided into four subgroups; subgroup 1 received pure curcumin (10 mg/kg), subgroup 2 received the long-acting curcumin derivative (2 mg/kg), subgroup 3 received the long-acting curcumin derivative (10 mg/kg), and subgroup 4 received sildenafil (4 mg/kg). Subgroups were sacrificed after the first, second, and third hour. Group 3 (N = 72) was equally divided into the same four subgroups already mentioned and were sacrificed after 24 hours, 48 hours, and 1 week. Group 4 (N = 72) was subjected to intracavernosal pressure (ICP) measurements 1 hour following oral administration of the same previous doses in the same rat subgroups. MAIN OUTCOME MEASURE Cavernous tissue HO enzyme activity, cGMP, and ICP. RESULTS In group 2, there was a significant progressive maintained elevation of HO activity and cGMP tissue levels starting from the first hour in subgroups 3 and 4, whereas, the rise in HO activity and cGMP started from second hour regarding the other rat subgroups. Sildenafil effect decreased after 3 hours. In group 3, there was a significant maintained elevation of HO activity and cGMP tissue levels extended to 1 week as compared to controls for all rat subgroups that received both forms of curcumin. In group 4, long-acting curcumin derivative exhibited more significant potentiation of intracavernosal pressure as compared to control and to the pure curcumin. CONCLUSION Water-soluble long-acting curcumin derivative could mediate erectile function via upregulating cavernous tissue cGMP.

Effect of fire smoke on some biochemical parameters in firefighters of Saudi Arabia

BackgroundFirefighters who are facing fires, are frequently exposed to hazardous materials including carbon monoxide, hydrogen cyanide, hydrogen chloride, benzene, sulphur dioxide, etc. This study aimed to evaluate some relevant serum biochemical and blood hematological changes in activity involved firefighters in comparison to normal subjects.Subjects and MethodsTwo groups of male firefighters volunteered to participate in the study. The first included 28 firefighters from Jeddah, while the second included 21 firefighters from Yanbu, with overall age ranged 20–48 years. An additional group of 23 male non-firefighters volunteered from both cities as normal control subjects, of age range 20–43 years. Blood samples were collected from all volunteer subjects and investigated for some relevant serum biochemical and blood hematological changes.ResultsThe results obtained showed that, there were statistically significant differences in liver function, kidney function, serum lipid profile, cortisol, creatine kinase, lactate dehydrogenase, iron and its biologically active derivatives, and blood picture in firefighters as compared with the normal control group. These results indicate that, fire smoke mainly affects serum biochemical and blood hematological parameters. Such results might point out to the need for more health protective and prophylactic measures to avoid such hazardous health effects that might endanger firefighters under their highly drastic working conditions.ConclusionBesides using of personal protective equipments for firefighters to protect them against exposure to toxic materials of fire smoke, it is recommended that, firefighters must be under continuous medical follow up through a standard timetabled medical laboratory investigations to allow for early detection of any serum biochemical or blood hematological changes that might happen during their active service life and to allow for early treatment whenever necessary.

Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function.

The present study was conducted to assess the efficacy of a novel curcumin derivative (NCD) versus sildenafil citrate in erectile signaling. The study was conducted on 10 control male rats and 50 diabetic male rats divided into the following groups: diabetic, curcumin, NCD, sildenafil and NCD combined with sildenafil. Cavernous tissue (CC) gene expression levels of heme oxygenase (HO)-1, Nrf2, NF-κβ and p38, enzyme activities of HO and nitric oxide synthase (NOS), cyclic guanosine monophosphate (cGMP) and intracavernosal pressure (ICP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction was confirmed by the significant decrease in ICP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant elevation of NF-κβ, p38 genes. Administration of all therapeutic interventions led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1 and Nrf2 gene expression, and a significant decrease in NF-κβ, p38 gene expression. NCD or its combination with sildenafil showed significant efficacy and more prolonged duration of action. In conclusion, NCD could enhance erectile function with more efficacy and more prolonged duration of action.

Novel Anticancer Curcumin Derivative with Conserved Functional Groups

Abstract Background: Curcumin, a polyphenol from turmeric, has potent anticancer properties in human cancer cell lines. Nevertheless, its multitargeting clinical application in cancer and other diseases is hampered by

Phytochemical analysis of Convolvulus hystrix Vahl and its biological effects in rats

“Convolvulus hystrix Vahl” is a plant that has been known to Ancient Egyptians and to Arabs and its root was used traditionally as a purgative. Our attention was directed to the root bark as we observed that the largest part of the plant is deeply impeded underground. The work plan involved testing experimental animals for the influence of aqueous root bark extract on carbohydrate, fat and protein metabolisms as reflected on the growth and relevant laboratory metabolic assessment parameters. Proximate analysis showed high percentages of moisture (85%) and total lipids (7.2%) and surprising amounts of elements such as barium, strontium, rhodium and tellurium (1.7 mg, 3.1 mg, 8 mg and 9.1 mg/g ash, respectively). Random serum glucose value showed a significant decrease in the treated female group (p < 0.05). Serum total proteins of treated female group were found to be increased significantly (p < 0.001), while it was found to be decreased in the relevant treated male group (p < 0.01), together with a significant decrease in blood urea nitrogen (p < 0.05), with a significant increase in the serum creatinine (p < 0.05). Concerning serum fat metabolic parameters, a significant decrease in the serum triglycerides and high-density lipoproteins (p < 0.01 and p < 0.01, respectively) were found. We concluded that the presence of huge amount of polyphenolics such as tannins is responsible for the overall results documented as growth retarding and antinutritional factors. The results were motivating and pointed out to the possible opening of vast areas of research in the field of natural products. We recommend a series of biochemical and pharmacological studies concerning different parts of the plant as well.

Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction.

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase‐1 (HO‐1), Nrf2, NF‐B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO‐1 gene and a significant increase in NF‐Ҡβ, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO‐1 and NOS enzymes, a significant increase in HO‐1, and Nrf2 gene expression, and a significant decrease in NF‐Ҡβ, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.