Water-soluble Curcumin Derivative Research Articles

Galactose-Clicked Curcumin-Mediated Reversal of Meropenem Resistance among Klebsiella pneumoniae by Targeting Its Carbapenemases and the AcrAB-TolC Efflux System.

In over eighty years, despite successive antibiotics discoveries, the rapid advent of multidrug resistance among bacterial pathogens has jolted our misapprehension of success over them. Resistance is spreading faster than the discovery of new antibiotics/antimicrobials. Therefore, the search for better antimicrobials/additives becomes prudent. A water-soluble curcumin derivative (Curaq) was synthesised, employing a Cu (I) catalysed 1, 3-cyclo addition reaction; it has been evaluated as a potential treatment for multidrug-resistant isolates and as an antibiotic adjuvant for meropenem against hypervirulent multidrug-resistant Klebsiella pneumoniae isolates. We also investigated its solubility and effect over carbapenemase activity. Additionally, we investigated its impact on the AcrAB-TolC system. We found that Curaq inhibited bacterial growth at a minimal concentration of 16 µg/mL; at a 32 µg/mL concentration, it killed bacterial growth completely. Only nine (9.4%) Klebsiella isolates were sensitive to meropenem; however, after synergising with Curaq (8 µg/mL), 85 (88.54%) hvKP isolates became sensitive to the drug. The Curaq also inhibited the AcrAB-TolC efflux system at 1 µg/mL concentration by disrupting the membrane potential and causing depolarisation. The kinetic parameters obtained also indicated its promise as a carbapenemase inhibitor. These results suggest that Curaq can be an excellent drug candidate as a broad-spectrum antibacterial and anti-efflux agent.

Small molecule induced toxic human-IAPP species characterized by NMR.

In this study, the effect of CurDAc, a water-soluble curcumin derivative, on the formation and stability of amyloid fibers is revealed. CurDAc interaction with amyloid is structurally selective, which is reflected in a strong interference with hIAPP aggregation while showing weaker interactions with human-calcitonin and amyloid-β1-40 in comparison. Remarkably, CurDAc also exhibited potent fiber disaggregation for hIAPP generating a toxic oligomeric species.

Efficacy of a novel water soluble curcumin derivative versus Tadalafile in mediating erectile function

Efficacy of a novel water soluble curcumin derivative versus Tadalafile in mediating erectile function

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.

The Anti-Apoptotic Mechanism of Action of a Water Soluble Curcumin Derivative and Mscs in Alzheimer Disease Induced In Rats

The Anti-Apoptotic Mechanism of Action of a Water Soluble Curcumin Derivative and Mscs in Alzheimer Disease Induced In Rats

The Anti-Inflammatory Mechanism of Action of a Water Soluble Curcumin Derivative and Mscs in Alzheimer Disease Induced In Rats

The objective is to evaluate the possible mechanisms of action of a water soluble curcumin derivative and MSCs in Alzheimer disease (AD). Materials and Methods: This work included: Seventy rats which were divided equally into: control group, AD group (induced by lipopolysaccharide), AD group received a novel curcumin derivative (NCD), AD group received pure curcumin, AD group received MSCs then NCD, AD group received MSCs, AD group received MSCs with NCD. Histopathological examination and estimation of serum IL-10 and IL-6 by ELISA, estimation of MDA and GSH in brain tissue by colorimetry and estimation of tissue cholesterol were performed. Results: Histopathological examination of brain tissue from AD animals revealed the presence of plaques. Administration of MSCs or MSCs with NCD into rats after induction of experimental AD improved the histopathological picture with plaque disappearance, while other groups showed decrease of plaque formation. Levels of IL-10 were increased while of IL-6 were decreased in all treated groups. MDA and cholesterol levels were decreased while GSH levels were increased in all treated groups.Conclusion: Administration of BM-derived MSCs either alone or with the NCD exert a therapeutic effect on the brain lesion in Alzheimer’s disease. This effect may be through the anti-inflammatory and antioxidant action of both MSCs and curcumin. These data suggests that MSCs and curcumin may be a therapeutic target in treatment of AD.

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.

Novel Water-soluble Curcumin Derivative Mediating Erectile Signaling

Curcumin is an inducer of heme oxygenase enzyme-1 (HO-1) that is involved in erectile signaling via elevating cyclic guanosine monophosphate (cGMP)levels. To assess the effect of oral administration of a water-soluble long-acting curcumin derivative on erectile signaling. 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. Cavernous tissue HO enzyme activity, cGMP, and ICP. 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. Water-soluble long-acting curcumin derivative could mediate erectile function via upregulating cavernous tissue cGMP.