Effect of nano-micelle curcumin on hepatic enzymes: A new treatment approach for non-alcoholic fatty liver disease (NAFLD).

Objective: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes with no consumption of alcohol. Recently, curcumin is a natural polyphenol found in turmeric has been examined for the treatment of NAFLD. This study aimed to assess the efficacy of 160 mg/day nano-micelle curcumin on the amelioration of NAFLD by measuring liver enzymes. Materials and Methods: Patients with NAFLD were randomly divided into curcumin (intervention group n=33) and placebo (n=33) groups and at the end of the study, the data of 56 participants who completed the 2-month intervention were analyzed. Laboratory tests and questionnaires were used to gather information. Both groups received recommendations for lifestyle modification, and were advised to other necessary advices. Patients in the curcumin group received 160 mg/day of nano-micelle curcumin in two divided doses for 60 days. The 2 groups were followed up for two months and clinical and laboratory indices were compared. Results: Our data showed a significant decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the curcumin group (p<0.01) as well as a significant difference between the groups before and after the intervention in curcumin group (p<0.05). Interestingly, a meaningful decrease in AST serum level was observed in the intervention group (p<0.01). Conclusion: Our study demonstrated that short-term supplementation with nano-micelle curcumin results in the reduction of AST and ALT and is beneficial for the treatment of NAFLD.

Three months of combination therapy with nano-curcumin reduces the inflammation and lipoprotein (a) in type 2 diabetic patients with mild to moderate coronary artery disease: Evidence of a randomized, double-blinded, placebo-controlled clinical trial.

Diabetes is one of the most common chronic diseases worldwide. Systemic inflammation (high-sensitivity C-reactive protein (hs-CRP)) and lipid metabolism disruption (lipoprotein A, LipoPr (a)) play a critical role in developing and progressing atherosclerosis and acute coronary syndrome in diabetic patients. The anti-oxidant and anti-inflammatory effects of curcumin have been emphasized previously. Therefore, we aimed to evaluate the impact of nano-curcumin on cardiovascular risk factors in type 2 diabetic patients with mild to moderate coronary artery disease (CAD). We performed a randomized, double-blinded, placebo-controlled clinical trial with type 2 diabetic patients (n = 64), and mild to moderate CAD (<70% stenosis in angiography). The patients received nano-curcumin (80 mg/day) or placebo along with optimal medications for 90 days. The biofactors, including hs-CRP and LipoPr (a), and lipid profile, were measured at the admission of patients and end of the study. Nano-curcumin significantly mitigated the hs-CRP and LipoPr (a) levels following 90 days of treatment (P < 0.001 and P = 0.043, respectively). In addition, the mean percentage of change (%Δ) in the hs-CRP and LipoPr (a) levels were meaningfully reduced in the nano-curcumin group compared to the placebo group (P < 0.001 and P = 0.007, respectively). Surprisingly, nano-curcumin notably propagated the number of patients with mild (34.35%) and moderate (62.5%) hs-CRP level category and strikingly diminished the number of patients with severe hs-CRP level category (3.125%) compared to the placebo group (P = 0.016). Nano-curcumin (80 mg/day) might prevent atherosclerosis progression and, in terms of attenuating hs-CRP levels as an inflammation index, succedent cardiovascular events in diabetic heart patients.

Evaluation of curcumin as add-on therapy in patients with Parkinson's disease: A pilot randomized, triple-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Preclinical studies suggest that curcumin might be a potential neuroprotective agent in Parkinson's disease (PD). This clinical trial aimed to evaluate the efficacy of adding nanomicelle curcumin on improving the motor and non-motor symptoms of PD patients and their quality of life. MATERIAL AND METHODS: Idiopathic PD patients aged ≥30≥ 30 whose symptoms were under control were included in this pilot, randomized, triple-blind, placebo-controlled, add-on trial. Eligible patients were randomly assigned to either the curcumin (n = 30, 80 mg/day) or placebo (n = 30) groups and were followed for nine months. Primary outcomes were the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Parkinson's Disease Questionnaire (PDQ-39). These variables, along with demographic data, drug history, and possible side effects of curcumin, were gathered at the beginning of the study and every three months. A mixed effects model was used to compare the group-by-time interaction, followed by post hoc analysis. RESULTS: Although the mean MDS-UPDRS and PDQ-39 scores were not significantly different between the curcumin and placebo groups at any time points, MDS-UPDRS part III (P = 0.04) showed a significant difference in its overall trend between the study groups. However, post hoc analysis failed to spot this difference at study time points. The most common side effects of curcumin were nausea and vomiting (P = 0.25) and gastroesophageal reflux (P = 0.42). CONCLUSION: While curcumin is a well-tolerated natural compound, this trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients.

Targeting Nuclear Factor-Kappa B Signaling Pathway by Curcumin: Implications for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which involves an auto-immune mechanism that leads to perivascular demyelination. The role of nuclear factor-kappa B (NF-κB) signaling pathway in the pathogenesis of MS has been suggested by genome-wide association studies. Therefore, strategies targeting this pathway could be potentially beneficial. Curcumin is the active component of turmeric and a phenolic phytochemical. This phytochemical has anti-inflammatory properties and has been shown by multiple studies to downregulate NF-κB and its downstream gene targets including cyclooxygenase-2, tumor necrosis factor-α, interleukin-1, and interleukin-6. This review discusses the modulatory effects of curcumin on the NF-κB signaling pathway and its downstream effectors, and the therapeutic implications of this modulation on MS.

The effects of nano-curcumin supplementation on glycemic control, blood pressure, lipid profile, and insulin resistance in patients with the metabolic syndrome: A randomized, double-blind clinical trial.

Metabolic syndrome (MetS) is one of the most important health hazards. Curcumin is extracted from Curcuma longa (turmeric), which can affect the components of MetS. To increase the oral bioavailability of curcumin, nano-micelle curcumin is used instead of curcumin powder. In this randomized, double-blind, controlled clinical trial, 50 patients with MetS were randomly assigned to two groups to receive either 80 mg/day nano-curcumin (n = 25) or placebo (n = 25), for 12 weeks anthropometric measurements, blood pressure, and biochemical factors-including fasting blood sugar (FBS), Hemoglobin A1c (HbA1c), homeostatic model assessment (HOMA) for insulin resistance (HOMA-IR), pancreatic ß cell function (HOMA-ß) and lipid profile-were assessed at the baseline and the end of the study. Statistical analyses were done using SPSS software (Version 23). The analysis between the two groups has illustrated a significant reduction in the average change of triglyceride (TG) levels (-60.5 ± 121.7 vs. 13.1 ± 78.1 mg/dL; p < .05) and HOMA-ß (-5.7 ± 48.2 vs. -4.01 ± 16.9; p < .05). But there were no significant differences in anthropometric measurements, blood pressure and biochemical factors-including FBS, HbA1c, HOMA-IR, HOMA-ß, and lipid profile variables include (total cholesterol, LDL-C, and HDL-C) at the end of the study. In conclusion, supplementation with nano-micelle curcumin significantly improved serum TG in MetS patients.

Bioactive anti-oxidative polycaprolactone/gelatin electrospun nanofibers containing selenium nanoparticles/vitamin E for wound dressing applications.

In this study, polycaprolactone/gelatin (PCL/GEL) electrospun nanofibers containing biogenic selenium nanoparticles (Se NPs) and Se NPs/vitamin E (VE) with average diameters of 397.8 nm and 279.5 nm, respectively (as determined by SEM inspection) were prepared and their effect on wound healing was evaluated using in-vivo studies. The energy dispersive X-ray (EDX) mapping, TEM micrograph, and FTIR spectra of the prepared nanofibers strongly demonstrated well entrapment of Se NPs and VE into scaffolds. An amount of 57% Se NPs and 43% VE were gradually released from PCL/GEL/Se NPs/VE scaffold after 4 days immersion in PBS solution (pH 7.4). The both PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds supported 3T3 cell proliferation and attachment as confirmed by MTT assay and SEM imaging. Complete re-epithelialization, low level of edema and inflammatory cells in coordination with high level of oriented collagens demonstrated the wound healing activity of PCL/GEL/Se NPs/VE. Besides, significant antioxidant efficacy of PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds was demonstrated according to GSH and MDA assays. To sum up, the prepared PCL/GEL/Se NPs/VE scaffold in the present study represented suitable healing effect on animal model which candidate it for further studies.

Rapid and Facile Microwave-Assisted Synthesis of Palladium Nanoparticles and Evaluation of Their Antioxidant Properties and Cytotoxic Effects Against Fibroblast-Like (HSkMC) and Human Lung Carcinoma (A549) Cell Lines.

We report here a simple microwave irradiation method (850 W, 3 min) for the synthesis of palladium nanoparticles (Pd NPs) using ascorbic acid (as reducing agent) and sodium alginate (as stabilizer agent). The synthesized nanoparticles were characterized using transmission electron microscopy (TEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-Visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. Antioxidant properties and cytotoxic effects of as-synthesized Pd NPs and Pd (II) acetate were also assessed. UV-Vis study showed the formation of Pd NPs with maximum absorption at 345 nm. From TEM analysis, it was observed that the Pd NPs had spherical shape with particle size distribution of 13-33 nm. Based on DPPH radical scavenging activity and reducing power assay, the antioxidant activities of Pd NPs were significantly higher than the Pd (II) acetate (p < 0.05). At the same concentration of 640 µg/mL, the scavenging activities were 32.9 ± 3.2% (Pd (II) acetate) and 27.2 ± 2.1% (Pd NPs). For A549 cells treated 48 h with Pd NPs, Pd (II) acetate, and cisplatin, the measured concentration necessary causing 50% cell death (IC50) was 7.2 ± 1.7 µg/mL, 32.1 ± 2.1 µg/mL, and 206.2 ± 3.5 µg/mL, respectively. On HSkMC cells, the IC50 of the Pd NPs (320 µg/mL) was higher compared to Pd (II) acetate (228.7 ± 3.6 µg/mL), which confirmed lower cytotoxicity of the Pd NPs.

Antioxidant, cytotoxic and hyperalgesia-suppressing activity of a native Shilajit obtained from Bahr Aseman mountains.

Shilajit, a blackish-brown exudation obtained from steep rocks of different mountains, has been longly used as a therapeutic agent in traditional medicine. The present study was designed to evaluate the antioxidant, cytotoxic and hyperalgesia-suppressing activity of the aqueous and DMSO extracts of a native Shilajit. The antioxidant and cytotoxic effects of Shilajit extracts was determined using DPPH scavenging activity and MTT assay methods, respectively. In order to examine the hyperalgesia-suppressing activity of the Shilajit aqueous extract the STZ-induced diabetic animals were subjected to oral administration of the extract (50, 100 and 200 mg/kg daily) for six weeks followed by evaluating the behavioral examination (hot plate and tail flick tests) compared to those of diabetic control (Sham) and vehicle groups. The obtained results of antioxidant evaluation of Shilajit represented scavenging activity of 50% at concentration of 2500 µg/mL and 6000 µg/mL in the case of aqueous and DMSO extracts, respectively. Cytotoxic study of water extract of Shilajit revealed IC50 of 727.5±1.9 µg/mL and 1103±3.2 µg/mL on cell lines of MCF-7 (breast cancer) and A549 (lung cancer), respectively. Thermal pain response examination of diabetic rats treated with aqueous extract of Shilajit (100 mg/kg and 200 mg/kg) for six weeks reduced hyperalgesia compared to vehicle and Sham groups. To sum up, considering the moderate antioxidant and hyperalgesia-suppressing activity of this native Shilajit make it as a suitable candidate for further investigation after isolation and characterization of the active compounds.

Toxicity of microwave-assisted biosynthesized zinc nanoparticles in mice: a preliminary study.

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD50) of Zn NPs and the subacute toxicity after 14 days of exposure was performed as a measurement of substance toxicity through general toxicological, hematological, serum, and histopathological investigations. The western blotting was used to determine the cleaved-caspase-3 expression in the sampled tissues. Flame atomic absorption spectrophotometer (AAS) was applied to estimate the Zn levels in tissues. The SEM analyses revealed that the biogenic Zn NPs were spherical-shaped with the size range of 30-80 nm. The LD50 value above 5 g/kg indicated that biogenic Zn NPs could be classified as non-toxic chemicals. In subacute toxicity, no significant differences were found in the body weight as well as hematological and oxidative stress (OS) biomarkers after exposure to Zn NPs at the dose of 1 g/kg in comparison to the control. The AAS results indicated that Zn NPs were mainly distributed in the testis, liver, and brain. The findings of histology images of Zn NPs at the dose of 1 g/kg were similar to those of the control. Furthermore, no significant differences were observed in cleaved-caspase-3 expression after exposure to Zn NPs at the dose of 5 g/kg. The results demonstrated that changes in the OS were not related to caspase pathway and the no-observed-adverse-effect level (NOAEL) dose of biogenic Zn NPs in 14-days subacute toxicity study was lower than 1 g/kg.

Barberry in the treatment of obesity and metabolic syndrome: possible mechanisms of action.

Obesity is a consequence of an imbalance between energy intake and energy expenditure. It affects people of both genders and all age groups, ethnicity and socioeconomic groups, and in developed and developing countries. Obesity is often accompanied by the metabolic syndrome (MetS). MetS is characterized by a clustering of cardiovascular risk factors, including high blood pressure, adiposity, dyslipidemia and glucose intolerance, which together increase the risk of atherosclerotic cardiovascular disease, type 2 diabetes mellitus and other causes of mortality. Nowadays, there is a growing interest in the use of plant-based agents instead of synthetic drugs to manage chronic diseases such as MetS; one such example is Berberis vulgaris. B. vulgaris contains isoquinonline alkaloids such as berberine, berberrubine and berbamine. Recent studies have proved that berberine exhibits pharmacological activities and positive effects on the risk factors of obesity and MetS. We have reviewed original articles related to the possible molecular mechanisms of action of berberine on obesity and MetS. Berberine suppresses adipocyte differentiation and decreases obesity. It also regulates glucose metabolism via decreasing insulin resistance and increasing insulin secretion. Other effects of berberine include antihyperlipidemic and antihypertensive activities and endothelial protection.

Sulfasalazine-induced renal injury in rats and the protective role of thiol-reductants.

Sulfasalazine is widely used for inflammatory-mediated disorders in human. Renal damage is a serious adverse effect accompanied sulfasalazine administration. No specific therapeutic option is available against this complication so far. Oxidative stress seems to play a role in sulfasalazine-induced renal injury. Current investigation was designed to evaluate the effect of N-acetyl cysteine (NAC) and dithiothreitol (DTT) as thiol reductants against sulfasalazine-induced renal injury in rats. Oral administration of sulfasalazine (600 mg/kg for 14 consecutive days) caused renal injury as judged by increase in serum level of creatinine and blood urea nitrogen. Furthermore, the level of reactive oxygen species and lipid peroxidation were raised in kidney tissue after sulfasalazine administration. Additionally, it was also found that renal glutathione reservoirs were significantly depleted in sulfasalazine-treated animals. Histopathological examination of kidney endorsed organ injury in drug-treated rats. Daily intraperitoneal administration of NAC (250 and 500 mg/kg/day) and/or DTT (15 and 30 mg/kg/day) effectively alleviated renal damage induced by sulfasalazine. Data suggested that thiol reductants could serve as potential protective agents with therapeutic capabilities against sulfasalazine adverse effect toward kidney.

Acute and subacute toxicity of novel biogenic selenium nanoparticles in mice.

CONTEXT: In the present investigation, acute and subacute toxicity of the biogenic Se nanoparticles (Se NPs) has been reported. OBJECTIVE: To characterize the Se NPs produced by a bacterium species and to evaluate their toxicity and impact on clinical chemistry and hematological parameters of NMRI mice. MATERIALS AND METHODS: The Se NPs were prepared by Bacillus sp. MSh-1 in a culture medium containing SeO(2) (1.26 mM) and their physiochemical properties investigated using TEM, XRD and FT-IR. The LD(50) of Se NPs and SeO(2) were determined and the subacute toxicity evaluated by orally administration of 0, 2.5, 5, 10 and 20 mg kg(-1) of Se NPs to male mice for 14 consecutive days. Parameters of blood cells, AST, ALT, ALP, creatinine, BUN, cholesterol, bilirubin, triglyceride and CPK were experimentally measured. RESULTS: The XRD and TEM analyses showed that the spherical NPs were amorphous, in the size range of 80-220 nm. The toxicological evaluation showed that the LD(50) values of SeO(2) and Se NPs were 7.3 and 198.1 mg kg(-1), respectively. No biochemical changes were observed from the administration of 2.5, 5 and 10 mg kg(-1) of Se NPs, but a dose of 20 mg kg(-1) was accompanied with signs of toxicity including lower body weight and changes in clinical chemistry and hematological parameters. CONCLUSION: The biogenic Se NPs were less toxic than synthetic Se NPs and much less (26-fold) toxic than the SeO(2), which demonstrates the important role of Bacillus sp. MSh-1 in conversion of a highly toxic Se compound to the less toxic Se NPs.