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1.
Paraptosis in human glioblastoma cell line induced by curcumin.
Garrido-Armas, M, Corona, JC, Escobar, ML, Torres, L, Ordóñez-Romero, F, Hernández-Hernández, A, Arenas-Huertero, F
Toxicology in vitro : an international journal published in association with BIBRA. 2018;:63-73
Abstract
Curcumin is a polyphenol compound extracted from Curcuma longa plant, is a molecule with pleiotropic effects that suppresses transformation, proliferation and metastasis of malignant tumors. Curcumin can cause different kinds of cell death depending of its concentration on the exposed cell type. Here we show that exposure of the glioblastoma cell line A172 to curcumin at 50 μM, the IC50, causes morphological change characteristic of paraptosis cell-death. Vesicles derived from the endoplasmic reticulum (ER) and low membrane potential of the mitochondria were constantly found in the exposed cells. Furthermore, changes in expression of the ER Stress Response (ERSR) genes IRE1 and ATF6, and the microRNAs (miRNAs) miR-27a, miR-222, miR-449 was observed after exposure to curcumin. AKT-Insulin and p53-BCL2 networks were predicted being modulated by the affected miRNAs. Furthermore, AKT protein levels reduction was confirmed. Our data, strongly suggest that curcumin exerts its cell-death properties by affecting the integrity of the reticulum, leading to paraptosis in the glioblastoma cells. These data unveils the versatility of curcumin to control cancer progression.
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2.
The emerging role of curcumin for improving vascular dysfunction: A review.
Campbell, MS, Fleenor, BS
Critical reviews in food science and nutrition. 2018;(16):2790-2799
Abstract
Curcumin, when administered in a bioavailable form, has potential to influence vascular health of various populations, leading to decreases in cardiovascular disease risk. Clinical intervention studies with curcumin have demonstrated significant improvements in endothelial function, arterial compliance, arterial stiffness, and other measures of vascular hemodynamics in young, middle-aged, old, post-menopausal, healthy, diabetic, and obese individuals. Mechanistically, curcumin is believed to improve vascular function through its effects on inflammation, oxidative stress, nitric oxide bioavailability, and structural proteins of the artery. Current data give support for curcumin to be administered for improvements in vascular health to individuals that may or may not be at risk for cardiovascular disease. This review briefly summarizes the techniques used for the establishment of vascular health and overviews the literature investigating the role of curcumin in the improvement of vascular health.
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3.
Effects of Environmental Heat and Antioxidant Ingestion on Blood Markers of Oxidative Stress in Professional Firefighters Performing Structural Fire Exercises.
McAllister, MJ, Basham, SA, Smith, JW, Waldman, HS, Krings, BM, Mettler, JA, Butawan, MB, Bloomer, RJ
Journal of occupational and environmental medicine. 2018;(11):e595-e601
Abstract
OBJECTIVE Firefighters (FFs) involved in fire suppression have the greatest on-duty risk of cardiovascular disease (CVD), which may be caused by oxidative stress (OS). METHODS Healthy, active FFs performed a victim "search and clear" exercise involving three conditions: (1) no heat, (2) heat + antioxidant, and (3) heat + placebo. Blood samples were analyzed for OS markers glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), and advanced oxidation protein products (AOPP). RESULTS Increased GSH was found during both heat conditions compared with no heat. CAT activity was higher immediately post exercise. AOPP was reduced post exercise. CONCLUSIONS Antioxidant supplementation did not impact the OS response to exercise. Added heat did not cause OS and exercise resulted in reductions in OS markers. These findings can be attributed to the training status of the FFs involved.
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4.
Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study.
Kanchanatawan, B, Tangwongchai, S, Sughondhabhirom, A, Suppapitiporn, S, Hemrunrojn, S, Carvalho, AF, Maes, M
Neurotoxicity research. 2018;(3):621-633
Abstract
Activation of immune-inflammatory and oxidative-nitrosative (IO&NS) stress pathways plays a role in major depression (MDD). Evidence suggests that curcumin (500-1000 mg/day), a polyphenol with strong anti-IO&NS properties, may have efficacy either as monotherapy or as an adjunctive treatment for depression. Further controlled trials with extended treatment periods (> 8 weeks) and higher curcumin doses are warranted. This 12-week study was carried out to examine the effects of adjunctive curcumin for the treatment of MDD. In this double-blind, placebo-controlled trial, 65 participants with MDD were randomized to receive either adjunctive curcumin (increasing dose from 500 to 1500 mg/day) or placebo for 12 weeks. Four weeks after the active treatment phase, a follow-up visit was conducted at week 16. Assessments of the primary, i.e., the Montgomery-Asberg Depression Rating Scale (MADRS), and secondary, i.e., the Hamilton Anxiety Rating Scale (HAM-A), outcome measures were rated at baseline and 2, 4, 8, 12, and 16 weeks later. Curcumin was more efficacious than placebo in improving MADRS scores with significant differences between curcumin and placebo emerging at weeks 12 and 16. The effects of curcumin were more pronounced in males compared to females. There were no statistically significant treatment-emerging adverse effects and no significant effects of curcumin on blood chemistry and ECG measurements. Adjunctive curcumin has significant antidepressant effects in participants with MDD as evidenced by significant benefits occurring 12 and 16 weeks after treatment initiation. Curcumin administration was safe and well-tolerated even when combined with antidepressants. Future trials should include treatment-by-sex interactions to examine putative antidepressant effects of immune-modifying compounds.
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5.
MicroRNA: A novel target of curcumin in cancer therapy.
Mirzaei, H, Masoudifar, A, Sahebkar, A, Zare, N, Sadri Nahand, J, Rashidi, B, Mehrabian, E, Mohammadi, M, Mirzaei, HR, Jaafari, MR
Journal of cellular physiology. 2018;(4):3004-3015
Abstract
Curcumin is known as a natural dietary polyphenol which is extracted from Curcuma longa L. It has been shown that curcumin has a variety of pharmacological effects such as antioxidant, anti-cancer, anti-inflammatory, and anti-microbial activities. Anti-cancer effects of curcumin are due to targeting of a wide range of cellular and molecular pathways involved in cancer pathogenesis including NF-kB, MAPK, PTEN, P53, and microRNAs (miRNA) network. Multiple lines of evidence have indicated that curcumin exerts its therapeutic effects via regulating miRNA expression (e.g., miR-1, miR-7, miR-9, miR-34a, miR-181, miR-21, and miR-19) which could lead to the regulation of underlying cellular and molecular pathways involved in cancer pathogenesis. Exosomes are one of the important classes of biological vehicles which could be released from various types of cells such as cancer cells and stem cells and could change the behavior of recipient cells. It has been shown that treatment of cancer cells with different dose of curcumin leads to the release of exosomes containing curcumin. These exosomes could induce anti-cancer properties in recipient cells and reduce tumor growth. Hence, exosomes containing curcumin could be applied as powerful tools for cancer treatment. Here, we highlighted various miRNAs which could be affected by curcumin in various types of cancer. Moreover, we highlight exosomes containing curcumin as suitable therapeutic tools in cancer therapy.
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6.
Curcumin and fisetin internalization into Saccharomyces cerevisiae cells via osmoporation: impact of multiple osmotic treatments on the process efficiency.
Medeiros, FGM, Correia, RTP, Dupont, S, Beney, L, Pedrini, MRS
Letters in applied microbiology. 2018;(4):363-369
Abstract
UNLABELLED Cell osmoporation is a simple and straightforward procedure of creating food-grade biocapsules. This study proposes a new protocol of sequential cell osmoporation stages and evaluates its impact on the efficiency of curcumin and fisetin internalization into Saccharomyces cerevisiae cells. To the best of our knowledge, this is the first report in the literature regarding the subject. To assess how multiple osmoporation stages influence the encapsulation efficiency (% EE), encapsulated amount of curcumin (IC) and fisetin (IF) into S. cerevisiae cells and cell viability, the residual supernatant was used for the subsequent encapsulation stages and viability was assessed by the CFU method. Quantification was carried through direct extraction, using an ultrasonic bath and UV-Vis spectrophotometry. Experimental data demonstrated that the addition of a second osmoporation stage increases both the EE (% EE) and the amount of encapsulated curcumin and fisetin (IC and IF). As a result, the EE was considerably improved and the obtained microcapsules contained a higher amount of the targeted bioactive compounds in its internal structure. However, adding a third osmoporation stage proved to less beneficial to the process efficiency due to its lower yield and the significant negative impact to cell viability. SIGNIFICANCE AND IMPACT OF THE STUDY For the first time in the literature, a protocol of serial osmoporation stages to enhance the encapsulation efficiency of hydrophobic low molecular weight molecules (curcumin and fisetin) into Saccharomyces cerevisiae cells was determined. By increasing overall efficiency, this protocol empowers the encapsulation process and creates a rational way to reduce waste for future industrial osmoporation applications.
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7.
A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study.
T Krishnareddy, N, Thomas, JV, Nair, SS, N Mulakal, J, Maliakel, BP, Krishnakumar, IM
BioMed research international. 2018;:9159281
Abstract
Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade free-curcuminoids delivery system (curcumin-galactomannoside complex; CGM) in improving the hepatic function markers (inflammation and oxidative stress) in chronic alcoholics. The double-blinded, placebo-controlled study randomized 48 subjects with elevated serum transaminases and gamma-glutamyl transferase (GGT) levels, who were allocated to two groups (n=24) and to receive either placebo or CGM at (250 mg × 2)/day for 8 weeks. While liver function markers (transaminases and GGT) in the placebo group showed an increase (~ 9.5%), CGM group indicated a significant decrease in transaminases (31%) and GGT (29%) from the baseline levels. The beneficial effect of CGM was also clear from the significant increase (p <0.001) in endogenous antioxidants (GSH, SOD, and GPx) and decrease in inflammatory markers (IL-6 and CRP) levels (p <0.001) as compared to both the baseline and placebo group. To summarize, the nutritional intervention of CGM-curcumin was found to offer a significant hepatoprotective effect to attenuate the alcohol induced alterations to hepatic function markers. The Indian Medical Council and Drug Controller General of India approved Clinical Trial Registry No. CTRI/2018/03/012385.
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8.
Curcumin potentiates cholesterol-lowering effects of phytosterols in hypercholesterolaemic individuals. A randomised controlled trial.
Ferguson, JJA, Stojanovski, E, MacDonald-Wicks, L, Garg, ML
Metabolism: clinical and experimental. 2018;:22-35
Abstract
BACKGROUND Dietary phytosterols (PS) are well-known hypocholesterolaemic agents. Curcumin elicits hypolipidaemic and anti-inflammatory effects in preclinical studies, however, consistent findings in humans are lacking. OBJECTIVE Concurrent PS and curcumin supplementation may exhibit enhanced hypocholesterolaemic and anti-inflammatory effects to optimise cardio-protection. The objective of this trial was to investigate the effects of dietary intervention with PS with or without curcumin on blood lipids (primary outcome) in hypercholesterolaemic individuals. METHODS A double-blinded, randomised, placebo-controlled, 2 × 2 factorial trial was conducted in hypercholesterolaemic individuals. Participants received either placebo (PL, no phytosterols or curcumin), phytosterols (PS, 2 g/d), curcumin (CC, 200 mg/d) or a combination of PS and curcumin (PS-CC, 2 g/d-200 mg/d respectively) for four weeks. Primary outcomes included fasting total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides (TG), TC-to-HDL-C ratio (TC:HDL-C). Secondary outcomes included anthropometrics and fasting blood glucose concentrations. RESULTS Seventy participants with a mean (±SEM) fasting TC concentration of 6.57 ± 0.13 mmol/L completed the study (PL, n = 18; PS, n = 17; CC, n = 18; PS-CC, n = 17). PS and PS-CC supplementation significantly lowered TC, LDL-cholesterol and TC:HDL-C post-intervention (p < 0.05). Reductions from baseline in the PS group were 4.8% and 8.1% for TC and LDL-cholesterol respectively (p < 0.05). CC exhibited non-significant reduction (2.3% and 2.6%) in TC and LDL-C respectively, however, the PS-CC resulted in a greater reduction in TC (11.0%) and LDL-cholesterol (14.4%) than either of the treatments alone (p < 0.0001). The reduction in the PS-CC treatment was significantly greater compared to those for CC (p < 0.05) or PL (p < 0.01) alone. Plasma HDL-cholesterol and TG concentrations remained unchanged across all groups. No adverse side effects were reported. CONCLUSIONS The addition of curcumin to phytosterol therapy provides a complementary cholesterol-lowering effect that is larger than phytosterol therapy alone. Implications of these findings include the development of a single functional food containing both the active ingredients for enhanced lipid-lowering and compliance in hypercholesterolaemic individuals. ANZCTR identifier: 1261500095650.
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9.
Ameliorative effects of curcumin towards cyclosporine-induced genotoxic potential: an in vitro and in silico study.
Shah, AJ, Prasanth Kumar, S, Rao, MV, Pandya, HA
Drug and chemical toxicology. 2018;(3):259-269
Abstract
Several studies documented the ameliorative effects of curcumin which plays a pivotal role in radical scavenging activities. It also participates in various cellular pathways and interacts with multiple targets. In the present study, we investigated the ameliorative effect of curcumin upon chromosomal genotoxicity induced by cyclosporine, an immunosuppressant, using in vitro approaches. A plausible mechanism of how curcumin mitigates the genotoxic implications of cyclosporine was ascertained using in silico tools. We observed that the curcumin reduces the genotoxic consequences made by cyclosporine upon cell cycle checkpoints and associated chromosomal/DNA manifestations. In addition, we presented the mechanistic details of curcumin interaction with various biomacromolecule types using docking experiments which showed that the possible radical scavenging activities can only be emerged by inducing the expression of antioxidant enzymes, supported by available experimental evidences. We anticipate that the induction of antioxidant enzymes by curcumin would activate Nrf2-Keap1 pathway as the plausible mechanism to exert anti-inflammatory response as demonstrated in renal epithelial cells.
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10.
Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial.
Ahmadi, M, Agah, E, Nafissi, S, Jaafari, MR, Harirchian, MH, Sarraf, P, Faghihi-Kashani, S, Hosseini, SJ, Ghoreishi, A, Aghamollaii, V, et al
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2018;(2):430-438
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Abstract
The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list. All patients and research investigators were blinded to treatment allocation. The primary outcome was survival, and event was defined to be death or mechanical ventilation dependency. Analysis was by intention-to-treat and included all patients who received at least one dose of study drug. A total of 54 patients were randomized to receive either nanocurcumin (n = 27) or placebo (n = 27). After 12 months, events occurred in 1 patient (3.7%) in the nanocurcumin group and in 6 patients (22.2%) in the placebo group. Kaplan-Meier analysis revealed a significant difference between the study groups regarding their survival curves (p = 0.036). No significant between-group differences were observed for any other outcome measures. No serious adverse events or treatment-related deaths were detected. No patients withdrew as a result of drug adverse events. The results suggest that nanocurcumin is safe and might improve the probability of survival as an add-on treatment in patients with ALS, especially in those with existing bulbar symptoms. Future studies with larger sample sizes and of longer duration are needed to confirm these findings.