Different Doses Of Curcumin Research Articles

Curcumin suppresses copper accumulation in non-small cell lung cancer by binding ATOX1

BackgroundNon-small cell lung cancer (NSCLC) is associated with intracellular copper accumulation. Antioxidant 1 (ATOX1) is a copper chaperone. This study aimed to analyze the anti-cancer effects of curcumin on the ATOX1-mediated copper pathway in NSCLC.MethodsA binding activity between curcumin and ATOX1 was measured using molecular docking. NSCLC cells, A549 and H1299, were treated with different doses of curcumin (10, 20, 40 µM) or DC-AC50 (5, 10, 20 µM) for 24 h. The cell viability and levels of ATOX1, ATP7A and COX17 proteins were observed in cells. Overexpressing ATOX1 in cells was established by pcDNA3.1-ATOX1 transfection for 24 h. The ATOX1 overexpressing cells were treated with 40 µM curcumin or 20 µM DC-AC50 for 24 h to analyze the mechanism of curcumin in NSCLC treatment. Cell viability was measured by CCK-8, and levels of proteins were measured by western blotting. The copper level in cells was labeled by copper sensor-1. Moreover, nude mice models were induced by injection of A549 cells and treated with 20 mg/kg/d DC-AC50 or 40 mg/kg/d curcumin. Tumor growth was observed by measuring tumor volume and tumor weight. The levels of ATOX1, ATP7A and COX17 in tumors were measured by immunohistochemistry and western blotting.ResultsCurcumin bound to ATOX1 (score = −6.1 kcal/mol) and decreased the levels of ATOX1, ATP7A and COX17 proteins in NSCLC cells. The curcumin or DC-AC50 treatment suppressed cell viability by inhibiting the ATOX1-mediated copper signaling in NSCLC cells. The ATOX1 overexpression in cells significantly weakened the effects of curcumin on suppressing copper accumulation and the ATOX1-mediated copper pathway (p < 0.05). In mice models, curcumin or DC-AC50 treatment also suppressed tumor growth by suppressing the ATOX1-mediated copper pathway in tumors.ConclusionThis study demonstrated that curcumin bound ATOX1 to suppress copper accumulation in NSCLC cells, providing a new mechanism of curcumin for NSCLC treatment.

In Vitro Effects of Curcumin in Free and Phytosomal Forms on the Expression of T Helper1 and Regulatory T Cells' Transcription Factors in Collagen-Induced Arthritis.

Curcumin as a polyphenolic compound has a potential capacity to reduce autoimmune reactions by skewing the balance of Thelper1 (Th1)/regulatory T cells (Treg) toward Treg cells. However, the low absorption and bioavailability of this agent have prompted researchers to use various drug delivery systems such as phytosomes to reduce these drawbacks. To date, few studies have evaluated the effects of phytosomal curcumin (nano-curcumin) on immune responses. Hence, we compared the modulatory effects of curcumin in free and phytosomal form on the expression of Th1 and Treg transcription factors, T-bet (T-box-containing protein) and Foxp3 (forkhead box p3), respectively, in a collagen-induced arthritis model (CIA). Following the induction of CIA, splenocytes were isolated and re-stimulated with collagen in the absence or presence of two different doses of curcumin in free and phytosomal form. Then, expression of T-bet and Foxp3 was assessed by real-time PCR. The expression of T-bet was reduced in curcumin and phytosomal curcumin groups rather than in the untreated group. The level of T-bet was not significantly different between free and phytosomal groups. Moreover, mRNA expression of Foxp3 enhanced after treatment with curcumin, while phytosomal curcumin groups showed no difference in comparison with the untreated group. curcumin in nano/free form showed a modulatory effect on the expression of T-bet. However, only free-form enhanced Foxp3 expression, which could be owing to the low amount of curcumin in the phytosomal complex rather than free-form at the same dose or due to leakage of curcumin from the complex.

Curcumin mitigates acrylamide-induced ovarian antioxidant disruption and apoptosis in female Balb/c mice: A comprehensive study on gene and protein expressions.

Curcumin is known for its antioxidant properties. This study aimed to investigate the impact of curcumin on acrylamide (ACR)-induced alterations in the first-line antioxidant defense of ovarian tissue. Female Balb/c mice were divided into control, ACR (50 mg/kg), ACR/CUR100 (received Acr + curcumin100 mg/kg), and ACR/CUR200 (Acr + curcumin 200 mg/kg) groups, and received oral treatments for 35 days. Evaluation of antioxidant enzyme expression (Sod, Cat, Gpx genes), pro-apoptotic gene expressions (Bax, Caspase 3), and anti-apoptotic gene expression (Bcl2l1) at mRNA and protein levels was done. Percentage of apoptotic cells using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed. The model group (ACR) showed decreased mRNA expression of Sod, Cat, and Gpx genes compared with the control group. Treatment with two different doses of curcumin (CUR100 and CUR200) significantly increased Sod, Cat, and Gpx gene expression, with CUR200 demonstrating significant recovery. SOD, CAT, and GPX protein levels were similar to mRNA expression trends, significantly increased with curcumin administration. Acrylamide exposure significantly increased Bax and Caspase 3 expression and decreased Bcl2l1 gene expression leading to a notable rise in apoptosis in ACR group as compared to the control group. Conversely, curcumin administration, significantly reduced Bax and Caspase 3 expressions, with an increase in Bcl2l1expression, though not statistically significant. TUNEL assay revealed a substantial decrease in apoptosis in curcumin-received groups. In our study, ACR exposure adversely affected ovarian antioxidant defense thereby leading to increased pro-apoptotic markers. Notably, curcumin treatment effectively mitigated these effects, restored antioxidant potential, and reduced acrylamide-induced toxicity in female mouse ovaries.

The Dose-Dependent Effect of Curcumin Supplementation on Inflammatory Response and Gut Microbiota Profile in High-Fat Fed C57BL/6 Mice.

The prevalence of obesity has increased, with excessive consumption of high-fat foods being one of the primary causes. Curcumin, a polyphenol extracted from Curcuma longa L., exhibits anti-inflammatory activity. The study aims to investigate the effects of curcumin supplementation in different doses on the biochemical profile, inflammatory response, and gut microbiota profile in mice that are fed with high-fat diet (HFD). C57BL/6 male mice are fed a standard diet, or a HFD with or without different doses of curcumin (50, 250, and 500mgkg-1 of body weight). Throughout the experimental period, food intake and body weight are assessed weekly. At euthanasia, blood, stool, and tissue samples are collected for biochemical, histological, and molecular analyses. Curcumin increases the IL-10 protein expression in the white adipose tissue. In the liver, there is a reduction in tumor necrosis factor alpha (TNF-α) and an increase in IL-10 gene expression. Also, curcumin promotes the growth of butyrogenic bacteria, such as Clostridium clusters IV and XIVa. The findings suggest that curcumin has the potential to improve the inflammatory response and modulate healthy gut microbiota. Further studies are needed to clarify the role of curcumin as a preventive and effective strategy for obesity.

Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2

Osteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death associated with lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis in chondrocytes of OA is unknown. This study aimed to investigate the protective effect and potential mechanism of curcumin on chondrocytes induced by erastin, a ferroptosis inducer. CCK-8 assays were used to assess cell viability in mouse primary chondrocytes treated with 3.33 μM erastin alone or in combination with different doses of curcumin. Various parameters were detected, including LDH, SOD, GSH-PX, MDA, ROS and Fe2+ contents. The ferroptosis-related proteins, such as SLC7A11, GPX4, TFR1, ACSL4, and FTH1, were examined using immunofluorescence and western blotting. Nrf2 was knocked down using siRNA to explore the molecular mechanism through which curcumin protects chondrocytes from erastin-induced ferroptosis. In a mouse model of knee ferroptosis induced by intracavity injection of 10 μL erastin (5 mg/mL), HE staining, Safranin O-Fast Green staining, and immunohistochemistry were employed to evaluate articular cartilage injury. The results demonstrated that erastin significantly suppressed the expression of SOD, GSH-PX, SLC7A11, GPX4, and FTH1 while upregulating the levels of LDH, MDA, ROS, ACSL4, and TFR1 in chondrocytes. Moreover, erastin-induced chondrocyte ferroptosis, lipid ROS, and Fe2+ production were reversed by curcumin. Additionally, curcumin significantly upregulated the expression level of the Nrf2 gene and protein. Silencing Nrf2 reversed the protective effect of curcumin on erastin-induced chondrocyte ferroptosis. In animal experiments, silencing Nrf2 counteracted the impact and damage of curcumin on erastin-induced ferroptosis of cartilage tissue in vivo, leading to significant inhibition of OA progression. Taken together, these findings suggest that curcumin can inhibit chondrocyte ferroptosis by activating the Nrf2 signaling pathway, providing further insight into the regulatory mechanism of curcumin in OA and supporting its potential therapeutic use in OA treatment.

Effects of Curcumin on Growth Performance, Ruminal Fermentation, Rumen Microbial Protein Synthesis, and Serum Antioxidant Capacity in Housed Growing Lambs.

This experiment was conducted to investigate growth performance, ruminal fermentation, rumen microbial protein synthesis, and serum antioxidant capacity with different doses of curcumin (CUR) included in the diet of housed growing lambs. Forty-eight four-month-old Dorper × Thin-tailed Han F1 crossbred male lambs (body weight = 20.89 ± 1.15 kg, age = 120 ± 10 days; mean ± SD) were randomly divided into four groups for a single-factor, completely randomized experiment. Treatments comprised the following: the basal diet supplemented with 0 (Control), 300 mg/kg (300 CUR), 600 mg/kg (600 CUR), or 900 mg/kg (900 CUR) CUR, respectively. The results showed that dietary CUR increased average daily gain (ADG), and the 300 CUR group evidenced the highest value. There were no significant effects on dry matter intake (DMI) and DMI/ADG. Lambs in the 300 CUR group showed higher totals of volatile fatty acids (VFA) and acetate than other groups, while decreased valerate was observed with supplementary CUR. The ruminal pH and ammonia N (NH3-N) concentration decreased with increasing CUR, with the greatest effect in the 300 CUR group. The quadratic effects were found in pectinase, carboxymethyl cellulose, and protease, with the greatest value in the 300 CUR group. The microbial populations of total bacteria and Ruminococcus albus also responded quadratically, and the methanogens, protozoan, and Fibrobacter succinogenes populations decreased linearly with increasing CUR. Lambs receiving additional CUR showed increased Prevotella ruminicola population. Microbial protein (MCP) synthesis was promoted by supplementary CUR. As supplementation with CUR increased, the serum activity of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) was enhanced, with the greatest value in the 300 CUR group. In conclusion, dietary CUR improved ruminal fermentation, promoted rumen microbial protein (MCP) synthesis, and enhanced serum antioxidant activity, as well as promoting growth performance in housed growing lambs.

Curcumin alleviated oxidation stress injury by mediating osteopontin in nephrolithiasis rats.

To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG). Thirty male rats were divided into normal control, model, positive (10% potassium citrate), Cur-10 (10 mg/kg curcumin) and Cur-20 (20 mg/kg curcumin) groups. The results of kidney tissue section stained by hematoxylin-eosin and von Kossa showed that curcumin treatment can inhibit the formation of kidney stones. The biochemical test results showed that the urea (Ur), creatinine (Cr), uric acid (UA), inorganic phosphorus and Ca2+ concentrations in urine decreased after being treated with curcumin. There were significant differences between different doses of curcumin (P < 0.05). Compared with the Cur-10 group, Cur-20 had a more significant inhibitory effect on malondialdehyde (MDA) (P < 0.05). In addition, reverse transcription polymerase chain reaction (PCR) detection and immunohistochemical results indicated that the osteopontin (OPN) in the kidney was significantly reduced after curcumin treatment. Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.

Curcumin Induces Ferroptosis in A549 CD133+ Cells through the GSH-GPX4 and FSP1-CoQ10-NAPH Pathways.

Cancer stem cells (CSCs) are characterized by an ability for unlimited proliferation and efficiency of self-renewal. The targeting of lung CSCs (LCSCs)-related signaling pathways represent a promising therapeutic strategy for treatment of lung cancer. Ferroptosis a potential strategy for LCSCs treatment, and curcumin cloud induce ferroptosis. In this study, we aimed to observe the effects of curcumin on LCSCs via ferroptosis-related pathways. In this study, A549 cluster of differentiation (CD)133+ and A549 CD133- cells were isolated using magnetic bead-based separation. Colony formation and sphere formation assays, as well as cells injection in non-obese diabetes/severe combined immune deficiency (NOD/SCID) mice, were used to analyze the tumorigenic ability of cells differentially expressing CD133. A549 CD133+ cells were treated with different doses of curcumin (0, 10, 20, 40, 80 μM). Cell viability, glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) expressions were measured. The 50% inhibitory concentration (IC50) of curcumin, two ferroptosis inducers, inhibitor of GPX4 (RSL3) and inhibitor of FSP1 (iFSP1), and a ferroptosis inhibitor, ferrostatin-1 (Fer-1), were used to investigate the mechanism underlying the effect of curcumin on ferroptosis in A549 CD133+ cells. A549 CD133+ cells had greater tumorigenic ability than A549 cells. Curcumin treatment suppressed the expressions of GPX4 (glutathione peroxidase 4) and FSP1 in A549 CD133+ cells, thereby inducing ferroptosis. RSL3 and iFSP1 respectively suppressed the GSH (glutathione)-GPX4 and FSP1 (ferroptosis suppressor protein 1)-CoQ10 (coenzyme Q10)-nicotinamide adenine dinucleotide (NADH) pathways in A549 CD133+ cells. However, the roles of curcumin were blocked by Fer-1 treatment. In this study, curcumin induced ferroptosis through inhibiting the GSH-GPX4 and FSP1-CoQ10-NADH pathways in A549 CD133+ cells, resulting in the inhibition of their self-renewal potential.

The ketogenic diet could improve the efficacy of curcumin and Oldenlandia diffusa extract in the treatment of gastric cancer by increasing miR340 expression and apoptosis mediated by autophagy, oxidative stress, and angiogenesis.

The pathogenesis of gastric cancer is a multistage process that involves glucose metabolism, inflammation, oxidative damage, angiogenesis, autophagy, and apoptosis. Moreover, microRNA-340 (miR340) also plays a vital role in tumorigenesis and the biology of gastric cancer as an epigenetic factor. It seems that the use of ketogenic diets (KDs) and plant extracts that have antitumor, anti-inflammatory, and antioxidant properties can be good treatment options to cure gastric cancer. The aim of this study was to investigate the role of miR-340 on pathways involved in the pathogenesis of gastric cancer and the improving effects of the KD, Oldenlandia diffusa extract (ODE), and curcumin in the animal model of gastric cancer. One hundred and ten male Wistar rats were divided into control and treatment groups. The expression of miR-340 along with genes involved in inflammation, oxidative damage, angiogenesis, and apoptosis were assessed. The results showed that the KD and different doses of curcumin and ODE in a dose-dependent behavior could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue of rats with cancer. In addition, there was no significant difference between cancer groups receiving ODE and curcumin. These results also showed that consumption of KD could significantly increase the efficacy of ODE and curcumin which may be due to increasing miR-340 expression. The results of this study suggested well that the KD along with conventional therapies in traditional medicine can be a useful solution for the prevention and treatment of gastric cancer. PRACTICAL APPLICATIONS: Gastric cancer is the third leading cause of cancer death, and genetic and epigenetic factors, including miR-340, are involved in its pathogenesis. However, the use of ketogenic diets (KDs) and plant products such as curcumin and Oldenlandia diffusa extract (ODE) can play an effective role in inhibiting tumorigenesis in some cancers. Our results showed that the KD and different doses of curcumin and ODE could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue. Moreover, the KD could significantly increase the efficacy of ODE and curcumin which may be due to an increase in miR-340 expression. These findings provide novel perceptions about the mechanisms of the KD, curcumin, and ODE to cure gastric cancer. It suggested that the KD as adjunctive therapy along with conventional therapies in traditional medicine could be considered a useful solution to prevent and treat gastric cancer.

Observation of zebrafish embryonic and larval development at different doses of curcumin solution: the disparity between safe and toxic

The aim of the study is to perform a fast and efficient toxicity test that demonstrates the safety or toxicity levels in the embryonic development of zebrafish exposed to different doses of curcumin. Embryotoxicity tests were performed according to the OECD guideline. A standard dose of 100 mg/kg curcumin per zebrafish embryo weight was determined. A stock solution was dissolved in dimethylsulfoxide and then used to perform a serial dilution in dechlorinated water to identify safe levels of curcumin concentration. The test was performed at concentrations of 0.6; 1.25; 2.50; 5; 6.25; 10; 12.5; 25; 50; 100 μM/mL, together with a control standard containing only dechlorinated water. After the start of exposure, the embryos were monitored with an optical microscope at 8, 24, 48, 72, and 96 hours post-exposure to identify possible changes and mortality. We observed that higher doses of curcumin solution influence the appearance of teratogenic characteristics such as eye malformation, retarded growth, yolk edema, crooked syrup, and short syrup. The results were also analyzed from the embryonic survival rate from the doses used, concluding that at higher concentrations, there was a significant difference in survival.

Effects of dietary curcumin in growth performance, oxidative status and gut morphometry and function of gilthead seabream postlarvae

An imbalance in the production and detoxification of reactive oxygen species and other oxidants can disrupt all types of cellular compounds, and lead to a state of oxidative stress. Preventing this state is essential to improve growth and health in animal production. Therefore, the aim of this work was to assess if the dietary supplementation of curcumin could improve the antioxidant status and intestine structure and functionality of gilthead seabream postlarvae, with the global objective of improving fish growth performance and robustness. Two experimental diets supplemented with different doses of curcumin (LOW and HIGH diets), and a commercial diet were fed to quadruplicate groups of postlarvae, for 20 days. At the end of the feeding trial fish fed the supplemented diets significantly improved their antioxidant status compared to CTRL fed fish. LOW and HIGH fed fish presented lower protein oxidative damage (P < 0.05) and higher total antioxidant capacity (P < 0.05). Moreover, postlarvae fed curcumin supplemented diets also presented an upregulation of nuclear factor erythroid 2 – related factor 2 (nrf2) and glutathione-disulfide reductase (gr) in HIGH (P < 0.05) and heat shock protein 70 (hsp70) in LOW treatments (P < 0.05). No differences were observed in growth performance, intestine morphometry, and digestive enzymes activities among treatments (P > 0.05). In conclusion, dietary curcumin supplementation was able to enhance gilthead seabream postlarvae robustness through a modulation of the oxidative status, increasing total antioxidant capacity and decreasing protein oxidative damage. This data provide evidence that curcumin can be a suitable feed additive to promote heath status and robustness of fish at early stages of development, therefore contributing for the development and sustainability of marine fish hatchery production.

Effect of curcumin on the non-alcoholic steatohepatitis via inhibiting the M1 polarization of macrophages.

Non-alcoholic steatohepatitis (NASH) is a global medical problem and macrophages' activation is closely related to the pathogenesis of NASH. Curcumin is a polyphenol from turmeric with significant anti-inflammatory activity. The objective of present study was to observe the effect of curcumin on macrophages' activation and secretion of pro-inflammatory cytokines in NASH. Hematoxylin and eosin and TUNEL staining were used to observe the hepatic function. RT-PCR was conducted to evaluate the hepatic mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Flow cytometry was adopted to detect the M1 polarization of macrophages. The RAW264.7 macrophage was pretreated with different doses of curcumin, and then lipopolysaccharide (LPS) and interferon-γ (IFN-γ) were given to activate the M1 macrophage. The activation ratio of M1 macrophage was observed by flow cytometry, and IL-1β and TNF-α expression was detected by RT-PCR and ELISA. After treatment with curcumin, the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the mRNA expression of TNF-α and IL-1β, and M1 polarization of macrophages were significantly decreased. Hematoxylin and eosin and TUNEL staining showed that inflammation and apoptosis in the liver were improved. What is more, curcumin can effectively inhibit M1 macrophage activation induced by lipopolysaccharide and IFN-γ and reduce the secretion of IL-1β and TNF-α. Curcumin can effectively improve NASH and reduce hepatic cell necrosis by inhibiting the M1 polarization of macrophages and the secretion of inflammatory factors.

Evaluation of the Hepatoprotective Effect of Different Doses of Curcumin and Vitamin c in Methotrexate-Induced Hepatotoxicity in Mice

Background: Methotrexate, the antineoplastic and immunosuppressive drug, is used in the treatment of different types of cancers and the management of chronic inflammatory diseases. Hepatotoxicity is one of its major side effects. Objectives: The present study assesses the hepatoprotective effect of different doses of curcumin and Vitamin C in methotrexate-induced hepatotoxicity. Materials and Methods: The prospective experimental study was conducted at the College of Medicine, Mustansiriyah University, Baghdad, Iraq, and in the animal's house of the Iraqi Center for Cancer Research, Baghdad-Iraq, from November 2020 to June 2021, and comprised Swiss albino female mice aged 3–4 months and weighing 30–40 g each. The mice were divided into 6 groups, the first group was considered as control which received only distilled water, the second group was considered as methotrexate group, third and fourth groups orally supplemented with 10 mg/kg and 20 mg/kg curcumin, respectively, fifth and sixth groups orally supplemented with 100 mg/kg and 200 mg/kg Vitamin C, respectively, The experiment continued for 10 days, and on the 10th day all groups, except the control one, received 20 mg/kg methotrexate intraperitoneally to induce hepatotoxicity. Parameters measured were serum alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), and liver tissue malondialdehyde (MDA), superoxide dismutase, and glutathione. SPSS 16 was used for data analysis. Results: The results show significant hepatoprotection produced by curcumin reflected by a decrease in LDH and MDA. Vitamin C also produced a significant hepatoprotection demonstrated by a decrease in ALT, ALP, LDH, and MDA. Conclusion: Curcumin and Vitamin C were found to provide hepatoprotection against methotrexate-induced hepatotoxicity through the modulation of oxidative stress biomarkers in a dose-dependent manner.

Immunomodulatory Effect of Curcumin in the Upregulation of Inflammasome Pathway Genes Induced by Sulfur Mustard Analog: An In-vitro Study

Sulfur Mustard (SM) induces cell injury via exerting oxidative stress, protease-anti protease imbalance, and inflammation. Inflammasome as one part of innate immunity has a critical role in the recognition of cell injuries and the initiation of the inflammation process by releasing IL-1β. Hence, the present study investigated the effects of the sub-lethal doses of 2-chloroethyl ethyl sulfide (CEES) as SM analog on the gene expression level of inflammasome-related genes as well as the potential protective effects of curcumin on this process. The effects of sub-lethal doses (500, 1000, and 2500 mM) of CEES on pulmonary epithelial cell line (A549) were determined at various time points (12, 24, and 48 h). Following the treatment of cells with CEES, the kinetic alterations of the expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB1), NLR family pyrin domain containing 1 (NLRP1), Caspase-1 (Casp1), and Interleukin-1β (IL-1β) genes were analyzed; using real-time PCR. In addition, the concurrent protective effects of different doses of curcumin (20, 40, 80, and 160 mM) on modulating the effects of CEES were studied. Although it was found that the lowest sub-lethal dose of CEES (500 mM) was able to up-regulate the inflammasome-related genes, the maximum alterations occurred 48 h after the treatment with the higher sub-lethal dose (2500 mM) of CEES. The maximum alteration occurred in Casp1 (38 fold), IL-1β (19 fold), and NLRP1 (~4 fold) genes (p<0.0001). However, the NF-ĸB gene expression level did not alter following CEES exposure. Even though low doses of curcumin (20, 40, and 80 mM) were able to down-regulate the studied genes, it was found that the treatment of cells with 160 mM of curcumin for 48 h was able to normalize the expression level of all genes. The present study concludes that curcumin as an anti-inflammatory agent may have beneficial immunomodulatory effects following CEES exposure.

Curcumin inhibits the growth of liver cancer by impairing myeloid-derived suppressor cells in murine tumor tissues.

Curcumin, one of the active ingredients of Curcuma longa (Jianghuang), has been reported to exert multiple bioactivities, including pro-apoptotic and anti-inflammatory activities. In recent years, curcumin has been extensively studied, and it has been revealed that curcumin inhibits the growth of numerous types of cancer. However, to the best of our knowledge, the inhibitory effects of curcumin on the activation or expansion of myeloid-derived suppressor cells (MDSCs) in liver cancer and the underlying mechanism have not yet been determined. Therefore, the present study aimed to investigate the inhibitory effect of curcumin on MDSC activity and the associated anti-neoplastic mechanism in a HepG2 ×enograft mouse model. The effect of curcumin on the viability of Huh-7, MHCC-97H and HepG2 cells in vitro was analyzed using a Cell Counting Kit-8 assay. The effects of curcumin on tumor growth, numbers of MDSCs, expression levels of proteins involved in the toll-like receptor 4 (TLR4)/NF-κB signaling pathway, levels of related inflammatory factors and angiogenesis were determined in HepG2 ×enograft model mice, which were given different doses of curcumin via intragastrical administration. The results of the present study revealed that curcumin inhibited the viability of Huh-7, MHCC-97H and HepG2 cells and the growth of HepG2 ×enograft tumors in mice. Flow cytometric analysis indicated that curcumin reduced the number of MDSCs in mouse xenograft tumors. In addition, the results demonstrated that curcumin inhibited the TLR4/NF-κB signaling pathway and the expression of inflammatory factors, including IL-6, IL-1β, prostaglandin E2 and cyclooxygenase-2, in mouse xenograft tumors. Furthermore, curcumin suppressed the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF), which are essential factors for MDSCs modulation, in tumor tissues. Additionally, curcumin was revealed to inhibit angiogenesis, which was demonstrated by the downregulation of the expression levels of vascular endothelial growth factor, CD31 and α-smooth muscle actin in western blotting, immunohistochemistry and immunofluorescence experiments. In conclusion, the findings of the present study identified a novel mechanism via which curcumin may suppress the growth of liver cancer by reducing the numbers of MDSCs and subsequently disrupting the process of angiogenesis. These conclusions were supported by the observed inactivation of the TLR4/NF-κB signaling pathway-mediated inflammatory response and the downregulation of GM-CSF and G-CSF secretion in xenograft tissues.

Pharmacological and Molecular Evidence of Neuroprotective Curcumin Effects Against Biochemical and Behavioral Sequels Caused by Methamphetamine: Possible Function of CREB-BDNF Signaling Pathway.

Introduction:The neuroprotective impact of curcumin and the role of CREB (Cyclic AMP Response Element Binding protein)-BDNF (Brain-Derived Neurotrophic Factor) signaling pathway was evaluated in Methamphetamine (METH)-induced neurodegeneration in rats.Methods:Sixty adult male rats were randomly divided into 6 groups. While normal saline and 10 mg/kg METH were administered intraperitoneally in groups 1 and 2, groups 3, 4, 5, and 6 received METH (10 mg/kg) and curcumin (10, 20, 40, and 80 mg/kg, respectively) simultaneously. Morris water maze test was administered, and oxidative hippocampal, antioxidant, inflammatory, apoptotic, and CREB and BDNF were assessed.Results:We found that METH disturbs learning and memory. Concurrent curcumin therapy (40 and 80 mg/kg) decreased cognitive disturbance caused by METH. Multiple parameters, such as lipid peroxidation, the oxidized form of glutathione, interleukin 1 beta, tumor necrosis factor-alpha, and Bax were increased by METH therapy, while the reduced type of glutathione, Bcl-2, P-CREB, and BDNF concentrations in the hippocampus were decreased.Conclusion:Different doses of curcumin adversely attenuated METH-induced apoptosis, oxidative stress, and inflammation but enhanced the concentrations of P-CREB and BDNF. The neuroprotection caused by curcumin against METH-induced neurodegeneration is mediated through P-CREB-BDNF signaling pathway activation.

Antitumor effects of curcumin in pediatric rhabdomyosarcoma in combination with chemotherapy and phototherapy invitro.

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, has an unfavorable outcome in advanced tumor stages with less than 30%failure‑free survival. Curcumin (CUR) is a promising drug in complementary oncology with few side effects but proven efficacy in various adult oncological entities. The present study analyzed the effects of CUR on pediatric (RMS) cell lines invitro. RMS cell lines (RD and RH30), and skeletal muscle cells (SKMC) were treated with different doses of CUR (1.5‑30µM) alone, with phototherapy (PDT, 488nm) or in combination with vincristine (VCR) or dactinomycin (DAC). MTT assays were used for analysis of RMS tumor cell viability. Clonal cell growth was assessed via colony forming assays and migration of the cells was analyzed with scratch tests. Annexin V staining was used to determine apoptosis in flow cytometry. Possible RMS resistance towards CUR after long‑term treatment was analyzed with MTT assays. CUR decreased cell viability in all assessed RMS cell lines in a concentration‑dependent manner with IC50=14‑20µM. CUR enhanced the effects of the cytotoxic drugs VCR or DAC, and led to reduced migration and increased cell apoptosis. In combination with PDT, CUR decreased the cell viability in minute quantities with up to a 10‑fold lower IC50 than without PDT. CUR effectively inhibited the malignant properties of pediatric RMS cells and should be focused on as a useful additional agent in standard chemotherapy of RMS in children.

Influense of curcumin on lifespan if it is applied at the larval stage of drosophila melanogaster

In this study we have applied the different doses of curcumin at the larval stages of a fruitfly Drosophila melanogaster and subsequently ivestigated its effect on the developmental duration and life expectancy of imago. It has been shown a 2-day delay in the hatching of the flies, which were developing in the medium containing 500 mM of curcumin. Exposure to curcumin significantly influenced on the average and maximum lifespan (ALS and MLS respectively) of all Drosofila in the study: ALS – F=13.01, p&lt;0.001 for males and F=14.3, p&lt;0.001 for females; MLS – F=35.9, p&lt;0.001 for males and F=16.7, p &lt;0.001 for females. Thus, the ALS in the males, which at the larval stage were kept in the medium containing 125 mM, 250 mM and 500 mM of curcumin, was significantly higher (p&lt;0.001) comparing to the control. In females, such kind of significant increase in ALS has been shown at a dose of 500 mM of curcumin (p&lt;0.001) in the medium during the developmental stage comparing to the control. In other words, the ALS of the imago has increased in correlation to the increase in the dose of curcumin applied at the developmental stage in males by 9%, 16%, 13%, and 23% and in females by 0%, 1%, 3%, 16% respectively. There has been also shown the sharp raise in MLS in both males and females, which at the larval stage were kept in the medium containing more than 125 mM of curcumin. To sum up we can assume that in this study consumption of curcumin at the larval stage of fruit flies significantly increased the developmental duration and life span of adult Drosophila, and this may demonstrate the effect of curcumin on the epigenetic programming of pace of life. Keywords: Development; Life span; Curcumin; Drosophila

Curcumin supplementation improved inflammatory and gut microbiota profile despite not preventing weight gain in C57bl/6 male mice receiving high-fat diet

Rationale: Curcumin has been investigated for its anti-inflammatory effects. This study investigated the effect of different doses of curcumin on weight gain, pro and anti-inflammatory profile, and gut microbiota of mice fed a high-fat diet.

The Preventive Effect of Curcumin on the Experimental Rat Epidural Fibrosis Model

The aim of the study was to evaluate the effect of systemically administrated curcumin on the prevention of peridural fibrotic tissue and adhesion formation in a rat laminectomy model. Thirty-two Wistar albino rats were randomly selected and equally divided into 4 groups as follows: negative control group (group I) did not undergo operation; positive control group (group II) underwent laminectomy without treatment; group III (low-dose curcumin; 100 mg/kg); and group IV (high-dose curcumin; 200 mg/kg). Curcumin was administered intraperitoneally per day for 7 days after surgery starting from day 0. Twenty-eight days after surgery, T12 and L4 vertebral columns, paraspinal tissues, and epidural scar tissue were dissected en bloc and prepared for histopathologic examinations. All specimens were examined for inflammation, epidural fibrosis (EF), foreign body reaction, medulla spinalis retraction, granulation tissue, and arachnoid involvement. A Kruskal-Wallis test followed by a Dunn multiple comparison test were used for statistical analysis, and a P value <0.05 was considered as statistically significant. Curcumin treatment significantly reduced inflammation, foreign body reaction, granulation tissue formation, medulla spinalis retraction, and EF formation compared with positive control group (P < 0.05); however, no significant differences were found between the 2 groups that received different doses of curcumin. The results of the present study showed that systemic administration of curcumin was effective in reducing EF formation, inflammation, granulation tissue formation, medulla spinalis retraction, and foreign body reaction in the laminectomy area. Our results suggest that antiinflammatory activities of curcumin are beneficial for attenuation of EF formation.