Inhibitory Effect Of Curcumin Research Articles

Curcumin inhibits cancer progression through regulating expression of microRNAs.

Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

Curcumin Suppresses Intestinal Fibrosis by Inhibition of PPARγ-Mediated Epithelial-Mesenchymal Transition.

Intestinal fibrotic stricture is a major complication of Crohn's disease (CD) and epithelial-to-mesenchymal transition (EMT) is considered as an important contributor to the formation of intestinal fibrosis by increasing extracellular matrix (ECM) proteins. Curcumin, a compound derived from rhizomes of Curcuma, has been demonstrated with a potent antifibrotic effect. However, its effect on intestinal fibrosis and the potential mechanism is not completely understood. Here we found that curcumin pretreatment significantly represses TGF-β1-induced Smad pathway and decreases its downstream α-smooth muscle actin (α-SMA) gene expression in intestinal epithelial cells (IEC-6); in contrast, curcumin increases expression of E-cadherin and peroxisome proliferator-activated receptor γ (PPARγ) in IEC-6. Moreover, curcumin promotes nuclear translocation of PPARγ and the inhibitory effect of curcumin on EMT could be reversed by PPARγ antagonist GW9662. Consistently, in the rat model of intestinal fibrosis induced by 2,4,5-trinitrobenzene sulphonic acid (TNBS), oral curcumin attenuates intestinal fibrosis by increasing the expression of PPARγ and E-cadherin and decreasing the expression of α-SMA, FN, and CTGF in colon tissue. Collectively, these results indicated that curcumin is able to prevent EMT progress in intestinal fibrosis by PPARγ-mediated repression of TGF-β1/Smad pathway.

Curcumin Induces Autophagy, Apoptosis, and Cell Cycle Arrest in Human Pancreatic Cancer Cells.

Objective Curcumin is an active extract from turmeric. The aim of this study was to identify the underlying mechanism of curcumin on PCa cells and the role of autophagy in this process. Methods The inhibitory effect of curcumin on the growth of PANC1 and BxPC3 cell lines was detected by CCK-8 assay. Cell cycle distribution and apoptosis were tested by flow cytometry. Autophagosomes were tested by cell immunofluorescence assay. The protein expression was detected by Western blot. The correlation between LC3II/Bax and cell viability was analyzed. Results Curcumin inhibited the cell proliferation in a dose- and time-dependent manner. Curcumin could induce cell cycle arrest at G2/M phase and apoptosis of PCa cells. The autophagosomes were detected in the dosing groups. Protein expression of Bax and LC3II was upregulated, while Bcl2 was downregulated in the high dosing groups of curcumin. There was a significant negative correlation between LC3II/Bax and cell viability. Conclusions Autophagy could be triggered by curcumin in the treatment of PCa. Apoptosis and cell cycle arrest also participated in this process. These findings imply that curcumin is a multitargeted agent for PCa cells. In addition, autophagic cell death may predominate in the high concentration groups of curcumin.

Efflux Pump Inhibition Effect of Curcumin and Phenylalanine Arginyl β- Naphthylamide (PAβN) against Multidrug Resistant Pseudomonas Aeruginosa Isolated from Burn Infections in Tanta University Hospitals

Introduction : Multidrug resistant (MDR) Pseudomonas aeuroginosa strains are very important pathogens causing hospital acquired infections especially in intensive care units. One of the mechanisms of developing drug resistance is efflux pump through which bacteria extrude antibiotics. If these efflux channels are blocked or inhibited, increased drug concentration can be obtained inside a bacterial cell with optimal drug dose. This study was aimed to investigate the role of curcumin and phenylalanine arginyl β-naphthylamide(PAβN) as efflux pump inhibitors (EPIs). Materials and Methods : A total of 40 Pseudomonas aeruginosa isolates were taken from burn wounds. Antibiotic susceptibility was performed using disc diffusion test, then minimum inhibitory concentration (MIC) against selected antibiotics before and after adding PAβN (20mg/L, 50mg/L) and curcumin (from 5 to 50μg/ml) was tested. Results : MDR isolates showed significant reduction in MIC after adding curcumin (50μg/ml) and PAβN (20mg/L) with selected antibiotics, while no change in MIC was observed when were used alone, indicating their efflux pump inhibitor activity. Conclusion : curcumin and PAβN potentiated the effect of antibiotics and thus change their susceptibility pattern which can be attributed to efflux pumps inhibition. Further genotypic studies may be needed to confirm.

Protective effects of curcumin against liver fibrosis through modulating DNA methylation

Recent research has demonstrated that advanced liver fibrosis in patients could be reversed, but no approved agents are available for the treatment and prevention of liver fibrosis in humans. Curcumin (CUR) is the principal curcuminoid of turmeric. Inhibitory effects of CUR and its underlying mechanisms in liver fibrogenesis have been explored. In the present study, we hypothesized that epigenetic mechanisms contribute to the protective effects of CUR against liver fibrosis. We used CCl4-induced liver injury in BALB/c mice and the rat hepatic stellate cell line HSC-T6 as experimental models. Genomic DNA methylation was analyzed by MeDIP-chip and verified by real-time PCR on MeDIP-enriched DNA. The mRNA and protein expressions of DNMT1, α-SMA, and Col1α1 were determined by real-time PCR and Western blotting, respectively. The methylation statuses of FGFR3, FZD10, Gpx4, and Hoxd3 were further confirmed by quantitative methylation-specific PCR (qMSP). Our results showed that CUR treatment reversed liver injury in vivo and in vitro, possibly through down regulation of DNMT1, α-SMA, and Col1α1 and by demethylation of the key genes. In conclusion, aberrant methylation is closely associated with liver fibrosis and CUR treatment may reverse liver fibrosis by epigenetic mechanisms.

Curcumin directly inhibits the transport activity of GLUT1.

Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin's inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin.

Vitamin E-like molecules potentiate the curcumin-induced suppression of Caco-2 cell proliferation

We previously reported that curcumin inhibited the proliferation of a human colorectal cancer cell line Caco-2 by both apoptosis and G 2 /M cell cycle arrest. A variety of biological functions of curcumin have been suggested to be involved in its modulatory capacity to oxidative stress. The aim of this study was to investigate the modulation of antioxidants, N -acetyl- L -cysteine (NAC), a-tocopherol (TOC) and trolox, on the suppression of Caco-2 cell proliferation via G 2 /M cell cycle arrest induced by curcumin. NAC (2 mM) reduced the curcumin-induced suppression of Caco-2 proliferation. Inversely, both TOC (0.2 mM) and trolox (0.2 mM) potentiated the curcumin effect. Trolox at the same concentration amplified both G 2 /M cell cycle arrest and p21 elevation induced by curcumin independent of oxidative stress status. These results suggest that Vitamin E-like molecules have the potential to amplify the inhibitory effect of curcumin on Caco-2 proliferation through reactive oxygen species-independent cell cycle modulation, and could offer new insights for preventive measures against colorectal cancer incidence.

Inhibitory effect of curcumin on angiogenesis in a streptozotocin-induced diabetic rat model: An aortic ring assay

BackgroundCurcumin (diferuloylmethane) has been associated with the inhibition of angiogenesis, as well as the prevention of cancers and inflammatory processes. The aim of this study was to assess the efficacy of curcumin in suppressing angiogenesis in the cultured endothelial cells of rat aortic rings. MethodsEight-week-old male Wistar rats were randomized into five groups each with a different treatment and cell culturing paradigm: controls cultured in the absence of VEGF (vascular endothelial growth factor) (C), controls cultured in the presence of VEGF (C-V), controls treated with curcumin and then cultured in media lacking VEGF (C-TC), diabetics cultured in media supplemented with VEGF (D-V) and diabetics treated with curcumin and then cultured in media supplemented with VEGF (D-V-TC). Each group consisted of 8 animals. Diabetes was induced in by streptozotocin (STZ; 60 mg/kg body weight, IV). After 8 weeks, animals were sacrificed and their aortas were excised. Ring-shaped explants were embedded in a 96-well culture plate. Angiogenesis response was measured by counting the number of primary microtubules in each well. ResultsOptic microscopy revealed that the D-V group had the highest number of microvessels, while angiogenesis was not observed in the C or C-TC groups. The number of primary microtubules was significantly lower in the D-V-TC group compared to the D-V group (P < 0.05). The D-V-TC group had a significantly higher number of microvessels compared to the C-TC group (P < 0.05). ConclusionCurcumin attenuates angiogenesis response in stertozotocin-induced diabetic rats.

Antibacterial Activity of Curcumin Against Periodontopathic Bacteria.

Curcumin is a polyphenol extracted from root of turmeric and known to possess multifunctional properties, including antibacterial activity. Although previous studies have investigated the effects of curcumin on microorganisms, available knowledge on the effects of curcumin on periodontopathic bacteria is still limited. In this study, the antibacterial effect of curcumin on periodontopathic bacteria is investigated, particularly Porphyromonas gingivalis. Representative periodontopathic bacteria were cultured in media with and without various curcumin concentrations, and the optical density at 600 nm was measured for 60 hours. The inhibitory effect of curcumin on P. gingivalis Arg- and Lys-specific proteinase (RGP and KGP, respectively) activities were assessed using spectrofluorophotometric assay. Analysis of biofilm formation by P. gingivalis with or without Streptococcus gordonii was conducted using confocal laser-scanning microscopy (CLSM). Curcumin inhibited the growth of P. gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Treponema denticola in a dose-dependent manner. Bacterial growth was suppressed almost completely at very low concentrations of curcumin. Conversely, 100 μg/mL curcumin did not suppress the growth of Aggregatibacter actinomycetemcomitans. It also demonstrated inhibitory effects against RGP and KGP activities in a dose-dependent manner. CLSM revealed that curcumin suppressed P. gingivalis homotypic and P. gingivalis-S. gordonii heterotypic biofilm formation in a dose-dependent manner. A concentration of 20 μg/mL curcumin inhibited these P. gingivalis biofilm formations by >80%. Curcumin possesses antibacterial activity against periodontopathic bacteria and may be a potent agent for preventing periodontal diseases.

Inhibitory effect of curcumin on testosterone induced benign prostatic hyperplasia rat model.

BackgroundBenign prostatic hyperplasia (BPH) is one of the common male diseases, which is provoked by dihydrotestosterone (DHT) and androgen signals. Several studies showed that curcumin has various effects of prevention and treatment to diseases. We investigated whether curcumin may repress the development of BPH in male Wistar rats.MethodsSeven weeks male Wistar rats were and divided into 4 groups (normal group, BPH group, finasteride group, curcumin group; n = 8 for each group). In order to induce BPH in rats, rats were castrated and testosterone was injected subcutaneously everyday (s.c., 20 mg/kg). Rats in the curcumin group were treated 50 mg/kg, administered orally for 4 weeks. After 4 weeks, all rats were sacrificed and their prostate and serum were analyzed.ResultsCompared to the finasteride group as positive group, the curcumin group showed similarly protective effect on BPH in histopathologic morphology, prostate volume. Results of immunohistochemistry and western-blot showed decreased expressions of VEGF, TGF-ß1, and IGF1 were also decreased in the curcumin group.ConclusionsThese results suggested that curcumin inhibited the development of BPH and might a useful herbal treatment or functional food for BPH.

Inhibitory effects of curcumin on inflammatory cytokines in rats with paraquat poisoning

To explore the mechanism of paraquat (PQ) poisoning and to observe the changes in inflammatory cytokines in PQ-exposed rats treated in different ways. Fifty 8-week-old clean male Wistar rats were randomly divided into high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, PQ poisoning group, and blank control group. On days 1, 3, 5, 7, 14, and 21 after PQ exposure, serum levels of transforming growth factor-β₁(TGF-β₁) , tumor necrosis factor-α (TNF-α) , and interleukin-6 (IL-6) were measured. The pathological changes in lung tissue were evaluated by HE staining. Compared with the blank control group, the high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, and PQ poisoning group had significantly increased serum levels of TGF-β₁, TNF-α, and IL-6 (P<0.05) , and the three cytokines in each group reached peak levels on day 14 after exposure. Compared with the PQ poisoning group, the high-dose curcumin group had significantly reduced serum levels of TGF-β₁, TNF-α, and IL-6 (P<0.05). On day 21 after exposure, there were no significant differences in serum levels of TGF-β₁, TNF-α, and IL-6 between the high-dose curcumin plus conventional treatment group and the low-dose curcumin plus conventional treatment group (P>0.05). The HE staining revealed alveolar inflammatory changes on days 1~7 and massive pulmonary fibrosis on days 14~21 in the high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, and PQ poisoning group, but the above changes were milder in the high-dose curcumin group than in the PQ poisoning group. For rats with PQ poisoning, curcumin can significantly reduce inflammatory response and pathological changes in lung tissue and inhibit and delay the development and progression of body injury.

Abstract 2817: Dietary chemopreventive agent (curcumin), hypomethylates 5′ promoter of DCLK1 gene in human colon cancer cells and restores expression of long isoform of DCLK1

Abstract Curcumin, a dietary chemopreventive agent, inhibits proliferation of colon cancer cells by inhibiting multiple oncogenic pathways. Curcumin has also emerged as a non-toxic epigenetic modulator in recent years. Direct interaction of curcumin with DNA methyl transferases (DMTs), inhibits their enzymatic activity, resulting in hypomethylation of specific genes. DCLK1 is a cancer stem cell (CSC) marker, critically required for colon tumorgenesis and for maintaining tumoregenic/metastatic potential of colon cancers. The 5′ promoter of DCLK1 gene in human colorectal cancers (hCRCs) is epigenetically silenced due to DNA methylation, resulting in loss of expression of long isoform of DCLK1 (DCLK1-L). However, a short isoform (DCLK1-S) is expressed from an alternate promoter within IntronV, in response to several oncogenic pathways, including activation of NF-κB pathway, and is required for maintaining tumorigenic/metastatic potential of hCRC cells. Since a subset of DCLK1+CSCs survive inhibitory effects of curcumin, resulting in relapse of the disease (Can Res, 2014), we hypothesized that curcumin will likely inhibit DCLK1-S expression, by inhibiting NF-κB pathway, but cause re-expression of DCLK1-L by hypomethylating the 5′promoter. A representative hCRC cell line, devoid of DCLK1-L expression due to hypermethylation of 5′promoter (HCT116), was used. Dose and time dependent effects of curcumin were examined on 2D/3D growths of HCT116 cells. As expected, proliferation of curcumin treated cells was significantly decreased in a time and dose dependent manner. DCLK1-L was re-expressed, corresponding to de-methylation of 5′ promoter; curcumin (5-10μM) was optimally effective as an epigenetic modifier at 72h. Higher doses were required for inhibiting DCLK1-S expression and corresponded with loss of binding of NF-κBp65 to the NF-κB cis element in IntronV promoter of DCLK1 gene. The loss in DCLK1-S expression, likely explains significant inhibitory effects of curcumin on the growth of colon cancers and CSCs, as reported by many investigators. Re-expression of DCLK1-L, marker of quiescent stem cells in normal colons, may allow curcumin-treated cancer cells to survive and become dormant/quiescent. It is speculated that ‘CSCs’, re-expressing DCLK1-L, are initially induced into dormancy, but revert back to expressing DCLK1-S after a period of dormancy, resulting in relapse of the disease, as previously reported; this intriguing possibility will be examined in future studies. Citation Format: Shubhashish Sarkar, Malaney O'Connell, Pomila singh. Dietary chemopreventive agent (curcumin), hypomethylates 5′ promoter of DCLK1 gene in human colon cancer cells and restores expression of long isoform of DCLK1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2817. doi:10.1158/1538-7445.AM2015-2817

Curcumin attenuates ethanol-induced hepatic steatosis through modulating Nrf2/FXR signaling in hepatocytes.

Alcoholic liver disease (ALD) is a common health problem worldwide, characterized by aberrant accumulation of lipid in hepatocytes. Inhibition of lipid accumulation has been well recognized as a promising strategy for ALD. Previous studies showed that curcumin has potential effect on ALD by regulating oxidative stress and ethanol metabolism. However, the effects of curcumin on lipid accumulation and its mechanism remain unclear. Recent researches have indicated that farnesoid X receptor (FXR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) have excellent effects on reducing lipid deposition. This study demonstrated that curcumin alleviated ethanol-induced liver injury by ameliorating activities of serum marker enzymes and inflammation. Moreover, curcumin alleviated the symptom of hyperlipidemia and hepatic steatosis via modulating the expression of sterol regulatory element-binding protein-1c, fatty acid synthase, and peroxisome proliferator-activated receptor-alpha as well as the activity of carnitine palmitoyltransferase 1. Additionally, curcumin induced the expression of Nrf2 and FXR in liver, strongly implying close relationship between inhibitory effect of curcumin on hepatic steatosis and the above two genes. The following in vitro experiments further verified the protective effects of curcumin against hepatotoxicity and lipid accumulation in hepatocytes induced by ethanol. Gain- or loss-of-function analyses revealed Nrf2 and FXR mediated the effect of curcumin on lipid deposition in hepatocytes, and curcumin modulated the expression of FXR mediated by Nrf2. Collectively, we drew a conclusion that curcumin attenuated ALD by modulating lipid deposition in hepatocytes via a Nrf2/FXR activation-dependent mechanism. The findings make curcumin a potential agent for ALD and broaden the horizon of the molecular mechanism involved.

Inhibitory effect of curcumin on invasion of skin squamous cell carcinoma A431 cells.

To investigate the regulatory effect of curcumin on expression of signal transducer and activator of transcription 3 (STAT3) in skin squamous cell carcinoma tissues as well as possible mechanisms of curcumin in prevention and treatment of skin squamous cell carcinoma. Highly invasive A431 cells were treated with curcumin at various doses .The cytotoxic effects of treatment with 5, 10, 15, 20, 25, 30, 35, 40 and 50 umol/L curcumin for 24, 48 and 72 hours on A431 cells were measured by MTT assay. The invasion capacity of cells treated with 5, 10 and 15 umol/L curcumin was measured by Transwell test, while adhesive ability was assessed by cell adhesion assay. The effects of 5,10 and 15 umol/L curcumin on expression levels of STAT3 were determined by Western blotting and on transcription levels of STAT3 mRNA by RT-PCR. Treatment with curcumin at a doses of more than 15 umol/L for more than 24 hour inhibited the growth of A431 cells in a time-and dose-dependent fashion (p<0.001). The doses of 15 umol/L and less for 24 hours showed no significant cytotoxic effects on the cells, survival rates being more than 85%.The invasion and adhesive abilities decreased gradually with the increasing curcumin concentration, 15 umol/L exerting the strongest inhibitory effects (p<0.05). Curcumin showed significant dose-dependent inhibitory effects on the transcription level of STAT3 mRNA (p<0.05). Curcumin may reduce the invasive ability of A431 cells by inhibiting the activation of STAT3 signal pathway and expression of STAT3 as a target gene in the pathway.

Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1

Colorectal cancer remains the most prevalent malignancy in humans. The impact of epigenetic alterations on the development of this complex disease is now being recognized. The dynamic and reversible nature of epigenetic modifications makes them a promising target in colorectal cancer chemoprevention and treatment. Curcumin (CUR), the major component in Curcuma longa, has been shown as a potent chemopreventive phytochemical that modulates various signaling pathways. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene with reduced transcriptional activity and promoter hypermethylation in various cancers, including colorectal cancer. In the present study, we aimed to investigate the inhibitory role of DLEC1 in anchorage-independent growth of the human colorectal adenocarcinoma HT29 cells and epigenetic regulation by CUR. Specifically, we found that CUR treatment inhibited colony formation of HT29 cells, whereas stable knockdown of DLEC1 using lentiviral short hairpin RNA vector increased cell proliferation and colony formation. Knockdown of DLEC1 in HT29 cells attenuated the ability of CUR to inhibit anchorage-independent growth. Methylation-specific polymerase chain reaction (MSP), bisulfite genomic sequencing, and methylated DNA immunoprecipitation revealed that CUR decreased CpG methylation of the DLEC1 promoter in HT29 cells after 5 days of treatment, corresponding to increased mRNA expression of DLEC1. Furthermore, CUR decreased the protein expression of DNA methyltransferases and subtypes of histone deacetylases (HDAC4, 5, 6, and 8). Taken together, our results suggest that the inhibitory effect of CUR on anchorage-independent growth of HT29 cells could, at least in part, involve the epigenetic demethylation and up-regulation of DLEC1.

Curcumin Treatment Suppresses CCR7 Expression and the Differentiation and Migration of Human Circulating Fibrocytes

Background/Aim: Recent studies have demonstrated that circulating fibrocytes contribute to the formation and development of fibrosis. Curcumin, a polyphenolic compound isolated from turmeric, has been shown to have anti-fibrotic effects in various organs. We and others have demonstrated that curcumin beneficially affects the development of fibrosis. However the effect of curcumin on circulating fibrocytes has not been reported. Methods: Human circulating fibrocytes were isolated from leukocyte concentrates of healthy human donors and identified based on the expression of CD34, CD45, collagen I (COLI), and chemokine receptor CCR7 (CCR7) via flow cytometry. Cell Counting Kit-8 was used to evaluate cell viability. The effect of curcumin on the differentiation and migration of human circulating fibrocytes was evaluated by immunofluorescence staining, flow cytometry and a transwell migration assay. Transforming growth factor (TGF)-β1 secretion was examined by ELISA. Results: Curcumin treatment (72 h; 20 μM) significantly decreased the expression of COL I, α-SMA and CCR7, as well as TGF-βl secretion, in human circulating fibrocytes. The inhibitory effect of curcumin on the differentiation and migration of human circulating fibrocytes is likely via regulating the CCR7/CCL21 signaling pathway, in particular by reducing CCR7 expression. These observed effects may be beneficial in resolving fibrosis by suppressing TGF-β1 secretion. Conclusion: Our results suggest that curcumin has the potential to suppress the differentiation and migration of circulating fibrocytes, which would provide new explanation for curcumin's application in the development of fibrosis in various organs.

Inhibitory effect of curcumin on the contractility of isolated caprine detrusor muscle.

Curcumin is a naturally occurring compound which has been used in traditional medicine in India for a long time. This study investigated the ability of curcumin to inhibit the contractility of isolated caprine (goat) detrusor muscle. The ability of three concentrations of curcumin (30, 100 and 300 µM) to inhibit the 100 µM acetylcholine-induced contractility of the isolated caprine urinary bladder detrusor muscle was investigated. The effect of raising the concentration of acetylcholine from 100, 200 and 400 µM to overcome the curcumin-induced inhibition of detrusor contractility and the effects of the reversal agents tetraethylammonium, a potassium channel blocker (100 µM), glibenclamide, an ATP-sensitive potassium channel blocker (10 µM), and propranolol, a beta adrenergic receptor blocker (1 µM), on the inhibitory effect of detrusor contractility was also studied. Curcumin caused a concentration-dependent inhibition of acetylcholine-induced contractility of the isolated detrusor muscle which was statistically significant at all three concentrations of curcumin used. This inhibition was partially overcome by raising the concentration of ACh to 200 and 400 µM. The inhibition was overcome by the concurrent administration of tetraethylammonium. Glibenclamide reversed the inhibitory effect of 100 µM curcumin, but not that of 300 µM curcumin. Propranolol reversed the inhibitory effect of 100 µM curcumin but not that of 300 µM curcumin. These results suggest that curcumin inhibited the contractions of the isolated detrusor muscle. The results further suggest that the inhibitory effect is mediated by various mechanisms: stimulation of beta adrenergic receptors; an anticholinergic effect; and the opening of ATP-sensitive potassium channels.

Evaluation of the Neuroprotective Effects of Curcuminoids on B35 and SH-SY5Y Neuroblastoma Cells

Curcumin is the main curcuminoid found in the yellow spice turmeric, a prominent member of the ginger family. Studies have revealed that curcumin exhibits numerous beneficial effects such as the ability to reduce inflammation and oxidative stress. The present study examines the neuroprotective effects of curcumin in vitro by subjecting B35 and SH-SY5Y neuroblastoma cells to hydrogen peroxide (H2 O2 ) followed or preceded by treating them with curcumin. Using curcumin concentrations of 5, 10 and 20 µM before and after damaging the cells with H2 O2 has resulted in an increase in cell viability of B35 neuroblastoma cells. In contrast, SH-SY5Y neuroblastoma cells showed an increase in their viability only upon the post-treatment with curcumin. The inhibitory effect of curcumin on caspase-3 and caspase-9, two of the most important mediators in the process of apoptosis, was also examined. We found that curcumin inhibited caspase-3 in a concentration-dependent manner, but not caspase-9. Using 5, 10, and 20 µM of curcumin resulted in 2.6%, 7.9% and 12.2% caspase-3 inhibition, respectively. These findings suggest that curcumin acts as a neuroprotectant and an anti-apoptotic agent through the inhibition of caspase-3, thereby introducing a potential agent for the treatment or prevention of neurodegenerative diseases.

Adsorption and inhibition effect of curcumin on mild steel corrosion in hydrochloric acid

The inhibition effect of curcumin on the corrosion of mild steel in 1.0 M HCl solution was studied by weight loss, potentiodynamic polarization curves and electrochemical impedance spectroscopy (EIS) methods. The experimental results suggest that this compound is an efficient corrosion inhibitor and the inhibition efficiency increases with the increase in inhibitor concentration. Adsorption of this compound on mild steel surface obeys Langmuir isotherm. Also the objective of this work is to attempt to find relationships between electronic structure and inhibition efficiency. The structural parameters, such as the frontier molecular orbital energies (EHOMO and ELUMO), gap of energy ΔE, from the molecule to iron as well as electronic parameters such as Mulliken atomic populations were calculated and discussed using the Density Functional Theory method (DFT).

Curcumin inhibits the development of food allergy by suppressing mast cell function in an NF-κB-dependent manner (HYP7P.308)

Abstract Mast cells play critical roles in the establishment of allergic responses to food antigens. We have previously shown that frequent ingestion of the curry spice curcumin, inhibits mast cell expansion and suppresses intestinal anaphylaxis in a murine model of ovalbumin (OVA)-induced food allergy. Here, we demonstrate that the protective effects of curcumin are conferred during the mast cell-dependent, OVA-challenge phase of the model and are mediated by inhibition of NF-κB activation. Exposure to curcumin during OVA-challenge, but not OVA-sensitization, results in inhibition of allergic diarrhea, intestinal mastocytosis and Th2 cytokine production. This suggests that while curcumin has limited inhibitory effects on Th2 sensitization, it has direct suppressive effects on mast cell homeostasis and function. Suppression of mast cell activation was also associated with inhibition of NF-κB in OVA-gavaged, curcumin-treated animals suggesting that the inhibitory effects of curcumin may be mediated in an NF-κB-dependent manner. In summary, our data demonstrate that curcumin inhibits allergic responses to food antigens by blocking NF-κB activation and suppression of mast cell-dependent responses.