Toxicity Of Curcumin Research Articles

Repeated dose, 28-day oral toxicity study of curcumin, anthocyanins, and sodium nitrite in Wistar rats

ObjectiveThe goal of the present study was to examine the repeated dose 28-day oral toxicity of curcumin, anthocyanins, and sodium nitrite in Wistar rats. MethodsFor this purpose, forty-eight male Wistar rats were randomly divided into 8 groups (n = 6 each), encompassing untreated controls and experimental groups treated with curcumin, anthocyanins, and sodium nitrite. Three rats from each group were sacrificed by cervical dislocation under di-ethyl ether anesthesia after 2 and 4 weeks of therapy, respectively. Blood samples were collected for serum chemistry. All of the animals' livers, hearts, and kidneys were removed and sent for histopathological examination. ResultsAfter two weeks of inquiry, certain groups displayed higher hematological values, while others had lower values compared to the control group. AST, CK, and LDH enzyme activity were higher in groups 2–8, but urea concentrations were higher in groups 6 and 8. After four weeks, the Hb, MCH, and MCHC values in group 4 were greater, as were the WBC levels in groups 4 and 6, whereas other groups had lower MCV and WBC values. The weekly body weight gain was insignificantly different between treatment groups. Throughout the experiment, none of the animals perished. Male rats' liver, kidney, and heart underwent histopathological changes after ingesting curcumin, sodium nitrite, and anthocyanin. ConclusionBased on the findings, rats were more detrimental when curcumin, sodium nitrite, and anthocyanin were ingested together than when they were consumed individually, as evidenced by histopathological abnormalities in the liver, kidneys, and heart.

Layer by layer self-assembly for coating a nanosuspension to modify drug release and stability for oral delivery

Layer-by-layer (LbL) modification is an effective way to tune the properties of particles. However, the traditional LbL process involves repeated washing steps which are not compatible with nanoparticles with a partial solubility. In this work, we demonstrate the use of a titration method for producing LbL coatings onto a nanosuspension of curcumin (a compound with a limited aqueous solubility). The aim of the work was to show how LbL can be used to enhance the release behaviour and stability of the curcumin in a nanosuspension form. Coated nanosuspension samples were produced using biocompatible and biodegradable polyelectrolytes, poly-l-arginine, and sodium alginate and was sizes approximately 500 nm. A stimuli-responsive nanosuspension was prepared by coating the nanosuspension with 5 layers of poly-l-arginine and alginate and Eudragit L100 as an outmost layer. The in vitro release of these nanosuspensions revealed that the use of a pH-responsive layer (Eudragit L100) as an outermost shell resulted in delay the release of curcumin (5%) in acidic pH and facilities its release in neutral pH (11%) over 72 h. Additionally, the bioaccessibility study showed that increasing the number of layers resulted in increasing the stability curcumin in nanosuspension when exposed to conditions that mimic the gastrointestinal tract from 20% for uncoated nanosuspension to 40% and 90% for 4-layered coated nanosuspension and stimuli-responsive (6-layered) coated nanosuspension, respectively. The cytotoxicity of LbL-coating of nanosuspension revealed a reduction in the toxicity of curcumin. This work shows how a titrated LbL modification approach could be used to tailor the stability and the release behaviour of nanosuspensions for oral drug delivery applications.

Analisis Potensi Farmakokinetik dan Toksisitas Pada Curcumin (Curcuma xanthorrhiza) Sebagai Brightening Terhadap Reseptor Protein Tirosinase Secara in Silico

Tyrosinase enzyme is an enzyme that plays an important role in melanin synthesis. This enzyme will oxidize the amino acid L-tyrosine into L- 3,4 dihydroxyphenylalanine (L-DOPA) and convert L-DOPA into DOPAquinone. Tyrosinase protein from Bacillus megaterium in complex with inhibitor kojic acid is the target protein that will interact with the ligand (Drug Candidate), Temulawak (Curcuma xanthorrhiza) is one of the medicinal plants of the Zingiberaceae family which is widely grown and used as a raw material for traditional medicine in Indonesia, the main content in Temulawak is curcumin which has antioxidant properties. Antioxidants in curcumin content can be used as ingredients for whitening preparations. In silico tests are used to predict pharmacokinetic activity and toxicity by docking using the Molegro Virtual Docker computer program. The receptor used was Protein Tyrosinase PDB code 3NQ1 with ligand KOJ_B_1351. Prediction of pharmacokinetic properties (ADME) and toxicity of Curcumin and Kojic Acid was performed using the pkCSM online tool program. Data analysis was performed by comparing the binding energy of docking results between Curcumin, Kojic Acid, and ligand on the target receptor. The in silico test results showed that the binding energy of Kurkumin =-142.766 kcal/mol, Kojic Acid = -60.6899 kcal/mol, and KOJ_B_1351 ligand =-62.266 kcal/mol. The results of in silico tests using the pkCSM online tool program show that Kurkumin compounds have good pharmacokinetic properties, and cause relatively low toxicity, and can be used as candidates for whitening materials.

Pharmacokinetic profiles, cytotoxicity, and redox metabolism of free and nanoencapsulated curcumin

To analyze the biodistribution, pharmacokinetics, and toxicity of curcumin, we made in silico predictions and performed in vitro tests to demonstrate the differences in the behavior of two cells types (peripheral blood mononuclear cells, PBMCs, and fibroblasts, HFF-1 cell line) treated with curcumin nanocapsule formulations and curcumin solution with respect to cytotoxic effects and redox metabolism. We generated in silico, ADME/Tox profile predictions of curcumin using computational tools. We produced and characterized Eudragit® L-100 and PCL nanocapsules containing curcumin using interfacial deposition of preformed polymer, evaluation of hemolytic potential in erythrocytes, cytotoxic capacity (MTT and dsDNA PicoGreen® assay), and influence on redox metabolism (nitric oxide and DCF production) of PBMCs and HFF-1 treated with curcumin nanoformulations and solution response curves. Computational results showed low biodistribution, no permeation at of the blood-brain barrier (BBB), discreet gastrointestinal absorption, a potential inhibitor of cytochrome P450 isoforms (CYP2C9 and CYP3A4), toxicity class IV, and immunomodulatory action. In vitro tests showed that cell type influenced curcumin behavior. For cytotoxicity, PBMCs showed a concentration-dependent standard, while HFF-1 cells showed that incubation time was an important variable. Redox interactions showed that nanocapsules induced NO production, and all treatments reduced DCF levels. We highlight the pleiotropic biological activities of curcumin and drug release models so that the therapeutic properties of this polyphenol might be better used. Finally, we emphasize that pharmacological safety must always be evaluated in drug delivery systems and, especially, for substances with multiple interaction pathways.

Curcumin promotes cholesterol efflux by regulating ABCA1 expression through miR-125a-5p/SIRT6 axis in THP-1 macrophage to prevent atherosclerosis.

To seek out the effect of curcumin on cholesterol efflux in THP-1 macrophages and clarify its specific mechanism. THP-1 macrophages were cultured with curcumin at different concentrations, followed by detection of the toxicity of curcumin to cells utilizing CCK-8 assay. Following culturing with serum-free ox-LDL, THP-1 macrophages were transfected with mi-miR-125a-5p, or in-miR-125a-5p, or pcDNA3.1-SIRT6, or si-SIRT6 for 24 hr, prior to treatment with curcumin at different concentrations. Oil red O staining was applied to examine the formation rate of foam cells, the kits were used for measuring intracellular lipid content of THP-1 macrophages, and the fluorescence detection kit for observing the cholesterol efflux rate. The expressions of miR-125a-5p, SIRT6, and ABCA1 were assayed by qRT-PCR and Western blot. ELISA was adopted to assess the contents of TNF-α, IL-6, and MCP-1. The interaction between miR-125a-5p and SIRT6 was evaluated by dual-luciferase reporter gene assay. The optimal dosage of curcumin could reduce foam cell formation and intracellular lipid content, and promote cholesterol efflux in THP-1 macrophages. Meanwhile, curcumin markedly suppressed the expression of miR-125a-5p and upregulated the expression of SIRT6. MiR-125a-5p negatively targeted SIRT6. Overexpression of SIRT6 partially reversed the inhibition role of miR-125a-5p mimic in the biological function of curcumin. Silencing of SIRT6 could partially reverse the effect of the miR-125a-5p inhibitor on the biological function of curcumin. urcumin could promote cholesterol efflux of THP-1 macrophages through miR-125a-5p/SIRT6 axis and regulate the expression of ABCA1.

Curcumin promotes oxidative stress, apoptosis and autophagy in H9c2 rat cardiomyoblasts

Curcumin, a polyphenol derived from Curcuma longa, has some adverse effects on heart; however, its toxic effects on cardiac cells are poorly understood. To evaluate the toxicity of curcumin on H9c2 rat cardiomyoblasts. To this, H9c2 cells were exposed to different concentrations of curcumin and proliferation, viability, cell cycle, oxidative stress, mitochondrial membrane potential (ΔΨm), death and autophagy were evaluated. Curcumin caused concentration-dependent inhibition of H9c2 cells proliferation and viability. A higher sub-G1 population was observed in cells treated with curcumin, which was related with phosphatidylserine translocation and increase of activated caspase-9, indicating apoptotic death. Curcumin induced oxidative stress and decreased ΔΨm causing mitochondrial dysfunction. Additionally, it promoted autophagy, revealed by higher LC3B and beclin-1 protein expression and mitophagy. Curcumin exhibited toxic effects in cardiac cells and further studies are required to validate its therapeutic potential and use as anti-inflammatory and anti-oxidant agent in the cardiovascular system.

Curcumin-loaded poly(ϵ-caprolactone) lipid-core nanocapsules: Evaluation of fetal and maternal toxicity

This study was designed to examine fetal and maternal toxicity of curcumin (CURC) loaded lipid-core nanocapsules (LNC) prepared with poly(ϵ-caprolactone) as a polymer, administered during the organogenesis period. Free CURC and CURC loaded-LNC (C-LNC) (2 mg/kg), blank LNC (B-LNC) and saline (CONTROL) were administered per oral route from the 7° to 13° gestational day (GD). Dams were evaluated daily for body weight gain, clinical signs, water and food intake. On 20° GD, dams were euthanized, organs were weighed and blood was collected for biochemical determinations. Fetal biometrics and external morphological anomalies were assessed. Also, were performed histopathological analysis of placenta and measurement of cytokines levels in placental and fetal liver tissues. All groups did not cause changes in dams during the pregnancy. Furthermore, treatments did not cause external morphological changes and delayed fetal development. Still, for histopathological analysis of placental tissue, treatments did not cause alterations in evaluated parameters. For cytokines levels, CURC and C-LNC caused a decrease in placental levels of TNF-α. Therefore, we have demonstrated that C-LNC did not cause toxicological effects (mother and fetus), in the same manner as pattern bioactive compound, proving to be a promising nutraceutical delivery system for maternal supplementation with CURC.

HSA-curcumin nanoparticles: a promising substitution for Curcumin as a Cancer chemoprevention and therapy.

Many solutions have been evaluated to deal with "chemotherapy and radiation-resistant cancer cells' as well as "severe complications of chemotherapy drugs". One of these solutions is the use of herbal compounds with antioxidant properties. Among these antioxidant compounds, curcumin is identified as the strongest one to inhibit cancerous cells proliferation. However, its clinical trials have encountered many constraints, because curcumin is insoluble in water and unstable in physiological conditions. To overcome these limitations, in this study, curcumin was conjugated with human serum albumin (HSA) and its effects on breast cancer cell lines were also measured. After making of HSA-curcumin nanoparticles (NPs) by the desolvation technique, they were characterized by the FTIR, DLS, TEM, and SEM method. At the end, its anticancer effects have been examined using MTT test and apoptosis assay. The FTIR graph confirmed that curcumin and HSA have been conjugated along with each other. Particles size was reported to be 220nm and 180nm by DLS and SEM, respectively. The zeta potential of HSA-curcumin NPs was -7mV, while it was -37mV for curcumin. The MTT and apoptosis assay results indicated that the toxicity of HSA-curcumin NPs on the normal cell are less than curcumin; however, its anti-cancer effects on the cancer cells are much greater, compared to curcumin. HSA-curcumin NPs increase curcumin solubility in water as well as its stability in physiological and acidic conditions. These factors have the ability of overwhelming the limitations on using curcumin alone, and they could result in a significant increase in the toxicity of curcumin on the cancer cells without increasing its toxicity on the normal cells. Grapical abstract.

Abstract C33: Effects of curcumin on pancreatic ductal adenocarcinoma

Abstract Without an early method of diagnosis or effective treatment plan, the prognosis for pancreatic ductal adenocarcinoma (PDAC) is grim, which begs for the development of additional treatment options. The plant-derived chemical, curcumin, has recently shown some promise as a potential therapy when tested in xenograft models of PDAC, glioblastoma, lung, breast, cervical, and colon tumors and is currently being tested in early clinical trials of certain cancers. However, efficacy studies against PDAC have not included preclinical mouse models with an intact immune system. To address the potential complication of a fully functional immune system on curcumin effectiveness, we assessed the effects of curcumin on murine PDAC cell lines both in vitro and in vivo. Murine PDAC lines were previously derived from genetically engineered KrasG12D; Trp53R172H; Pdx-1 Cre (KPC) mice, which spontaneously produce metastatic PDAC that closely mimics human disease. The dose- and time-dependent toxicity of curcumin was assessed using various cell lines in vitro, and our findings support previously published results. To assess effectiveness in vivo, tumor cells were implanted subcutaneously into syngeneic, C57Bl/6J mice. Once tumors were established, curcumin (or vehicle alone) was administered via intraperitoneal (i.p.) or intratumoral injection. Treatment efficacy was assessed by measuring tumor growth and the overall survival of mice. We found that curcumin treatment had no impact on tumor growth or overall survival of immunocompetent mice. To circumvent potential solubility issues common to curcumin and illustrate the importance of the immune system in treatment resistance, we repeated our in vivo studies using curcumin encapsulated in liposomes. In addition, we used T cell-depleting antibodies for a subset of mice to mimic athymic mice used in previously published xenograft models. T-cell depletion was verified prior to tumor cell implantation by flow cytometry. Once tumors were established, liposomal curcumin or mock treatment was administered via i.p. injection. For T cell-depleted mice, we found that treatment with liposomal curcumin stalled tumor growth and increased overall survival compared to mock treated mice. For T cell-replete mice, we found that treatment with liposomal curcumin had no impact on tumor growth or overall survival compared to mock treated mice, which agrees with our findings. Taken together, our data suggest that the presence of T cells causes a difference in responsiveness to curcumin in vivo. This finding warrants additional studies in order to understand this mechanism and enhance its potential success in the clinic. Citation Format: Adrianna M. Vaskas, Joseph A. Fraietta, Kristen B. Long. Effects of curcumin on pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C33.

Curcumin Attenuates Adipogenesis by Inducing Preadipocyte Apoptosis and Inhibiting Adipocyte Differentiation.

Patients with metabolic syndrome are at an increased risk of developing type 2 diabetes and cardiovascular diseases. The principal risk factor for development of metabolic syndrome is obesity, defined as a state of pathological hyperplasia or/and hypertrophy of adipose tissue. The number of mature adipocytes is determined by adipocyte differentiation from preadipocytes. The purpose of the present study is to investigate the effects of curcumin on adipogenesis and the underlying mechanism. To examine cell toxicity of curcumin, 3T3-L1 preadipocytes were treated with 0–50 µM curcumin for 24, 48, or 72 h, then cell viability was measured using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The effect of curcumin on the cell cycle was determined by flow cytometry. Curcumin-induced cell apoptosis was determined by the TUNEL assay and curcumin-induced caspase activation was measured by immunoblotting. The effect of curcumin on adipocyte differentiation was determined by measuring mitotic clonal expansion (MCE), expression of adipogenic transcription factors, and lipid accumulation. Results showed the viability of preadipocytes was significantly decreased by treatment with 30 µM curcumin, a concentration that caused apoptosis in preadipocytes, as assessed by the TUNEL assay, and caused activation of caspases 8, 9, and 3. A non-cytotoxic dose of curcumin (15 µM) inhibited MCE, downregulated the expression of PPARγ and C/EBPα, prevented differentiation medium-induced β-catenin downregulation, and decreased the lipid accumulation in 3T3-L1 adipocytes. In conclusion, our data show that curcumin can induce preadipocyte apoptosis and inhibit adipocyte differentiation, leading to suppression of adipogenesis.

Long-term biodistribution and toxicity of curcumin capped iron oxide nanoparticles after single-dose administration in mice

AimIn this study, in vivo biodistribution, clearness and toxicity of curcumin capped iron oxide nanoparticles (Cur-IONPs) were addressed in different body organs. Materials and methodsThe physicochemical properties of the prepared Cur-IONPs were investigated. Long term (3 weeks) biodistribution, clearness and toxicity were assessed for a single-dose administration of Cur-IONPs (5 mg/kg). The iron content in liver, kidney, spleen and brain was quantified using atomic absorption spectroscopy. Serum biochemical parameters were also measured. Key findingsThe integrated in vivo results demonstrated that Cur-IONPs was mostly taken up in the liver and spleen reaching its highest levels on days 1 and 2, respectively. In the brain, the results showed significant accumulation of Cur-IONPs between 1 h to 1-day post injection. This represented the successful penetration Cur-IONPs across the blood-brain barrier. Serum biochemical analysis demonstrated a temporal disturbance in the performance of body organs. Also, the body weights showed no alteration throughout the experiment. SignificanceIt has been deduced that the promising green synthesized Cur-IONPs as an “All in One” nanoplatform is safe enough to be used in diagnostic and therapeutic purposes.

Interactive anticancer effect of nanomicellar curcumin and galbanic acid combination therapy with some common chemotherapeutics in colon carcinoma cells.

In the current investigation, we aimed to study the combined cytotoxicity of curcumin, as a nanomicellar formulation, and galbanic acid (Gal), dissolved in DMSO against the murine C26 and human Caco-2 colon carcinoma cells. Further, curcumin potential for cisplatin and doxorubicin (Dox) co-therapy was studied. The combined cytotoxic effect of these phytochemicals at varying dose ratios were examined using the MTT colorimetric assay. Moreover, the time-dependent toxicity of curcumin, cisplatin, Dox, and pegylated liposomal Dox (Doxil) was determined. The interactive anti-proliferative behavior of these compounds was examined using the CompuSyn software. Nanomicellar curcumin showed considerable cytotoxicity in C26 cells 24 hr post-treatment. Co-treatment of cells with curcumin nanomicelles: Gal had a synergistic effect in C26 (at 10:1 molar ratio), and Caco-2 (at 1:5 molar ratio) cell lines in cell cultures. Nanomicellar curcumin showed strong and mild synergistic inhibitory effects in C26 cells when co-administered with Doxil and cisplatin, respectively. Curcumin nanomicelles and Gal had a synergistic effect in C26 and Caco-2 cell lines. It is speculated that nanomicellar curcumin shows synergistic cancer cell killing if administered 24-hr post-injection of Doxil and cisplatin.

Rapid and sensitive electrochemical detection of anticancer effects of curcumin on human glioblastoma cells

Curcumin, a hydrophobic polyphenol derived from the Curcuma longa plant, is known to affect various cellular activities such as cell cycle regulation, oncogene expression, apoptosis, and mutagenesis, and is thus considered a promising candidate for an anticancer drug. In this study, we report the development of a platform that is effective to evaluate the anticancer effects of curcumin on one of the most aggressive tumors, glioblastoma. To generate platforms that satisfy both rapid and sensitive detection of curcumin effects, the surface of transparent conductive electrodes was first modified with two different types of electrocatalytic materials, gold and silver nanoparticles, with different densities. Among the four different substrates fabricated, a high-density gold nanostructure film (HDGN) in combination with peptide modification was found to be the best in terms of measuring the electrochemical signals of human glioblastoma cells (U87MG). The electrical signals of U87MG cells (Epc = -0.05 V vs. Ag/AgCl), obtained from cyclic voltammetry, showed excellent linearity (R2 = 0.99) within the range of 20,000–60,000 cells, and were thus demonstrated to be suitable for assessment of curcumin anticancer effects on U87MG cells. A clear curcumin toxicity on human glioblastoma was found with concentrations higher than 30 μM, which was consistent with the results obtained from cell counting kit-8 (CCK-8) assays. Remarkably, unlike the conventional colorimetric methods, the HDGN/peptide-modified platform was completely free from a possible signal interference from curcumin (absorbance: 425 nm). In addition, it enabled rapid (detection time < 3 min) and precise (limit of quantification: 9379 cells/chip) assessments of the potential toxicity of curcumin for cancer cells. Hence, we conclude that the developed platform is highly promising for use as a high-throughput screening tool for the discovery of new types of less toxic plant-derived natural anticancer drugs.

Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy.

Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti-inflammatory drugs such as nonsteroidal anti-inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well-documented herbal anti-inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor κB (NF-κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF-κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis.

Curcumine (Turmeric – Curcuma longa) as a Supportive Phytotherapeutic Treatment in Oncology

Turmeric (Curcuma longa) is mainly known as a constituent of curry spice. The main active ingredient, responsible for most of its biological effects, is the polyphenol curcumin. This review aims to provide a comprehensive overview of studies evaluating the benefits of therapeutic curcumin use in oncology. Preclinical studies provide information on the mechanism of action and potential toxicity of curcumin. Clinical studies have so far focused mainly on safety, pharmacokinetics, and determination of the optimal dose of curcumin. However, there are a growing number of trials evaluating the anti-tumor and oncopreventive effects of curcumin and its effect in alleviating the adverse effects of chemotherapeutics and radiotherapy. So far, the results have been optimistic and should encourage further research. The main problem associated with curcumin treatment is its low oral bioavailability, which means it must administrated at high doses to be effective. Therefore, curcumin is more appropriate as a local treatment for areas such as the intestine, mucous membrane, or the skin, where there is no need for a strong systemic effect. Curcumin has a good safety profile when used up to several grams. Curcumin can also be used as a food supplement for people at increased risk of oncological disease, such as heavy smokers or those with pre-cancerous lesions. Due to its good safety profile, curcumin can be recommended to oncological patients who request a natural treatment.Key words: phytotherapy - drug-herb interactions - cancer - adverse effects - curcumine - turmeric - Curcuma longaSubmitted: 20. 7. 2017Accepted: 25. 9. 2017 This publication was written at Masaryk University as part of the project "Behavioural psychopharmacology and pharmacokinetics in preclinical drug research", number MUNI/A/1132/2017 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2018. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

The curcumin derivative WZ35 activates ROS-dependent JNK to suppress hepatocellular carcinoma metastasis.

Tumor metastasis is the leading cause of cancer death; due to the progress made in the elucidation of the mechanism of cancer cell metastasis, there is hope for patients with severe stages of cancer. Curcumin, as a novel anti-cancer drug, has been applied in cancer therapy; however, the toxicity of curcumin hinders its application. Herein, we constructed a novel derivative, WZ35, and evaluated its metastatic inhibition properties in vitro and in vivo. CCK-8 assay was performed to evaluate the tumor suppressive activity of WZ35. Cell apoptosis was detected by flow cytometry analysis. Transwell cell migration assay and RTCA were used to detect cell migration in mock and WZ35-treated cells. Western blotting was performed to analyze molecular alteration with different treatments. In this study, we found that curcumin and its derivative WZ35 could dramatically suppress proliferation, invasion, and migration of the hepatocellular HCCLM3, HepG2, and Huh7 cancer cells. Moreover, the cancer cell metastatic markers MMP-2, MMP-9, and N-cadherin were decreased, and E-cadherin was up-regulated. In addition, our data show that WZ35 promotes ROS-dependent JNK activation that is essential for WZ35-caused cell metastasis suppression. Moreover, the NAC and JNK inhibitor SP600125 could dramatically reverse WZ35-caused MMP-2, MMP-9, and N-cadherin reduction and E-cadherin up-regulation. We have also found that WZ35 exhibits powerful anti-metastasis activity of HCCLM3 in vivo. In conclusion, our data indicated that WZ35 could be a candidate for the treatment of metastatic liver cancer patients.

Overdose Intake of Curcumin Initiates the Unbalanced State of Bodies.

Curcumin is the major active component of turmeric and widely used as a spice and coloring agent in food. However, its safety evaluation has been little investigated. To evaluate the 90-day subchronic toxicity of curcumin in rats, its general observation, clinical biochemistry, pathology, and metabolomics were evaluated. The results showed that curcumin induced liver injury through the generation of the overexpression of reactive oxygen species (ROS) and pro-inflammatory cytokines IL-6 and the decreases of the levels of antioxidant enzyme SOD and detoxified enzyme GST. Meanwhile, for the self-protection of rats, curcumin treatment activated the transcription of Nrf-2 and elevated the expression of HO-1 to reduce tissue damage. Furthermore, curcumin significantly increased key mRNA levels of HK2, PKM2, LDHA, CES, Cpt1, Cpt2, FASN, and ATP5b and decreased levels of GLUT2 and ACC1 to enhance glycolysis and inhibit lipid metabolism and TCA cycle. Therefore, overdose or long-term intake of curcumin could initiate the unbalanced state of bodies through oxidative stress, inflammation, and metabolic disorders, which induces liver injury. Intermittent administration of curcumin is necessary in our daily lives.

Curcumin-p-sulfonatocalix[4]resorcinarene (p-SC[4]R) interaction: thermo-physico chemistry, stability and biological evaluation

The target to enhance the solubility, bioavailability, stability and anti-oxidant activity, as well as the decrease in the acute oral toxicity of curcumin by 1 : 1 curcumin–p-SC[4]Rinclusion complexation.

Sonodynamic inactivation of methicillin-resistant Staphylococcus aureus in planktonic condition by curcumin under ultrasound sonication

Methicillin-Resistant Staphylococcus aureus (MRSA) is an important cause of difficult-to-treat infections. The present study aims to investigate sonodynamic inactivation of MRSA in planktonic condition using curcumin under ultrasound sonication. Dark toxicity of curcumin to MRSA was investigated to choose the concentration range of curcumin used in the study. The uptake of curcumin in MRSA was observed before ultrasound sonication. After sonication colony forming units (CFUs) and bacterial viability were investigated using fluorescence assay. Additionally, chromosomal DNA fragmentation was also analyzed. Curcumin showed no dark toxicity to MRSA in the concentration range of⩽500μM. The maximum uptake of curcumin in MRSA occurred in 50min after curcumin incubation. Counting of CFUs showed that curcumin had significantly sonodynamic killing effect on MRSA in a curcumin dose-dependent manner, and 5-log reduction in CFU was observed after curcumin treatment (40μM) at room temperature in the dark for 50min followed by exposure to ultrasound with intensity of 1.56W/cm2 for 5min. The ratio of green-fluorescent intensity to red-fluorescent intensity was obviously decreased after curcumin treatment under ultrasound sonication. No significant change in chromosomal DNA was found in the cultured MRSA after the combined treatment of curcumin and ultrasound. These results demonstrated that sonodynamic action of curcumin had significant inactivation of MRSA in planktonic condition.

Curcumin may impair iron status when fed to mice for six months

Curcumin has been shown to have many potentially health beneficial properties in vitro and in animal models with clinical studies on the toxicity of curcumin reporting no major side effects. However, curcumin may chelate dietary trace elements and could thus potentially exert adverse effects. Here, we investigated the effects of a 6 month dietary supplementation with 0.2% curcumin on iron, zinc, and copper status in C57BL/6J mice. Compared to non-supplemented control mice, we observed a significant reduction in iron, but not zinc and copper stores, in the liver and the spleen, as well as strongly suppressed liver hepcidin and ferritin expression in the curcumin-supplemented mice. The expression of the iron-importing transport proteins divalent metal transporter 1 and transferrin receptor 1 was induced, while hepatic and splenic inflammatory markers were not affected in the curcumin-fed mice. The mRNA expression of other putative target genes of curcumin, including the nuclear factor (erythroid-derived 2)-like 2 and haem oxygenase 1 did not differ between the groups. Most of the published animal trials with curcumin-feeding have not reported adverse effects on iron status or the spleen. However, it is possible that long-term curcumin supplementation and a Western-type diet may aggravate iron deficiency. Therefore, our findings show that further studies are needed to evaluate the effect of curcumin supplementation on iron status.