Curcumin alleviated oxidation stress injury by mediating osteopontin in nephrolithiasis rats

Purpose: To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG). Methods: 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. Results: 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. Conclusion: Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.

A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications / 中西医结合学报

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235.

Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress / 中华危重病急救医学

OBJECTIVE@#To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS).@*METHODS@#A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1β (IL-1β) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope.@*RESULTS@#Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (μg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1β [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1β mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05).@*CONCLUSIONS@#Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.

Efficacy of Curcumin on Cognitive Function Scores in Women with Premenstrual Syndrome and Dysmenorrhea: A Triple-Blind, Placebo-Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome (PMS) and dysmenorrhea.@*METHODS@#A randomized, triple-blind, placebo-controlled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days (7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups.@*RESULTS@#Administration of curcumin was associated with a significant increase in memory score (P=0.002), inhibitory control and selective attention (P=0.020), and total cognitive ability task (P=0.024). In addition, significant increments were found in scores of memory (3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively; P=0.035), inhibitory control and selective attention (3.0±3.7 vs. 0.4±3.7; P=0.027) and total cognitive abilities (8.3±12.3 vs. 2.2±12.4; P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial.@*CONCLUSION@#Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention. (Registration No. IRCT20191112045424N1, available at: https://www.irct.ir ).

Establishment of a novel co-cultured liver cancer model based on tumor microenvironment / 中华肿瘤杂志

Objective: To construct a new co-cultured liver cancer research model composed of activated hepatic stellate cells (aHSC) and liver cancer cells, explore the efficacy difference between it and traditional model, so as to establish a liver cancer research model in vitro and in vivo that can reflect the real clinical efficacy. Methods: A new co-culture model of liver cancer consisting of aHSC and liver cancer cells was constructed. The differences in efficacy between the new co-culture model and the traditional single cell model were compared by cytotoxicity test, cell migration test, drug retention test and in vivo tumor inhibition test. Western blot was used to detect the drug-resistant protein P-gp and epithelial-mesenchymal transition-related proteins. Masson staining was used to observe the deposition of collagen fibers in tumor tissues of tumor-bearing mice. CD31 immunohistochemical staining was used to observe the microvessel density in tumor tissues of tumor-bearing mice. Results: The cytotoxicity of single cell model and co-culture model was dose-dependent. With the increase of curcumin (CUR) concentration, the cell viability decreased, but the cell viability of single cell model decreased faster than that of co-culture model. When the concentration of CUR was 10 μg/ml, the cell viability of the co-culture model was 62.3% and the migration rate was (28.05±3.68)%, which were higher than those of the single cell model [38.5% and (14.91±5.92)%, both P<0.05]. Western blot analysis showed that the expressions of P-gp and vimentin were up-regulated in the co-culture model, which were 1.55 and 2.04 fold changes of the single cell model, respectively. The expression of E-cadherin was down-regulated, and the expression level of E-cadherin in the single cell model was 1.17 fold changes of the co-culture model. Drug retention experiment showed that the co-culture model could promote drug efflux and reduce drug retention. In vivo tumor inhibition experiment showed that the m-HSC+ H22 co-transplantation model had faster tumor growth and larger tumor volume than those of the H22 single cell transplantation model. After CUR treatment, the tumor growths of m-HSC+ H22 co-transplantation model and H22 single cell transplantation model were inhibited. Masson staining showed that the deposition of collagen fibers in tumor tissues of m-HSC+ H22 co-transplantation model mice was more than that of H22 single cell transplantation model. CD31 immunohistochemical staining showed that the microvessel density in tumor tissue of m-HSC+ H22 co-transplantation model was higher than that of H22 single cell transplantation model. Conclusions: The aHSC+ liver cancer cell co-culture model has strong proliferation and metastasis ability and is easy to be resistant to drugs. It is a new type of liver cancer treatment research model superior to the traditional single cell model.

Synergistic effects of dendrosomal nanocurcumin and oxaliplatin on oncogenic properties of ovarian cancer cell lines by down-expression of MMPs

BACKGROUND: Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. METHODS: and materials In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. RESULTS: Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. CONCLUSIONS: The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.

Curcumin Mediated Gold Nanoparticles and Analysis of its Antioxidant, Anti-inflammatory, Antimicrobial Activity Against Oral Pathogens

ABSTRACT Objective: To green synthesise gold nanoparticles using curcumin and to analyse its antioxidant, anti-inflammatory, and antimicrobial activity among oral pathogens. Material and Methods: Biosynthesised Curcumin Gold nanoparticles (CuAuNP) were evaluated by UV-visible spectrophotometer (UV-Vis), Transmission Electron Microscopy (TEM), and evaluation of antioxidant, anti-inflammatory and antibacterial activity against oral pathogens. Results: Synthesized CuAuNP were characterized using UV-visible spectrophotometry and showed peak absorption at 530nm. CuAuNp showed a 90.3% maximum scavenging ability of DPPH at a concentration of 50 μg/mL. CuAuNP exhibited 79.6 % of the highest anti-inflammatory activity at 50μg/mL than the standard drug diclofenac. TEM image clearly showed uniformly dispersed spherical-shaped gold nanoparticles with a size of about 20 nm. The biosynthesized nanoparticle was tested for its antimicrobial effect, and it showed a potent effect against S. aureus, E. faecalis, and C. albicans at 100µg/ mL. Enterococcus faecalis has a maximum zone of inhibition of 14 mm at 100µg/ mL of CuAuNp. Among gram-positive bacteria, a maximum zone of inhibition of 12 mm at 100µg/ mL was seen in S. aureus compared to S mutans. Candida albicans showed a maximum zone of inhibition of 18 mm at 25 μg/mL of CuAuNp. Conclusion: Curcumin-mediated gold nanoparticles with 20 nm size were effective and had strong antioxidant and anti-inflammatory activity at 50µg/ mL, antimicrobial action inhibiting microbes at 100µg/mL concentration that can be used in treating various Oral mucosal lesions.

Study on the mechanism of curcumin in the treatment of periodontitis through network pharmacology and mole-cular docking / 华西口腔医学杂志

OBJECTIVES@#This study aims to explore the therapeutic targets of curcumin in periodontitis through network pharmacology and molecular docking technology.@*METHODS@#Targets of curcumin and periodontitis were predicted by different databases, and the protein-protein interaction (PPI) network constructed by String revealed the interaction between curcumin and periodontitis. The key target genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was performed to analyze the binding potential of curcumin to periodontitis.@*RESULTS@#A total of 672 periodontitis-related disease targets and 107 curcumin-acting targets were obtained from the databases, and 20 key targets were screened. The GO and KEGG analyses of the 20 targets showed that curcumin might play a therapeutic role through the hypoxia-inducible factor (HIF)-1 and parathyroid hormone (PTH) signaling pathways. Molecular docking analysis showed that curcumin had good binding potential with multiple targets.@*CONCLUSIONS@#The potential key targets and molecular mechanisms of curcumin in treating periodontitis provide a theoretical basis for new drug development and clinical applications.

Curcumin-rich extract from Central Brazil Curcuma longa protects human umbilical vein endothelial cells under oxidative stress / Extrato rico em Curcumina do Brasil Central Curcuma longa protege células endoteliais de veias umbilicais humanas sob estresse oxidativo

INTRODUCTION: In vascular diseases, the interruption of the local blood flow and the subsequent reperfusion of oxygen can cause deleterious oxidative effects on the cells. Turmeric (Curcuma longa L.) presents the capacity to neutralize free radicals along with preventive and therapeutic effects for several diseases. OBJECTIVE: To analyze the bioactive compounds and the antioxidant capacity of the ethanolic extract of Curcuma (EEC), to evaluate its effect on human umbilical vein endothelial cells, and to analyze its effect on cellular signaling pathways. METHODS: Cells were exposed to different concentrations of EEC for 24, 48, and 72 h. Folin-Ciocalteau test, HPLC-Fluorescence analysis, and DPPH method were used to determine the phenolic compounds, curcumin content, and antioxidant action, respectively; the tetrazolium salt reduction to obtain cell viability, cytotoxicity, and the concentration that inhibits 50% of cell viability; and the immunocytochemistry technique to analyze the expression of caspase3, SIRT1, and mTOR. RESULTS: We found the presence of polyphenols in the classes of phenolic acids and curcuminoids in EEC, with 16.7% curcumin content. The number of antioxidants needed to reduce the initial DPPH concentration by 50% was 18.1 µmol/g. The extract mitigated cell damage at a dosage of 100 µg/ml, decreased the immunoexpression of caspase3, and promoted the signaling of the SIRT1 and mTOR survival pathways. CONCLUSION: EEC had a protective effect on human umbilical vein endothelial cells, subjected to oxidative stress, with decreased apoptosis (caspase3) at lower concentrations, cytoprotection by maintaining essential cell functions (mTOR), and signaling of the survival pathway (SIRT1).

INTRODUÇÃO: Em doenças vasculares, a interrupção do fluxo sanguíneo locale subsequente reperfusão de oxigênio pode causar efeitos deletérios e danos irreparáveis às células. Curcuma (Curcuma longa L.) neutraliza radicais livres além de apresentar efeitos preventivos e terapêuticos. OBJETIVO: Caracterizar os compostos bioativos e a capacidade antioxidante do extrato etanólico de cúrcuma (EEC); avaliar seu efeito nas células endoteliais da veia umbilical humana, e analisar a expressão de vias de sinalização celular. MÉTODOS: As células foram expostas a diferentes concentrações de EEC por 24, 48 e 72 horas. Utilizamos o teste de Folin-Ciocalteau, análise por HPLC-Fluorescência e método DPPH para determinar os compostos fenólicos, conteúdo de curcumina e ação antioxidante, respectivamente; o método de redução de tetrazólio para viabilidade celular, a citotoxicidade e a concentração que inibe 50% da viabilidade celular; e a técnica de imunocitoquímica para analisar a expressão de caspase3, SIRT1 e mTOR. RESULTADOS: Observou-se presença de polifenóis nas classes de ácidos fenólicos e curcuminóides no EEC, com teor de curcumina de 16,7%. A quantidade de antioxidante necessária para reduzir a concentração inicial de DPPH em 50% foi de 18,1 µmol/g. O extrato mitigou o dano celular na dosagem de 100 µg/ml, diminuiu a imunoexpressão da caspase3 e promoveu a sinalização das vias de sobrevivência SIRT1 e mTOR. CONCLUSÃO: O EEC teve efeito protetor nas células endoteliais de veia umbilical humana, submetidas ao estresse oxidativo, com diminuição da apoptose (caspase3) em concentrações mais baixas, citoproteção pela manutenção das funções celulares essenciais (mTOR) e sinalização da via de sobrevivência (SIRT1).

Activity of curcumin against human cytomegalovirus infection in vitro / 生物医学工程学杂志

This study aimed to investigate the effect of curcumin (Cur) against human cytomegalovirus (HCMV) in vitro. Human embryonic lung fibroblasts were cultured in vitro. The tetrazolium salt (MTS) method was used to detect the effects of Cur on cell viability. The cells were divided into control group, HCMV group, HCMV + (PFA) group and HCMV + Cur group in this study. The cytopathic effect (CPE) of each group was observed by plaque test, then the copy number of HCMV DNA in each group was detected by quantitative polymerase chain reaction (qPCR), and the expression of HCMV proteins in different sequence was detected by Western blot. The results showed that when the concentration of Cur was not higher than 15 μmol/L, there was no significant change in cell growth and viability in the Cur group compared with the control group (P>0.05). After the cells were infected by HCMV for 5 d, the cells began to show CPE, and the number of plaques increased with time. Pretreatment with Cur significantly reduced CPE in a dose-dependent manner. After the cells were infected by HCMV, the DNA copy number and protein expression gradually increased in a time-dependent manner. Pretreatment with Cur significantly inhibited HCMV DNA copies and downregulate HCMV protein expression levels in a concentration-dependent manner, and the difference was statistically significant (P<0.05). In conclusion, Cur may exert anti-HCMV activity by inhibiting the replication of HCMV DNA and down-regulating the expression levels of different sequence proteins of HCMV. This study provides a new experimental basis for the development of anti-HCMV infectious drugs.

Curcuma longa extract protects against 5-fluorouracil-induced oral mucositis in hamsters

Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1ß and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (p˂0.05), and decreased IL-1ß (p˂0.05) and TNF-α (p˂0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.

In vitro release mechanism and cytotoxic behavior of curcumin loaded casein nanoparticles

Abstract In the recent past, drug delivery through nanoparticles is considered an effective tool to treat various diseases. Biopolymeric nanoparticles such as protein based nanoparticles have vital role as drug carrier as it is non-antigenic, and easily biodegradable. Curcumin, plant polyphenolic anticancerous compound was loaded into the casein nanoparticles by coacervation method. Particle size and surface charge of spherical casein nanoparticles as observed to be 201.4 nm and -86.9 mV. The loading efficiency of curcumin loaded casein nanoparticles was found to 85.05 %. In vitro drug release was performed at different pH (7.4 and 3.0), and the cumulative release was observed to be 24.8 and 20.13% and at different temperatures (25°C and 37°C), the cumulative release was observed to be 24.8 and 28.60 % respectively in 48 h. Curcumin release from casein nanoparticles was shown to be in a steady, and prolonged rate. The nanoparticles were observed to have an effective antimocrobial activity than curcumin in free form. The drug loaded casein nanoparticles were found to be potent particles to protect cells from hydrogen peroxide and UV light damage. The cytotoxic activity of nanoparticles on MCF7 and A549 cells were assayed and was observed to have an IC50 value of 609 and 825.2µg/ml. Cell death was observed to be through apoptosis, accompanied by DNA fragmentation.

Curcumin solid dispersion based on three model acrylic polymers: formulation and release properties

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Curcumin nanoliposomes mitigate wound tissue inflammatory response caused by tooth extraction

Abstract Curcumin is a plant-derived compound with polypharmacological properties that are hampered by its poor solubility, fast degradation, etc. Wound closure complications that follow tooth extraction are numerous, and relatively frequently additional treatment is needed to prevent unwanted process chronification. The present study aims to compare the effects of free and the nanoliposome-encapsulated curcumin on tooth extraction wound closure. The experiments were performed on Wistar rats where both forms of curcumin were applied topically on a tooth extraction wound for seven days. Changes in tissue oxidative stress (malondialdehyde and oxidized proteins concentrations, and catalase activity) and inflammation (nitric oxide levels and myeloperoxidase activity) related parameters were studied three and seven days following the tooth extraction. Also, the extent of pathohistological changes and osteopontin immunohistochemical expression were studied. The obtained results indicate that both forms of curcumin prevent an increase in oxidative stress and inflammation-related parameters in the studied samples at 3-and 7-day time points. Additionally, we found that curcumin diminished tissue inflammatory response and osteopontin expression, while at the same time it caused faster granulation tissue maturation. The encapsulation of curcumin in nanoliposomes proved to be better in improving the extraction wound healing process than the free curcumin, giving this formulation a potential in the pharmaceutical industry.

Effect of curcumin on acute chronic kidney disease due to ischemia-reperfusion syndrome / Efecto de la curcumina en la enfermedad renal crónica agravada por el síndrome de isquemia-reperfusión / Efeito da curcumina na doença renal crônica agudizada pela síndrome isquemia-reperfusão

ABSTRACT Objective: To evaluate the effect of curcumin on renal function, hemodynamics, and renal oxidative profile of rats with chronic kidney disease (CKD) subjected to renal ischemia-reperfusion injury (IRI). Methods: Wistar rats, 250-300 g, distributed in four groups: Sham (n = 5), CKD simulation; CKD (n = 5), 5/6 renal ablation for CKD induction; CKD + IRI (n = 5), CKD and renal pedicle clamping for 30 minutes; and CKD + IRI+curcumin (n = 5), CKD + IRI, curcumin administration 30 mg/kg/day, orally, for 10 days. Renal function (inulin clearance, urine flow, plasma creatinine), hemodynamics (blood pressure), and oxidative profile (peroxides, TBARS, and urine nitrate, non-protein soluble thiols in renal tissue) were evaluated. Results: The CKD + IRI + curcumin group showed increased inulin clearance and reduced plasma creatinine, decreased RVR and increased RBF, decreased oxidative metabolites in urine and increased thiols in renal tissue when compared with the CKD + IRI group. Conclusion: The treatment with curcumin preserved renal function and hemodynamics of animals with acute CKD, improving oxidative profile, with reduction of oxidants and preservation of antioxidant reserve.

RESUMEN Objetivo: Evaluar el efecto de la curcumina sobre la función renal, hemodinámica y el perfil oxidativo renal en ratas con enfermedad renal crónica (ERC) sometidas a isquemia-reperfusión renal (I/R). Métodos: Ratas Wistar, entre 250-300 g, divididas en cuatro grupos: Sham (n = 5), simulación de ERC; ERC (n = 5), ablación de 5/6 de los riñones para inducción de ERC; ERC + I/R (n = 5), ERC y pinzamiento del pedículo renal durante 30 minutos; y ERC + I/R + curcumina (n = 5) y ERC + I/R, administración de curcumina 30 mg/kg/día, vía oral, durante 10 días. Se evaluaron la función renal (clearance de inulina, flujo urinario, creatinina plasmática), hemodinámica (presión arterial) y el perfil oxidativo (peróxidos, TBARS y nitrato urinario, tioles solubles no proteicos en tejido renal). Resultados: El grupo ERC + I/R + curcumina tuvo un aumento en el clearance de inulina y disminución de creatinina plasmática, disminución de la RVR y aumento del FSR, disminución de metabolitos oxidativos en orina y aumento de tioles en el tejido renal en comparación con el grupo ERC + I/R. Conclusión: El tratamiento con curcumina preservó la función renal y la hemodinámica de los animales con ERC agravada, promoviendo una mejora en el perfil oxidativo, con reducción de oxidantes y preservación de la reserva antioxidante.

RESUMO Objetivo: Avaliar o efeito da curcumina na função renal, hemodinâmica e perfil oxidativo renal de ratos com doença renal crônica (DRC) submetidos a isquemia-reperfusão renal (I/R). Métodos: Ratos Wistar, 250-300 g, distribuídos em quatro grupos: Sham (n = 5), simulação da DRC; DRC (n = 5), ablação de 5/6 dos rins para indução de DRC; DRC + I/R (n = 5), DRC e clampeamento do pedículo renal por 30 minutos; DRC + I/R + curcumina (n = 5) e DRC + I/R, administração de curcumina 30 mg/kg/dia, via oral, por 10 dias. Foram avaliadas a função renal (clearance de inulina, fluxo urinário, creatinina plasmática), hemodinâmica (pressão arterial) e perfil oxidativo (peróxidos, TBARS e nitrato urinário, tióis solúveis não proteicos no tecido renal). Resultados: O grupo DRC + I/R + curcumina apresentou elevação do clearance de inulina e redução da creatinina plasmática, diminuição da RVR e aumento do FSR, diminuição de metabólitos oxidativos na urina e aumento dos tióis no tecido renal quando comparado ao grupo DRC + I/R. Conclusão: O tratamento com curcumina preservou a função e hemodinâmica renal dos animais com DRC agudizada, promovendo melhora no perfil oxidativo, com redução de oxidantes e preservação de reserva antioxidante.

The potential inhibitory impact of curcumin, epigallocatechin gallate and their combinations on infectious bronchitis virus in vivo

Aims@#Infectious bronchitis virus (IBV) is a highly contagious, acute viral respiratory disease that mostly affects chickens. The poultry sector has suffered enormous losses as a result of IBV. Currently, live attenuated vaccines are routinely used to prevent and control IBV. However, due to the enormous genetic variety, vaccinations are becoming ineffective, with low cross-protection effects among vaccine serotypes. The present study aimed at investigating the possible antiviral effects of curcumin, epigallocatechin gallate (EGCG) and their mixtures against IBV in vivo.@*Methodology and results@#Curcumin, EGCG and their combinations were administered to infected and uninfected chicken groups and viral load titers were determined by real-time PCR. The clinical symptoms of both the negative and positive control groups were also compared. Finally, the trachea tissues of each group were examined histopathologically. According to our findings, the viral titer and the clinical signs dropped significantly during the pretreatment infection procedure. Curcumin, EGCG and their combinations also show significant antiviral activities.@*Conclusion, significance and impact of study@#This study clearly shown that natural compounds and their combinations, such as curcumin or/and ECGC can reduce viral pathogenicity in vivo, suggesting that they might have therapeutic implications in the poultry sector.

Curcumin alleviates the manganese-induced neurotoxicity by promoting autophagy in rat models of manganism / 北京大学学报(医学版)

OBJECTIVE@#To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl2), which mimics mangnism.@*METHODS@#Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H2O intragastrically (ig), MnCl2 group received 15 mg/kg MnCl2(Mn2+ 6.48 mg/kg) intraperitoneally plus dd H2O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl2+ CUR1 group received 15 mg/kg MnCl2 intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl2+ CUR2 group received 15 mg/kg MnCl2 intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum.@*RESULTS@#After exposure to MnCl2 for four weeks, MnCl2-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH+ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl2 group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl2 group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl2 group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl2+ CUR2 group were significantly improved compared with MnCl2 group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl2+ CUR2 group compared with MnCl2 group. Further, compared with MnCl2 group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl2+ CUR2 group (P < 0.05).@*CONCLUSION@#Curcumin alleviated the MnCl2-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.

Effect of Curcumin on Apoptosis of Acute T-Lymphoblastic Leukemia Cells induced by UMI-77 and Its Related Mechanism / 中国实验血液学杂志

AbstractObjective: To explore the effect and mechanism of curcumin on human T-cell acute lymphoblastic leukemia (T-ALL) cell apoptosis induced by Mcl-1 small molecule inhibitors UMI-77.@*METHODS@#T-ALL cell line Molt-4 was cultured, and the cells were treated with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77 for 24 h. The MTT method was used to detect the cell survival rate after different treatment; According to the results of curcumin and UMI-77, the experimental settings were divided into control group, curcumin group (20 μmol/L curcumin treated cells), UMI-77 group (15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells) and curcumin+ UMI-77 group (20 μmol/L curcumin and 15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells), MTT method was used to detect cell proliferation inhibition rate, Annexin V-FITC/PI double staining method and TUNEL staining were used to detect cell apoptosis, DCFH-DA probe was used to detect cell reactive oxygen species, JC-1 fluorescent probe was used to detect mitochondrial membrane potential, Western blot was used to detect the expression levels of apoptosis-related proteins and Notch1 signaling pathway-related proteins.@*RESULTS@#After the treatment of Molt-4 cells with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77, the cell survival rate was decreased (P<0.05); Compared with the control group, the cell proliferation inhibition rate of the curcumin group and the UMI-77 group were increased, the apoptosis rate of cell was increased, the level of ROS was increased, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, and the protein expression of Bcl-2 was reduced (P<0.05); Compared with the curcumin group or UMI-77 group, the cell proliferation inhibition rate and apoptosis rate of the curcumin+UMI-77 group were further increased, and the level of ROS was increased. At the same time, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, the protein expression of Bcl-2 was reduced (P<0.05); In addition, the mitochondrial membrane potential of the cells after curcumin treatment was decreased, and the proteins expression of Notch1 and HES1 were reduced (P<0.05).@*CONCLUSION@#Curcumin can enhance the apoptosis of T-ALL cells induced by Mcl-1 small molecule inhibitor UMI-77 by reducing the mitochondrial membrane potential, the mechanism may be related to the inhibition of Notch1 signaling pathway.

Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation though NF-κ B and AKT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of curcumin on viability of clear cell renal cell carcinoma (ccRCC) and analyze its possible mechanism.@*METHODS@#In cell lines of A498 and 786-O, the effects of curcumin (1.25, 2.5, 5 and 10 μ mol/L) on the viability of ccRCC were analyzed at 24, 48 and 72 h by MTT assay. The protein expression levels of ADAMTS18 gene, p65, phosphorylation p65 (pp65), AKT, phosphorylation AKT (pAKT) and matrix metallopeptidase 2 (MMP-2) before and after curcumin (10 μ mol/L) treatment were examined by Western blotting. Real-time PCR and methylation specific PCR (MSP) were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment (10 μ mol/L).@*RESULTS@#Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose- and time-dependent manner (P<0.01). Up-regulation of ADAMTS18 gene expression with down-regulation of ADAMTS18 gene methylation was reflected after curcumin treatment, accompanied by down-regulation of nuclear factor κ B (NF-κ kB) related protein (p65 and pp65), AKT related protein (AKT and pAKT), and NF-κ B/AKT common related protein MMP-2. With ADAMTS18 gene overexpressed, the expression levels of p65, AKT and MMP2 were downregulated, of which were conversely up-regulated in silenced ADAMTS18 (sh-ADAMTS18). The expression of pp65, pAKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC (NF-κ B inhibitor) and LY294002 (AKT inhibitor).@*CONCLUSIONS@#Curcumin could inhibit the viability of ccRCC by down-regulating ADAMTS18 gene methylation though NF-κ B and AKT signaling pathway.

Curcumin improves cardiac fibrosis by inhibiting endothelial-mesenchymal transition through NRF2-DDAH-ADMA-NO pathway / 中国中药杂志

The present study analyzed the correlations between curcumin(Cur), nuclear factor E2 related factor 2(NRF2)-dimethylarginine dimethylaminohydrolase(DDAH)-asymmetric dimethylarginine(ADMA)-nitric oxide(NO) pathway, and endothelial-mesenchymal transition(EndMT) based on SD rats with cardiac fibrosis, and explored the effect and mechanism of Cur in resisting cardiac fibrosis to provide an in-depth theoretical basis for its clinical application in the treatment of heart failure. The cardiac fibrosis model was induced by subcutaneous injection of isoprenaline(Iso) in rats. Thirty-two rats were randomly divided into a control group, a model group, a low-dose Cur group(100 mg·kg~(-1)·d~(-1)), and a high-dose Cur group(200 mg·kg~(-1)·d~(-1)), with eight in each group. After 21 days of treatment, cardiac function was detected by echocardiography, degree of cardiac fibrosis by Masson staining, expression of CD31 and α-SMA by pathological staining, expression of VE-cadherin, vimentin, NRF2, and DDAH by Western blot, and ADMA level by HPLC. Compared with the model group, the Cur groups showed alleviated cardiac fibrosis, accompanied by increased CD31 and VE-cadherin expression and decreased α-SMA and vimentin expression, indicating relieved EndMT. Additionally, DDAH and NRF2 levels were elevated and ADMA and NO expression declined. Cur improves cardiac fibrosis by inhibiting EndMT presumedly through the NRF2-DDAH-ADMA-NO pathway.