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).

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.

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 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.

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.

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.

Effects of turmeric (Curcuma longa) and its constituent (curcumin) on the metabolic syndrome: An updated review / 中西医结合学报

Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world's adult population is about 20%-25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitro, in vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects.

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.

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.

Efficacy-related substances of blood-activating and stasis-resolving medicinals derived from Curcuma plants: a review / 中国中药杂志

Derived from Curcuma plants, Curcumae Longae Rhizoma, Curcumae Rhizoma, Wenyujin Rhizoma Concisum, and Curcumae Radix are common blood-activating and stasis-resolving medicinals in clinical practice, which are mainly used to treat amenorrhea, dysmenorrhea, chest impediment and heart pain, and rheumatic arthralgia caused by blood stasis block. According to modern research, the typical components in medicinals derived from Curcuma plants, like curcumin, demethoxycurcumin, bisdemethoxycurcumin, curdione, germacrone, curcumol, and β-elemene, have the activities of hemorheology improvement, anti-platelet aggregation, anti-thrombosis, anti-inflammation, anti-tumor, and anti-fibrosis, thereby activating blood and resolving stasis. However, due to the difference in origin, medicinal part, processing, and other aspects, the efficacy and clinical application are different. The efficacy-related substances behind the difference have not yet been systematically studied. Thus, focusing on the efficacy-related substances, this study reviewed the background, efficacy and clinical application, efficacy-related substances, and "prediction-identification-verification" research method of blood-activating and stasis-resolving medicinals derived from Curcuma plants, which is expected to lay a theoretical basis for the future research on the "similarities and differences" of such medicinals based on integrated evidence chain and to guide the scientific and rational application of them in clinical practice.

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.

Comparative in vitro study of intracanal Enterococcus faecalis reduction using photosensitizers in aPDT

Aim: To compare Enterococcus faecalis reduction after antimicrobial photodynamic therapy (aPDT) used with methylene blue, toluidine blue, tannin, and curcumin as photosensitizers, an adjunct to endodontic chemomechanical preparation (CMP) in root canals of human teeth. Methods: A total of 120 single-rooted teeth were divided into 6 groups (n = 20): G1- CMP and 2.5% sodium hypochlorite (NaOCl); G2- CMP and saline solution; G3- CMP, 2.5% NaOCl, and aPDT with 0.005% methylene blue; G4- CMP, 2.5% NaOCl, and aPDT with 0.005% toluidine blue; G5- CMP, 2.5% NaOCl, and aPDT with 0.005% tannin; and G6- CMP, 2.5% NaOCl, and aPDT with 0.005% curcumin. A portable semiconductor laser was used (660 nm, 100 mW, 1.8 J, 180s) in groups 1, 2, 3, 4, 5, and a blue LED light-curing (420-480 nm, 1200 mV/cm2 ) in G6. For all groups, a 5 min pre-irradiation time was applied. Samples were collected before (initial collection), immediately after (intermediate collection) and 7 days after CMP (final collection) for colony-forming unit (CFU) counting. The Kruskal-Wallis test and analysis of variance (ANOVA) were performed (p < 0.05; 95% confidence interval). Results: In between-group comparisons, there was no significant difference observed in the number of CFUs at the initial (p >< 0.001) and final collections (p >< 0.001) for G2 and G3. In within-group comparisons, the number of CFUs showed a decreasing trend in G4 (p = 0.007) and G5 (p = 0.001). Conclusion: Photosensitizers promoted E. faecalis reduction, with better results for tannin and curcumin. Alternative photosensitizers should be the focus of further studies.>< 0.05; 95% confidence interval). Results: In between-group comparisons, there was no significant difference observed in the number of CFUs at the initial (p < 0.001) and final collections (p >< 0.001) for G2 and G3. In within-group comparisons, the number of CFUs showed a decreasing trend in G4 (p = 0.007) and G5 (p = 0.001). Conclusion: Photosensitizers promoted E. faecalis reduction, with better results for tannin and curcumin. Alternative photosensitizers should be the focus of further studies.>< 0.001) and final collections (p < 0.001) for G2 and G3. In within-group comparisons, the number of CFUs showed a decreasing trend in G4 (p = 0.007) and G5 (p = 0.001). Conclusion: Photosensitizers promoted E. faecalis reduction, with better results for tannin and curcumin. Alternative photosensitizers should be the focus of further studies>< 0.001) for G2 and G3. In within-group comparisons, the number of CFUs showed a decreasing trend in G4 (p = 0.007) and G5 (p = 0.001). Conclusion: Photosensitizers promoted E. faecalis reduction, with better results for tannin and curcumin. Alternative photosensitizers should be the focus of further studies

Photosensitizers and exposure times to light showed tissue compatibility in isogenic mice / Fotossensibilizadores e tempo de exposição a luz em relação a compatibilidade de tecidos em ratos isogênicos

Objective: The aim of this study was to evaluate the subcutaneous tissue response after different protocols to photodynamic therapy (PDT). In Phase 1, were tested the diode laser (used for 1min) associated to the photosensitizer phenothiazine chloride solution (PCS) in different concentrations. In Phase 2 ­ the diode laser and LED were tested associated to two different photosensitizers, PCS and Curcumin, in different exposure times of light application. Material and Methods: After 7, 21 and 63-days the animals were euthanized and the subcutaneous tissue processed to histological analysis. Qualitative and semi-quantitative descriptions of the inflammatory process and immunohistochemical technique were performed. The obtained data were analyzed by Kruskal-Wallis and Dunn's post-test (α= 0.5). Results: On Phase 1, the tissue response was very similar among the groups. For the inflammatory infiltrate, PCS with concentration of 10mg/mL exhibited the most intense reaction (p > 0.05). On Phase 2, at 7-days period, the analyzed parameters presented small magnitude and after 21 and 63-days, all the parameters demonstrated tissue compatibility. Conclusion: Both photosensitizers presented proper tissue compatibility regardless the different concentrations used on Phase 1 and different durations of light exposure on Phase 2 (AU)

Objetivo: Este estudo avaliou a resposta do tecido subcutâneo após terapia fotodinâmica, utilizando na Fase 1 - laser diodo por 1min e solução fotossensibilizadora de cloreto de fenotiazina (CF) em diferentes concentrações e Fase 2 - laser diodo e LED e dois fotossensibilizadores, CF e Curcumina, em diferentes tempos de exposição da aplicação de luz. Material e Métodos: Após 7, 21 e 63 dias, foram realizadas descrições qualitativas e semiquantitativas do processo inflamatório e técnica de imunoistoquímica. Os dados foram analisados pelo pós-teste de Kruskal-Wallis e Dunn (α = 0,5). Resultados: Na Fase 1, a resposta do tecido foi muito semelhante. O infiltrado inflamatório, na concentração de 10 mg / mL, exibiu reação mais intensa (p > 0,05). Na Fase 2, aos 7 dias, os parâmetros analisados apresentaram pequena magnitude. Aos 21 e 63 dias, todos os parâmetros demonstraram compatibilidade com o tecido. Conclusão: Ambos os fotossensibilizadores apresentaram compatibilidade de tecido adequada, independentemente das diferentes concentrações utilizadas na Fase 1 e diferentes durações de exposição à luz na Fase 2 (AU)

Effects of Curcumin on Sodium Arsenite Induced Neoplastic Cell Transformation in Balb/c 3T3 Cells

HIGHLIGHTS Sodium arsenite can cause neoplastic transformation in cells. Curcumin reduced cell viability and increased LDH activity in transformed Balb/c 3T3 cells. Curcumin caused DNA damage in transformed Balb/c 3T3 cells. Curcumin may play a protective role in sodium arsenite-induced toxicity.

Abstract Arsenic is a toxic substance that spreads widely around the environment and accumulates as metalloid in the earth's crust. Arsenic and its derivatives are found in drinking water, nutrients, soil, and air. Exposure to arsenic is associated with lung, blood, skin cancer and various lesions. Curcumin is a polyphenolic compound derived from Curcuma longa (turmeric) rhizome and is one of the main curcuminoids. Curcumin is known to be antioxidant, antibacterial, anti-inflammatory, analgesic effects. This study aimed to investigate the potential of sodium arsenite to transform embryonic fibroblast cells and to evaluate the cytotoxic and genotoxic effects of curcumin in neoplastic transformed cells. Neoplastic cells transformation was induced by sodium arsenite in Balb/c 3T3 cells at the end of 32 days. After transformation assay, the transformed cells were treated with various concentration of curcumin to evaluate cell viability, lactate dehydrogenase activity and DNA damage for 24h. The results revealed that curcumin decreased cell viability and increased the activity of lactate dehydrogenase enzyme in neoplastic transformed Balb/c 3T3 cells. In conclusion, the results demonstrated that curcumin has an anticancer effect on neoplastic transformed Balb/c 3T3 cells by causing DNA damage.

Study on quality identification of Curcumae Rhizoma from different origins based on quantitative analysis of appearance color and content of main components / 中国中药杂志

L~*, a~* and b~* values of prepared slices of Curcumae Rhizoma were measured by spectrophotometer. SPSS 21.0 was used for discriminant analysis to establish the color range and mathematical prediction model of prepared slices of Curcumae Rhizoma. The values of L~*, a~* and b~* of kwangsiensis ranged from 58.09-62.40, 4.53-5.66 and 23.61-24.29, while the values of L~*, a~* and b~* of phaeocaulis were between 64.02-70.71,-0.89-4.13 and 44.59-54.52, respectively. The values of L~*, a~* and b~* of wenyujin were 68.55-70.99,-0.11-1.47 and 28.26-32.19, respectively. The mathematical prediction model was proved to be able to realize 100% identification of Curcumae Rhizome of different origins through original and cross validation and external samples validation. A dual wavelength HPLC was established; the contents of 9 sesquiterpenoids and 3 Curcumae Rhizomes were determined simultaneously; and the contents of Curcumae Rhizome of different origins were determined. The results showed that kwangsiensis had higher contents of neocurdione, β-elemene and isocurcumaenol, phaeocaulis curcumin, furadienone, demethoxycurcumin and curcumin; and wenyujin mainly contained curdione, furadienes and guimarone. Pearson correlation analysis on L~*, a~*, b~* value and content of 12 components showed that curcumin, furadienone, demethoxycurcumin and curcumin had a significant positive correlation with b~* value(P<0.01). There was a significant negative correlation between neocurdione, β-elemene and isocurcumaenol and L~* value(P<0.01). Curdione, furadienes and guimarone were significantly correlated with L~* value(P<0.01),indicating that the appearance co-lor of Curcumae Rhizoma could reflect the change of the content of the internal components. This study provided reference for the rapid recognition of Curcumae Rhizoma and the establishment of quality evaluation system.

Production of curcumin by engineered Escherichia coli / 生物工程学报

Curcumin is exclusively isolated from Zingiberaceae plants with a broad spectrum of bioactivities. In the present study, we used the diketide-CoA synthase (DCS) and curcumin synthase (CURS) genes to construct a non-natural fusion gene encoding diketide-CoA synthase::curcumin synthase (DCS::CURS). This fusion protein, together with the acetyl coenzyme A carboxylase (ACC) and the 4-coumarate coenzyme A ligase (4CL), were introduced into Escherichia coli for the production of curcumin from ferulic acid. The process is divided into two stages, the growth stage using LB medium and the fermentation stage using the modified M9 medium. The yield of curcumin reached 386.8 mg/L by optimizing the induction of protein expression in the growth stage, and optimizing the inoculum volume, medium composition and fermentation time in the fermentation stage, as well as the addition of macroporous resin AB-8 into the second medium to attenuate the toxicity of the end product. The exploitation of the non-natural fusion protein DCS::CURS for the production of curcumin provides a new alternative to further promoting the production of curcumin and the related analogues.

Curcumin mediates IL-6/STAT3 signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer / 中国中药杂志

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1β and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.

Research progresses in the biosynthesis of curcuminoids / 生物工程学报

Curcuminoids are rare diketone compounds in plants and can be found in the rhizome of Curcuma longa as well as other Zingiberaceae and Araceae. Curcuminoids have been widely used in food and medical area owing to the yellow colors, as well as the antioxidant and many other pharmacological activities. Curcuminoids are a mixture of compounds containing curcumin, demethoxycurcumin and bisdemethoxycurcumin, which have distinct benzene ring substituents. Currently, curcuminoids are exclusively produced through plant extraction, which do not satisfy the meeting of the market demand. Empowered with new synthetic biology tools and metabolic engineering strategies, there is renewed interest in production of curcuminoids using microorganisms. Heterologous production of curcuminoids has been achieved using Escherichia coli, Yarrowia lipolytica, Pseudomonas putida and Aspergillus oryzae via engineering of curcuminoids biosynthesis pathway. In this review, we first describe the biological activities and various applications of curcuminoids. Next, we summarize the biosynthetic pathway of curcuminoids in Curcuma longa and discuss the catalytic mechanisms of curcumin synthases. Then, we thoroughly explore recent advances in the use of distinct microorganisms for the production of curcuminoids with a special focus on metabolic engineering strategies. Finally, we prospect the microbial production of curcuminoids by highlighting some promising techniques and approaches.

Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis / 华西口腔医学杂志

OBJECTIVES@#This study was performed to review the efficacy of curcumin in the treatment of oral submucous fibrosis systematically.@*METHODS@#We searched seven databases, including Web of Science, PubMed, EBSCO, The Cochrane Library, CNKI, WanFang Data, and VIP, to obtain randomized controlled trials related to the treatment of oral submucous fibrosis by curcumin. Each database was searched from inception to 30 June 2019. RevMan 5.3 software was used for the meta-analysis.@*RESULTS@#Six randomized controlled trials involving 350 patients were included in this study. Meta-analysis showed that curcumin can increase the maximal mouth opening and improve burning sensation compared with placebo treatment. Curcumin was not as effective as the controls in achieving maximal mouth opening after 1 month of treatment. However, no statistically significant difference was observed between the treatments from 2 months to 6 months. Curcumin significantly improved burning sensation compared with the controls after 3 months of treatment. No statistically significant diffe-rence in burning sensation was observed between the curcumin and control groups after 1, 2, and 6 months of treatment.@*CONCLUSIONS@#The current evidence shows that curcumin is an effective treatment for improving maximal mouth opening and burning sensation in patients with oral submucous fibrosis. Given the limited number and low quality of the included studies, however, more high-quality studies are needed to verify these findings.