RESUMEN

Turmeric (Curcuma longa) contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of Curcuma longa, on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.

Asunto(s)

RESUMEN

Turmeric (Curcuma longa L.) is a perennial tuberous plant from the genus Curcuma (Zingiberaceae) and has been widely used in foods for thousands of years. The present study examined the ethanol extract of turmeric for its chemical composition, antimicrobial activity, and free radical scavenging properties. UHPLC-MS/MS analysis tentatively identified eight compounds in the turmeric extract. Potential antimicrobial effects of 0.1, 1.0, and 10 mg turmeric equivalents (TE)/mL were evaluated in vitro against a variety of Gram-negative bacteria (i.e., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas sp.) and Gram-positive bacteria (i.e., Enterococcus faecalis, Listeria innocua, and Staphylococcus aureus). Concentrations of 0.1 and 1.0 mg TE/mL inhibited the growth of S. aureus and significantly suppressed that of Pseudomonas sp., E. faecalis, and L. innocua. The growth of all strains, including E. coli, was inhibited by 10 mg TE/mL. Moreover, free radical scavenging capacities were determined using HO●, ABTS●+, and DPPH● (HOSC, ABTS, and RDSC, respectively) radicals. The turmeric ethanol extract had a TPC value of 27.12 mg GAE/g, together with HOSC, RDSC, and ABTS values of 1524.59, 56.38, and 1.70 µmol TE/g, respectively. Our results suggest that turmeric extract has potential applications for use in functional foods to reduce microbial burdens and oxidative stress-related health problems.

RESUMEN

Vesicle delivery carriers, used to stabilize hydrophobic drugs, are characterized by the propensity to aggregate, and fuse, limiting its applications. Fortifying vesicle-entrapped drugs within a biodegradable polymeric film constitutes a promising solution. In this study, biodegradable poly (vinyl alcohol) copolymerized with gelatin-sericin film and integrated alongside vesicle-entrapped demethoxycurcumin (DMC) or bisdemethoxycurcumin (BDMC) was developed, extensively characterized for improve efficacy, and compared. Vesicle-entrapped DMC or BDMC was spherical in shape with no changes in size, zeta-potential, and morphology after storing at 4 °C for 30 days. Antibacterial activity of vesicle-entrapped DMC formulations against Acinetobacter baumannii and Staphylococcus epidermidis was more effective than that of its free form. DMC and BDMC demonstrated dose dependent reduction in lipopolysaccharides (LPS)-induced nitric oxide (NO) levels either in free or in entrapped form. Moreover, vesicle-entrapped DMC/BDMC suppressed NO production at lower concentrations, compared with that of their free form and significantly improved the viability of RAW264.7 and HaCaT cells. Furthermore, functionalized film with vesicle-entrapped DMC/BDMC demonstrated excellent radical scavenging, biocompatibility, and cell migration efficacy. Thus, incorporating vesicle, entrapped DMC/BDMC within biodegradable polymeric film may comprised a promising strategy for improving stability, wound healing, and inflammation attenuation efficacy.

Asunto(s)

RESUMEN

Many biological functions of curcumin have been reported. As certain bioactivities of curcumin are eliminated by antioxidants, reactive oxygen species generated by curcumin have been suggested as a relevant mechanism. In the present study, the effects of different types of antioxidants on the stability and bioactivities of curcumin were analyzed. High concentrations (>4 mM) of thiol antioxidants, including N-acetylcysteine (NAC), glutathione (GSH), and ß-mercaptoethanol, accelerated the decomposition of curcumin and other curcuminoids; the submillimolar levels (<0.5 mM) of GSH and NAC rather improved their stability. Ascorbic acid or superoxide dismutase also stabilized curcumin, regardless of their concentration. The cellular levels and bioactivities of curcumin, including its cytotoxicity and the induction of heme oxygenase-1, were significantly reduced in the presence of 8 mM of GSH and NAC. The effects were enhanced in the presence of submillilmolar GSH and NAC, or non-thiol antioxidants. The present results indicate that antioxidants with a reduced thiol group could directly interact with the α,ß-unsaturated carbonyl moiety of curcuminoids and modulate their stability and bioactivity.

Asunto(s)

RESUMEN

Juvenile hormones (JHs) play a central role in insect development, reproduction, and various physiological functions. Curcuminoids generally exhibit a wide range of biological activities, such as antioxidant, anti-inflammatory, antibacterial, and insecticidal, and they exhibit insect growth inhibitory effects. However, research on insecticidal properties of curcuminoids has been limited. Moreover, to the best of our knowledge, studies on JHs of insects and curcuminoids are lacking. Therefore, this study aimed to identify the substances that act as JH disruptors (JHDs) from edible plants. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), two curcuminoids from the turmeric plant Curcuma longa L. inhibited the formation of a methoprene-tolerant (Met)-Taiman (Tai) heterodimer complex in Drosophila melanogaster, as shown through in vitro yeast two-hybrid assays. An artificial diet containing 1% (w/v) DMC or BDMC significantly reduced the number of D. melanogaster larvae in a concentration-dependent manner; larval development was disrupted, preventing the progression of larvae to pupal stages, resulting in an absence of adults. Building on the results obtained in this study on curcuminoids, researchers can use our study as a reference to develop eco-friendly pesticides.

RESUMEN

Citrullination is a post-translational modification catalysed by peptidyl arginine deiminase (PAD) enzymes, and dysregulation of protein citrullination is involved in various pathological disorders. During the past decade, a panel of citrullination inhibitors has been developed, while small molecules activating citrullination have rarely been reported so far. In this study, we screened citrullination activator using an antibody against citrullinated histone H3 (cit-H3), and a natural compound demethoxycurcumin (DMC) significantly activated citrullination. The requirement of PAD2 for DMC-activated citrullination was confirmed by a loss of function assay. Notably, DMC directly engaged with PAD2, and showed binding selectivity among PAD family enzymes. Point mutation assay indicated that residue E352 is essential for DMC targeting PAD2. Consistently, DMC induced typical phenotypes of cells with dysregulation of PAD2 activity, including citrullination-associated cell apoptosis and DNA damage. Overall, our study not only presents a strategy for rationally screening citrullination activators, but also provides a chemical approach for activating protein citrullination. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.

Asunto(s)

RESUMEN

The re-emergence of monkeypox (MPX), in the era of COVID-19 pandemic is a new global menace. Regardless of its leniency, there are chances of MPX expediting severe health deterioration. The role of envelope protein, F13 as a critical component for production of extracellular viral particles makes it a crucial drug target. Polyphenols, exhibiting antiviral properties have been acclaimed as an effective alternative to the traditional treatment methods for management of viral diseases. To facilitate the development of potent MPX specific therapeutics, herein, we have employed state-of-the-art machine learning techniques to predict a highly accurate 3-dimensional structure of F13 as well as identify binding hotspots on the protein surface. Additionally, we have effectuated high-throughput virtual screening methodology on 57 potent natural polyphenols having antiviral activities followed by all-atoms molecular dynamics (MD) simulations, to substantiate the mode of interaction of F13 protein and polyphenol complexes. The structure-based virtual screening based on Glide SP, XP and MM/GBSA scores enables the selection of six potent polyphenols having higher binding affinity towards F13. Non-bonded contact analysis, of pre- and post- MD complexes propound the critical role of Glu143, Asp134, Asn345, Ser321 and Tyr320 residues in polyphenol recognition, which is well supported by per-residue decomposition analysis. Close-observation of the structural ensembles from MD suggests that the binding groove of F13 is mostly hydrophobic in nature. Taken together, this structure-based analysis from our study provides a lead on Myricetin, and Demethoxycurcumin, which may act as potent inhibitors of F13. In conclusion, our study provides new insights into the molecular recognition and dynamics of F13-polyphenol bound states, offering new promises for development of antivirals to combat monkeypox. However, further in vitro and in vivo experiments are necessary to validate these results.

Asunto(s)

RESUMEN

SCOPE: Turmeric curcuminoids mainly consist of curcumin (CUR), demethoxycurcumin (dCUR), and bisdemethoxycurcumin (bdCUR). CUR displays low bioavailability, partly due to poor solubilization in the intestinal lumen during digestion, while data for dCUR and bdCUR are scarce. The study aims to investigate the bioaccessibility of curcuminoids from turmeric extracts or from gamma-cyclodextrins, considering potential interactions with food. METHODS AND RESULTS: Using an in vitro digestion model (correlation with CUR bioavailability: r = 0.99), the study shows that curcuminoid bioaccessibility from turmeric extract without food is low: bdCUR (11.5 ± 0.6%) > dCUR (1.8 ± 0.1%) > CUR (0.8 ± 0.1%). Curcuminoids incorporated into gamma-cyclodextrins display higher bioaccessibilities (bdCUR: 21.1 ± 1.6%; dCUR: 14.3 ± 0.9%; CUR: 11.9 ± 0.7%). Curcuminoid bioaccessibility is highest without food (turmeric extract: 2.0 ± 0.1%; gamma-cyclodextrins: 12.4 ± 0.8%) and decreases with a meat- and potato-based meal (turmeric extract: 1.1 ± 0.2%; gamma-cyclodextrins: 2.4 ± 0.3%) or a wheat-based meal (turmeric extract: 0.1 ± 0.0%; gamma-cyclodextrins: 0.3 ± 0.1%). Curcuminoids exhibit low (<10%) incorporation efficiencies into synthetic mixed micelles (bdCUR > dCUR > CUR). CONCLUSIONS: bdCUR and dCUR show greater bioaccessibilities versus CUR. Food diminishes curcuminoid bioaccessibility, likely by adsorption mechanisms. Gamma-cyclodextrins improve curcuminoid bioaccessibility.

Asunto(s)

RESUMEN

OBJECTIVE: Myocardial ischemia-reperfusion (IR) injury is an unresolved medical problem with a high incidence. This study aims to analyze the novel molecular mechanism by which curcuminoids protect cardiomyocytes from IR injury. METHODS: A IR model In Vitro of rat cardiomyocytes H9c2 cells was structured. Curcumin (CUR) and its derivatives, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) treated H9c2 cells, and reactive oxygen species (ROS) production, viability, apoptosis, mitochondrial membrane potential (MMP), oxidative stress and total RNA m6A levels of H9c2 cells were detected by using DCFH-DA stain, CCK-8, flow cytometry, Hoechst 33342 stain, TMRM stain, ELISA and RTqPCR. FB23 was used in rescue experiments. RESULTS: IR significantly increased ROS production, decreased cell viability, and induced apoptosis, MMP loss, and oxidative stress. In addition, IR induced an increase in total RNA m6A levels and changes in m6A-related proteins expression. CUR (10 µM), DMC (10 µM) and BDMC (10 µM), significantly inhibited IR-induced ROS production, apoptosis, MMP loss and oxidative stress, and enhanced cell viability. Furthermore, CUR, DMC and BDMC altered the expression pattern of m6A-related proteins and reduced IR-induced total m6A levels. There was no significant difference in the effects of the three. CUR's protective effect was partially reduced by FB23. CONCLUSION: Curcuminoids attenuate myocardial IR injury by regulating total RNA m6A levels.

Asunto(s)

RESUMEN

The extraction of curcuminoids and aromatic (ar)-turmerone from Curcuma longa L. using organic solvents produces chemical waste, and is therefore incompatible with food applications. To address this issue, this study presents the design of hydrophobic deep eutectic solvents (HDESs) and HDES-based microemulsions. Using the response surface methodology (RSM), the optimal extraction conditions were identified as follows: HDES = OA:menthol (1:3.6 M ratio), solid-to-liquid ratio = 10:1 (mg/mL), and extraction duration = 90 min (prediction accuracy ≥ 85 %). Under these conditions, the HDES extraction yields of bisdemethoxycurcumin, demethoxycurcumin, curcumin, and ar-turmerone were 2.49 ± 0.25, 5.61 ± 0.45, 9.40 ± 0.86, and 3.83 ± 0.19 % (w/w, dry basis), respectively, while those obtained using the HDES-based microemulsion were 2.10 ± 0.18, 6.31 ± 0.48, 12.6 ± 1.20, and 2.58 ± 0.19 % (w/w, dry basis), respectively. The HDES and its microemulsions are more effective and environmentally friendly than conventional organic solvents for the extraction of curcuminoids and ar-turmerone, and these solvents are also compatible with food and pharmaceutical formulations.

Asunto(s)

RESUMEN

Background: Demethoxycurcumin (DMC) is a curcumin analog with antitumor properties. However, its effects have not been investigated in human head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to verify the antitumor effect and cellular signaling pathways of DMC in FaDu HNSCC cells. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell Live/Dead staining, hematoxylin and eosin staining, DAPI staining, FACS, western blotting, caspase-3 activity assay, and nuclear translocation were performed to verify apoptosis and the cellular signaling pathway of DMC in FaDu cells. Results: DMC increased FaDu cell death, with cells presenting altered morphology and condensed nuclei. DMC increased significantly the apoptotic population of FaDu cells. Sequentially, DMC increased the expression of cleaved caspase-3 and PARP through the up-regulation of pro-apoptotic factors such as FasL, cleaved caspase-8, Bax, Bad, and cleaved caspase-9 and the suppression of anti-apoptotic factors including Bcl-xL and Bcl-2 in FaDu cells. Furthermore, DMC not only suppressed the phosphorylation of NF-κB, but also inhibited the translocation of NF-κB from cytosol to nucleus of FaDu cells. Conclusions: Present study demonstrates that DMC-induced cell death is mediated caspase-dependently by death receptor-mediated extrinsic and mitochondria-dependent intrinsic apoptosis through the inhibition of NF-κB translocation from the cytosol to the nucleus of FaDu cells. DMC is a curcuminoid with antitumor properties that modulates the NF-κB cellular signaling pathway in FaDu cells. Taken together, this study suggests that DMC has a considerable chemotherapeutic potential for HNSCC.

RESUMEN

BACKGROUND: Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the main components of turmeric that commonly used to treat neuropathic pain (NP). However, the mechanism of the therapy is not sufficiently clarified. Herein, network pharmacology, molecular docking and molecular dynamics (MD) approaches were used to investigate the mechanism of curcuminoids for NP treatment. METHODS: Active targets of curcuminoids were obtained from the Swiss Target database, and NP-related targets were retrieved from GeneCards, OMIM, Drugbank and TTD databases. A protein-protein interaction (PPI) network was built to screen the core targets. Furthermore, DAVID was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and curcuminoids were assessed by molecular docking and the MD simulations were run for 100ns to validate the docking results on the top six complexes. RESULTS: CUR, DMC, and BDMC had 100, 99 and 100 targets respectively. After overlapping with NP there were 33, 33 and 31 targets respectively. PPI network analysis of TOP 10 core targets, TNF, GSK3ß were common targets of curcuminoids. Molecular docking and MD results indicated that curcuminoids bind strongly with the core targets. The GO and KEGG showed that curcuminoids regulated nitrogen metabolism, the serotonergic synapse and ErbB signaling pathway to alleviate NP. Furthermore, specific targets in these three compounds were also analysed at the same time. CONCLUSIONS: This study systematically explored and compared the anti-NP mechanism of curcuminoids, providing a novel perspective for their utilization.

Asunto(s)

RESUMEN

The inflammatory radicular pain induced by lumbar disc herniation (LDH) is a serious problem worldwide. Demethoxycurcumin (DMC) is a yellow pigment derived from turmeric. Although it is considered a safe natural compound for managing inflammation-associated diseases, but the molecular mechanisms of LDH remain to be elucidated. In the current study, DMC reduced the production of IL-1ß, IL-4, and IL-6 in nucleus pulposus (NP) cells subjected to TNF-α-induced inflammation. Moreover, the inhibitory mechanism was activated upon suppression of activation of MAPKs and NF-κB signalling in NP cells. Further experiments with LDH model rats supported the in vitro results. These studies expand our knowledge of the effect of DMC on LDH; DMC may be a viable alternative to the drugs used to treat LDH.

Asunto(s)

RESUMEN

Curcuma longa constitutes an important source of secondary metabolites that have been associated with multiple health benefits. For instance, curcumin, demethoxycurcumin and bisdemethoxycurcumin, have been found to perform important biological activities, such as anti-inflammatory, antioxidant, anticancer, antimicrobial, antihypertensive and anticoagulant. These promising results prompted this research to evaluate the polyphenols of C. longa rhizomes in Costa Rica. The present work reports a comprehensive study on the polyphenolic profile and the contents of the three main curcuminoids as well as the antioxidant activity of extracts from C. longa rhizomes (n = 12) produced in Costa Rica. Through UPLC-QTOF-ESI MS, a total of 33 polyphenols were identified, grouped in eight types of structures. In addition, our findings on the main curcuminoids using UPLC-DAD show all rhizomes complying with total curcuminoids (TC) content established by the United States Pharmacopeia (USP). At an individual level, samples NW-3 and NE-1 show the higher contents (118.7 and 125.0 mg/g dry material), representing more than twice the average values of the lowest samples. These samples also exhibit the highest Folin−Ciocalteu (FC) reducing capacity results as well as the best DPPH (IC50 15.21 and 16.07 µg extract/mL) and NO (IC50 between 52.5 and 54.3 µg extract/mL) antioxidant values. Further, Pearson correlation analysis findings indicated positive correlation (p < 0.05) between TC, CUR with FC results (r = 0.833 and r = 0.867 respectively) and negative correlation (p < 0.05) between CUR, TC and FC with DPPH results (r = −0.898, r = −0.911, and r = −0.890, respectively) and between NO results and DPPH (r = −0.805, p < 0.05). Finally, results for Principal Component Analysis (PCA) showed composition variability associated with their region of origin with products from the Northeastern (NE) region exhibiting higher average values for FC, TC and antioxidant activities. Further, PCA confirmed that two samples, namely NE-1 and NW-3, stand out by presenting the highest PC1 due to their particularly high TC, CUR and antioxidant activities. Consequently, our findings agree with previous results indicating the importance of C. longa extracts to elaborate products with potential benefits for health, while delivering extracts with higher levels of curcuminoids than previous reports and exhibiting high antioxidant activity.

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disease associated with aging, and the number of people affected is rapidly increasing. Abnormally hyperphosphorylated tau filaments and extracellular deposits of amyloid ß-peptides (Aß) fibrils are two important pathological hallmarks of AD. Currently, stopping the production of Aß and blocking its aggregation is the main strategy for the treatment of AD. Turmeric is effective in treating neurodegenerative diseases, but there is no effective way to identify active compounds from their complicated chemical compositions. Instead of using conventional extraction and separation methods with low efficiency and time-consuming, our group tried to use atomic materials in high-throughput chemical screening due to their structural characteristics and the unique advantages of surface atomic. Herein, a novel atomic zinc sites with hierarchical porous carbon (Zn-HPC) was synthesized to quickly screen potential inhibitors of Aß aggregation in turmeric. As-combined Aß@Zn-HPC demonstrates superior storage stability and high selectivity, outperforming the most reported supporters for ligand fishing. Five compounds with strong affinity on Aß@Zn-HPC were selected by high-performance liquid chromatography-hybrid linear ion trap/orbitrap mass spectrometer after incubation with turmeric extract. Finally, it was shown that curcumin and bisdemethoxycurcumin can inhibit Aß aggregation by using thioflavin-T fluorescence assay and biolayer interferometry. A new application for the accurate identification of Aß aggregation inhibitors from turmeric were developed based on the active compounds possessing binding affinity to Aß to inhibit its aggregation. The developed method could provide a promising tool for efficient drug discovery from natural product resources.

Asunto(s)

RESUMEN

BACKGROUND: Curcuminoids, flavoring, and coloring agents in food have potent antioxidant, anti-tumor activity, and anti-inflammatory effects. However, they are rapidly metabolized to lesser active metabolites. Therefore, various studies have been conducted to synthesize new and stable curcumin analogues with enhanced therapeutic activity. METHODS: Fluorinated curcumin compounds (2a-2f) were synthesized by Knoevenagel condensation between fluorobenzaldehydes (1a-1f) with curcumin. Fluorinated demethoxycurcumin (3a) was synthesized by condensation between demethoxycurcumin and 3,4-difluorobenzaldehyde (1f). The structures of these compounds were confirmed by FTIR, 1H-NMR, 13C-NMR, 19FNMR, and mass spectroscopy. Antiproliferative activities of these synthetic compounds were evaluated against breast cancer cells (4T1), melanoma cancer cells (B16F10), and normal cell lines (NIH 3T3) using MTT assay. The interaction of curcumin, 2f and 3a with several proteins (1HCL, 2ZOQ, 3D94, 5EW3, 4WA9, 1XKK, 6CCY) was investigated. The structural preservation of the epidermal growth factor receptor (EGFR) was investigated by molecular dynamics simulation. RESULTS: The spectroscopic data obtained confirmed the proposed structure of fluorinated analogues. The results showed that compounds 2f and 3a inhibited cancer cells proliferation significantly more than other compounds. Compounds 2f and 3a showed the highest affinity and lowest binding energy with EGFR. The binding energies were -7.8, -10, and - 9.8 kcal/mol for curcumin, 2f and 3a with EGFR, respectively. The molecular docking results demonstrated that compounds 2f and 3a were firmly bound in a complex with EGFR via the formation of a hydrogen bond. CONCLUSION: In summary, we found that fluorinated demethoxycurcumin and fluorinated curcumin induces cancer cell death and binds to EGFR with high affinity.

Asunto(s)

RESUMEN

The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF2 group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al2O3) or silica (SiO2) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms "click" and "unclick" applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80-92% yield), in pure form and excellent yields.

Asunto(s)

RESUMEN

Polymeric lipid hybrid nanoparticles (PLHNs) are the new generation of drug delivery systems that has emerged as a combination of a polymeric core and lipid shell. We designed and optimized a simple method for the preparation of Pluronic F-127-based PLHNs able to load separately demethoxycurcumin (DMC) and bisdemethoycurcumin (BDM). CUR was used as a model compound due to its greater availability from turmeric and its structure similarity with DMC and BDM. The developed method produced DMC and BDM-loaded PLHNs with a size average of 75.55 ± 0.51 and 15.13 ± 0.014 nm for DMC and BDM, respectively. An FT-IR analysis confirmed the encapsulation and TEM images showed their spherical shape. Both formulations achieved an encapsulation efficiency ≥ 92% and an exhibited significantly increased release from the PLHN compared with free compounds in water. The antioxidant activity was enhanced as well, in agreement with the improvement in water dissolution; obtaining IC50 values of 12.74 ± 0.09 and 16.03 ± 0.55 for DMC and BDM-loaded PLHNs, respectively, while free curcuminoids exhibited considerably lower antioxidant values in an aqueous solution. Hence, the optimized PHLN synthesis method using CUR as a model and then successfully applied to obtain DMC and BDM-loaded PLHNs can be extended to curcuminoids and molecules with a similar backbone structure to improve their bioactivities.

RESUMEN

Proliferative vitreoretinopathy (PVR) involves retinal pigment epithelium (RPE) cell proliferation and migration and leads to tractional retinal detachment. Demethoxycurcumin (DMC), a curcuminoid, has anti-inflammatory and anti-tumour properties. However, whether DMC affects the migration of RPE cells and the molecular mechanism of human PVR remains unclear. The aim of the current study was to investigate the effects of DMC on the inhibition of migration and proteinase expression of human ARPE-19 cells. Herein, we provided molecular evidence associated with PVR prevention through DMC by inhibiting ARPE-19 cell migration. We performed gelatin zymography, Western blot and RT-PCR and respectively found that DMC is sufficient to reduce matrix metalloproteinase-2 (MMP-2) activity, protein level and mRNA expression. DMC suppressed the nuclear levels of transcriptional factors specificity protein 1 and c-Fos, which are involved in the modulation of the transcriptional activation of the MMP-2 gene. DMC also inhibited STAT-3 phosphorylation in ARPE-19 cells. Selective STAT-3 induction by a STAT-3 activator, colivelin, reverted MMP activity and protein expression and cell migration, which were reduced in response to DMC. The results proved the inhibitory effect of DMC on RPE cell migration and MMP-2 expression by the down-regulation of the STAT-3 signalling pathway.

Asunto(s)

RESUMEN

BACKGROUND/AIM: Demethoxycurcumin (DMC), one of the components of curcuminoids, has antitumor activities in many human cancer cells and is known to induce apoptosis in human leukemia cells. However, there are no reports showing the effects of DMC on the immune response in leukemia mice in vivo. Herein, we evaluated the impact of DMC on immune responses in WEHI-3-generated leukemia mice in vivo. MATERIALS AND METHODS: Fifty male BALB/c mice were separated randomly into five groups. Group I is normal mice, and groups II-V mice of generated leukemia by WEHI-3 cells. Group II-V mice were intraperitoneally injected with dimethyl sulfoxide (DMSO, as the positive control), 15, 30, and 60 mg/kg of DMC, respectively, every two days for 14 days. The body weight, blood, peritoneal fluid, liver, and spleen were individually analyzed. RESULTS: DMC did not significantly affect animal appearance and body weight. It decreased liver and spleen weight at a high dose. DMC did not affect the cluster of differentiation 3 (CD3) and CD19 cell populations but induced decrease of CD11b at 30 mg/kg treatment. However, DMC at low dose significantly increased the cluster of macrophage (Mac-3) cell populations, but at high dose it decreased them. DMC increased macrophage phagocytosis from peripheral blood mononuclear cells at 15 mg/kg treatment and peritoneal cavity at 15, 30 and 60 mg/kg of DMC treatments. DMC did not significantly affect the cytotoxic activity of natural killer (NK) cells. Furthermore, DMC decreased B and T cell proliferation at high doses. CONCLUSION: DMC elevated macrophage phagocytosis in leukemia mice in vivo.

Asunto(s)