The effect of curcumin supplementation on endothelial function and blood pressure in patients with metabolic disorders: A meta-analysis of meta-analyses.

Several interventional studies have revealed the beneficial impact of curcumin supplementation on blood pressure and endothelial function, but the findings are conflicting. Therefore, this study was conducted to investigate the effects of curcumin supplementation on blood pressure and endothelial function. A meta-analyses of randomized clinical trials were performed by searching PubMed, Embase, Scopus, and Web of Science were searched up to March 31, 2024. Random effects models were used to calculate weighted mean differences (WMD). Pooled estimates of 10 studies revealed that curcumin decreased diastolic blood pressure (DBP) [WMD = -0.94, 95 % CI: -1.59, -0.30; p = 0.004], pulse wave velocity (PWV) [WMD = -45.60, 95 % CI: -88.16, -3.04; p = 0.03, I2 = 0.0 %, p = 0.59], and vascular cell adhesion molecule-1 (VCAM-1) [WMD = -39.19; 95 % CI: -66.15, -12.23, p =0.004; I2=73.0 %, p = 0.005] significantly, and increased flow-mediated dilation (FMD) [WMD = 1.64, 95 % CI: 1.06, 2.22; p < 0.001, I2 = 0.0 %, p = 0.61. However, curcumin did not significantly change systolic blood pressure (SBP) [WMD = -0.64, 95 % CI: -1.96, 0.67; p =0.34, I2 = 83.5 %, p <0.001], and Intercellular Adhesion Molecule 1 (ICAM1) [WMD = -17.05; 95 % CI: -80.79, 46.70, p =0.601; I2=94.1 %, p < 0.001]. These results suggest that curcumin has a beneficial effect on DBP, PWV, VCAM-1 and FMD levels and may be an effective adjunctive therapy for improving blood pressure and endothelial function.

The effect of curcumin supplementation on glycemic indices in adults: A meta-analysis of meta-analyses.

Curcumin, an inherent polyphenolic compound, has the potential to influence glycemic indices. Nevertheless, the conclusions drawn from extant meta-analyses remain contentious. To determine the impact of curcumin supplementation on these indices, the current umbrella meta-analysis included existing systematic reviews and meta-analyses. A thorough systematic search was conducted using databases Embase, PubMed, WOS, Scopus, and the Cochrane Library to acquire peer-reviewed literature published before January 2024. The random-effects model was employed to conduct a meta-analysis. The present analysis incorporated a total of 22 meta-analytic studies. The findings of our study indicate that the administration of curcumin supplements leads to a significant decrease in fasting blood sugar levels (FBS) (ES: -1.63; 95 % CI: -2.36, -0.89, P<0.001; I2=88.4 %, P<0.001), homeostasis model assessment-estimated insulin resistance (HOMA-IR) (ES: -0.38; 95 % CI: -0.48, -0.28, P<0.001; I2=35.9 %, P=0.142), hemoglobin A1c (HbA1c) (ES: -0.44; 95 % CI: -0.67, -0.21, P<0.001; I2=65.0 %, P=0.014), and insulin (ES: -0.86; 95 % CI: -1.52, -0.21, P=0.010; I2=92.5 %, P<0.001). The results of this study suggest that the administration of curcumin supplements may be a beneficial intervention for enhancing glycemic indices.

Curcumin-Dichloroacetate Hybrid Molecule as an Antitumor Oral Drug against Multidrug-Resistant Advanced Bladder Cancers.

Tumor cells produce excessive reactive oxygen species (ROS) but cannot detoxify ROS if they are due to an external agent. An agent that produces toxic levels of ROS, specifically in tumor cells, could be an effective anticancer drug. CMC-2 is a molecular hybrid of the bioactive polyphenol curcumin conjugated to dichloroacetate (DCA) via a glycine bridge. The CMC-2 was tested for its cytotoxic antitumor activities and killed both naïve and multidrug-resistant (MDR) bladder cancer (BCa) cells with equal potency (<1.0 µM); CMC-2 was about 10-15 folds more potent than curcumin or DCA. Growth of human BCa xenograft in mice was reduced by >50% by oral gavage of 50 mg/kg of CMC-2 without recognizable systemic toxicity. Doses that used curcumin or DCA showed minimum antitumor effects. In vitro, the toxicity of CMC-2 in both naïve and MDR cells depended on increased intracellular ROS in tumor cells but not in normal cells at comparable doses. Increased ROS caused the permeabilization of mitochondria and induced apoptosis. Further, adding N-Acetyl cysteine (NAC), a hydroxyl radical scavenger, abolished excessive ROS production and CMC-2's cytotoxicity. The lack of systemic toxicity, equal potency against chemotherapy -naïve and resistant tumors, and oral bioavailability establish the potential of CMC-2 as a potent drug against bladder cancers.

Curcumin Inhibits TORC1 and Prolongs the Lifespan of Cells with Mitochondrial Dysfunction.

Aging is an inevitable biological process that contributes to the onset of age-related diseases, often as a result of mitochondrial dysfunction. Understanding the mechanisms behind aging is crucial for developing therapeutic interventions. This study investigates the effects of curcumin on postmitotic cellular lifespan (PoMiCL) during chronological aging in yeast, a widely used model for human postmitotic cellular aging. Our findings reveal that curcumin significantly prolongs the PoMiCL of wildtype yeast cells, with the most pronounced effects observed at lower concentrations, indicating a hormetic response. Importantly, curcumin also extends the lifespan of postmitotic cells with mitochondrial deficiencies, although the hormetic effect is absent in these defective cells. Mechanistically, curcumin inhibits TORC1 activity, enhances ATP levels, and induces oxidative stress. These results suggest that curcumin has the potential to modulate aging and offer therapeutic insights into age-related diseases, highlighting the importance of context in its effects.

Curcumin suppresses colorectal tumorigenesis through restoring the gut microbiota and metabolites.

BACKGROUND: Curcumin has been reported to have activity for prevention and therapy of CRC, yet its underlying mechanisms remain largely unknown. Recently, emerging evidence suggests that the gut microbiota and its metabolites contribute to the causation and progression of Colorectal cancer (CRC). In this study, we aimed to investigate if curcumin affects the tumorigenesis of CRC by modulating gut microbiota and its metabolites. METHODS: Forty male C57BL/6JGpt mice were randomly divided into four groups: negative control (NC), curcumin control, CRC model, and curcumin treatment (CRC-Cur) groups. CRC mouse model was induced by using azoxymethane (AOM) and dextran sodium sulfate (DSS), and the mice in CRC model and curcumin treatment groups received oral PBS or curcumin (150 mg/kg/day), respectively. Additionally, fecal samples were collected. 16 S rRNA sequencing and Liquid Chromatography Mass Spectrometry (LC-MS)-based untargeted metabolomics were used to observe the changes of intestinal flora and intestinal metabolites. RESULTS: Curcumin treatment restored colon length and structural morphology, and significantly inhibited tumor formation in AOM/DSS-induced CRC model mice. The 16S rRNA sequencing analysis indicated that the diversity and richness of core and total species of intestinal microflora in the CRC group were significantly lower than those in the NC group, which were substantially restored in the curcumin treatment group. Curcumin reduced harmful bacteria, including Ileibacterium, Monoglobus and Desulfovibrio, which were elevated in CRC model mice. Moreover, curcumin increased the abundance of Clostridia_UCG-014, Bifidobacterium and Lactobacillus, which were decreased in CRC model mice. In addition, 13 different metabolites were identified. Compared to the NC group, ethosuximide, xanthosine, and 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) were elevated in the CRC model group, whereas curcumin treatment significantly reduced their levels. Conversely, glutamylleucine, gamma-Glutamylleucine, liquiritin, ubenimex, 5'-deoxy-5'-fluorouridine, 7,8-Dihydropteroic acid, neobyakangelicol, libenzapril, xenognosin A, and 7,4'-dihydroxy-8-methylflavan were decreased in the CRC group but notably upregulated by curcumin. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed enrichment in seven pathways, including folate biosynthesis (P < 0.05). CONCLUSIONS: The gut microecological balance was disrupted in AOM/DSS-induced CRC mice, accompanied by metabolite dysbiosis. Curcumin restored the equilibrium of the microbiota and regulated metabolites, highly indicating that curcumin may alleviate the development of AOM/DSS induced colorectal cancer in mice by regulating intestinal flora homeostasis and intestinal metabolites.

Curcumin nanoparticles in heat stroke management.

OBJECTIVE: The exacerbation of extreme high-temperature events due to global climate change poses a significant challenge to public health, particularly impacting the central nervous system through heat stroke. This study aims to develop Poly(amidoamine) (PAMAM) nanoparticles loaded with curcumin (PAMAM@Cur) to enhance its therapeutic efficacy in hypothalamic neural damage in a heat stroke model and explore its potential mechanisms. METHODS: Curcumin (Cur) was encapsulated into PAMAM nanoparticles through a hydrophobic interaction method, and various techniques were employed to characterize their physicochemical properties. A heat stroke mouse model was established to monitor body temperature and serum biochemical parameters, conduct behavioral assessments, histological examinations, and biochemical analyses. Transcriptomic and proteomic analyses were performed to investigate the therapeutic mechanisms of PAMAM@Cur, validated in an N2a cell model. RESULTS: PAMAM@Cur demonstrated good stability, photostability, cell compatibility, significant blood-brain barrier (BBB) penetration capability, and effective accumulation in the brain. PAMAM@Cur markedly improved behavioral performance and neural cell structural integrity in heat stroke mice, alleviated inflammatory responses, with superior therapeutic effects compared to Cur or PAMAM alone. Multi-omics analysis revealed that PAMAM@Cur regulated antioxidant defense genes and iron death-related genes, particularly upregulating the PCBP2 protein, stabilizing SLC7A11 and GPX4 mRNA, and reducing iron-dependent cell death. CONCLUSION: By enhancing the drug delivery properties of Cur and modulating molecular pathways relevant to disease treatment, PAMAM@Cur significantly enhances the therapeutic effects against hypothalamic neural damage induced by heat stroke, showcasing the potential of nanotechnology in improving traditional drug efficacy and providing new strategies for future clinical applications. SIGNIFICANCE: This study highlights the outlook of nanotechnology in treating neurological disorders caused by heat stroke, offering a novel therapeutic approach with potential clinical applications.

Cytotoxicity of Doxorubicin-Curcumin Nanoparticles Conjugated with Two Different Peptides (CKR and EVQ) against FLT3 Protein in Leukemic Stem Cells.

A targeted micellar formation of doxorubicin (Dox) and curcumin (Cur) was evaluated to enhance the efficacy and reduce the toxicity of these drugs in KG1a leukemic stem cells (LSCs) compared to EoL-1 leukemic cells. Dox-Cur-micelle (DCM) was developed to improve the cell uptake of both compounds in LSCs. Cur-micelle (CM) was produced to compare with DCM. DCM and CM were conjugated with two FLT3 (FMS-like tyrosine kinase)-specific peptides (CKR; C and EVQ; E) to increase drug delivery to KG1a via the FLT3 receptor (AML marker). They were formulated using a film-hydration technique together with a pH-induced self-assembly method. The optimal drug-to-polymer weight ratios for the DCM and CM formulations were 1:40. The weight ratio of Dox and Cur in DCM was 1:9. DCM and CM exhibited a particle size of 20-25 nm with neutral charge and a high %EE. Each micelle exhibited colloidal stability and prolonged drug release. Poloxamer 407 (P407) was modified with terminal azides and conjugated to FLT3-targeting peptides with terminal alkynes. DCM and CM coupled with peptides C, E, and C + E exhibited a higher particle size. Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells.

The Composition Optimization of Curcumin-Loaded Double Oil-Water-Oil Emulsions and Their Stability Evaluation.

This study aimed to optimize the preparation of multiple oil-water-oil (O/W/O) emulsions using varying amounts of Tween 20 emulsifier, different homogenization methods, and optimal preparation temperatures as carriers for encapsulated curcumin. Following the optimization process, the optimal preparation temperature was found to be 25 °C, with a homogenization speed of 10,000 RPM and an emulsifier concentration of 0.5% Tween 20. Subsequently, the effects of physicochemical and viscoelastic properties on the different types of oils used in the outer phase, as well as the impact of storage time, were monitored. The novelty of this work lies in its comprehensive analysis of the stability and encapsulation efficiency of multiple emulsions using various oils, an area that has not been extensively explored before. After identifying the optimal preparation procedure, all samples with different edible oils demonstrated excellent stability and encapsulation efficiency, showing minimal variation in results. The most stable multiple emulsion was found to be the one with coconut oil in the outer phase, exhibiting half the particle size compared to other samples and the lowest encapsulation efficiency losses over 50 days of storage. This study provides new insights into the formulation of stable multiple emulsions for the effective delivery of curcumin and similar bioactive compounds.

Radiolabeled Probes from Derivatives of Natural Compounds Used in Nuclear Medicine.

Natural compounds are important precursors for the synthesis of new drugs. The development of novel molecules that are useful for various diseases is the main goal of researchers, especially for the diagnosis and treatment of many diseases. Some pathologies need to be treated with radiopharmaceuticals, and, for this reason, radiopharmaceuticals that use the radiolabeling of natural derivates molecules are arousing more and more interest. Radiopharmaceuticals can be used for both diagnostic and therapeutic purposes depending on the radionuclide. ß+- and gamma-emitting radionuclides are used for diagnostic use for PET or SPECT imaging techniques, while α- and ß--emitting radionuclides are used for in metabolic radiotherapy. Based on these assumptions, the purpose of this review is to highlight the studies carried out in the last ten years, to search for potentially useful radiopharmaceuticals for nuclear medicine that use molecules of natural origin as lead structures. In this context, the main radiolabeled compounds containing natural products as scaffolds are analyzed, in particular curcumin, stilbene, chalcone, and benzofuran. Studies on structural and chemical modifications are emphasized in order to obtain a collection of potential radiopharmaceuticals that exploit the biological properties of molecules of natural origin. The radionuclides used to label these compounds are 68Ga, 44Sc, 18F, 64Cu, 99mTc, and 125I for diagnostic imaging.

Efficient delivery of curcumin by functional solid lipid nanoparticles with promoting endosomal escape and liver targeting properties.

In the realm of intracellular drug delivery, overcoming the barrier of endosomal entrapment stands as a critical factor influencing the effectiveness of nanodrug delivery systems. This study focuses on the synthesis of an acid-sensitive fatty acid derivative called imidazole-stearic acid (IM-SA). Leveraging the proton sponge effect attributed to imidazole groups, IM-SA was anticipated to play a pivotal role in facilitating endosomal escape. Integrated into the lipid core of solid lipid nanoparticles (SLNs), IM-SA was paired with hyaluronic acid (HA) coating on the surface of SLNs loading with curcumin (CUR). The presence of IM-SA and HA endowed HA-IM-SLNs@CUR with dual functionalities, enabling the promotion of endosomal escape, and specifical targeting of liver cancer. HA-IM-SLNs@CUR exhibited a particle size of ∼228 nm, with impressive encapsulation efficiencies (EE) of 87.5 % ± 2.3 % for CUR. Drugs exhibit significant pH sensitive release behavior. Cellular experiments showed that HA-IM-SLN@CUR exhibits enhanced drug delivery capability. The incorporation of IM-SA significantly improved the endosomal escape of HA-IM-SLN@CUR, facilitating accelerated intracellular drug release and increasing intracellular drug concentration, exhibiting excellent growth inhibitory effects on HepG2 cells. Animal experiments revealed a 3.4-fold increase in CUR uptake at the tumor site with HA-IM-SLNs@CUR over the free CUR, demonstrating remarkable tumor homing potential with the tumor growth inhibition rate of 97.2 %. These findings indicated the significant promise of HA-IM-SLNs@CUR in the realm of cancer drug delivery.

Identification of novel natural compounds against CFTR p.Gly628Arg pathogenic variant.

Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ion channel found in numerous epithelia and controls the flow of water and salt across the epithelium. The aim of our study to find natural compounds that can improve lung function for people with cystic fibrosis (CF) caused by the p.Gly628Arg (rs397508316) mutation of CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands that included Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and one Trikafta (R*) reference drug were screened out from PubChem database. Autodock vina software carried out docking, and binding energies between the drug and the target were included using docking-score. The following tools examined binding energy, interaction, stability, toxicity, and visualize protein-ligand complexes. The compounds having binding energies of -6.4, -5.1, -6.6, -5.1, and - 6.5 kcal/mol for Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and R*-drug, respectively with mutated CFTR (Gly628Arg) structure were chosen as the most promising ligands. The ligands bind to the mutated CFTR protein structure active sites in hydrophobic bonds, hydrogen bonds, and electrostatic interactions. According to ADMET analyses, the ligands Armepavine and Quercetin also displayed good pharmacokinetic and toxicity characteristics. An MD simulation for 200 ns was also established to ensure that Armepavine and Quercetin ligands attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that Armepavine and Quercetin have stronger capacity to inhibit the effect of mutated CFTR protein through improved trafficking and restoration of original function.

A comprehensive update on the potential of curcumin to enhance chemosensitivity in colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related mortality worldwide. The efficacy of chemotherapy agents in CRC treatment is often limited due to toxic side effects, heterogeneity of cancer cells, and the possibility of chemoresistance which promotes cancer cell survival through several mechanisms. Combining chemotherapy agents with natural compounds like curcumin, a polyphenol compound from the Curcuma longa plant, has been reported to overcome chemoresistance and increase the sensitivity of cancer cells to chemotherapeutics. Curcumin, alone or in combination with chemotherapy agents, has been demonstrated to prevent chemoresistance by modulating various signaling pathways, reducing the expression of drug resistance-related genes. The purpose of this article is to provide a comprehensive update on studies that have investigated the ability of curcumin to enhance the efficacy of chemotherapy agents used in CRC. It is hoped that it can serve as a template for future research on the efficacy of curcumin, or other natural compounds, combined with chemotherapy agents to maximize the effectiveness of therapy and reduce the side effects that occur in CRC or other cancers.

An In Silico Study on Withania somnifera Bioactives and Curcumin Analogs as Potential Inducers of Smoothened (Smo) Receptor of Sonic Hedgehog (SHH) Pathway to Promote Oligodendrogenesis.

Demyelinating disorder is a subset of neurodegenerative conditions wherein factors such as aging and/or auto-immune attack cause damage and degradation of myelin sheath which enwraps the neuronal axons. Lowered axonal integrity and sub-par conduction of nerve impulses due to impaired action potentials make neurodegeneration imminent as the neurons do not have mitotic ability to replenish their numbers. Oligodendrocytes (OLs) myelinate the axonal segments of neurons and perform neuronal maintenance. Neuroregenerative stem cell therapy exploits this property for remyelination by targeting OL replenishment using in vitro stem cell differentiation protocols for inducing OL lineage cells. But some shortcomings of such protocols are over-reliance on synthetic inducers, lengthy differentiation process, low differentiation efficiency besides being financially expensive. This in silico study sought to identify herbal substitutes of currently available OL-lineage-specific synthetic inducers from a virtual library of curcumin analogs and Withania somnifera bioactives. Smoothened (Smo) receptor belonging to the canonical sonic hedgehog (SHH) signaling pathway promotes in vivo differentiation of OLs as well as their subsequent lineage progression to myelinating OLs. Therefore, we performed pharmacokinetics prediction for the bioactives followed by their molecular docking and molecular dynamics simulation with Smo. From a pool of 1289 curcumin analogs and 80 Withania somnifera-derived bioactives, the best docked ligands were identified as the compounds with PubChem IDs 68815167 and 25880, respectively. Molecular dynamics simulation of these ligands further concluded the Withania somnifera bioactive 25880 to have the best activity with Smo. This compound may be deemed as a potential lead molecule for an agonistic interaction with and activation of Smo to initialize its downstream signaling cascade for enriching OL differentiation.

Highly efficient and broad-spectrum antibacterial carbon dots combat antibiotic resistance.

Bacterial infections have become a major global public health issue, particularly with the emergence of multidrug-resistant strains. Therefore, developing non-antibiotic antimicrobial agents is crucial for treating drug-resistant bacterial infections. Building on previous research into natural products as novel antibacterial agents, this study synthesized curcumin-derived carbon dots using curcumin and ethylenediamine as raw materials through a hydrothermal method. The resulting carbon dots not only improved the water solubility and stability of curcumin but also exhibited highly efficient broad-spectrum antibacterial activity. Detailed investigations into the antibacterial performance and mechanisms of the carbon dots were conducted through experiments such as minimum inhibitory concentration (MIC) determination, live/dead bacterial staining, morphological studies, nucleic acid concentration detection, and reactive oxygen species (ROS) detection. The results indicated that the carbon dots significantly damaged the structural integrity of bacteria and generated large amounts of ROS. They exhibited remarkable antibacterial effects against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and effectively inhibited drug-resistant MRSA. Their antibacterial efficacy was notably superior to that of broad-spectrum antibiotics such as chloramphenicol and Sulfadiazine. This study highlights the potential application of curcumin-derived carbon dots in combating bacterial infections and provides valuable insights for developing novel antibacterial agents derived from natural products.

Tailored alginate sponges loaded with κ-carrageenan beads for controlled release of curcumin.

This study presents an innovative approach to develop and characterize an alginate sponge containing κ-carrageenan (κ-CRG) beads loaded with curcumin. The beads were fabricated using varying concentrations of κ-CRG, and their properties were extensively evaluated using inverted phase-contrast microscopy, Scanning Electron Microscopy (SEM), FTIR, swelling behavior, mass distribution, encapsulation efficiency, in vitro drug release and kinetics of drug release. Beads formulated with specific concentrations of κ-CRG that exhibited optimal performance were then integrated into an alginate sponge matrix, which underwent similar comprehensive testing procedures as the individual beads. The characterized beads displayed a spherical morphology, a notable swelling degree of approximately 146 %, excellent mass uniformity, encapsulation efficiencies higher than 90 % and drug release rate exceeding 70 %. Moreover, the alginate sponge formulation demonstrated a satisfactory drug release profile of 67.9 ±â€¯0.6 %. In terms of drug release kinetics, the Higuchi model was the most effective in explaining the release of curcumin from beads and sponge. These findings underscore the potential of both the beads and the sponge as effective vehicles for the controlled delivery of curcumin, positioning them as promising candidates for pharmaceutical applications across various fields.

Comparative effects of curcumin, nano curcumin and their combination on reproductive traits and spawning performance of red tilapia (Oreochromis Niloticus X O. Mossambicus).

Curcumin, the main polyphenol component of turmeric powder, has garnered increasing attention as an effective supplement in fish diets. A comparative trial was conducted to evaluate the impacts of dietary supplementation with different forms of curcumin (free, in combination, or nanoparticles) on hemato-biochemical parameters, reproductive capacity, and related gene expressions of red tilapia (Oreochromis niloticus x O. mossambicus) broodstock. Fish (n = 168) were fed an isonitrogenous (30% CP), isocaloric (18.72 MJ kg - 1) diet containing basal diet (Control), 60 mg kg-1 of either free curcumin (Cur), curcumin/nano-curcumin blend (Cur/NCur), or nano-curcumin (NCur) for 56 days. Red tilapia broodstock (155 ± 5.65 g) were stocked at a male: female ratio of 1:3. Blood samples and gonads were collected to assess hemato-biochemical parameters, reproductive capacity, and related gene expression at the end of the feeding trial. The results indicated that the values of hematological parameters (RBCs, WBCs, hemoglobin), total protein, albumin values, and reproductive hormones (T, LH, and FSH) were significantly increased, while liver function enzymes were decreased in the NCur group (P < 0.05). Reproductive performances (GSI, gonad maturation, total number of fry per female) were significantly improved in the NCur group compared with those in other groups (p < 0.05). The expression of reproductive genes (CYP19A1A, FSHR, LHR, FOXL2A, ESR1, ESR2A, and PGR) were significantly up-regulated in the gonads of fish fed NCur. Collectively, feeding red tilapia diets containing NCur led to noticeably better results followed by Cur/NCur blend, then free Cur compared to the control diet. These results indicate the superiority of NCur over its free or blended form, suggesting that a diet containing about 60 mg/kg of NCur is beneficial for enhancing hemato-biochemical parameters, improving reproductive performance, and enhancing the gonadal architecture of red tilapia.

Harnessing curcumin in a multifunctional biodegradable metal-organic framework (bio-MOF) for targeted colorectal cancer theranostics.

Despite significant advancements in managing colorectal cancer (CRC), the issues of efficient diagnosis and targeted therapy remain demanding. To address these challenges and improve treatment outcomes while reducing the cost and side effects, there is a need for more effective theranostic systems that combine diagnostic techniques with therapeutic modalities. This study introduces a pioneering approach for the synthesis of a porous bio-MOF (biodegradable metal-organic framework) using iron as the metal component and curcumin as the pharmaceutical ingredient. Subsequently, the developed drug delivery system was equipped with the anticancer drug doxorubicin (DOX), coated with biocompatible polyethylene glycol (PEG), and targeted with a CRC-specific aptamer (EpCAM). The physicochemical characterization confirmed the successful synthesis of the bio-MOF, demonstrating high encapsulation efficiency and pH-dependent release of DOX. In vitro studies for anticancer activity, cellular uptake, and mechanism of cell death demonstrated that in the case of positive EpCAM HT-29 cells, Apt-PEG-MOF@DOX had enhanced internalization that resulted in massive apoptosis. In vivo studies of the nanoparticles were then conducted in immunocompromised C57BL/6 mice bearing HT-29 tumors. These studies showed that the targeted platform could induce efficient tumor regression with reduced systemic toxicity. The targeted bio-MOF also exhibited MRI imaging properties useful for monitoring tumors. Significantly, the biocompatibility of the introduced bio-MOF was enhanced by pursuing the green synthesis method, which does not engage toxic solvents and strong acids. Overall, this multimodal system acts diversely as a tumor imaging agent and a therapeutic delivery platform suitable for CRC theranostics.

Enhancement of gold-curcumin nanoparticle mediated radiation response for improved therapy in cervical cancer: a computational approach and predictive pathway analysis.

Radiotherapy is prevalently applied for highly effective cancer therapy while the low specificity of radiation is deleterious to the nearby healthy cells. High-Z-based nanomaterials offer excellent radio-enhancement properties while natural products provide radioprotection. Modulation of the radiotherapeutic index via applying nanomaterials is feasible for effective treatment however, the scenario changes when simultaneous protection of non-cancerous cells is required. Here, we report the modulatory radiotherapeutic effect of curcumin conjugated gold nanoparticles in a single nanoformulation to pave the long-awaited hope of a single combination-based, cell-selective radio enhancer, and protectant for cancer radiotherapy. We have validated the effective radiation dose along with the combination of the radio-nano-modulator by a reverse experimentation statistical model. The concept was supported by different sets of experiments, like quantification of ROS generation, cell cycle monitoring, mitochondrial membrane potential measurement, etc. along with gene expression study, and predictive modeling of molecular pathways of the killing mechanism. In conclusion, the nanoconjugate showed a promise to become a candidate for the pH-dependent cell-specific radio-modulator.

Potential Roles and Mechanisms of Curcumin and its Derivatives in the Regulation of Ferroptosis.

Ferroptosis is a recently discovered iron-dependent mode of oxidatively regulated cell death. It is not only associated with a wide range of diseases, but it is also a key component of many signaling pathways. In general, ferroptosis is a double-edged sword. On one hand, it induces nonapoptotic destruction of cancer cells, but on the other, it may lead to organ damage. Therefore, ferroptosis can be drug-targeted as a novel means of therapy. The properties of curcumin have been known for many years. It has a positive impact on the treatment of diseases such as cancer and inflammation. In this review, we focus on the regulation of ferroptosis by curcumin and its derivatives and review the main mechanisms by which curcumin affects ferroptosis. In conclusion, curcumin is a ferroptosis inducer with excellent anticancer efficacy, although it also exhibits organ protective and reparative effects by acting as a ferroptosis inhibitor. The differential regulation of ferroptosis by curcumin may be related to dose and cell type.

Curcumin promotes ferroptosis in hepatocellular carcinoma via upregulation of ACSL4.

BACKGROUND: Ferroptosis, a novel iron-ion-dependent metabolic cell death mode with lipid peroxides as the main driving substrate, plays an irreplaceable role in the development and preventive treatment of hepatocellular carcinoma. Curcumin has potent pharmacological anti-tumor effects. AIM OF THE STUDY: We aimed to evaluate the ex vivo and in vivo cancer inhibitory activity of curcumin and its specific mechanism of action. MATERIALS AND METHODS: We used the hepatocellular carcinoma cell lines HepG2 and SMMC7721 to assess the direct inhibition of hepatocellular carcinoma proliferation by curcumin in vitro and a tumor xenograft model to evaluate the in vivo cancer inhibitory effect of curcumin. RESULTS: In this study, we found that ferroptosis's inhibitors specifically reversed the curcumin-induced cell death pattern in HCC. After curcumin intervention, there was a substantial increase in MDA levels and iron ion levels, and a decrease in intracellular GSH levels. Meanwhile, the expression of GPX4 and SLC7A11 was significantly reduced at the protein levels, while ACSL4 and PTGS2 expression was significantly increased. CONCLUSIONS: This study showed that curcumin significantly decreased the proliferation of HCC cells and significantly increased the sensitivity of ferroptosis. These results suggest that ACSL4 is a viable target for curcumin-induced ferroptosis in treating HCC.