Curcumin Targets Research Articles

Curcumin is an efficacious therapeutic agent against Chilodonella uncinata via interaction with tubulin alpha chain as protein target

Chilodonella, a parasitic ciliate that infects both cold water and warm water fish, can impede the growth of juvenile fish and cause considerable economic losses globally to freshwater aquaculture. In this study, the parasite was collected from both the gills and zygotes of largemouth bass (Micropterus salmoides). Isolated from diseased fish, the parasites were identified as Chilodonella uncinata based on morphological features and genetical diagnostic characterization using the partial small subunit ribosomal RNA gene. To develop an effective approach to treat chilodonellosis caused by C. uncinata in largemouth bass farming, we first developed an in vivo culture model for propagating C. uncinate and thus could use for morphological characterization, molecular analyses and antiparasitic drug screening. Curcumin was successfully identified as an efficacious anti-C. uncinata agent from 26 phytochemical compounds. When administered at a concentration of 6 mg/L, curcumin not only completely cured infected largemouth bass but also shielded uninfected fish from C. uncinata infections. The 24 h median effective concentration (EC50) of curcumin against C. uncinata was 3.098 mg/L. Remarkably, the 96 h median lethal concentration (LC50) of curcumin against largemouth bass was determined to be 17.143 mg/L, approximately 5.533 times higher than EC50. The mechanism of action of curcumin was investigated by the cellular thermal shift assay, demonstrating that tubulin alpha chain was the binding target for curcumin. Moreover, SEM investigations further provided morphological evidence suggesting that curcumin induces parasite demise by disrupting the parasite's body surface and subsequently infiltrating its interior. These findings collectively emphasize the potential of curcumin as a safe and effective therapeutic agent for controlling C. uncinata in aquaculture.

Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin

AbstractDiabetes mellitus is a chronic metabolic disorder affecting millions of people worldwide and causes serious complications such as diabetic nephropathy. Curcumin, a natural polyphenol derived from turmeric, has demonstrated antidiabetic, anti‐inflammatory, and antioxidant properties. However, the molecular mechanisms underlying curcumin's anti‐diabetic effects remain incompletely understood. This study employed network pharmacology, molecular docking, and simulation techniques to explore the potential targets, and key pathways of curcumin in the treatment of diabetes. Using SwissTarget prediction and Superpred databases, we predicted the molecular targets for curcumin, while diabetes‐associated genes were obtained from DisGeNet. We identified 60 common targets for curcumin in diabetes. Protein‐protein interaction (PPI) analysis revealed three sub‐networks and ten hub genes with AKT1, TNF‐α, EGFR, and STAT3 identified as key hub genes that could serve as potential biomarkers. Gene enrichment analysis indicated that these genes primarily regulate insulin resistance and other metabolic pathways. Quantum‐polarized ligand docking (QPLD) showed that curcumin establishes multiple hydrogen and hydrophobic interactions with the essential amino acids of these hub targets. Molecular simulation results demonstrated stable dynamic behavior, a compact structure, and variations in residue flexibility. Binding free energy calculations using MM/GBSA and MM/PBSA methods validate curcumin's strong binding to the potential targets. Total binding free energy using MM/GBSA ranged from −21.35 to −30.94 kcal/mol while MM/PBSA calculations showed total binding free energy values between −19.80 and −26.66 kcal/mol. Altogether, this study provides valuable insights into the molecular targets of curcumin in diabetes and lays the foundation for future advancements in diabetes treatment.

Common Mitochondrial Targets of Curcumin and Cinnamic Acid, the Membrane-Active Natural Phenolic Compounds

Background: Research has shown the multiple actions of curcumin on different cell systems, including enzymes and mitochondria. The detected effects of curcumin on mitochondria are diverse, ranging from protective to toxic. Objectives: In this present work, the influence of curcumin, as well as cinnamic acid, which is a microbial metabolite and a possible product of the microbial breakdown of curcumin, on isolated mitochondria, was investigated. Methods: Membrane potential, swelling, respiration, and calcium retention capacity were studied using selective electrodes, fluorescence and spectral methods. Results: It was found that curcumin at low concentrations (10–20 μM) activated the opening of the calcium-dependent permeability transition pore (mPTP) and decreased the calcium retention capacity and threshold concentrations necessary for the mPTP opening. Moreover, curcumin caused a concentration-dependent stepwise decrease in the membrane potential, accompanied by the activation of respiration and a decrease in oxidative phosphorylation, which indicates that curcumin is a typical mitochondrial uncoupler. The uncoupling effect strongly depended on the concentration of curcumin, which also increased, stepwise, from weak uncoupling at 25 µM to complete uncoupling at 75–100 µM. Cinnamic acid had similar effects, with the exception of the depolarizing effect, at concentrations that were an order of magnitude higher. Conclusions: Presumably, the uncoupling action of curcumin is a priming event that modulates any energy- and redox-dependent mitochondrial functions, from positive stimulation to toxic disorder. This effect can also underlie the curcumin-induced changes in different cellular processes and be achieved by targeted delivery of curcumin to certain cells, bypassing the microbiota.

Causal relationship between fertility nutrients supplementation and PCOS risk: a Mendelian randomization study.

Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder in women of reproductive age, is mainly ameliorated through drugs or lifestyle changes, with limited treatment options. To date, numerous researchers have found that fertility nutrient supplements may benefit female reproductive health, but their direct impact on polycystic ovary syndrome risk remains unclear. Our research employs Mendelian Randomization to assess how fertility nutrients affect PCOS risk. Initially, we reviewed 49 nutrients and focused on 10: omega-3 fatty acids, calcium, dehydroepiandrosterone, vitamin D, betaine, D-Inositol, berberine, curcumin, epigallocatechin gallate, and metformin. Using methodologies of Inverse Variance Weighting and Mendelian Randomization-Egger regression, we examined their potential causal relationships with PCOS risk. Our findings indicate omega-3 fatty acids reduced PCOS risk (OR=0.73, 95% CI: 0.57-0.94, P=0.016), whereas betaine increased it (OR=2.60, 95% CI: 1.09-6.17, P=0.031). No definitive causal relations were observed for calcium, dehydroepiandrosterone, vitamin D, D-Inositol, and metformin (P>0.05). Drug target Mendelian Randomization analysis suggested that increased expression of the berberine target gene BIRC5 in various tissues may raise PCOS risk (OR: 3.00-4.88; P: 0.014-0.018), while elevated expressions of curcumin target gene CBR1 in Stomach and epigallocatechin gallate target gene AHR in Adrenal Gland were associated with reduced PCOS risk (OR=0.48, P=0.048; OR=0.02, P=0.018, respectively). Our research reveals that specific fertility nutrients supplementation, such as omega-3 fatty acids, berberine, and curcumin, may reduce the risk of PCOS by improving metabolic and reproductive abnormalities associated with it.

Effects of Curcumin on Radiation/Chemotherapy-Induced Oral Mucositis: Combined Meta-Analysis, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

The study aims to investigate the effects of curcumin on radiation/chemotherapy-induced oral mucositis (R/CIOM) and preliminarily explore its mechanism. Randomized controlled trials were identified from the PubMed, Embase, Web of Science, Cochrane Library, Medline, and Google Scholar databases. RevMan 5.4 was used for statistical analysis to calculate the combined risk ratios (RRs). The mechanism was analyzed through network pharmacology, molecular docking, and a molecular dynamics simulation. The targets of curcumin were collected in HERB, PharmMapper, Targetnet, Swiss Target Prediction, and SuperPred. OMIM, GeneCards, and Disgenet were used to collect relevant targets for R/CIOM. Cytoscape software 3.8.0 was used to construct the component-target-pathway network. Protein-Protein Interaction (PPI) networks were constructed using the STRING database. GO and KEGG enrichment analyses were performed by Metascape. AutoDock Vina 4.2 software was used for molecular docking. The molecular dynamics simulation was performed by Gromacs v2022.03. It is found that 12 studies involving 565 patients were included. Meta-analyses showed that curcumin reduced the incidence of severe R/CIOM (RR 0.42 [0.24, 0.75]) and the mean severity of R/CIOM (MD -0.93 [-1.34, -0.52]). Eleven core target genes were identified in the treatment of R/CIOM with curcumin. The results of molecular docking and the molecular dynamics simulation showed that curcumin had strong binding energy and stability with target proteins including MAPK3, SRC, and TNF. Overall, these findings suggest curcumin can effectively improve severe R/CIOM, perhaps by affecting MAPK3, SRC, and TNF.

Binary nanoconjugation of zein–methylcellulose for improving curcumin properties: solubility, controlled release and anticancer activity

AbstractFor cancer treatment, a novel nanocarrier has been developed, utilizing natural compounds. Zein protein (Z) and methylcellulose (MC) polysaccharide were formulated as a nanocarrier for nutraceutical curcumin (Cur). The zein–methylcellulose nanoconjugate (ZMC) appeared spherical/monodispersed in transmission electron microscopy images. Hydrodynamic sizes were 164 ± 20.2 and 190 ± 28.2 nm for ZMC and ZMC@Cur, respectively. For both formulations, zeta potential, differential scanning calorimetry, Fourier transform infrared spectroscopy and X‐ray diffraction analyses were conducted. Curcumin encapsulation efficiency was 92%, and its release profile was pH responsive. Using MTT assay, ZMC@Cur demonstrated a significant cytotoxic effect against MCF‐7 and HepG2, surpassing the impact of curcumin. This underscores the pivotal role of ZMC@Cur in enhancing curcumin properties, thereby potentiating cancer cell death. Compared with free curcumin, ZMC@Cur markedly promoted DNA damage in cancer cells, owing to precise curcumin targeting into the nucleus. Accordingly, the proposed bionanocomposite stands as an efficient vehicle for curcumin, showcasing its crucial role in combating cancer via improving the pharmaceutical properties of curcumin. © 2024 Society of Chemical Industry.

Bioinformatics and validation reveal the potential target of curcumin in the treatment of diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a common nerve-damaging complication of diabetes mellitus. Effective treatments are needed to alleviate and reverse diabetes-associated damage to the peripheral nerves. Curcumin is an effective neuroprotectant that plays a protective role in DPN promoted by Schwann cells (SCs) lesions. However, the potential molecular mechanism of curcumin remains unclear. Therefore, our aim is to study the detailed molecular mechanism of curcumin-mediated SCs repair in order to improve the efficacy of curcumin in the clinical treatment of DPN. First, candidate target genes of curcumin in rat SC line RSC96 cells stimulated by high glucose were identified by RNA sequencing and bioinformatic analyses. Enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out by Metascape, followed by 8 algorithms on Cytoscape to determine 4 hub genes, namly Hmox1, Pten, Vegfa and Myc. Next, gene set enrichment analysis (GSEA) and Pearson function showed that Hmox1 was significantly correlated with apoptosis. Subsequently, qRT-PCR, MTT assay, flow cytometry, caspase-3 activity detection and westernblot showed that curcumin treatment increased RSC96 cell viability, reduced cell apoptosis, increased Hmox1, Pten, Vegfa and Myc expression, and up-regulated Akt phosphorylation level under high glucose environment. Finally, molecular docking predicted the binding site of curcumin to Hmox1. These results suggest that curcumin can reduce the apoptosis of SCs induced by high glucose, and Hmox1 is a potential target for curcumin. Our findings provide new insights about the mechanism of action of curcumin on SC as a potential treatment in DPN.

Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network-based pharmacological and cellular assay.

Hepatocellular carcinoma currently has the third highest mortality rate in the world. Patients with hepatocellular carcinoma are on the rise and at a younger age, but research into the pharmacological effects of cancer is mostly single-component, and natural plant products can have additive or synergistic effects that can better amplify the effects of intervention in cancer. To evaluate the synergistic therapeutic effects of 6-shogaol and curcumin against hepatocellular carcinoma line HepG2 cells. In this study, a network pharmacology approach was used to predict and validate the mol ecular targets and pathways of the hepatocellular carcinoma (HCC) of 6-shogaol and curcumin in combination and to investigate their mechanism of action. The results were also validated by cellular assays. HepG2 cells were treated with 6-shogaol and curcumin as well as the combination of the two. The combination index of 6-shogaol and curcumin in HepG2 cells was calculated using Compusyn software according to the Chou-Talalay equation. The synergistic anti-cancer effect was next investigated by MTT assay, apoptosis assay and cell cycle assay. The combined anti-hepatocellular carcinoma effect of the Ras-mediated PI3K/AKT and MAPK signalling pathways was analysed using protein blotting assays. A network pharmacology-based screening identified 72 core targets of 6-curcumin and curcumin in hepatocellular carcinoma, and predicted that the main signalling pathway is the Ras signalling pathway. The anti-cancer effects of 6-shogaol and curcumin were validated in cell-based assays and the optimal synergistic concentrations of 5μmoL/L for 6-shogaol and 30μmoL/L for curcumin were determined. 6-shogaol and curcumin synergistically blocked the cell cycle in the G2/M phase and promoted apoptosis. Immunoblot analysis confirmed for the first time the combined action of both in down-regulating the Ras-mediated PI3K/AKT and MAPK signaling pathways. In addition, 6-shogaol and curcumin acting together downregulated Cyclin-B, CDK-1, Bcl-2, and upregulated BAX. 6-shogaol and curcumin act synergistically to alter the morphology of hepatocellular carcinoma cells, block the cell cycle in the G2/M phase, inhibit proliferation and division, and effectively promote late apoptosis. The combined action of these two components provides a theoretical basis for the further development of novel anti-liver cancer products.

Bioinformatic analysis of the molecular targets of curcumin in colorectal cancer

Colorectal cancer (CRC) is a major global health concern, with rising incidence and mortality rates. Conventional treatments often come with significant complications, prompting the exploration of natural compounds like curcumin as potential therapeutic agents. Using bioinformatic tools, this study investigated the role of curcumin in CRC treatment. Significant protein interactions between curcumin and target proteins were identified in the STITCH database. Differentially expressed genes (DEGs) associated with CRC were then analyzed from GEO databases. Comparing curcumin targets and CRC-related DEGs, nine significant common targets were identified: DNMT1, PCNA, CCND1, PLAU, MMP3, SOX9, FOXM1, CXCL2, and SERPINB5. Pathway enrichment analyses revealed that curcumin-targeted pathways were primarily related to p53, IL-17, NF-kappa B, TNF, and cell cycle signaling, all crucial in CRC development and progression. Further analyses using DAID and EnrichR algorithms showed that the curcumin targets exhibited greater specificity to bronchial epithelial cells and colorectal adenocarcinoma than other diseases. Analyses via the DSigDB database indicated that curcumin ranks highly among other drugs targeting the identified CRC-related genes. Docking studies revealed favorable binding interactions between curcumin and the key CRC-related proteins, suggesting potential molecular mechanisms by which curcumin may exert its effects. In summary, this study provides bioinformatic and docking evidence that curcumin may exert beneficial effects on CRC by modulating the expression or activity of multiple CRC-susceptibility genes involved in critical signaling pathways. These findings warrant further experimental validation and support the potential of curcumin as a therapeutic agent for CRC.

Epigenetic Orchestration of Neurodegenerative Disorders: A Possible Target for Curcumin as a Therapeutic.

Epigenetic modulations play a major role in gene expression and thus are responsible for various physiological changes including age-associated neurological disorders. Neurodegenerative diseases such as Alzheimer's(AD), Parkinson's(PD), Huntington's disease(HD), although symptomatically different, may share common underlying mechanisms. Most neurodegenerative diseases are associated with increased oxidative stress, aggregation of certain proteins, mitochondrial dysfunction, inactivation/dysregulation of protein degradation machinery, DNA damage and cell excitotoxicity. Epigenetic modulations has been reported to play a significant role in onset and progression of neurodegenerative diseases by regulating these processes. Previous studies have highlighted the marked antioxidant and neuroprotective abilities of polyphenols such as curcumin, by increased activity of detoxification systems like superoxide dismutase (SOD), catalase or glutathione peroxidase. The role of curcumin as an epigenetic modulator in neurological disorders and neuroinflammation apart from other chronic diseases have also been reported by a few groups. Nonetheless, the evidences for the role of curcumin mediated epigenetic modulation in its neuroprotective ability are still limited. This review summarizes the current knowledge of the role of mitochondrial dysfunction, epigenetic modulations and mitoepigenetics in age-associated neurological disorders such as PD, AD, HD, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis(MS), and describes the neuroprotective effects of curcumin in the treatment and/or prevention of these neurodegenerative diseases by regulation of the epigenetic machinery.

Curcumin suppresses colorectal cancer by induction of ferroptosis via regulation of p53 and solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 signaling axis.

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.

Exploring the therapeutic mechanism of curcumin in prostate cancer using network pharmacology and molecular docking

ObjectiveCurcumin, a phenolic compound extracted from turmeric rhizomes, exhibits antitumour effects in preclinical models of tumours. However, its mechanism of action in prostate cancer remains unclear. Exploring the molecular mechanisms of curcumin in prostate cancer based on network pharmacology and molecular docking provides a new theoretical basis for prostate cancer treatment. MethodUsing tools such as PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction, we obtained information on curcumin-related targets. We comprehensively collected prostate cancer-related targets from several databases, including GeneCards, CTD, DisGeNET, OMIM, and PharmGKB. Cross-cutting drug-disease targets were then derived by screening using the Venny 2.1.0 tool. Subsequently, we used the DAVID platform to perform in-depth GO and KEGG enrichment analyses of the drug-disease-shared targets. To construct a PPI network map of the cross-targets and screen the 10 core targets, we combined the STRING database and Cytoscape 3.7.2. Molecular docking experiments were performed using AutoDockTools 1.5.7 software. Finally, we used several databases such as GEPIA, HPA, cBioPortal, and TIMER to further analyse the screened core targets in detail. ResultWe identified 307 key targets of curcumin in cancer treatment. After GO functional enrichment analysis, we obtained 1119 relevant entries, including 782 biological progression (BP) entries, 112 cellular component (CC) entries, and 225 molecular function (MF) entries. In addition, KEGG pathway enrichment analysis revealed 126 signalling pathways, which were mainly involved in the cancer pathway, such as lipid and atherosclerosis pathway, PI3K-Akt signal pathway, MAPK signal pathway, Ras signal pathways, and chemical carcinogenesis-reactive oxygen species. By applying Cytoscape 3.7.2 software, we identified SRC, PIK3R1, STAT3, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1 as core targets. Molecular docking experiments showed that the binding energies of curcumin to these core targets were all below −1.85 kJ mol−1, which fully demonstrated that curcumin could spontaneously bind to these core targets. Finally, these results were validated at multiple levels, including mRNA expression, protein expression, and immune infiltration. ConclusionThrough in-depth network pharmacology and molecular docking studies, we have found that curcumin may have anticancer potential by upregulating the expression of PIK3R1 and STAT3, and downregulating the binding ability of molecules such as SRC, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1. In addition, curcumin may interfere with the cyclic process of prostate cancer cells by inhibiting key signalling pathways such as the PI3K-Akt signalling pathway, MAPK signalling pathway, and Ras, thereby inhibiting their growth. This study not only reveals the potential molecular mechanism of curcumin in the treatment of prostate cancer but also provides an important theoretical basis for subsequent research.

Exploring the Targets and Molecular Mechanisms of Curcumin for the Treatment of Bladder Cancer Based on Network Pharmacology, Molecular Docking and Molecular Dynamics.

Curcumin, a phenolic compound derived from turmeric, has demonstrated anti-tumor properties in preclinical models of various cancers. However, the exact mechanism of curcumin in treating bladder cancer remains unclear. This study aimed to elucidate the therapeutic targets and molecular mechanisms of curcumin in the treatment of BC through an integrated approach of network pharmacology, molecular docking, and molecular dynamics simulations. PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction were utilized to acquire targets associated with curcumin, while GeneCards, CTD, DisGeNET, OMIM, and PharmGKB databases were utilized to obtain targets related to bladder cancer. The drug-disease interaction targets were obtained using Venny 2.1.0, and GO and KEGG enrichment analyses were then conducted with the DAVID tool. We constructed a protein-protein interaction (PPI) network and identified tenkey targets. In conclusion, AutoDock Tools 1.5.7 was utilized to conduct molecular docking simulations, followed by additional analysis of the central targets through the GEPIA, HPA, cBioPortal, and TIMER databases. A total of 305 potential anticancer targets of curcumin were obtained. The analysis of GO functional enrichment resulted in a total of 1105 terms, including 786 terms related to biological processes (BP), 105 terms related to cellular components (CC), and 214 terms related to molecular functions (MF). In addition, KEGG pathway enrichment analysis identified 170 relevant signaling pathways. Treating bladder cancer could potentially involve inhibiting pathways like the PI3K-Akt signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, and IL-17 signaling pathway. Activating TNF, ALB, CASP3, and ESR1 while inhibiting AKT1, EGFR, STAT3, BCL2, SRC, and HSP90AA1 can also hinder the proliferation of bladder tumor cells. According to the results of molecular docking, curcumin binds to these central targets in a spontaneous manner, exhibiting binding energies lower than -1.631kJ/mol. These findings were further validated at the transcriptional, translational and immune infiltration levels. By utilizing network pharmacology and molecular docking techniques, it was discovered that curcumin possesses diverse effects on multiple targets and pathways for treating bladder cancer. It has the potential to impede the growth of bladder tumor cells by suppressing various pathways including the PI3K-Akt and MAPK signaling pathways, as well as pathways associated with EGFR tyrosine kinase inhibitor resistance and the IL-17 signaling pathway. Curcumin could potentially disrupt the cell cycle advancement in bladder cancer cells by increasing the expression of TNF, ALB, CASP3, and ESR1 while decreasing AKT1, EGFR, STAT3, BCL2, SRC, HSP90AA1, and other targeted genes. These findings reveal the possible molecular pathways through which curcumin exerts its anticancer effects in bladder cancer, and this novel research strategy not only provides an important basis for an in-depth understanding of the anticancer mechanism of curcumin, but also offers new potential drugs and targets for the clinical treatment of bladder cancer. Therefore, this study is of great scientific significance and practical application value for promoting the development of bladder cancer therapeutic field. This finding provides strong support for the development of novel, safe and effective drugs for bladder cancer treatment.

Effect of phospholipid curcumin Meriva on liver histology and kidney disease in nonalcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial.

NASH confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed the safety and efficacy of Meriva in NASH. In this double-blind trial, 52 patients with biopsy-proven NASH (71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a chronic kidney disease) were randomized 1:1 to receive Meriva 2g/d or placebo for 72 weeks. The primary endpoint was NASH resolution with no worsening of fibrosis. The secondary endpoints included a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant (ie, stage ≥F2) fibrosis and CKD; and improvement in renal, glucose, lipid, and inflammatory parameters. We also explored the treatment effect on hepatic activation of NF-kB, a key proinflammatory transcription factor and a major target of curcumin. Fifty-one patients (26 on Meriva and 25 on placebo) completed the trial. Sixteen (62%) patients on Meriva versus 3 (12%) patients on placebo had NASH resolution (RR = 5.33 [95% CI = 1.76-12.13]; p = 0.003). Thirteen (50%) patients on Meriva versus 2 (8%) patients on placebo had ≥1 stage fibrosis improvement (RR = 6.50 [1.63-21.20]; p = 0.008). Eleven (42%) patients on Meriva versus 0 (0%) on placebo had regression of significant liver fibrosis (RR = 18.01 [1.43-36.07]; p = 0.02). Hepatic NF-kB inhibition predicted NASH resolution (AUC = 0.90, 95% CI = 0.84-0.95) and fibrosis improvement (AUC = 0.89, 95% CI = 0.82-0.96). Thirteen (50%) patients on Meriva versus 0 (0%) on placebo had chronic kidney disease regression (RR = 10.71 [1.94-17.99)]; p = 0.004). Compared with placebo, Meriva improved eGFR (difference in adjusted eGFR change: +3.59 [2.96-4.11] mL/min/1.73m 2 /y, p = 0.009), fasting glucose(-17mg/dL; 95% CI = -22, -12), HbA1c (-0.62%; 95% CI = -0.87%, -0.37%), LDL-C (-39mg/dL; 95% CI = -45, -33), triglycerides (-36mg/dL, 95% CI = -46, -26), HDL-C (+10mg/dL; 95% CI = +8, +11), and inflammatory markers. Adverse events were rare, mild, and evenly distributed. In patients with NASH, Meriva administration for 72 weeks was safe, well-tolerated, and improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile.

A Docking and Network Pharmacology Study on the Molecular Mechanisms of Curcumin in Dental Caries and Streptococcus mutans.

Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as Streptococcus mutans and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and Streptococcus mutans. We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking. Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in Streptococcus mutans. Curcumin affects both host carious processes and Streptococcus mutans.

Identification of Curcumin Targets in the Brain of Epileptic Mice Using DARTS.

Curcumin, a compound derived from turmeric, is traditionally utilized in East Asian medicine for treating various health conditions, including epilepsy. Despite its involvement in numerous cellular signaling pathways, the specific mechanisms and targets of curcumin in epilepsy treatment have remained unclear. Our study focused on identifying the primary targets and functional pathways of curcumin in the brains of epileptic mice. Using drug affinity responsive target stabilization (DARTS) and affinity chromatography, we identified key targets in the mouse brain, revealing 232 and 70 potential curcumin targets, respectively. Bioinformatics analysis revealed a strong association of these proteins with focal adhesions and cytoskeletal components. Further experiments using DARTS, along with immunofluorescence staining and cell migration assays, confirmed curcumin's ability to regulate the dynamics of focal adhesions and influence cell migration. This study not only advances our understanding of curcumin's role in epilepsy treatment but also serves as a model for identifying therapeutic targets in neurological disorders.

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic β-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor β1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1β), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Smartphone-based imaging colorimetric assay for monitoring the quality of curcumin in turmeric powder.

This research developed a colorimetric assay for semi-quantitative curcumin detection. The screening test was performed using a ferric chloride to form a brownish color which was further used to evaluate the amount of curcumin in the turmeric powder samples. The quantitative assay was performed based on the color intensity of the curcumin target using a smartphone digital image colorimetry with a developed lightbox constructed with a white light-emitting diodes (LED) light source as the measurement device. Images in red, green, and blue (RGB) color were processed to obtain relevant colors from the image and the color values were used to analyze curcumin concentrations. The intensity of the ΔB was correlated to the concentration of curcumin with high sensitivity. The method showed a linear range between 0.25 and 5mg L-1 with the LOD and LOQ of 0.12 and 0.41mg L-1, respectively. Sample analysis was carried out in turmeric powders. Curcumin in turmeric powder samples was simply extracted using acetonitrile followed by dilution 100 times for sample preparation. The accuracy was tested by spiking 0.25, 1.00, and 4.00mg L-1 of standard curcumin into the turmeric sample solution. The average percentage recoveries were acceptable in all samples (90-104%). The method was validated by comparing the results obtained from the proposed method and high-performance liquid chromatography (HPLC). There was no statistically significant difference between the two methods (P = 0.05).

Curcumin targeting miR-761 influences proliferation and apoptosis of colon cancer cells through GSK-3β regulation

Abnormal miR-761 expression involves in colon cancer and curcumin has a significant anti-tumor cell proliferation effect. In this study, we investigated whether curcumin targeting miR-761 can affect colon cancer cells. Control group (NC group), miR-761 Mimics group, and miR-761 Mimics+curcumin group were set up. miR-761 and GSK-3β levels were detected by RT-qPCR. Dual fluorescein report detected the relation between miR-761 and GSK-3β along with analysis of cell proliferation by cloning assay and apoptosis by flow cytometry. Compared with normal tissues, miR-761 expression in colon cancer tissues was lower (P <0.01), while GSK-3β level was higher (P < 0.01). Dual fluorescein report analysis showed GSK-3β as a target of miR-761. Compared with NC group, clone number in miR-761 Mimics group decreased, the proliferation capacity decreased, and apoptotic number increased. While compared with miR-761 Mimics group, clone number in miR-761 Mimics+curcumin cells increased, proliferation capacity increased, and apoptotic number decreased. Curcumin targeting miR-761 can inhibit GSK-3β expression, inhibit colon cancer cells proliferation and promote apoptosis. However, when the pCDNA-GSK-3β plasmid overexpresses GSK-3β, it can prevent the action of miR-761.

Curcumin Inhibits the Growth of Hepatocellular Carcinoma via the MARCH1-mediated Modulation of JAK2/STAT3 Signaling.

Curcumin has been reported to have anti-hepatocellular carcinoma (HCC) effects, but the underlying mechanism is not well known. To investigate whether membrane-associated RING-CH 1 (MARCH1) is involved in the curcumin-induced growth suppression in HCC and its underlying molecular mechanism. A few recent patents for curcumin for cancer are also reviewed in this article. The effect of curcumin on growth inhibition of HCC cells was analyzed through in vitro and in vivo experiments, and the expression levels of MARCH1, Bcl-2, VEGF, cyclin B1, cyclin D1, and JAK2/STAT3 signaling molecules were measured in HCC cells and the xenograft tumors in nude mice. Cell transfection with MARCH1 siRNAs or expression plasmid was used to explore the role of MARCH1 in the curcumin-induced growth inhibition of HCC cells. Curcumin inhibited cell proliferation, promoted apoptosis, and arrested the cell cycle at the G2/M phase in HCC cells with the decrease of Bcl-2, VEGF, cyclin B1, and cyclin D1 expression as well as JAK2 and STAT3 phosphorylation, resulting in the growth suppression of HCC cells. MARCH1 is highly expressed in HCC cells, and its expression was downregulated after curcumin treatment in a dose-dependent manner. The knockdown of MARCH1 by siRNA decreased the phosphorylation levels of JAK2 and STAT3 and inhibited the growth of HCC cells. In contrast, opposite results were observed when HCC cells overexpressed MARCH1. A xenograft tumor model in nude mice also showed that curcumin downregulated MARCH1 expression and decelerated the growth of transplanted HCC with the downregulation of JAK2/STAT3 signaling and functional molecules. The ADC value of MRI analysis showed that curcumin slowed down the progression of HCC. Our results demonstrated that curcumin may inhibit the activation of JAK2/STAT3 signaling pathway by downregulating MARCH1 expression, resulting in the growth suppression of HCC. MARCH1 may be a novel target of curcumin in HCC treatment.