Magnesium metal-organic framework microneedles loaded with curcumin for accelerating oral ulcer healing.

Oral ulcers are a common oral mucosal disease that seriously affect the quality of life. Traditional drug treatments have shown unsatisfactory efficacy and potential adverse reactions. In this study, curcumin-loaded multifunctional magnesium metal-organic framework-embedded hyaluronic acid-soluble microneedles patches were developed to optimize treatment strategies for oral ulcers. This microneedles patch achieves efficient release of curcumin and Mg2+ in the ulcer through precisely targeted delivery and controllable release mechanism, significantly regulates inflammation, promotes cell migration and angiogenesis, and accelerates the ulcer healing process. At the same time, the synergistic effect of curcumin and gallic acid effectively alleviated oxidative stress, while the backplate ε-poly-L-lysine and needle tip Mg2+ jointly constructed an antibacterial barrier to effectively inhibit pathogens. Verification using an oral ulcer rat model showed that the microneedles patch exhibited excellent therapeutic effects. This not only opens up a new avenue for clinical oral treatment but also marks a breakthrough in nanobiomaterials science and drug delivery technology and heralds a broad prospect in the field of oral ulcer treatment in the future.

Impact of monocarbonyl analogs of curcumin (MACs) C66 and B2BrBC on the expression of diabetes-associated genes in streptozotocin-treated rat pancreatic RIN-m cells-Quantitative RT-PCR array data.

This paper presents a dataset obtained from an RT2-qPCR array analysis of rat pancreatic RIN-m cells treated with two monocarbonyl analogs of curcumin (MACs), C66 and B2BrBC in the presence or absence of streptozotocin (STZ). The array quantified the expression of 84 genes associated with the onset, development, and progression of diabetes. This dataset provides information on the gene expression profiles of pancreatic cells modulated by two specific MACs in a diabetic context. The data can serve as a foundation for developing new hypotheses, designing follow-up experiments, and identifying novel targets for treatment. It can be used to investigate further the molecular mechanisms underlying the therapeutic effects of these MACs and in comparative studies using other experimental antidiabetic compounds.

The pharmacokinetics and tissue distribution of curcumin following inhalation administration in rats-A comparative analysis with oral and intravenous routes.

A sensitive and simple method using ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated to determine the concentration of curcumin in rat plasma and tissue samples. Emodin was selected as the internal standard (IS), and biological samples were pretreated with simple one-step acetonitrile precipitation. The calibration curves exhibited linearity within the range of 1-1000 ng/ml for both rat plasma and tissue samples. The accuracy and precision of intra-day as well as inter-day determinations ranged from 99.3% to 117.3% and from 98.2% to 105.1%, respectively. This method demonstrated excellent recovery rates ranging from 76.4% to 96.4% along with minimal matrix effect ranging from 86.5% to 99.6%. The effectiveness of this method was successfully demonstrated through its application in an in vivo pharmacokinetic and tissue distribution study after single administration via inhalation (100 mg/kg), oral gavage (100 mg/kg) and intravenous injection (2.5 mg/kg) of curcumin in rats. The results revealed that inhalation significantly improved the bioavailability of curcumin, with most of the drug being deposited in the lung. These findings highlight inhalation as an effective route for targeted delivery of drugs directly into lung tissues, thus suggesting potential future applications for treating pulmonary diseases utilizing inhaled curcumin.

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.

Synergistic effect of curcumin and tamoxifen loaded in pH-responsive gemini surfactant nanoparticles on breast cancer cells.

BACKGROUND: Drug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines. METHODS: The synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation. RESULTS: The tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effects, with combination indices of 0.561 and 0.353, respectively. CONCLUSION: The combined drug delivery system had a greater toxic effect on cell lines than single-drug delivery. The synergistic effect of TMX and Cur with decreasing inhibitory concentrations could be a more promising system for BC-targeted therapy using GS NPs.

Curcumin and nanodelivery systems: New directions for targeted therapy and diagnosis of breast cancer.

As the global incidence of breast cancer continues to surge, the pursuit of novel, low-toxicity, and highly efficacious therapeutic strategies has emerged as a pivotal research focus. Curcumin (CUR), an active constituent of traditional Chinese medicine (TCM) renowned for its antimicrobial, anti-inflammatory, antioxidant, and antitumor properties, exhibits immense potential in breast cancer therapy. Nevertheless, CUR's poor water solubility, chemical instability, and unfavorable pharmacokinetics have impeded its clinical utilization. To address these challenges, nano-delivery systems have been extensively exploited for CUR administration, enhancing its in vivo stability and bioavailability, and facilitating precise targeting of breast cancer lesions. Therefore, we elaborate on CUR's chemical foundations, drug metabolism, and safety profile, and elucidate its potential mechanisms in breast cancer therapy, encompassing inducing apoptosis and autophagy, blocking cell cycle, inhibiting breast cancer metastasis, regulating tumor microenvironment and reversing chemotherapy resistance. The review primarily emphasizes recent advancements in CUR-based nano-delivery systems for the treatment and diagnosis of breast cancer. Liposomes, nanoparticles (encompassing polymer nanoparticles, solid lipid nanoparticles, mesoporous silica particles, metal/metal oxide nanoparticles, graphene nanomaterials, albumin nanoparticles, etc.), nanogels, and nanomicelles can serve as delivery carriers for CUR, exhibiting promising anti-breast cancer effects in both in vivo and in vitro experiments. Furthermore, nano-CUR can be integrated with fluorescence imaging, magnetic resonance imaging, computed tomography imaging, ultrasound, and other techniques to achieve precise localization and diagnosis of breast cancer masses. While this article has summarized the clinical studies of nano-curcumin, it is noteworthy that the research literature on nano-CUR applied to breast cancer diagnosis and the translation of nano-CUR clinical studies in BC patients remain limited. Therefore, future research should intensify exploration in this direction.

The Potential Role of Curcumin as a Regulator of microRNA in Colorectal Cancer: A Systematic Review.

INTRODUCTION: Curcumin is known as a bioactive component that is found in the rhizomes of Curcuma longa. Curcumin is well known for its chemo-preventive and anticancer properties. However, its anticancer mechanism in colorectal cancer treatment is unclear, and some studies have shown that many microRNAs (miRs) could be potential targets for curcumin in colorectal cancer (CRC) treatment, so there is a need for their integration and clarification. METHODS: We systematically searched international databases, including PubMed, Scopus, and Web of Science, until July 2021 by using some relevant keywords. RESULTS: The search resulted in 87 papers, among which there were 18 related articles. Curcumin was found to cause the upregulation of miR-497, miR-200c, miR-200b, miR-409-3p, miR-34, miR-126, miR-145, miR-206, miR-491, miR-141, miR-429, miR-101, and miR-15a and the downregulation of miR-21, miR-155, miR-221, miR-222, miR-17-5p, miR-130a, miR-27, and miR-20a. CONCLUSION: The present review study suggests that curcumin may be useful as a novel therapeutic agent for CRC by altering the expression level of miRs.

A Molecular Dynamic Simulation, Structural Analysis, and Ex Vivo Insights into the P-glycoprotein-Mediated Interactions of Dietary Polyphenols with Cyclin-dependent Kinase Inhibitors: A Potential Strategy to Counteract Drug Efflux.

INTRODUCTION: P-glycoprotein, an ATP-dependent efflux transporter, plays a crucial role in eliminating cellular toxins and affects the intracellular concentration and bioavailability of CDK 4/6 inhibitors. Moreover, dietary flavonoids are natural bio-enhancers that can effectively inhibit the efflux function of these transporters. Therefore, this study aimed to assess the impact of dietary polyphenols on the inhibition of P-glycoprotein and the subsequent efflux of CDK inhibitors palbociclib and ribociclib. METHODS: A molecular docking approach was implemented to evaluate the binding interaction characteristics of CDK4/6 inhibitors in the presence of dietary polyphenols at the ATP binding site. Furthermore, the stability of the complexes was evaluated in two conformations of P-glycoprotein, followed by an ex vivo everted gut sac experiment. RESULTS: The findings demonstrated that the binding of curcumin and quercetin with high affinity (-51.63 and 47.16 Kcal/mol) to ATP binding sites of P-glycoprotein-palbociclib and ribociclib inward conformation complexes resulted in good stability of complex and minimal fluctuation throughout the course of the simulation. It was evident from the everted gut sac ex vivo study that the presence of 100µM of curcumin resulted in an increase of 1.77 and 4.20-fold in the intestinal transit of palbociclib and ribociclib, respectively. CONCLUSION: The study emphasizes the significance of curcumin and quercetin as inhibitors of P-glycoprotein, demonstrating their potential to decrease the efflux of palbociclib and ribociclib, consequently contributing to their bioavailability enhancement.

L48H37, a curcumin analog, suppresses matrix metalloproteinase-9 expression and activity to hamper nasopharyngeal cancer cell migration.

OBJECTIVE: Metastatic disease is a major issue of treatment failure in nasopharyngeal carcinoma (NPC) patients and often linked to high mortality. L48H37, a synthetic analog of curcumin with augmented bioavailability over its parent compound, has demonstrated several oncostatic characteristics. This study was aimed to explore the anti-metastatic effect of L48H37 on NPC cancer cells and its underlying mechanism. METHODS: Cell viability was evaluated using MTT assay. Regulation of signaling pathways was elucidated by immunoblotting, and specific kinase inhibitors. RESULTS: In this study, we showed that L48H37 suppressed TPA-stimulated invasive and migratory capacities of NPC cell lines and gave rise to very little cytotoxic responses. Such anti-cancer effect of L48H37 was accompanied with attenuated expression levels and enzymatic activities of matrix metalloproteinase-9 (MMP-9), a pivotal mediator of metastatic processes. In addition, L48H37 interfered with TPA-induced JNK activation, and the treatment of L48H37 combined with a JNK antagonist demonstrated a synergistic effect on restraining TPA-stimulated MMP-9 activity and migration events in NPC cells. CONCLUSIONS: Our results revealed that L48H37 impeded the invasive potential of NPC cells via impairment of MMP-9 function and abundance, highlighting possible complementary therapies using curcumin or its effective analogs to manage NPC dissemination.

The effectiveness of phytosomal curcumin on clinical and laboratory parameters of patients with multiple trauma admitted to the intensive care unit: a double-blind randomized placebo-controlled trial.

BACKGROUND: Multiple trauma has serious complications, which increases the risk of morbidity and mortality in the patients. This study aimed to evaluate the impact of supplementation with phytosomal curcumin on clinical and laboratory factors in critically ill patients with multiple trauma. METHODS: In this double-blind trial, 53 patients with multiple trauma, who were admitted to the intensive care unit (ICU) were randomized to receive either 2 capsules, each capsule containing 250 mg phytosomal (a total of 500 mg daily) as an intervention group or 2 identical capsules (placebo capsules), each containing 250 mg maltodextrin for 7 days. Clinical and laboratory were parameters assessed before and after the intervention. RESULTS: After seven days of intervention, the mean increase from baseline in the Glasgow coma scale (GCS) score was significantly higher in the curcumin compared with the placebo group (P-value: 0.028), while the reduction in the APACHE-II score in the curcumin group was greater than that the placebo group in a marginally non-significant fashion (P-value: 0.055). Serum total bilirubin (P-value: 0.036) and quantitative C-reactive protein (CRP) (P-value: 0.044) levels significantly decreased while potassium (P-value: 0.01) significantly increased in the curcumin compared with the placebo group. Moreover, supplementation with phytosomal curcumin significantly increased platelet count (P-value: 0.024) as compared with placebo. The 28-day mortality rate was 7.7% (n: 2 patients) and 3.7% (n: 1 patients) in the placebo and curcumin groups, respectively (P-value > 0.05). CONCLUSION: Phytosomal curcumin had beneficial effects on several clinical and laboratory factors including GCS, APACHEII, serum total bilirubin, CRP, and platelet count in ICU-admitted patients with multiple trauma. TRIAL REGISTRATION: IRCT20090306001747N1, Available on: https://www.irct.ir/trial/52692 . The first registration date was 12/01/2021.

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.

Therapeutic effects of curcumin nanoemulsion on cyclophosphamide-induced testicular toxicity in adult male mice.

Objective: Several chemotherapeutic agents, including cyclophosphamide (CP) and busulfan, have been shown to interfere with spermatogenesis. Accordingly, the main objective of this study was to evaluate the potential therapeutic effects of curcumin nanoemulsion (CUR-NE) on spermatogenesis in mice with CP-induced testicular toxicity. Methods: A total of 28 adult male mice were equally divided into four groups: control, CUR-NE (30 mg/kg, daily for 5 weeks), CP (200 mg/kg, single dose), and CP+CUR-NE. Each group was evaluated regarding sperm parameters, DNA fragmentation index, chromatin maturation, reactive oxygen species (ROS) levels, and histological parameters of the testes. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone, and testosterone were also assessed in all groups. Results: In CP-induced mice, CUR-NE treatment significantly improved sperm parameters, including total sperm count, motility, morphology, and DNA integrity. CUR-NE administration was also associated with significantly higher serum levels of testosterone and FSH, as well as testis weight and volume, in the mice treated with CP. Furthermore, CUR-NE treatment significantly increased the number of spermatogonia, primary spermatocytes, round spermatids, and Leydig cells in the testicular tissue of these animals. A marked reduction in ROS levels in the testes tissue was observed following administration of CUR-NE to CP-induced mice. Conclusion: CUR-NE appears to promote spermatogenesis in mice with CP-induced testicular toxicity by reducing ROS levels, improving testicular stereological parameters, and strengthening the reproductive hormone profile.

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.

Lipid-based nanodelivery systems of curcumin: Recent advances, approaches, and applications.

Despite its many beneficial effects, pharmaceutical applications of curcumin (CUR) are limited due to its chemical instability, low solubility/absorption and weak bioavailability. Recent advances in nanotechnology have enabled the development of CUR-loaded nanodelivery systems to tackle those issues. Within many different nanocarriers developed for CUR up to date, lipid-based nanocarriers (LBNs) are among the most extensively studied systems. LBNs such as nanoemulsions, solid lipid carriers, nanostructured phospholipid/surfactant carriers are shown to be potential delivery systems capable of improving the solubility, bioavailability, and chemical stability of CUR. The particle characteristics, stability, bioavailability, and release properties of CUR-loaded LBNs can be tailored via optimizing the formulation and processing parameters. This paper reviews the most recent studies on the development of various CUR-loaded LBNs. Approaches to the improvement of CUR bioavailability and release characteristics of LBNs are discussed. Furthermore, challenges in the development of CUR-loaded LBNs and their potential applications are presented.

Curcumin attenuates neuroinflammatory damage induced by LPS: implications for the role of S100B.

Brain disease results in inflammatory damage that alters cell function in microglia and astrocytes as well as other neuronal cell types. Astrocytes modulate blood flow, regulate glutamate metabolism, and exert antioxidant protection. When responding to inflammatory damage, astrocytes enhance immune cell infiltration and amplify inflammatory responses via the upregulation of cytokine production. Several molecules have been proposed to attenuate neuroinflammation and control neurological diseases. Curcumin gained attention due to its capacity to cross the blood-brain barrier and its well-described anti-inflammatory and antioxidant activities. Our study aimed to understand if oral curcumin administration could protect against central nervous system inflammatory damage induced by intracerebroventricular injection of LPS while focusing on astrocyte function. Despite its poor bioavailability, we found that curcumin reaches the central nervous system, prevents the locomotory damage caused by LPS, and reduces inflammatory signaling via IL-1ß and COX-2. Furthermore, we observed that curcumin was protective against LPS-induced S100B secretion in the cerebrospinal fluid and GSH reduction in the hippocampal tissue. However, curcumin could not protect the animals from anhedonia, assessed by the sucrose preference test, and weight loss induced by LPS. Our results indicate that oral curcumin administration exerts a protective anti-inflammatory action in the central nervous system, attenuating the sickness behavior induced by ICV LPS. This work demonstrates that curcumin has an important modulative effect on astrocytes, thus suggesting that astrocytes are critical to the anti-inflammatory effects of curcumin.

Oral mucositis management with photobiomodulation, Bidens pilosa L. (Asteraceae) and Curcuma longa L. (Zingiberaceae), the FITOPROT herbal medicine, and its influence on inflammatory cytokine levels: a randomized clinical trial.

PURPOSE: This randomized clinical trial aimed to compare the effects of a mucoadhesive formula, containing curcuminoids from Curcuma longa L. and glycerinated extract of Bidens pilosa L. (FITOPROT), associated with photobiomodulation (PBM), and of PBM exclusively, on the incidence of oral mucositis (OM)-induced by radiotherapy (RT) in the head and neck region, and the salivary expression of inflammatory cytokines, in patients with head neck cancer. METHODS: Patients were randomly assigned into two intervention groups-FITOPROT + PBM (n = 25) or PBM (n = 27). PBM protocol comprised a wavelength of 660 nm, 25 mW, 0.25 J/point, and daily irradiation from the first until the last day of RT. FITOPROT was gargled twice a day. All patients underwent a preventive oral care program throughout the study. OM degree, salivary concentration of nitrite, and inflammatory (IL-1, TNFα, IL-6, IL-8, and IL-12p70), and anti-inflammatory (IL-10) cytokines were assessed at baseline, and at the 7th, 14th, 21st, and 30th RT sessions. RESULTS: There were no differences in the OM degree between groups, but the RT dose significantly affected the OM. The RT significantly affected the salivary nitrite, TNFα, IL-1ß, and IL-10 concentrations. CONCLUSION: FITOPROT associated with PBM showed limited effects on preventing the incidence of severe OM compared to PBM alone. However, FITOPROT + PBM may be associated with nitrite and cytokine balance, which may contribute to the occurrence of fewer cases of severe OM. TRIAL REGISTRATION: Brazilian Clinical Trials database (ReBEC; RBR-9vddmr), registered UTN code: U1111-1193-2066, registered in August 8th, 2017.

Isolation and Identification of Human Gut Bacteria Capable of Converting Curcumin to Its Hydrogenated Metabolites.

Curcumin is widely recognized for its health benefits, though the role of gut microbiota in its metabolic transformation was not well studied. In this study, bacterial strains capable of metabolizing curcumin were isolated from human stool samples. Using 16S rRNA and whole-genome sequencing, two novel strains (Clostridium butyricum UMA_cur1 and Escherichia coli UMA_cur2) were identified. In addition, the metabolic products were analyzed using liquid chromatography-mass spectrometry. These strains efficiently converted curcumin into dihydro-curcumin (DHC) and tetrahydro-curcumin (THC). Notably, E. coli UMA_cur2 also produced hexahydro-curcumin (HHC) and octahydro-curcumin (OHC), marking the first identification of a strain capable of such transformations. The absence of the YncB gene (typically involved in curcumin conversion) in C. butyricum UMA_cur1 suggests an alternative metabolic pathway. Curcumin metabolism begins during the stationary growth phase, indicating that it is not crucial for primary growth functions. Furthermore, E. coli UMA_cur2 produced these metabolites sequentially, starting with DHC and THC and progressing to HHC and OHC. These findings identified two novel strains that can metabolize curcumin to hydrogenated metabolites, which enhance our understanding of the interaction between curcumin and gut microbiota.