Monocarbonyl curcuminoids as potential photosensitizers in photodynamic therapy against skin cancer.

Two monocarbonyl dimethylamino curcuminoids, one derived from acetone (C3) and the second one from cyclohexane (C6), were synthesized aiming to study their photophysical properties and anticancer photodynamic potential. Compound C6 exhibited lower absorbance and fluorescence than C3. Photobleaching studies showed that C3 and C6 photostability behavior in DMSO differ significantly. C3 was completely photoconverted into a new species absorbing at lower wavelength than the parent compound, whereas, C6, upon a 30 min irradiation at λ = 440 nm with 15 mW/cm2 reached a photostationary phase where a smaller amount of the initial compound coexists with some photoproducts of higher and lower absorbance. Both compounds were able to generate significant amounts of ROS upon irradiation in an aqueous environment and exhibited successful intracellular localization in skin cancer cells (A431 cells). After dark cytotoxicity studies the concentrations of 5 µM and 1 µM for C3 and C6, respectively, were selected for the PDT assessment. C3 presented light dose-dependent photodynamic activity against A431 cells, resulting in 40 % cell viability after 12 min of light irradiation (440 nm, 15 mW/cm2). On the other side, C6 showed a biphasic light dose PDT effect with cell viability gradually decreasing up to 50 % after 5 min of light exposure, and then increasing again after 8 and 12 min of light exposure. The photodynamic performance of C6 may provide a new insight into the development of PSs with reduced prolonged photosensitivity.

Curcumin and its Analogues in Oral Squamous Cell Carcinoma: State-of-the-art and Therapeutic Potential.

Oral Squamous Cell Carcinoma (OSCC) is the most common cancer arising from squamous epithelium in the oral cavity and is characterized by high aggressiveness and metastatic potential, which together with a late diagnosis results in a 5-year survival rate of only 50% of patients. The therapeutic options for OSCC management are limited and largely influenced by the cancer stage. While radical surgery can be curative in early stage of disease, most cases require adjuvant therapies, including chemotherapy and radiotherapy which, however, often achieve poor curative rates and are associated with important negative effects. Therefore, there is an urgent need to discover new alternative treatment strategies to improve patients' outcomes. Several medicinal herbs are being studied for their preventive or therapeutic effect in several diseases, including cancer. In particular, the Indian spice curcumin, largely used in oriental countries, has been studied as a chemopreventive or adjuvant agent for different malignancies. Indeed, curcumin is characterized by important biological properties, including antioxidant, anti-inflammatory, and anticancer effects, which could also be exploited in OSCC. However, due to its limited bioavailability and poor aqueous solubility, this review is focused on studies designing new synthetic analogues and developing novel types of curcumin delivery systems to improve its pharmacokinetic and biological properties. Thus, this review analyses the potential therapeutic role of curcumin in OSCC by providing an overview of current in vitro and in vivo studies demonstrating the beneficial effects of curcumin and its analogues in OSCC.

Innovative Delivery Systems for Curcumin: Exploring Nanosized and Conventional Formulations.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nanodelivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nanoencapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nanoencapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nanoencapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

Molecular docking of curcumin and curcuminoids as human Zn+ dependent histone deacetylase (HDAC) enzyme inhibitors.

Chemotherapy is one of the most well-established and effective cancer treatments available. However, non-tumor-associated damage restrict the treatment's effectiveness and safety. Our growing understanding of cancer epigenetics has resulted in new therapeutic options and the potential of better patient outcomes in recent decades. In cancer, epigenetic changes are widespread, particularly increased expression and activity of histone deacetylases (HDACs). Epi-drugs are chemical agents that modify the structure of DNA and chromatin facilitating disruption of transcriptional and post-transcriptional changes. First generation epi-drugs include HDAC inhibitors (HDACi) (approved to treat hematological malignancies) harbor various adverse effects demanding the discovery and development of potential natural HDACi that might benefit cancer treatment especially in hematological malignancies. Curcumin (diferuloylmethane), a polyphenolic, component of Curcuma longa, is a well-known anti-inflammatory, anti-oxidative, and anti-lipidemic agent and has recently been shown to be a pan HDACi. Yet the potential of other curcuminoids in Curcuma longa as pan HDACi remains unexplored. (i) To virtually screen curcumin and curcuminoids (Desmethoxycurcumin [DMC] & Bisdemethoxycurcumin [BDMC]) against human Histone deacetylase (HDAC) class I, II and IV enzymes in comparison to their pan HDAC inhibition activity with FDA approved human HDACis available in market and also (ii) to predict the drug likeness property and ADME/ toxicity of curcumin, curcuminoids and approved HDACis via computational approach. Homology modelling followed by docking was performed for human HDAC class I, II and IV enzymes with curcumin, Desmethoxycurcumin, Bisdemethoxycurcumin and with 5 reference HDACi compounds Vorinostat (SAHA), Trichostatin A (TSA), Chidamide, Romidepsin, and Panobinostat to understand the protein -ligand interactions and binding efficiencies. Further, the study ligands with low binding energy were predicted for pharmacokinetic properties and Lipinski's rule of 5. Our study revealed that BDMC followed by DMC and curcumin had high inhibitory effect by interacting at the active site of Zn+ HDACs similar to that of the standard HDACi (curcumin, DMC, BDMC, Belinostat, Chidamide, Romidepsin, Panobinostat, Trichostatin A and Vorinostat). Likewise, all of the chosen ligand molecules, with the exception of Romidepsin (refractive index > 130 m3mol-1), adhered to Lipinski's rule of five and none of the natural compounds (curcumin, DMC, BDMC) did report any toxicity and mutagenic property also, the lethal doses (LD50) of all the natural compounds were higher when compared to chemical drugs. BDMC could be a potential pan HDACi than curcumin and DMC owing to high binding affinity among human Zn+ HDACs. The results of our present study can be useful for the design and development of novel compounds having better HDAC inhibitory activity against several types of cancers. Moreover, these findings could be validated with invitro investigations and by clinical trials to evaluate the survival outcomes in cancer patients when treated with the natural HDACi along with standard chemo regimen. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00221-4.

Oil-Based Curcuminoid Phospholipid Formulation Mimicking Natural Digestion Enhances Oral Bioavailability of Curcuminoids in Healthy Subjects.

Curcumin, the fat-soluble active ingredient and major compound of curcuminoids contained in the curcuma root, is known for its physiological low absorption and bioavailability. Various formulations and galenic technologies are currently available on the market. In this study, the product tested was provided as a soft gelatin capsule containing curcuminoids in an oily matrix mixed with phospholipids (oil/phospholipids [PL]-based, no new technologies applied or artificial excipients added). This was intended to improve bioavailability of curcuminoids as well as to mimic the natural digestion process of fat-soluble substances. In particular, the oral bioavailability of curcuminoids in the oil/PL-based formulation was compared with the pure curcuminoids extract alone (reference product), in a randomized, cross-over, single oral dose study design. Twelve healthy subjects were administered 200 mg curcuminoids under fasting conditions. Pharmacokinetic parameters were analyzed from individual concentration-time curves of total curcuminoids, as well as the curcumin metabolite tetrahydrocurcumin (THC). Results showed significantly higher AUC0-8h levels after the intake of the oil/PL-based formulation for total curcuminoids (205.60 vs. 112.50 ng/mL*h, P = .0001) as well as for THC (347.30 vs. 118.90 ng/mL*h, P < .0001) in comparison to the pure curcuminoids extract. Cmax was also significantly higher for both parameters analyzed (total curcuminoids: 47.54 vs. 21.16 ng/mL, P = .0001; THC: 96.69 vs. 29.83 ng/mL, P < .0001). In addition, the uptake kinetic of total curcuminoids was significantly fastened with the oil/PL-based curcuminoids formulation compared with the pure curcuminoids extract (P = .0446). These data suggest an improved impact on curcuminoids uptake of the oil/PL-based formulation and confirms its good tolerability.

Anti-inflammatory effect of curcuminoids and their analogs in hyperosmotic human corneal limbus epithelial cells.

BACKGROUND: To assess the efficacy of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin [BDC]) and their analogs (tetrahydrocurcumin [THC], tetrahydrodemethoxycurcumin [THDC], tetrahydrobisdemethoxycurcumin) in reducing inflammatory cytokines and their toxicity to primary human corneal limbal epithelial cells, these cells were cultured and exposed to these compounds. METHODS: The PrestoBlue assay assessed cell viability after treatment. Anti-inflammatory effects on hyperosmotic cells were determined using real-time polymerase chain reaction and significance was gauged using one-way analysis of variance and Tukey's tests, considering p-values < 0.05 as significant. RESULTS: Curcuminoids and their analogs, at 1, 10, and 100 µM, exhibited no effect on cell viability compared to controls. However, cyclosporin A 1:500 significantly reduced cell viability more than most curcuminoid treatments, except 100 µM curcumin and BDC. All tested curcuminoids and analogs at these concentrations significantly decreased mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-17 A, matrix metallopeptidase-9, and intercellular adhesion molecule-1 after 90 mM NaCl stimulation compared to untreated cells. Furthermore, proinflammatory cytokine levels from hyperosmotic cells treated with 1, 10, and 100 µM curcumin, 100 µM BDC, 100 µM THC, 1 and 100 µM THDC mirrored those treated with cyclosporin A 1:500. CONCLUSION: The anti-inflammatory efficiency of 1 and 10 µM curcumin, 100 µM THC, 1 and 100 µM THDC was comparable to that of cyclosporin A 1:500 while maintaining cell viability.

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin.

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment.

Curcumin, a natural polyphenolic component from Curcuma longa roots, is the main bioactive component of turmeric spice and has gained increasing interest due to its proposed anti-cancer, anti-obesity, anti-inflammatory, antioxidant, and lipid-lowering effects, in addition to its thermogenic capacity. While intake from dietary sources such as curry may be sufficient to affect the intestinal microbiome and thus may act indirectly, intact curcumin in the body may be too low (<1 microM) and not sufficient to affect signaling and gene expression, as observed in vitro with cultured cells (10-20 microM). Several strategies can be envisioned to increase curcumin levels in the body, such as decreasing its metabolism or increasing absorption through the formation of nanoparticles. However, since high curcumin levels could also lead to undesired regulatory effects on cellular signaling and gene expression, such studies may need to be carefully monitored. Here, we review the bioavailability of curcumin and to what extent increasing curcumin levels using nanoformulations may increase the bioavailability and bioactivity of curcumin and its metabolites. This enhancement could potentially amplify the disease-preventing effects of curcumin, often by leveraging its robust antioxidant properties.

Recent Trends in Curcumin-Containing Inorganic-Based Nanoparticles Intended for In Vivo Cancer Therapy.

Curcumin is a natural compound that has been widely investigated thanks to its various biological properties, including antiproliferative. This molecule acts on different cancers such as lung, breast, pancreatic, colorectal, etc. However, the bioactive actions of curcumin have limitations when its physicochemical properties compromise its pharmacological potential. As a therapeutic strategy against cancer, curcumin has been associated with inorganic nanoparticles. These nanocarriers are capable of delivering curcumin and offering physicochemical properties that synergistically enhance anticancer properties. This review highlights the different types of curcumin-based inorganic nanoparticles and discusses their physicochemical properties and in vivo anticancer activity in different models of cancer.

Bioaccessibility, Intestinal Absorption and Anti-Inflammatory Activity of Curcuminoids Incorporated in Avocado, Sunflower, and Linseed Beeswax Oleogels.

Beeswax oleogels (OGs), with a mechanical strength similar to pork backfat, were formulated with avocado (A), sunflower (S), and linseed (L) oils, applying a central composite design plus star point, and were evaluated as oral delivery vehicles of curcuminoids (OGACur, OGSCur, OGLCur). The incorporation of curcumin into the OG matrix significantly delayed both the formation of peroxides and conjugated trienes (K268 values), and the degradation rate of curcumin decreased with the increase of the oil polyunsaturated fatty acids (PUFA) content. The oil structuring did not affect the bioaccessibility of curcuminoids (>55% in all the OGs, regardless of the oil type), but it did reduce the release of fatty acids (~10%) during in vitro gastrointestinal digestion. The intestinal absorption, evaluated in Caco-2 cell monolayers, was higher for the micelle-solubilized curcumin from the digested OG than from unstructured oils, and it showed high anti-inflammatory potential by inhibiting the tumor necrosis factor-α (TNF-α) production compared to the positive control, both before and after the stimulation of ThP-1 cells with LPS. Regardless of the oil type, these beeswax-based OGs with gel-like behavior designed as fat replacers may be promising vehicles for the oral delivery of curcuminoids.

Effect of Curcuminoids on Contrast-Induced Acute Kidney Injury after Elective Coronary Angiography or Intervention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: The role of curcuminoids, a striking antioxidant, in prevention of contrast-induced acute kidney injury (CI-AKI) remains unknown. We aimed to evaluate the efficacy and safety of curcuminoids in preventing CI-AKI in patients undergoing elective coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). METHODS: We randomized 114 patients who were undergoing elective CAG and/or PCI to receive curcuminoids, 4 g/day (1 day before and 1 day after the procedure, n = 56), or placebo (n = 58). Serum creatinine was assessed at baseline, 12, 24, and 48 h after contrast exposure. The primary endpoint was development of CI-AKI defined as serum creatinine increase ≥0.3 mg/dL within 48 h after contrast exposure. The secondary endpoint was the occurrence of kidney injury defined by >30% increase in urine neutrophil gelatinase-associated lipocalin (NGAL). RESULTS: Baseline characteristics were comparable between the two groups. Seven (12.7%) in curcuminoids group and eight (14.0%) in placebo group developed CI-AKI (p = 0.84). The incidence of increased urine NGAL was comparable in the placebo and curcuminoids group (39.6% vs. 50%, respectively; p = 0.34). None in both groups had drug-related adverse events. CONCLUSION: This is a pilot study to demonstrate the safety and tolerability of curcuminoids in patients undergoing elective CAG and/or PCI. Curcuminoids have no protective effects against kidney injury after elective CAG and/or PCI.

Curcumin and Ferroptosis: a Promising Target for Disease Prevention and Treatment.

Ferroptosis is a recently identified form of cell death characterized by iron accumulation and lipid peroxidation. Unlike apoptosis, necrosis, and autophagy, ferroptosis operates through a distinct molecular pathway. Curcumin, derived from turmeric rhizomes, is a natural compound with diverse therapeutic benefits, including neuroprotective, anti-metabolic syndrome, anti-inflammatory, and anti-cancer properties. Growing evidence suggests that curcumin possesses both pro-oxidant and antioxidant properties, which can vary depending on the cell type. In this review, we explore the relationship between the effects of curcumin and the molecular mechanisms underlying the ferroptosis signaling pathway, drawing from current in vivo and in vitro research. Curcumin has been found to induce ferroptosis in cancer cells while acting as an inhibitor of ferroptosis in tissue injuries. Notably, curcumin treatment leads to alterations in key ferroptosis markers, underscoring its significant impact on this process. Nonetheless, further research focused on elucidating this important attribute of turmeric is crucial for advancing disease treatment.

Plant-Derived Polyphenols to Prevent and Treat Oral Mucositis Induced by Chemo- and Radiotherapy in Head and Neck Cancers Management.

Oral Mucositis (OM) is the most common side effect due to chemotherapy and radiotherapy, which are the conventional treatment options for head and neck cancers. OM is a severe inflammatory condition characterized by multifactorial etiopathogenesis. It further negatively affects patients' quality of life by severe impairment of normal oral functions. Consequently, it is mandatory to identify new effective therapeutic approaches to both prevent and treat OM while also avoiding any recurrence. Polyphenols recently attracted the interest of the scientific community due to their low toxicity and wide range of biological activities making them ideal candidates for several applications in the odontostomatological field, particularly against OM. This review collects the in vivo studies and the clinical trials conducted over the past 13 years evaluating the preventive and curative effects of several polyphenolic compounds towards chemo- and radiotherapy-induced OM, both when administered alone or as a plant-extracted phytocomplex. The literature fully confirms the usefulness of these molecules, thus opening the possibility of their clinical application. However, polyphenol limitations (e.g., unfavourable physicochemical properties and susceptibility to degradation) have emerged. Consequently, the interest of the scientific community should be focused on developing innovative delivery systems able to stabilize polyphenols, thus facilitating topical administration and maximizing their efficacy.

Curcumin-loaded nanostructured systems for treatment of leishmaniasis: a review.

Leishmaniasis is a neglected tropical disease that has affected more than 350 million people worldwide and can manifest itself in three different forms: cutaneous, mucocutaneous, or visceral. Furthermore, the current treatment options have drawbacks which compromise efficacy and patient compliance. To face this global health concern, new alternatives for the treatment of leishmaniasis have been explored. Curcumin, a polyphenol obtained from the rhizome of turmeric, exhibits leishmanicidal activity against different species of Leishmania spp. Although its mechanism of action has not yet been fully elucidated, its leishmanicidal potential may be associated with its antioxidant and anti-inflammatory properties. However, it has limitations that compromise its clinical use. Conversely, nanotechnology has been used as a tool for solving biopharmaceutical challenges associated with drugs, such as curcumin. From a drug delivery standpoint, nanocarriers (1-1000 nm) can improve stability, increase solubility, promote intracellular delivery, and increase biological activity. Thus, this review offers a deep look into curcumin-loaded nanocarriers intended for the treatment of leishmaniasis.

Non-therapeutic plasma levels in individuals utilizing curcumin supplements in daily life.

Introduction: The spice curcumin and its metabolites are widely used by cancer patients but have not shown proven health benefits in clinical studies, likely due to low plasma concentrations after oral intake. However, public interest in curcumin continues to grow, and companies claim enhanced absorption in their formulations. This study aims to determine if daily oral intake of curcumin leads to sufficient plasma concentrations for health effects. The study was registered in the Dutch Clinical Trial Register with ID NL5931. Methods: We used a validated HPLC-MS/MS method to measure curcumin and its metabolites in 47 individuals using their own curcumin formulations. Questionnaires assessed other supplement and medication use. Plasma samples were collected before and 1.5 h after intake, analyzing curcumin and metabolite levels with and without ß-glucuronidase pretreatment to measure conjugated and unconjugated forms. Results: Plasma concentrations of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin, ranged between 1.0 and 18.6 ng/mL. Adding ß-glucuronidase resulted in an increase of unconjugated curcumin plasma levels to 25.4 ng/mL; however still significantly below (1000-fold) a plasma concentration that is expected to have a beneficial health effect. The use of adjuvants like piperine did not result in higher curcumin plasma concentrations. Discussion: Our study shows that using oral curcumin supplements still does not result in therapeutic plasma levels. Health care practitioners need to be critical toward the claimed beneficial systemic health effects of current curcumin supplement use by their patients. Clinical Trial Registration: https://onderzoekmetmensen.nl/en/trial/25480, NL5931.

Clinical trials on curcumin in relation to its bioavailability and effect on malignant diseases: critical analysis.

Curcumin is an ingredient of the root Curcuma longa, which is responsible for the characteristic yellow color of curcuma. Curcumin is said to have the potential ability to fight malignant diseases and to have an anti-inflammatory effect. In addition, it is used as a dietary supplement. However, one problem with the use of curcumin is its extremely low bioavailability. The aim of this study is to systematically review and critically analyze clinical studies related to the pharmacokinetics (or bioavailability) and to the use of curcumin in the treatment of malignant diseases. The platforms clinicaltrials.gov and PubMed served as the database for the literature research. A total of 293 available studies on curcumin were filtered according to their focus (bioavailability, therapy of malignant diseases) and other criteria (study results, main substance, topic reference, existing disease/other research purpose, reference to malignant diseases). The studies were further analyzed regarding their outcome measures, their design (number of participants, randomization, placebo group, masking, ethical standards, sponsor, primary outcome measures, secondary outcome measures, study bias) and their findings. The analysis failed to convincingly demonstrate that curcumin has a significant, positive effect on the therapy of malignant diseases. Regarding the increase in bioavailability, positive results have been obtained, which are in proximity to the pharmaceutical industry. Independent studies could not achieve increased bioavailability of curcumin. The available reviews in the literature also do not provide convincing evidence for the efficacy of curcumin. Thus, at the time being, the use of curcumin in malignant diseases is not justified scientifically.

Ruthenium(II)-Arene Curcuminoid Complexes as Photosensitizer Agents for Antineoplastic and Antimicrobial Photodynamic Therapy: In Vitro and In Vivo Insights.

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical-physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising.

First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential.

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

Curcuminoids as cell signaling pathway modulators: A potential strategy for cancer prevention.

Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidences reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoids, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/ß-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoids also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoids against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKß, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology-based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.

Effects of Curcuminoids and Surfactant-Formulated Curcumin on Chemo-Resistant Colorectal Cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related death in the United States, and chronic gut inflammation is a risk factor for CRC initiation and development. Curcuma longa L., or turmeric, has become one of the most studied herbal medicines in recent years due to its anticancer potentials. It is generally accepted that the major component in turmeric is curcuminoids, and the active constituent in curcuminoids is curcumin. However, unprocessed curcumin is characterized by poor water solubility, which means low bioavailability in humans. To increase the bioavailability of curcumin, in this study, we utilized a novel surfactant-formulated curcumin (CuminUP60[Formula: see text]) and evaluated its CRC chemopreventive activities. Compared with the chemo-sensitive CRC cell line HCT-116, the management of the CRC SW-480 cell line is a challenge, since the latter is chemo-resistant. In other words, these cancer cells resist the effects of the chemotherapy. Using the newly formulated CuminUP60[Formula: see text] water solution, this study demonstrated its strong antiproliferative effects on the SW-480 cells in a dose- and time-dependent manner. This new formulation induced early apoptosis and arrested the cell cycle in the G2/M phase via the upregulation of cyclin B1. We also observed that this new formulation possessed inhibitory effects on Th17 cell differentiation, which regulates the body's immune response against gut malignancies. In summary, our results exhibited a potential clinical utility of the surfactant-formulated curcumin in chemo-resistant colorectal cancer management.