Curcumin Complex Research Articles

Interaction of gallium, indium, and vanadyl curcumin complexes with hen egg-white lysozyme (HEWL): Mechanistic aspects and evaluation of antiamyloidogenic activity

Many proteins and peptides can aggregate into amyloid fibrils with high-ordered and cross-β rich structure characteristics. Amyloid deposition is a common feature of neurodegenerative diseases called amyloidosis. Various natural polyphenolic compounds such as curcumin exhibited antiamyloidogenic activities, but less researches were focused on the metal complexes of these compounds. In this study, the inhibitory effects of gallium curcumin (Ga(cur)3), indium curcumin (In(cur)3), and vanadyl curcumin (VO(cur)2) on the amyloid fibrillation of hen egg white lysozyme (HEWL) have been investigated. Moreover, the details of binding interactions of these metal complexes with HEWL have been explored. The results of fluorescence quenching analyses revealed that In(cur)3 and VO(cur)2 have much higher binding affinities than Ga(cur)3 toward HEWL. The interactions of these metal complexes were accompanied by partial conformational changes in the tertiary structure of HEWL. The kinetic curves of the fibrillation process demonstrated that In(cur)3 and VO(cur)2 have higher inhibitory effects than Ga(cur)3 on the amyloid fibrillation of HEWL. The strength of binding to HEWL is completely in accordance with inhibitory activities of these metal complexes of curcumin.

Antibacterial Photodynamic Therapy by Zn(II)-Curcumin Complex: Synthesis, Characterization, DFT Calculation, Antibacterial Activity, and Molecular Docking.

The increase in antibacterial drug resistance is threatening global health conditions. Recently, antibacterial photodynamic therapy (aPDT) has emerged as an effective antibacterial treatment with high cure gain. In this work, three Zn(II) complexes viz., [Zn(en)(acac)Cl] (1), [Zn(bpy)(acac)Cl] (2), [Zn(en)(cur)Cl] (3), where en=ethylenediamine (1 and 3), bpy=2,2'-bipyridine (2), acac=acetylacetonate (1 and 2), cur=curcumin monoanionic (3) were developed as aPDT agents. Complexes 1-3 were synthesized and fully characterized using NMR, HRMS, FTIR, UV-Vis. and fluorescence spectroscopy. The HOMO-LUMO energy gap (Eg), and adiabatic splittings (ΔS1-T1 and ΔS0-T1 ) obtained from DFT calculation indicated the photosensivity of the complexes. These complexes have not shown any potent antibacterial activity under dark conditions but the antibacterial activity of these complexes was significantly enhanced upon light exposure (MIC value up to 0.025 μg/mL) due to their light-mediated 1 O2 generation abilities. The molecular docking study suggested that complexes 1-3 interact efficiently with DNA gyrase B (PDB ID: 4uro). Importantly, 1-3 did not show any toxicity toward normal HEK-293 cells. Overall, in this work, we have demonstrated the promising potential of Zn(II) complexes as effective antibacterial agents under the influence of visible light.

Single-crystal X-ray, spectroscopy, quantum chemical calculations, and molecular docking investigation of ruthenium (II) polypyridyl complexes of curcumin as a potential chemotherapy drug in the treatment of malignant glioblastoma (GBM)

Single-crystal X-ray, spectroscopy, quantum chemical calculations, and molecular docking investigation of ruthenium (II) polypyridyl complexes of curcumin as a potential chemotherapy drug in the treatment of malignant glioblastoma (GBM)

Clinical Effects of Oral Supplementation of Gamma-Cyclodextrin Curcumin Complex in Male Patients with Moderate-To-Severe Benign Prostatic Hyperplasia-Related Lower Urinary Tract Symptoms

Introduction: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTSs) in males. Curcumin exhibits anti-inflammatory and anti-tumor properties which may be effective for BPH. This multi-arm observational study evaluated the real-world efficacy of QURMIN^® (Gamma-cyclodextrin-curcumin Complex-CAVACURMIN^®) as single or combination therapy for BPH. Methods: Men with moderate-severe LUTS/BPH, receiving a 6-month supplementation with QURMIN^® alone or in combination with BPH-specific medication were propensity score matched with patients not taking curcumin and then divided into subgroups based on concomitant baseline treatment. Cohorts were compared in the 6-month variation of IPSS, quality of life (IPSS-QoL), Benign Prostatic Hyperplasia Impact Index (BII) and uroflowmetry parameters. Curcumin tolerability was evaluated in terms of discontinuations and adverse effects. Results: The 1:1 propensity score matching resulted in a treatment-naïve (n = 152), an alpha-blocker only (AB) (n = 138) and AB + 5-alpha reductase inhibitors (5-ARIs) (n = 78) subgroup. After 6 months, drug-naïve patients taking curcumin reported significant improvement in IPSS-storage (−3.9, p < 0.001), IPSS-voiding (−2.0, p = 0.011), IPSS-total (−5.9, p < 0.001), IPSS-QoL (−3.9, p < 0.001), BII (−2.0, p < 0.001), Q_max (+3.1 mL/s, p < 0.001), Q_mean (+1.9 mL/s, p = 0.005), post-void residual volume (−7.7 mL, p < 0.001), and PSA (−0.3 ng/mL, p = 0.003), compared to controls. Patients taking ABs and curcumin showed improvement in IPSS-storage (−2.7, p < 0.001), IPSS-voiding (−1.3, p = 0.033), IPSS-total (−3.5, p < 0.001), IPSS-QoL (−1.1, p = 0.004), BII (−1.7, p = 0.006), Q_max (+1.0 mL/s, p = 0.006), and PSA (−0.2 ng/mL, p = 0.01). Patients taking curcumin and AB + 5-ARI showed improvement in IPSS-storage (−1.3, p = 0.007), IPSS-total (−1.6, p = 0.034), IPSS-QoL (−1.1, p < 0.001), and BII (−2.0, p < 0.001). No adverse reactions were reported for curcumin supplementation. Conclusion: QURMIN^® (CAVACURMIN^®) led to significant improvements in symptom burden, uroflow parameters, and QoL, without significant additional side effects, thus proving to be a potential new treatment for BPH, either as a single therapy or in addition to standard treatment.

Porous Microgels for Delivery of Curcumin: Microfluidics-Based Fabrication and Cytotoxicity Evaluation.

Polymeric microgels, fabricated via microfluidic techniques, have garnered significant interest as versatile drug delivery carriers. Despite the advances, the loading and release of hydrophobic drugs such as curcumin from polymeric microgels is not trivial. Herein, we report that effective drug loading can be achieved by the design of porous particles and the use of supramolecular cyclodextrin-based curcumin complexes. The fabrication of porous microgels through the judicious choice of chemical precursors under flow conditions was established. The evaluation of the curcumin loading dependence on the porosity of the microgels was performed. Microgels with higher porosity exhibited better curcumin loading compared to those with lower porosity. Curcumin-loaded microgels released the drug, which, upon internalization by U87 MG human glioma cancer cells, induced cytotoxicity. The findings reported here provide valuable insights for the development of tailored drug delivery systems using a microfluidics-based platform and outline a strategy for the effective delivery of hydrophobic therapeutic agents such as curcumin through supramolecular complexation.

Highly robust quantum mechanics and umbrella sampling studies on inclusion complexes of curcumin and β-cyclodextrin

The poor aqueous solubility of curcumin (CUR) obstructs its wide utilization in nutraceuticals, cosmetics, and pharmaceutical companies. This study is dedicated to investigate the stability of CUR inside the hydrophobic pocket of β-cyclodextrin (β-CD), hydroxypropyl-β-CD (HP-β-CD), and 2,6-Di-O-methyl-β-CD (DM-β-CD). Initially, molecular mechanics (MM) calculations and subsequently quantum mechanical (QM) calculations were performed on inclusion complexes to strengthen the MM results. We performed microsecond timescale MD simulations to observe the structural dynamics of CUR inside the cavity of CDs. We elucidated the most stable binding orientations of CUR inside the cavity of CDs based on binding free energy obtained from the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) and umbrella sampling simulations. Furthermore, the two-layered ONIOM (B3LYP/6-311+G(2d,p):PM7) method with CPCM implicit water model was used to derive the complete energetics and thermodynamics of inclusion complexes at 1:1 stoichiometry. Each inclusion reaction was exothermic and spontaneous. The chemical reactivity and kinetic stability of inclusion complexes were described by HOMO-LUMO molecular orbital energies. In conclusion, our studies revealed that HP-β-CD had the highest binding affinity for CUR with the most negative complexation energy (−6520.69 kJ/mol) and Gibb's free energy change (−6448.20 kJ/mol). The atomic-level investigation of noncovalent interactions between CUR and the hydroxypropyl groups in HP-β-CD/CUR complex may be helpful to drive new derivatives of HP-β-CD with better host capacity. The computational strategy adopted here might serve as a benchmark for increasing the solubility of numerous clinically significant molecules.

Influence of CurQfen®-curcumin on cognitive impairment: a randomized, double-blinded, placebo-controlled, 3-arm, 3-sequence comparative study.

Although curcumin is a blood-brain-barrier permeable molecule with the ability to bind and segregate β-amyloid plaques and neurofibrillary tangles of hyperphosphorylated tau proteins, its poor oral bioavailability, rapid biotransformation to inactive metabolites, fast elimination from the systemic circulation, and hence the poor neuronal uptake has been limiting its clinical efficacy under neurodegenerative conditions. We hypothesized that the highly bioavailable CurQfen-curcumin (CGM), which has been shown to possess significant blood-brain-barrier permeability and brain bioavailability, would ameliorate dementia in neurodegenerative conditions. In the present double-blinded placebo-controlled 3-arm 3-sequence comparative study, 48 subjects characterized with moderate dementia due to the onset of Alzheimer's disease were randomized into three groups (N = 16/group) and supplemented with 400 mg × 2/day of either placebo (MCC), unformulated standard curcumin complex with 95% purity (USC), or CGM as a sachet for six months. The relative changes in cognitive and locomotor functions and biochemical markers were compared. Supplementation with CGM produced significant (P < 0.05) improvement in the Mini-Mental State Examination (MMSE) and the Geriatric Locomotive Function Scale (GLFS) scores in both intra- and inter-group comparison by 2 × 2 repeated measures (RM) ANOVA. Further, analysis of the serum levels of specific biomarkers (BDNF, Aβ42, tau protein, IL-6, and TNF-α) also revealed a significant (P < 0.05) improvement among CGM subjects as compared to placebo and the USC groups. Supplementation with CGM as sachet was found to offer significant delay in the progress of Alzheimer's disease, as evident from the improvements in locomotive and cognitive functions related to dementia. http://ctri.nic.in, identifier: CTRI/2018/03/012410.

Rapid on-demand in-situ gelling and dissociation of PEG bottlebrush hydrogel via light-mediated grafting-through polymerization for full-thickness skin wound repair

Developing light-triggered in situ forming dynamical hydrogels with on-demand dissolvable and antioxidation capacities to promote wound healing is highly desired yet challenging. Herein, we prepared an in situ forming bottlebrush hydrogel with on-demand dissolution capacity from two thioctic acid (TA)-functionalized poly(ethylene glycol)s (PEGs) telechelic (TA-PEGs) prepolymers via a light-mediated grafting-through polymerization strategy. In response to light irradiation, TA-PEGs could undergo rapid ring-opening polymerization to generate a highly branched bottlebrush network with dynamic disulfide bonds and simultaneously load water-soluble curcumin complexes with excellent antioxidant activity, enabling fast in situ gelation in 3 min to achieve perfect coverage of wound sites with different shapes. Furthermore, the resulting bottlebrush hydrogel dressing can achieve facile and painless removal of the dressing via rapid on-demand dissolution of the hydrogel during dressing changes. Meanwhile, thanks to its dynamical feature of the disulfide-based network, the hydrogel possesses excellent self-healing ability and shape adaptability that can maintain the interiority of the dressing during application and thus prolong its service life. In vitro evaluation demonstrates that this PEG bottlebrush hydrogel possesses favorable hemocompatibility, cytocompatibility, and antioxidant capacity. More importantly, in vivo experiments confirmed that the hydrogel promotes angiogenesis, dermal collagen synthesis, and alleviates the excessive ROS damage, thus providing more beneficial conditions to accelerate full-thickness skin wound healing.

The behavior of whey protein isolate-curcumin complex at the oil-water interface

It was very common to use nanoparticles and nanoemulsions with the combination of proteins and hydrophobic bioactives to effectively prevent and treat chronic diseases. This work was to evaluate the stability of whey protein isolate (WPI) and curcumin (CUR) complex made with the anti-solvent precipitation technique and the pH shifting methods in oil-water bulk and interface. The interaction between WPI and CUR were investigated using fluorescence spectroscopy, Fourier transform infrared spectroscopy and molecular docking. The changes of the WPI-CUR in the oil-water bulk and interface were characterized by the circular dichroism spectroscopy, UV spectroscopic, confocal laser scanning microscopy and molecular dynamics simulation. Results indicated that the interactions between WPI and CUR were hydrogen bonding and hydrophobic interaction. The WPI-CUR complex was unstable at the oil-water interface, CUR detached from the complex and migrated to the oil phase. These findings would be of importance in illustrating the behavior of whey protein isolate-curcumin complex at the oil-water interface.

Two-Stage Supramolecular Self-Assembly-Directed Collagen-Peptide-Decorated Liposomal Complexes of Curcumin Microspheres with Enhanced Solubility and Bioavailability.

Green formulations of phytonutrients with enhanced solubility and bioavailability are of great significance in nutrition therapy. In the present contribution, we hypothesized that the collagen peptides could be a safe, natural, food-grade, and cost-effective functional agent for the surface decoration and stabilization of liposomes in powder form and hence a "green" solution for the oral delivery of phytonutrients. The present study reports a two-stage supramolecular self-assembly-directed process for the preparation of collagen peptide-decorated liposomal complexes of curcumin (CCL) [10% (w/w)] as microspheres (125 ± 25 μm) with improved solubility (1.46 × 105-fold) and sustained-release properties under gastrointestinal pH conditions. The molecular self-assembly of collagen peptides around the lipid bilayers and the various noncovalent interactions and conformational changes leading to the supramolecular assembly to act as a matrix for the encapsulation of lipid vesicles of curcumin were clear from the spectroscopic studies (UV-vis, fluorescence, FTIR, and circular dichroism). Further investigation of pharmacokinetics following a randomized double-blinded controlled trial on healthy volunteers (n = 15) demonstrated that the oral administration of 2.5 g of CCL sachet (250 mg of curcumin) enhanced the plasma concentration (Cmax: 118 vs. 4.3 ng/mL), the elimination half-life (4.2 vs. 0.7 h), and bioavailability as per the area under the curve over 12 h [AUC0-12h (CCL) = 506·8 vs. AUC0-12h (C95) = 9.47 (53-fold)], when the plasma concentration of curcumin was estimated with triple quadruple tandem mass spectrometry (UPLC-ESI-MS/MS).

Z-scan and degenerate four wave mixing studies on newly synthesized copper complexes of curcumin

Designing novel metal complexes with high nonlinear optical (NLO) susceptibilities is a special interest for coordination compounds. They include a wider selection of metals with a variety of ligands and oxidation states, which can result in tuneable electronic capabilities. Paramagnetic Copper (II) complexes of curcumin were synthesized using different metal precursors and keeping curcumin as the base ligand. All the complexes were characterized by elemental analysis, magnetic susceptibility, and spectroscopic methods (UV–vis, FT-IR, ESR, and mass spectrometry). Nonlinear optical transmission measurements were carried out using nanosecond laser pulses with 532 nm wavelength, via a Z-scan and Degenerate four-wave mixing (DFWM) techniques. CuAcCur, CuClCur, and CuThCur complexes provided with 1.34 × 1024, 3.61 × 1024, and 4.05 × 1024 m3/W2, proved that these complexes possess excellent NLO properties and CuThCur being best among them. The NT dropped from 100 % to 78 %, 65 %, and 75 % in CuAcCur, CuClCur, and CuThCur respectively, showing that all the complexes have great potential for optical limiting (OL) application. The Conceptual-Density-Functional-Theory (CDFT) were employed to perform the theoretical analyses of complexes. Calculations on the various CDFT-based parameters such as electronegativity, HOMO-LUMO energy gap, molecular hardness, softness, dipole moment, and electrophilicity index of both species are performed. This work introduces three copper complexes with curcumin that show an excellent NLO and OL behavior.

Preparation and Characterization of Curcumin Complexes with Zinc(II), Nickel(II), Magnesium(II), Copper(II) and their Evaluation Against Gram-positive and Gram-negative Bacteria

Se han preparado complejos metálicos de cobre(II), zinc(II), níquel(II) y magnesio(II) con el ligando curcuminato, en la relación molar 2:1 ligando:metal, en etanol como disolvente: [M(curcumina)2] (M = Ni2+, Cu2+, Mg2+ y Zn2+). La relación estequiométrica ligando-metal (2:1) se determinó por el método espectrofotométrico de Job (método de las variaciones continuas). Los complejos fueron caracterizados por análisis elemental, espectrometría de masas, espectroscopia infrarroja, espectroscopia fotoelectrónica de rayos X (XPS) y resonancia magnética nuclear (1H-RMN, 13C-RMN). En el complejo, cada curcuminato se enlaza al metal a través de dos átomos de oxígeno (C=O y C-O-) formando anillos quelatos de 6 miembros que actúan como un ligando bidentado. Los resultados del estudio antibacteriano de los complejos preparados frente a Staphylococcus aureus (grampositivo) y Escherichia coli (gramnegativo), a través el método Kirby-Bauer (método de difusión en Agar), revelan que todos los complejos presentan importante actividad antibacteriana frente al Staphylococcus aureus, destacándose el complejo de curcumina-zinc que presenta actividad biológica frente a esta bacteria aun a concentraciones bajas.

Diving into the optoelectronic properties of Cu(II) and Zn(II) curcumin complexes: a DFT and wavefunction benchmark.

Curcumin is a popular food additive around the world whose medicinal properties have been known since ancient times. The literature has recently highlighted several biological properties, but besides the health-related usages, its natural yellowish color may also be helpful for light-harvesting applications. This research aims to close a knowledge gap regarding the photophysical description of curcumin and its metallic complexes. We conducted benchmark experiments comparing NEVPT calculations with several DFT functionals (B3LYP, M06-L, M06-2X, CAM-B3LYP, and ωB97X-D) for describing the UV spectra of curcumin and its metallo-derivative, curcumin-copper(II). Once we determined the most suitable functional, we performed tests with different basis sets and conditions, such as solvation and redox state, to identify their impact on excited state properties. These results are also reported for the curcumin-zinc(II) derivative. We found that the accuracy of DFT functionals depends strongly on the nature of curcumin's excitations. Intra-ligand transitions dominate the absorption spectra of the complexes. Curcumin absorption is marginally affected by solvation and chelation, but when combined with redox processes, they may result in significant modifications. This is because copper cation changes its coordination geometry in response to redox conditions, changing the spectrum. We found that, compared to a NEVPT reference, B3LYP is the best functional for a general description of the compounds, despite not being appropriate for charge transfer transitions. M06-L was the best for LMCT transitions. However, compared with NEVPT2 and PNO-LCCSD(T)-F12 results, no functional achieved acceptable accuracy for MLCT transitions.

Cover Feature: Polypyridyl CoII‐Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents (ChemBioChem 10/2023)

Visible light-induced anticancer and antibacterial profiles of Co(II) curcumin complexes. This cover illustrates Co(II)-curcumin conjugates exhibiting remarkable visible light-triggered anticancer activity against breast cancer (MCF-7) cells by ROS-induced apoptosis and the fluorescent nature of curcumin assisting in cell imaging. Also, antibacterial activity against both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacterial strains through the activation of the Co(II)-curcumin conjugates at the targeted site by light exposure, is depicted here. More information can be found in the Research Article by B. Koch, S. Banerjee.

Polypyridyl CoII -Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents.

Four new CoII complexes, [Co(bpy)2 (acac)]Cl (1), [Co(phen)2 (acac)]Cl (2), [Co(bpy)2 (cur)]Cl (3), [Co(phen)2 (cur)]Cl (4), where bpy=2,2'-bipyridine (1 and 3), phen=1,10-phenanthroline (2 and 4), acac=acetylacetonate (1 and 2), cur=curcumin monoanion (3 and 4) have been designed, synthesized and fully characterized. The X-ray crystal structures of 1 and 2 indicated that the CoN4 O2 core has a distorted octahedral geometry. The photoactivity of these complexes was tuned by varying the π conjugation in the ligands. Curcumin complexes 3 and 4 had an intense absorption band near 435 nm, which made them useful as visible-light photodynamic therapy agents; they also showed fluorescence with λem ≈565 nm. This fluorescence was useful for studying their intracellular uptake and localization in MCF-7 breast cancer cells. The acetylacetonate complexes (1 and 2) were used as control complexes to understand the role of curcumin. The white-light-triggered anticancer profiles of the cytosol targeting complexes 3 and 4 were investigated in detail. These non-dark toxic complexes displayed significant apoptotic photo-cytotoxicity (under visible light) against MCF-7 cells through ROS generation. The control complexes 1 and 2 did not induce significant cell death in the light or dark. Interestingly, 1-4 produced a remarkable antibacterial response upon light exposure. Overall, the reported results here can increase the boundary of the CoII -based anticancer and antibacterial drug development.

Exploring Self-Healing and Switchable Adhesives based on Multi-Level Dynamic Stable Structure.

It is a challenge to develop adhesives simultaneously capable of strong adhesion and efficient switchable ability. Herein, the authors report multifunctional switchable adhesives named Cu2+ -curcumin-imidazole-polyurethane (CIPUs:Cu2+ ) by introducing 1-(3-aminopropyl) imidazole and curcumin into polyurethane system crossed by Cu2+ forming dynamic metal-ligand bonds. This CIPUs:Cu2+ has strong adhesion (up to 2.46MPa) on various material surfaces due to their specially designed functional groups alike the secretions from mussels. It can achieve fast switching speed (30 s) and high switch efficiency through multiple contactless remote stimulations. Importantly, density functional theory (DFT) calculation reveals that such metal-ligand bonds consisting of two components: stronger Cu2+ -curcumin complexes and weaker Cu2+ -imidazole complexes can aggregate to form multi-level dynamic stable structure . The special structure can not only be acted as sacrificial sites for easily broken and reformed, allowing efficient switchable adhesion and enormous energy dissipation but also acted as firm sites to maintain the cohesion of the adhesive and the reversible reconstruction network. Intriguingly, the CIPUs:Cu2+ can achieve self-healing at room temperature without needing external stimuli. Overall, this strategy can further broaden the design of switchable adhesives in the fields of intelligent gadgets, wearable bio-monitoring devices, etc.

A spiral microfluidic chip endows high efficiency single cell alignment at extremely low flow for ICP-MS analysis

A spiral microfluidic chip integrating periodic micro pillars was designed to achieve focusing and sorting of cells at ultra-low flow rate. It enables high efficiency single cell analysis by combining with time resolved inductively coupled plasma mass spectrometry (TRA-ICP-MS). The spiral chip facilitates focusing of particles or cells through the action of secondary flow and inertial induced lift force. The simulation illustrated that the periodic micro-pillars enhanced the influence of secondary flow and resulted in a superb focusing of cells. The focusing capability of the chip was demonstrated by using fluorescent particles of 9.77 μm in diameter and MCF-7 cells stained with DiI, wherein excellent focusing/alignment was achieved at flow rates of as low as 5 μL min−1 for fluorescent particles and 10 μL min−1 for MCF-7 cells, respectively. Furthermore, the spiral microfluidic chip was used for focusing/alignment of MCF-7 and LoVo cells after incubating with anticancer metal prodrug (cobalt curcumin complex [Co(tpa)(cur)](ClO4)2). The uptake of this prodrug in individual MCF-7 and LoVo cell was investigated with detection by TRA-ICP-MS in single cell resolution. The two types of cancer cells exhibit different uptake behaviors of the complex, and differences among individual cells of each type were also identified. A single cell detection efficiency of 67.5 ± 4.6% was obtained at the flow rate of 50 μL min−1.

Crystal structure, photophysical properties, and DFT calculations of a boron difluoride curcumin complex

Abstract The crystal structure of a curcumin-BF2 complex has been successfully refined from single-crystal X-ray diffraction data of crystals with one molecule of co-crystallized dichloromethane. The complex has a nearly coplanar structure. The molecules form a mesh structure by intermolecular multiple hydrogen bonds, as well as weak hydrogen bonds with CH2Cl2 molecules. An investigation of the photo-physical properties has indicated that the curcumin-BF2 complex possesses a wide absorption band and an intense red emission in the solid state due to a strong electron-withdrawing effect of the BF2 groups. DFT calculations of a single molecule verify the relationships between the photo-physical properties and its intrinsic electronic features, but neglect the role of hydrogen bonding.

Insight into the inclusion mechanisms of curcumin in β-cyclodextrin using a screening strategy: Molecular simulation and experimental study

Materials Studio 2018 software was used to model β-cyclodextrin (β-CD) and 16 flavonoids, and Auto Dock 4.0 was used for molecular docking. From the molecular dynamics simulations, curcumin (CUR) was identified as the most suitable inclusion in β-CD. For comparison, the inclusion of CUR in 2, 6-dimethyl-β-cyclodextrin (DM-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was simulated. The calculated parameters included solubility parameters, binding energy, mean square displacement, radial distribution, and hydrogen bonding. The simulation results showed that DM-β-CD was most effective for the inclusion of CUR. Inclusion complexes of CUR with β-CD, DM-β-CD, and HP-β-CD were prepared by freeze-drying. The inclusion complexes were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and UV-visible (UV-vis) spectra. The experimental results also showed that DM-β-CD was most effective for the inclusion of CUR, which is in agreement with the simulation results.

Efficacy of TurmiZn, a Metallic Complex of Curcuminoids-Tetrahydrocurcumin and Zinc on Bioavailability, Antioxidant, and Cytokine Modulation Capability

Complexes of curcumin with metals have shown much-improved stability, solubility, antioxidant capability, and efficacy when compared to curcumin. The present research investigates the relative bioavailability, antioxidant, and ability to inhibit inflammatory cytokine production of a curcuminoid metal chelation complex of tetrahydrocurcumin-zinc-curcuminoid termed TurmiZn. In vitro uptake assay using pig intestinal epithelial cells showed that TurmiZn has an ~3-fold increase (p ≤ 0.01) in uptake compared to curcumin and a ~2-fold increase (p ≤ 0.01) over tetrahydrocurcumin (THC). In a chicken model, an oral 1-g dose of TurmiZn showed a ~2.5-fold increase of a specific metabolite peak compared to curcumin (p = 0.004) and a ~3-fold increase compared to THC (p = 0.001). Oral doses (5 g/Kg) of TurmiZn in rats also showed the presence of curcumin and THC metabolites in plasma, indicating bioavailability across cell membranes in animals. Determination of the antioxidant activity by a 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging assay indicated that TurmiZn was about 13x better (p ≤ 0.0001) than curcumin and about 4X better (p ≤ 0.0001) than THC, in reducing free radicals. In vitro experiments further showed significant (p ≤ 0.01) reductions of lipopolysaccharide (LPS)-induced proinflammatory cytokines such as interleukin (IL) IL-6, IL-8, IL-15, IL-18, and tumor necrosis factor (TNF)-alpha, while showing a significant (p ≤ 0.01) increase of granulocyte-macrophage colony-stimulating factor (GM-CSF) in dog kidney cells. In vivo cytokine modulations were also observed when TurmiZn was fed for 6 weeks to newborn chickens. TurmiZn reduced IL-1 and IL-6, but significantly reduced (p ≤ 0.01) IL-10 levels while there was a concurrent significant (p = 0.02) increase in interferon gamma compared to controls. Overall, these results indicate that TurmiZn has better bioavailability and antioxidant capability than curcumin or THC and has the ability to significantly modulate cytokine levels. Thus, TurmiZn could be an excellent candidate for a novel ingredient that can be incorporated into food and supplements to help overall health during the aging process.