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1.
ACS Appl Mater Interfaces ; 13(41): 48433-48448, 2021 Oct 20.
Article in English | MEDLINE | ID: mdl-34613687

ABSTRACT

The excessive colonization of Propionibacterium acnes (P. acnes) is responsible for the genesis of acne vulgaris, a common inflammatory disease of skin. However, the conventional anti-acne therapies are always limited by various side effects, drug resistance, and poor skin permeability. Microneedles (MNs) are emerging topical drug delivery systems capable of noninvasively breaking through the skin stratum corneum barrier to efficiently enhance the transdermal drug penetration. Herein, MNs loaded with intelligent pH-sensitive nanoplatforms were constructed for amplified chemo-photodynamic therapy against acne vulgaris, jointly exerting antimicrobial and anti-inflammatory effects. The photosensitizer indocyanine green (ICG) was loaded into the zeolitic imidazolate framework-8 (ZIF-8) to improve its photostability, which would be triggered by 808 nm laser irradiation to generate cytotoxic reactive oxygen species (ROS) to result in oxidative damage and disturbed metabolic activities of P. acnes. In addition to the efficient drug delivery, the ZIF-8 carrier could selectively degrade in response to the acidic microenvironment of acne lesions, and the released Zn2+ also exhibited a potent antimicrobial activity. The fabricated ZIF-8-ICG@MNs presented an outstanding synergistic anti-acne efficiency both in vitro and in vivo. This bioresponsive microneedle patch is expected to be readily adapted as a generalized, modular strategy for noninvasive therapeutics delivery against superficial skin diseases.


Subject(s)
Acne Vulgaris/drug therapy , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Imidazoles/therapeutic use , Indocyanine Green/therapeutic use , Metal-Organic Frameworks/therapeutic use , Photosensitizing Agents/therapeutic use , Acne Vulgaris/pathology , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/radiation effects , Anti-Bacterial Agents/toxicity , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/radiation effects , Anti-Inflammatory Agents/toxicity , HEK293 Cells , Humans , Imidazoles/chemistry , Imidazoles/radiation effects , Imidazoles/toxicity , Indocyanine Green/chemistry , Indocyanine Green/radiation effects , Indocyanine Green/toxicity , Infrared Rays , Male , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/radiation effects , Metal-Organic Frameworks/toxicity , Mice, Inbred BALB C , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/radiation effects , Photosensitizing Agents/toxicity , Propionibacterium acnes/drug effects , Rats , Skin/drug effects , Skin/pathology , Swine , Zinc/chemistry , Zinc/radiation effects , Zinc/therapeutic use , Zinc/toxicity
2.
ACS Appl Mater Interfaces ; 13(36): 42396-42410, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34472332

ABSTRACT

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Metal-Organic Frameworks/therapeutic use , Nitric Oxide Donors/therapeutic use , Photosensitizing Agents/therapeutic use , Staphylococcal Skin Infections/drug therapy , Wound Healing/drug effects , Animals , Anti-Inflammatory Agents/radiation effects , Anti-Inflammatory Agents/toxicity , Cell Line , Escherichia coli/drug effects , Light , Metal-Organic Frameworks/radiation effects , Metal-Organic Frameworks/toxicity , Mice, Inbred BALB C , Nitric Oxide Donors/radiation effects , Nitric Oxide Donors/toxicity , Photosensitizing Agents/radiation effects , Photosensitizing Agents/toxicity , Porphyrins/radiation effects , Porphyrins/therapeutic use , Porphyrins/toxicity , Staphylococcus aureus/drug effects
3.
Food Chem Toxicol ; 152: 112157, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33789119

ABSTRACT

The study aimed to study the effects on structural characteristics and anti-inflammatory activities of algal sulfated polysaccharides isolated from Gracilaria lemaneiformis (GLP) after a combined treatment of UV irradiation (average irradiance of 6500 mJ/cm2) and H2O2 (50 mmol/L) for various time periods up to 60 min. After a 30-min treatment, the molecular weight and particle size of GLP was decreased by 15 and 2.6 fold, respectively with small but significant decrease in the contents of total sugars, uronic acids and proteins. There seemed to have no starch and the presence of longer side chains of branches in the GLP samples before and after UV/H2O2 treatment based on the I2-KI assay. Scanning electron microscope and atomic force microscope analysis confirmed that the UV/H2O2 treatment could modify the surface morphology of GLP. GLP treated for 5 min possessed the strongest in vitro anti-inflammatory activity by inhibiting the production of nitric oxide, tumor necrosis factor-α and interleukin-6 by 60.49%, 62.81% and 36.29%, respectively in IEC-6 cells when compared to the model. Therefore, UV/H2O2 treatment had the potential to enhance the anti-inflammatory activity of algal sulfated polysaccharides.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Gracilaria/chemistry , Polysaccharides/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/radiation effects , Cell Line , Hydrogen Peroxide/chemistry , Interleukin-6/metabolism , Molecular Weight , Nitric Oxide/metabolism , Particle Size , Photolysis , Polysaccharides/chemistry , Polysaccharides/radiation effects , Rats , Tumor Necrosis Factor-alpha/metabolism , Ultraviolet Rays , Viscosity
4.
Chem Commun (Camb) ; 56(31): 4300-4303, 2020 Apr 21.
Article in English | MEDLINE | ID: mdl-32186557

ABSTRACT

Reaction of Fe(CO)4Br2 with 2-aminopyridine and 2-aminonapthalene yields ferracyclic iron(ii) complexes bearing two CO ligands. Irradiation with visible light releases these two CO molecules. Substitution of a halide in the parent complexes by thioglucose provides significantly enhanced water solublity and raises the quantum yield for CO release by around five times. The complexes show anti-inflammatory activity in a TNF assay in the dark.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Coordination Complexes/pharmacology , Animals , Anti-Inflammatory Agents/radiation effects , Carbon Monoxide/metabolism , Coordination Complexes/radiation effects , Horses , Humans , Iron/chemistry , Light , Lipopolysaccharides/pharmacology , Myoglobin/metabolism , THP-1 Cells , Tumor Necrosis Factor-alpha/metabolism
5.
Am J Phys Med Rehabil ; 99(1): 19-25, 2020 01.
Article in English | MEDLINE | ID: mdl-31335343

ABSTRACT

OBJECTIVE: The aim of this study was to analyze the effects of low-intensity pulsed ultrasound therapy under different pulse regimes on cultures of semiconfluent L929 fibroblasts, evaluating cell viability, anatomical structural alterations, modulation of vascular endothelial growth factor, interleukin 6, collagen type 1 alpha 1, collagen type 1 alpha 2, and fibroblast growth factor 7, as well as the amount of inflammatory mediators interleukin 2, interleukin 4, interleukin 6, interferon γ, tumor necrosis factor, interleukin 17A, and interleukin 10 at 24, 48, and 72 hrs. DESIGN: The design was experimental study. METHODS: The treatments consisted of 0.2 W/cm doses at a frequency of 1 MHz, with a pulse rate of 10% and 20%. Viability was assessed by the MTT assay (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide), gene expression by real-time quantitative polymerase chain reaction, and cytokine quantification by flow cytometry. RESULTS: At 48 hrs, ultrasound enhanced cell viability and affected interleukin 6 cytokine production, vascular endothelial growth factor, interleukin 6, type 1 alpha 1 and alpha 2 collagens, and fibroblast growth factor 7 gene modulation. CONCLUSIONS: Low-intensity pulsed ultrasound therapy had a biostimulatory effect on semiconfluent in vitro L929 fibroblast cells, where the group with a dose of 0.2 W/cm-10% (G2) presented higher responses, in all the analyzed aspects, toward the dose pulsed to 20%, confirming its therapeutic properties related to the initial phases of tissue healing.


Subject(s)
Anti-Inflammatory Agents/radiation effects , Cell Survival/radiation effects , Fibroblasts/radiation effects , Ultrasonic Therapy/methods , Ultrasonic Waves , Cells, Cultured , Collagen Type I/radiation effects , Cytokines/radiation effects , Fibroblast Growth Factor 7/radiation effects , Humans , Inflammation Mediators/radiation effects , Interleukin-6/radiation effects , Vascular Endothelial Growth Factor A/radiation effects
6.
Int Immunopharmacol ; 78: 106072, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31835082

ABSTRACT

Although the novel resveratrol derivative RM has therapeutic potential for the treatment of inflammatory bowel disease, little is currently known regarding the manner whereby RM regulates excessive inflammatory responses. In this study, we initially investigated the molecular mechanisms underlying the anti-inflammatory effects induced by RM in Toll-like receptor (TLR)-activated macrophages. Upon stimulation with lipopolysaccharide, we found that RM-treated activated macrophages down-regulated the increase in pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-12p70), nitric oxide (NO) production, and activating interleukin-1 receptor-associated kinase 1 (IRAK-1) phosphorylation, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Interestingly, the TLR negative regulator Toll-interacting protein (Tollip) was selectively enhanced during RM stimulation in time- and dose-dependent manners. In response to knockdown of Tollip expression by RNA interference, RM-treated activated macrophages showed augmented expression of inflammatory mediators (pro-inflammatory cytokines, NO, inducible nitric oxidase, and cyclooxygenase-2, and surface molecules) and restored the expression of MAPK and NF-κB signals inhibited by RM treatment. Taken together, our findings indicate that RM has therapeutic potential for treating TLR-induced inflammatory diseases via the promotion of Tollip expression.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Inflammation/drug therapy , Intracellular Signaling Peptides and Proteins/metabolism , Macrophages/drug effects , Resveratrol/pharmacology , Animals , Anti-Inflammatory Agents/radiation effects , Anti-Inflammatory Agents/therapeutic use , Down-Regulation/drug effects , Drug Evaluation, Preclinical , Gamma Rays , Gene Knockdown Techniques , Inflammation/immunology , Inflammation Mediators/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/immunology , Lipopolysaccharides/immunology , Macrophage Activation/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Primary Cell Culture , RAW 264.7 Cells , Resveratrol/analogs & derivatives , Resveratrol/radiation effects , Resveratrol/therapeutic use , Signal Transduction/drug effects , Signal Transduction/immunology , Toll-Like Receptors/metabolism , Up-Regulation
7.
ChemMedChem ; 13(22): 2408-2414, 2018 11 20.
Article in English | MEDLINE | ID: mdl-30203922

ABSTRACT

Three new gold(I)-coumarin-based trackable therapeutic complexes and two non-trackable analogues have been synthesised and fully characterised. They all display anti-proliferative properties on several types of cancer cell lines, including those of colon, breast, and prostate. Two complexes displayed significant anti-inflammatory effects; one displayed pro-inflammatory behaviour; this highlights the impact of the position of the fluorophore on the caffeine scaffold. Additionally, the three coumarin derivatives could be visualised in vitro by two-photon microscopy.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Caffeine/analogs & derivatives , Caffeine/pharmacology , Coordination Complexes/pharmacology , Coumarins/pharmacology , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/radiation effects , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Caffeine/chemical synthesis , Caffeine/radiation effects , Cell Line, Tumor , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/radiation effects , Coumarins/chemical synthesis , Coumarins/chemistry , Coumarins/radiation effects , Fluorescence , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacology , Fluorescent Dyes/radiation effects , Gold/chemistry , HEK293 Cells , Humans , Microscopy, Fluorescence, Multiphoton/methods , Ultraviolet Rays
8.
Chemosphere ; 212: 56-66, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30138856

ABSTRACT

Prednisolone (PDNN) as an emergent micropollutant directly influences the regional ecological security. In this study, the degradation of PDNN by ultraviolet activated chlorine (UV/chlorine) oxidation process was comprehensively evaluated. The quenching experiment suggested that the PDNN degradation in UV/chlorine process was involved in the participation of hydroxyl radical (OH) and reactive chlorine species (RCS). Influence factors including chlorine dosage, pH, common anion and cation, fulvic acid (FA) on PDNN degradation via UV/chlorine process were investigated. A low chlorine (≤7.1 mg L-1) promoted the PDNN degradation, while a high chlorine dosage (>7.1 mg L-1) was adverse. The pH (4.0-10.0) showed negligible effect, while the investigated anions (Cl-, Br-, HCO3- and SO42-), NH4+ and FA exerted negative impact on PDNN degradation. An efficient process to minimize pharmaceutical micropollutants was the disposal of human urine containing a high concentration of pharmaceutical and potential toxic metabolites. An inhibitory effect was observed in the synthetic urine (fresh urine and hydrolyzed urine). The intermediates/products were identified and the mechanism of PDNN degradation was proposed. PDNN gone through three degradation routes, involving the direct addition of α, ß-unsaturated ketone at C1 or C5, the photolysis of C17 and H-abstraction of C11. The main reactive sites were further determined by comparison of the frontier orbitals calculation and the proposed mechanism. Based on the toxicological tests for PDNN degradation, TP396 (TP396-C1Cl and TP396-C5Cl) and TP414-2-1 (TP414-C1ClC5OH) exhibited much higher toxicity than PDNN, and prolonging reaction time was necessary to achieve PDNN detoxification.


Subject(s)
Aliivibrio fischeri/drug effects , Chlorine/chemistry , Prednisolone/metabolism , Ultraviolet Rays , Water Pollutants, Chemical/urine , Water Purification/methods , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/radiation effects , Anti-Inflammatory Agents/toxicity , Humans , Hydroxyl Radical/chemistry , Kinetics , Oxidation-Reduction , Photolysis , Prednisolone/radiation effects , Prednisolone/toxicity , Toxicity Tests, Acute
9.
J Am Chem Soc ; 140(30): 9721-9729, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29983046

ABSTRACT

The delivery of controlled amounts of carbon monoxide (CO) to biological targets is of significant current interest. Very few CO-releasing compounds are currently known that can be rigorously controlled in terms of the location and amount of CO released. To address this deficiency, we report herein a new metal-free, visible-light-induced CO-releasing molecule (photoCORM) and its prodrug oxidized form, which offer new approaches to controlled, localized CO delivery. The new photoCORM, based on a 3-hydroxybenzo[ g]quinolone framework, releases 1 equiv of CO upon visible-light illumination under a variety of biologically relevant conditions. This nontoxic compound can be tracked prior to CO release using fluorescence microscopy and produces a nontoxic byproduct following CO release. An oxidized prodrug form of the photoCORM is reduced by cellular thiols, providing an approach toward activation in the reducing environment of cancer cells. Strong noncovalent affinity of the nonmetal photoCORM to albumin enables use of an albumin:photoCORM complex for targeted CO delivery to cancer cells. This approach produced cytotoxicity IC50 values among the lowest reported to date for CO delivery to cancer cells by a photoCORM. This albumin:photoCORM complex is also the first CO delivery system to produce significant anti-inflammatory effects when introduced at nanomolar photoCORM concentration.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Prodrugs/pharmacology , Quinolones/pharmacology , A549 Cells , Animals , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/radiation effects , Anti-Inflammatory Agents/toxicity , Antineoplastic Agents/metabolism , Antineoplastic Agents/radiation effects , Antineoplastic Agents/toxicity , Carbon Monoxide , Cattle , Human Umbilical Vein Endothelial Cells , Humans , Light , Mice , Prodrugs/metabolism , Prodrugs/radiation effects , Prodrugs/toxicity , Protein Binding , Quinolones/metabolism , Quinolones/radiation effects , Quinolones/toxicity , RAW 264.7 Cells , Serum Albumin, Bovine/metabolism
10.
PLoS One ; 12(7): e0182011, 2017.
Article in English | MEDLINE | ID: mdl-28759638

ABSTRACT

The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs.


Subject(s)
Anti-Inflammatory Agents/radiation effects , Flufenamic Acid/radiation effects , Mefenamic Acid/radiation effects , Microwaves , Anti-Inflammatory Agents/chemistry , Flufenamic Acid/chemistry , Mefenamic Acid/chemistry , Solubility
12.
Int Immunopharmacol ; 25(2): 249-59, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25701505

ABSTRACT

Resveratrol was irradiated at various doses of 15, 30, 50, and 70kGy for the development of physiological functionalities through modification of the structural properties. Gamma irradiation induced a decrease in the resveratrol peak, and the appearance of several new peaks by gamma irradiation was gradually increased up to 70kGy. Gamma-irradiated resveratrol did not exert cytotoxicity to macrophages in dose ranges from 15 to 70kGy; therefore, 70kGy gamma-irradiated resveratrol was used as the maximum dose throughout subsequent experiments. Treatment of LPS-stimulated macrophages with 70kGy gamma-irradiated resveratrol resulted in a dose-dependent decrease in iNOS-mediated NO, PGE2, and pro-inflammatory cytokine level, such as TNF-α, IL-6 and IL-1ß. 70kGy gamma-irradiated resveratrol significantly inhibited cyclooxygenase-2 levels, as well as the expression of cell surface molecules, such as CD80 and CD86, in LPS-induced macrophages. Furthermore, the inhibitory action of these pro-inflammatory mediators occurred through an inhibition of MAPKs (ERK1/2, p38 and JNK) and NF-κB signaling pathways based on a toll-like receptor 4 in macrophages, which may be closely mediated with the radiolysis products of resveratrol transformed by gamma-irradiation. From these findings, it seems likely that gamma irradiation can be an effective tool for a reduction of the toxicity and play a potent role in the treatment of inflammatory disease.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/radiation effects , Gamma Rays , Macrophages/drug effects , Stilbenes/pharmacology , Stilbenes/radiation effects , Animals , Anti-Inflammatory Agents/chemistry , B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , Cell Line , Cell Proliferation/drug effects , Cells, Cultured , Dinoprostone/metabolism , Female , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Lipopolysaccharides , Macrophages/metabolism , Mice, Inbred C57BL , Mitogen-Activated Protein Kinases/metabolism , Molecular Structure , NF-kappa B/metabolism , Nitric Oxide/metabolism , Resveratrol , Signal Transduction/drug effects , Stilbenes/chemistry , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism
13.
Food Chem Toxicol ; 74: 255-64, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25447760

ABSTRACT

Genistein was irradiated with γ-irradiation at doses of 0, 10, 30, 50, 100, and 150 kGy. We observed that the decrease in the genistein peak after gamma irradiation was concomitant with the appearance of several new peaks. 150 kGy gamma-irradiated genistein did not exert cytotoxicity in macrophages, and inhibited inducible nitric oxide synthase-mediated nitric oxide production and pro-inflammatory cytokines level, such as tumor necrosis factor-α, interleukin-6 and interleukin-1ß, in lipopolysaccharide (LPS)-induced macrophages. The treatment of LPS-stimulated macrophages with 150 kGy gamma-irradiated genistein resulted in a significant decrease in cyclooxygenase-2 levels, as well as the expression of cell surface molecules, such as CD80 and CD86. Furthermore, we also found that the anti-inflammatory action of 150 kGy gamma-irradiated genistein occurred through an inhibition of mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, p38 and c-Jun N-terminal kinase) and nuclear factor-κB signaling pathways based on a toll-like receptor 4 in macrophages, which may be speculated that several radiolysis products of genistein transformed by gamma-irradiation induce the inhibition of pro-inflammatory mediators. From these findings, it seems likely that gamma-irradiated genistein could play a potent role in the treatment of inflammatory disease as a value-added product in the medical industry.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/radiation effects , Genistein/pharmacology , Genistein/radiation effects , Lipopolysaccharides/toxicity , MAP Kinase Signaling System/drug effects , Macrophages/drug effects , NF-kappa B/antagonists & inhibitors , Animals , Anti-Inflammatory Agents/chemistry , B7-1 Antigen/biosynthesis , B7-2 Antigen/biosynthesis , Cell Line , Cell Proliferation/drug effects , Functional Food , Gamma Rays , Genistein/chemistry , Mice , Nitric Oxide/metabolism , Toll-Like Receptor 4/drug effects
14.
Appl Radiat Isot ; 90: 265-73, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24859334

ABSTRACT

Human radiation exposure is increasing due to radiation development in science and technology. The development of radioprotective agents is important for protecting patients from the side effects of radiotherapy and for protecting the public from unwanted irradiation. Radioprotective agents are used to reduce the damage caused by radiation in healthy tissues. There are several classes of radioprotective compounds that are under investigation. Analgesics and anti-inflammatory compounds are being considered for treating or preventing the effects of damage due to radiation exposure, or for increasing the chance of survival after exposure to a high dose of radiation. In this study, we investigated the radioprotective effects of some analgesic and anti-inflammatory compounds by evaluating buildup factors. The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) were calculated to select compounds in a 0.015-15 MeV energy region up to a penetration depth of 40 mfp (mean free path). Variations of EABF and EBF with incident photon energy and penetration depth elements were also investigated. Significant variations in both EABF and EBF values were observed for several compounds at the moderate energy region. At energies below 0.15 MeV, EABF and EBF values increased with decreasing equivalent atomic number (Z(eq)) of the samples. In addition, EABF and EBF were the largest for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06 MeV, respectively, and the EABF value was 0.1 MeV for aceclofenac. From these results, we concluded that the buildup of photons is less for aceclofenac compared to other materials.


Subject(s)
Absorption, Radiation , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/radiation effects , Models, Chemical , Photons , Radiation-Protective Agents/chemistry , Radiation-Protective Agents/radiation effects , Computer Simulation , Materials Testing
15.
Sci Rep ; 4: 4732, 2014 Apr 22.
Article in English | MEDLINE | ID: mdl-24751752

ABSTRACT

We conducted a preliminary investigation of the effects of visible light irradiation on plant extracts, and we observed a strong suppressive effect on interleukin (IL) 2 expression with the inhibition of c-Jun amino-terminal kinase (JNK) phosphorylation in Jurkat cells by visible light irradiation to ethanol extract from green soybeans (LIEGS). This effect was produced only by extracts from green soybeans (Glycine max) and not other-color soybeans. LIEGS suppressed the lipopolysaccharide-induced IL-6, IL-12 and TNF-α expression levels in human monocyte THP-1 cells in a concentration-dependent manner. LIEGS was applied for 8 weeks to NC/Nga mice. LIEGS suppressed the development of atopic dermatitis (AD)-like skin lesions and reduced the dermatitis scores of the mice. The light irradiation changed the various types of small-molecule compounds in extracts. Visible light irradiation to daidzein with chlorophyll b induced a novel oxidative product of daidzein. This product suppressed IL-2 expression in Jurkat cells.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/radiation effects , Glycine max/chemistry , Light , Plant Extracts/pharmacology , Plant Extracts/radiation effects , Animals , Anti-Inflammatory Agents/chemistry , Cytokines/metabolism , Dermatitis, Atopic/drug therapy , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , Interleukin-2/biosynthesis , Jurkat Cells , MAP Kinase Signaling System/drug effects , Male , Mice , Plant Extracts/chemistry
16.
Int J Pharm ; 452(1-2): 124-7, 2013 Aug 16.
Article in English | MEDLINE | ID: mdl-23639290

ABSTRACT

A certain number of filters have notable anti-inflammatory properties with percentage inhibition of PMA-induced edema in mice at over 70%. The question arose as to whether this effect was likely to continue after UV irradiation. It can be noted that 7 filters retain an equivalent anti-inflammatory effect before and after 2h of irradiation in a Suntest device (650 W/m(2)). For 9 filters, the anti-inflammatory effect decreases and for 5 filters, the anti-inflammatory effect increases. Various behaviors should be noted. 3 groups of substances can be distinguished: such as phenylbenzimidazole sulfonic acid which loses its anti-inflammatory character after irradiation (the percentage inhibition falls from 80 to 44%), oxybenzone which retains a constant anti-inflammatory character (89% inhibition before and after irradiation and also octyl methoxycinnamate which becomes very anti-inflammatory (with a percentage inhibition of 93%). The same phenomenon is observed in the case of commercial products. This should be made known as it can have a considerable impact on the results which are displayed on the packaging of sun products.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/radiation effects , Edema/drug therapy , Sunscreening Agents/administration & dosage , Sunscreening Agents/radiation effects , Ultraviolet Rays , Animals , Ear/pathology , Edema/chemically induced , Edema/pathology , Emulsions , Male , Mice , Tetradecanoylphorbol Acetate , Zinc Oxide/administration & dosage , Zinc Oxide/radiation effects
17.
J Pharm Biomed Anal ; 47(4-5): 771-7, 2008 Aug 05.
Article in English | MEDLINE | ID: mdl-18423938

ABSTRACT

Hydrocortisone 21-acetate (HCA) in methanol solution undergoes photodegradation under UVB light, as monitored by HPLC. Five main photoproducts have been isolated and characterized by means of NMR and mass spectroscopy. One of them derives from a Norrish I photoreaction which cleaves the C17-C20 bond of the steroid yielding the andro-derivative, a second product comes from a Yang-type photorearrangement which links C18 to C20 yielding a cyclobutane adduct. The former photoproduct, in turn, undergoes further photolysis giving rise to various photoproducts, of which three have been characterized. The first is a stereoisomer of the andro-derivative, the others arise from the opening of the five-membered ring. HCA also proved photounstable in the solid state and in a commercial formulation for topical use, thus confirming the requirements of the Pharmacopeias for light protection of this drug. Indeed, experiments on LPS-stimulated THP-1 cells demonstrated the loss of anti-inflammatory activity when HCA was UVB-photodegraded. The radical mechanism involved in HCA photolysis seems also responsible for the in vitro photohemolytic effect and lipid peroxidation induced by HCA in combination with UVB light.


Subject(s)
Anti-Inflammatory Agents/radiation effects , Hydrocortisone/analogs & derivatives , Photolysis , Ultraviolet Rays , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cell Differentiation/drug effects , Cell Line, Tumor , Chromatography, High Pressure Liquid , Culture Media, Conditioned/analysis , Culture Media, Conditioned/chemistry , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Erythrocytes/radiation effects , Hemolysis/radiation effects , Humans , Hydrocortisone/chemistry , Hydrocortisone/pharmacology , Hydrocortisone/radiation effects , Interleukin-1beta/analysis , Leukemia, Monocytic, Acute/pathology , Linoleic Acid/radiation effects , Lipid Peroxidation/radiation effects , Macrophages/drug effects , Mass Spectrometry , Mice , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Photobiology , Tetradecanoylphorbol Acetate/pharmacology , Time Factors
18.
Gastroenterology ; 126(2): 520-8, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14762789

ABSTRACT

BACKGROUND & AIMS: We tested whether the attenuation of experimental colitis by live probiotic bacteria is due to their immunostimulatory DNA, whether toll-like receptor (TLR) signaling is required, and whether nonviable probiotics are effective. METHODS: Methylated and unmethylated genomic DNA isolated from probiotics (VSL-3), DNAse-treated probiotics and Escherichia coli (DH5 alpha) genomic DNA were administered intragastrically (i.g.) or subcutaneously (s.c.) to mice prior to the induction of colitis. Viable or gamma-irradiated probiotics were administered i.g. to wild-type mice and mice deficient in different TLR or in the adaptor protein MyD88, 10 days prior to administration of dextran sodium sulfate (DSS) to their drinking water and for 7 days thereafter. RESULTS: Intragastric and s.c. administration of probiotic and E. coli DNA ameliorated the severity of DSS-induced colitis, whereas methylated probiotic DNA, calf thymus DNA, and DNase-treated probiotics had no effect. The colitis severity was attenuated to the same extent by i.g. delivery of nonviable gamma-irradiated or viable probiotics. Mice deficient in MyD88 did not respond to gamma-irradiated probiotics. The severity of DSS-induced colitis in TLR2 and TLR4 deficient mice was significantly decreased by i.g. administration of gamma-irradiated probiotics, whereas, in TLR9-deficient mice, gamma-irradiated probiotics had no effect. CONCLUSIONS: The protective effects of probiotics are mediated by their own DNA rather than by their metabolites or ability to colonize the colon. TLR9 signaling is essential in mediating the anti-inflammatory effect of probiotics, and live microorganisms are not required to attenuate experimental colitis because nonviable probiotics are equally effective.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Colitis/pathology , Colitis/physiopathology , DNA-Binding Proteins/metabolism , Probiotics/pharmacology , Receptors, Cell Surface/metabolism , Signal Transduction , Absorption , Adjuvants, Immunologic/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/radiation effects , Colitis/chemically induced , DNA/isolation & purification , DNA/pharmacology , DNA, Bacterial/pharmacokinetics , Dextran Sulfate , Escherichia coli/genetics , Gamma Rays , Mice , Mice, Inbred Strains , Probiotics/chemistry , Probiotics/radiation effects , Severity of Illness Index , Toll-Like Receptor 9
19.
J Org Chem ; 68(11): 4361-6, 2003 May 30.
Article in English | MEDLINE | ID: mdl-12762737

ABSTRACT

The photochemistry of six pregna-1,4-dien-3,20-diones has been compared and found to involve both the cyclohexadienone moiety in ring A and the isolated ketone at C-20. The two reactions take place proportionally to the fraction of light absorbed by each chromophore. The cross-conjugated ketone absorbs predominantly or exclusively at both 254 and 366 nm and undergoes the "lumi" rearrangement to bicyclo[3.1.0]hex-3-en-2-one. The quantum yield of the reaction diminished somewhat with increasing lambda(exc), e.g., for prednisolone Phi(254) (nm) = 0.42, Phi(366) (nm) = 0.3. A much stronger lowering is caused by halogen substitution in position 9 (by a factor of 3 for F, >50 for Cl), apparently due to a shortened triplet lifetime caused by heavy atom effect. At 310 nm, both chromophores absorb to a comparable degree and both may react. The reaction at C(20) ketone involves either quite efficient alpha-cleavage (C(17)-C(20)) for compounds bearing an acetal or hydroxyl function at C(17) or less effective (by a factor of ca. 10) hydrogen abstraction from the 18-methyl group in the other cases (finally resulting in Norrish II fragmentation or Yang cyclization). The results allow generalizing how the substitution pattern surrounding each chromophore affects the photoreactivity at that site and the competition between the two modes, allowing predicting the photochemistry of this family of antiinflammatory drugs.


Subject(s)
Anti-Inflammatory Agents/chemistry , Photochemistry , Pregnadienes/chemistry , Anti-Inflammatory Agents/radiation effects , Catalysis , Chemistry, Organic/methods , Molecular Structure , Prednisolone/chemistry , Pregnadienes/radiation effects
20.
AAPS PharmSciTech ; 3(2): E8, 2002.
Article in English | MEDLINE | ID: mdl-12916945

ABSTRACT

The purpose of this study was to examine the viscoelastic properties of topical creams containing various concentrations of microcrystalline cellulose and sodium carboxymethyl cellulose (Avicel(R) CL-611) as a stabilizer. Avicel CL-611 was used at 4 different levels (1%, 2%, 4%, and 6% dispersion) to prepare topical creams, and hydrocortisone acetate was used as a model drug. The viscoelastic properties such as loss modulus (G"), storage modulus (G'), and loss tangent (tan delta) of these creams were measured using a TA Instruments AR 1000 Rheometer and compared to a commercially available formulation. Continuous flow test to determine the yield stress and thixotropic behavior, and dynamic mechanical tests for determining the linear viscosity time sweep data, were performed. Drug release from the various formulations was studied using an Enhancer TM Cell assembly. Formulations containing 1% and 2% Avicel CL-611 had relative viscosity, yield stress, and thixotropic values that were similar to those of the commercial formulation. The elastic modulus (G') of the 1% and 2% formulation was relatively high and did not cross the loss modulus (G"), indicating that the gels were strong. In the commercial formulation, G' increased after preshearing and broke down after 600 seconds. The strain sweep tests showed that for all formulations containing Avicel CL-611, the G' was above G" with a good distance between them. The gel strength and the predominance of G' can be ranked 6% > 4% > 2%. The strain profiles for the 1% and 2% formulations were similar to those of the commercial formulation. The delta values for the 1% and 2% formulations were similar, and the formulations containing 4% Avicel CL-611 had lower delta values, indicating greater elasticity. Drug release from the commercial preparation was fastest compared to the formulations prepared using Avicel CL-611, a correlation with the viscoelastic properties. It was found that viscoelastic data, especially the strain sweep profiles of products containing Avicel CL-611 1% and 2%, correlated with the commercial formulation. Rheological tests that measure the viscosity, yield stress, thixotropic behavior, other oscillatory parameters such as G' and G" are necessary tools in predicting performance of semisolids.


Subject(s)
Carboxymethylcellulose Sodium/chemistry , Cellulose/chemistry , Hydrocortisone/analogs & derivatives , Hydrocortisone/chemistry , Ointment Bases/chemistry , Administration, Topical , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/radiation effects , Carboxymethylcellulose Sodium/metabolism , Carboxymethylcellulose Sodium/radiation effects , Cellulose/metabolism , Cellulose/radiation effects , Chromatography, High Pressure Liquid/methods , Drug Storage/methods , Elasticity/radiation effects , Hydrocortisone/metabolism , Hydrocortisone/radiation effects , Ointment Bases/metabolism , Ointment Bases/radiation effects , Rheology/methods , Stress, Mechanical , Technology, Pharmaceutical/instrumentation , Technology, Pharmaceutical/methods , Viscosity/radiation effects
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