curcumin and caffeic-acid

In recent years, the design of food-grade Pickering emulsion delivery systems has become an effective strategy for improving the low bioavailability of bioactive substances. Protein-based Pickering emulsions have received extensive attention because of a high biocompatibility and loading capacity. The bioavailability of active substances is mainly evaluated by simulating in vitro gastrointestinal digestion. As a model organism for antioxidation and anti-aging, Caenorhabditis elegans can provide additional biological information for the in vivo utilization of active substances.. After the introduction of caffeic acid, the average particle size and Zeta potential of the casein-caffeic acid covalent complex nanoparticles (CCP) were 171.11 nm and - 37.73 mV, respectively. The three-phase contact angle was also increased to 89.8°. By using CCP to stabilize Pickering emulsion (CCE), the retention quantity of the embedded curcumin increased by 2.19-fold after 28 days. In the simulated gastric digestion, curcumin degradation in CCE was reduced by 61.84%, released slowly in the intestinal environment, and the final bioaccessibility was increased by 1.90-fold. In C. elegans, CCE significantly reduced ROS accumulation, increased SOD activity by 2.01-fold and CAT activity by 2.30-fold, decreased MDA content by 36.76%, prolonging the lifespan of nematodes by 13.33% under H. The results indictae that CCP-stabilized Pickering emulsion can efficiently implement the physiological activities of bioactive compounds in vitro digestion and C. elegans, and thus it can be regarded as a reliable delivery system for food and medicine. © 2023 Society of Chemical Industry.

Topics: Animals; Biological Availability; Caenorhabditis elegans; Caseins; Curcumin; Emulsions; Nanoparticles; Particle Size

O'nyong-nyong virus is an alphavirus closely related to chikungunya virus, causing arthralgia, rash and fever. Alphaviruses mainly target synovial fibroblasts and persists in the joints of patients, possibly leading to chronic arthritis. To date, no specific antiviral treatment is available for ONNV infection and induced-inflammation. Primary human synovial fibroblasts cells were used to assess infection by ONNV and the resulting cytokine responses. Phenolics (gallic acid, caffeic acid and chlorogenic acid, curcumin and quercetin) and a curcuminoids-rich extract from turmeric were tested for their antiviral and anti-inflammatory capacities. We showed that infection occurred in HSF cells and increased gene expression and protein secretion of two major proinflammatory CCL-2 and IL-1β markers. In ONNV-infected HSF cells (MOI 1), we found that non-cytotoxic concentrations of phenolics (10 µM) reduced the level of viral RNA (E1, E2, nsP1, nsP2) and downregulated CCL-2 and IL-1β expression and secretion. These results highlighted the high value of the flavonol quercetin to reduce viral RNA levels and inflammatory status induced by ONNV in HSF cells.

Topics: Alphavirus Infections; Caffeic Acids; Chemokine CCL2; Chlorogenic Acid; Curcumin; Cytokines; Fibroblasts; Gallic Acid; Humans; Immunity, Innate; Interleukin-1beta; O'nyong-nyong Virus; Quercetin; Synovial Fluid

One of the pathologic hallmarks in Alzheimer's disease (AD) is extracellular senile plaques composed of amyloid-β (Aβ) fibrils. Blocking Aβ self-assembly or disassembling Aβ aggregates by small molecules would be potential therapeutic strategies to treat AD. In this study, we synthesized a series of rationally designed divalent compounds and examined their effects on Aβ fibrillization. A divalent amide (2) derived from two molecules of caffeic acid with a propylenediamine linker of ∼5.0 Å in length, which is close to the distance of adjacent β sheets in Aβ fibrils, showed good potency to inhibit Aβ(1-42) fibrillization. Furthermore, compound 2 effectively dissociated the Aβ(1-42) preformed fibrils. The cytotoxicity induced by Aβ(1-42) aggregates in human neuroblastoma was reduced in the presence of 2, and feeding 2 to Aβ transgenic C. elegans rescued the paralysis phenotype. In addition, the binding and stoichiometry of 2 to Aβ(1-40) were demonstrated by using electrospray ionization-traveling wave ion mobility-mass spectrometry, while molecular dynamic simulation was conducted to gain structural insights into the Aβ(1-40)-2 complex.

Topics: Alzheimer Disease; Amides; Amyloid beta-Peptides; Animals; Caenorhabditis elegans; Caffeic Acids; Humans; Models, Molecular; Peptide Fragments; Protein Multimerization

The intestinal epithelium of the gastrointestinal (GI) tract constantly renews itself to absorb nutrients and provide protection for the body from the outside world. Since the intestinal epithelium is constantly exposed to various chemicals and dietary components, it is critical to determine which constituents promote or inhibit intestinal epithelium health and growth rate. Intestinal organoids, three-dimensional miniature models of the intestines, represent an ex vivo tool to investigate intestinal physiology and growth patterns. In this study, we measured the growth rates of murine intestinal organoids exposed to various concentrations of different dietary constituents. Results indicate that caffeic acid inhibited organoid growth in a concentration-dependent manner, curcumin exhibited variable effectiveness, and vitamin C had no effect on organoid growth.

Topics: Animals; Ascorbic Acid; Caffeic Acids; Chlorogenic Acid; Coumaric Acids; Curcumin; Diet; Gastrointestinal Tract; Mice; Sodium Glutamate; Stem Cells

Substantial studies have shown that curcumin, a dietary compound from turmeric, has beneficial effects on many diseases. However, curcumin rapidly degrades at physiological pH, making it difficult to interpret whether the observed actions of curcumin are from curcumin itself or its degradation products. Therefore, it is important to better understand the mechanisms involved in curcumin degradation and the roles of degradation in its biological actions.. Here, we show that a series of redox active antioxidants with diverse chemical structures, including gallic acid, ascorbate (vitamin C), tert-butylhydroquinone (TBHQ), caffeic acid, rosmarinic acid, and Trolox (a water-soluble analog of vitamin E), dramatically increased curcumin stability in phosphate buffer at physiological pH. When treated in basal cell culture medium in MC38 colon cancer cells, curcumin rapidly degraded with a half-life of several minutes and showed a weak antiproliferative effect; co-addition of antioxidants enhanced stability and antiproliferative effect of curcumin. Finally, co-administration of antioxidant significantly increased plasma level of curcumin in animal models.. Together, these studies strongly suggest that a redox-dependent mechanism plays a critical role in mediating curcumin degradation. In addition, curcumin itself, instead of its degradation products, is largely responsible for the observed biological actions of curcumin.

Topics: Animals; Antioxidants; Ascorbic Acid; Caffeic Acids; Cell Line, Tumor; Cell Proliferation; Chromans; Cinnamates; Curcumin; Depsides; Drug Stability; Gallic Acid; Hydrogen-Ion Concentration; Hydroquinones; Male; Mice; Oxidation-Reduction; Rosmarinic Acid

Differential inhibitors are important for measuring the relative contributions of microbial groups, such as ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA), to biogeochemical processes in environmental samples. In particular, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) represents a nitric oxide scavenger used for the specific inhibition of AOA, implicating nitric oxide as an intermediate of thaumarchaeotal ammonia oxidation. This study investigated four alternative nitric oxide scavengers for their ability to differentially inhibit AOA and AOB in comparison to PTIO. Caffeic acid, curcumin, methylene blue hydrate and trolox were tested onNitrosopumilus maritimus, two unpublished AOA representatives (AOA-6f and AOA-G6) as well as the AOB representative Nitrosomonas europaea All four scavengers inhibited ammonia oxidation by AOA at lower concentrations than for AOB. In particular, differential inhibition of AOA and AOB by caffeic acid (100 μM) and methylene blue hydrate (3 μM) was comparable to carboxy-PTIO (100 μM) in pure and enrichment culture incubations. However, when added to aquarium sponge biofilm microcosms, both scavengers were unable to inhibit ammonia oxidation consistently, likely due to degradation of the inhibitors themselves. This study provides evidence that a variety of nitric oxide scavengers result in differential inhibition of ammonia oxidation in AOA and AOB, and provides support to the proposed role of nitric oxide as a key intermediate in the thaumarchaeotal ammonia oxidation pathway.

Topics: Ammonia; Archaea; Bacteria; Benzenesulfonates; Benzoates; Betaproteobacteria; Caffeic Acids; Chromans; Curcumin; Imidazoles; Nitric Oxide; Nitrification; Nitrosomonas europaea; Oxidation-Reduction; Phylogeny; Soil Microbiology

Eight phenolic compounds including: p-coumaric acid, vanillic acid, caffeic acid, chlorogenic acid, trolox, quercetin, curcumin, and resveratrol were treated with riboflavin (RF) photosensitization and in vitro antioxidant capacities of the mixtures were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2' azino bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Mixtures containing p-coumaric acid and vanillic acid under RF photosensitization showed increases in ferric ion reducing ability and radical scavenging activity of DPPH, whereas mixtures of other compounds had decreases in both radical scavenging ability and ferric reducing antioxidant power. Hydroxycoumaric acid and conjugated hydroxycoumaric and coumaric acids were tentatively identified from RF photosensitized p-coumaric acid, whereas dimmers of vanillic acid were tentatively identified from RF photosensitized vanillic acid. RF photosensitization may be a useful method to enhance antioxidant properties like ferric ion reducing abilities of some selected phenolic compounds.

Topics: Antioxidants; Benzothiazoles; Biphenyl Compounds; Caffeic Acids; Chlorogenic Acid; Chromans; Coumaric Acids; Curcumin; Light; Molecular Structure; Oxidation-Reduction; Phenols; Picrates; Plant Extracts; Propionates; Quercetin; Resveratrol; Riboflavin; Stilbenes; Sulfonic Acids; Vanillic Acid

Curcuminoids are phenylpropanoids with high pharmaceutical potential. Herein, we report an engineered artificial pathway in Escherichia coli to produce natural curcuminoids through caffeic acid. Arabidopsis thaliana 4-coumaroyl-CoA ligase and Curcuma longa diketide-CoA synthase (DCS) and curcumin synthase (CURS1) were used to produce curcuminoids and 70 mg/L of curcumin was obtained from ferulic acid. Bisdemethoxycurcumin and demethoxycurcumin were also produced, but in lower concentrations, by feeding p-coumaric acid or a mixture of p-coumaric acid and ferulic acid, respectively. Additionally, curcuminoids were produced from tyrosine through the caffeic acid pathway. To produce caffeic acid, tyrosine ammonia lyase from Rhodotorula glutinis and 4-coumarate 3-hydroxylase from Saccharothrix espanaensis were used. Caffeoyl-CoA 3-O-methyltransferase from Medicago sativa was used to convert caffeoyl-CoA to feruloyl-CoA. Using caffeic acid, p-coumaric acid or tyrosine as a substrate, 3.9, 0.3, and 0.2 mg/L of curcumin were produced, respectively. This is the first time DCS and CURS1 were used in vivo to produce curcuminoids and that curcumin was produced by feeding tyrosine. We have shown that curcumin can be produced using a pathway involvoing caffeic acid. This alternative pathway represents a step forward in the heterologous production of curcumin using E. coli.

Topics: Biotechnology; Caffeic Acids; Curcumin; Escherichia coli; Ligases; Metabolic Engineering; Tyrosine

This study demonstrated that 0.5% dietary rutin, ellagic acid, or curcumin markedly increased cecal succinate levels in rats fed a high-fat diet, whereas catechin, caffeic acid, and quercetin did not. Other organic acids were modestly or hardly affected by polyphenols. To clarify the effects of succinate levels increased by polyphenols, this study examined the effects of succinate on the growth and proliferation of colon cancer cells and angiogenesis. The growth and proliferation of HT29 human colon cancer cells and angiogenesis in an ex vivo model were significantly inhibited by succinate at a dose close to that in the cecum of rats fed polyphenols. Furthermore, succinate inhibited the migration of human umbilical vein endothelial cells. These findings suggest that the consumption of some polyphenols affects the health and diseases of the large intestine by elevating succinate.

Topics: Animals; Caffeic Acids; Catechin; Cecum; Cell Proliferation; Curcumin; Diet, High-Fat; Ellagic Acid; HT29 Cells; Human Umbilical Vein Endothelial Cells; Humans; Male; Polyphenols; Quercetin; Rats; Rats, Sprague-Dawley; Rutin; Succinic Acid

The effect of the simultaneous exposure to transition metals and natural antioxidants frequently present in food is a question that needs further investigation. We aimed to explore the possible use of the natural polyphenols caffeic acid (CA), resveratrol (RES) and curcumin (CUR) to prevent damages induced by copper-overload on cellular molecules in HepG2 and A-549 human cells in culture. Exposure to 100μM/24h copper (Cu) caused extensive pro-oxidative damage evidenced by increased TBARS, protein carbonyls and nitrite productions in both cell types. Damage was aggravated by simultaneous incubation with 100μM of CA or RES, and it was also reflected in a decrease on cellular viability explored by trypan blue dye exclusion test and LDH leakage. Co-incubation with CUR produced opposite effects demonstrating a protective action which restored the level of biomarkers and cellular viability almost to control values. Thus, while CA and RES might aggravate the oxidative/nitrative damage of Cu, CUR should be considered as a putative protective agent. These results could stimulate further research on the possible use of natural polyphenols as neutralizing substances against the transition metal over-exposure in specific populations such as professional agrochemical sprayers and women using Cu-intrauterine devices.

Topics: Antioxidants; Caffeic Acids; Cell Line, Tumor; Copper; Curcumin; Enzyme Inhibitors; Humans; Polyphenols; Resveratrol; Stilbenes

Caprine pancreatic thiol proteinase inhibitor (PTPI) a cystatin superfamily variant has high affinity for cysteine proteinases providing tight regulation of their proteolytic potential. Oxidative stress buildup in various pancreatic pathologies worsens the disease course often by disturbing the delicate balance between proteinases and their inhibitors. We aimed to study the effect of reactive oxygen species (ROS) on PTPI and to determine the potency of caffeic acid, curcumin and quercetin as agents against the inflicted damage. Fluorescence spectroscopy, polyacrylamide gel electrophoresis, and papain inhibitory assay revealed that photoilluminated riboflavin severely challenged the functional and structural integrity of the inhibitor. Three hundred and fifty micromolar affeic acid or quercetin prevented the damage. Curcumin, however, failed to reverse the changes completely. Conclusively, PTPI rendered dysfunctional by ROS may explain the increased necrotic damage to the host tissue. Also, dietary antioxidants can reverse the riboflavin-induced protein damage providing an economic and safe anti-ROS therapy.

Topics: Antioxidants; Caffeic Acids; Curcumin; Cystatins; Cysteine Proteinase Inhibitors; Flavins; Kinetics; Oxidative Stress; Pancreas; Papain; Polyphenols; Protective Agents; Quercetin; Reactive Oxygen Species; Riboflavin; Singlet Oxygen

In the light of known HDAC inhibitors, 33 carboxylic acid derivatives were tested to understand the structural requirements for HDAC inhibition activity. Several modifications were applied to develop the structure-activity relationships of carboxylic acid HDAC inhibitors. HDAC inhibition activities were investigated in vitro by using HeLa nuclear extract in a fluorimetric assay. Molecular docking was also carried out for the human HDAC8 enzyme in order to predict inhibition activity and the 3D poses of inhibitor-enzyme complexes. Of these compounds, caffeic acid derivatives such as chlorogenic acid and curcumin were found to be highly potent compared to sodium butyrate, which is a well-known HDAC inhibitor.

Topics: Caffeic Acids; Carboxylic Acids; Catalytic Domain; Chlorogenic Acid; Curcumin; Enzyme Inhibitors; HeLa Cells; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Models, Molecular; Molecular Structure; Protein Binding

This study was performed to examine the effect of dietary polyphenols on fecal secondary bile acids, such as deoxycholic acid and lithocholic acid, the risk factors of colon cancer, in rats fed a high-fat diet. In experiment 1, rats were fed a 30% beef tallow diet containing 0.5% polyphenols for 3 weeks. Dietary curcumin and caffeic acid significantly reduced the fecal concentration of deoxycholic acid. Dietary caffeic acid, catechin, rutin, and ellagic acid significantly reduced fecal lithocholic acid. Fecal hyodeoxycholic acid, a metabolite of lithocholic acid, was markedly lowered by dietary curcumin, caffeic acid, catechin, and rutin. In experiment 2, rats were fed a 30 or 5% beef tallow diet with or without the addition of 0.5% curcumin. In the rats without receiving curcumin, the fecal level of deoxycholic acid was significantly higher in the high-fat diet group than in the low-fat diet group. Fecal deoxycholic acid was significantly reduced by dietary curcumin in the high-fat diets but not in the low-fat diets. The results suggest novel effects of some polyphenols favorable for colon health by reducing secondary bile acids in animals fed a high-fat diet.

Topics: Animals; Anticarcinogenic Agents; Caffeic Acids; Colonic Neoplasms; Curcumin; Deoxycholic Acid; Diet; Dietary Fats; Feces; Flavonoids; Lithocholic Acid; Male; Phenols; Polyphenols; Rats; Rats, Sprague-Dawley; Risk Factors

The cytokine macrophage migration inhibitory factor (MIF) has recently emerged as a crucial factor in the pathogenesis of rheumatoid arthritis (RA). It is debated whether the MIF mediated tautomeric conversion of either phenylpyruvate or of its other phenolic substrates is implicated in the pro-inflammatory action of this cytokine. Traditional herbal remedies have been used for centuries to alleviate inflammatory ailments of many kinds including arthritis. Several of their active ingredients identified are mono- or poly-phenol derivatives. In the present study the effect of some anti-inflammatory plant phenols on MIF mediated tautomerism of phenylpyruvate was investigated. Curcumin and caffeic acid were found to be the most potent inhibitors, exhibiting IC(50) values in the submicromolar range in the ketonase assay. Resveratrol and umbelliferon were almost as potent inhibitors as the antipyretic-analgetic drug acetaminophen. Our results reveal MIF as a possible target for the herbal anti-rheumatic agents.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Caffeic Acids; Cattle; Curcumin; Enzyme Inhibitors; Humans; In Vitro Techniques; Intramolecular Oxidoreductases; Kidney; Macrophage Migration-Inhibitory Factors; Phenols; Phenylpyruvic Acids; Phloretin; Phytotherapy; Plants, Medicinal; Resveratrol; Stilbenes

Previous studies have shown that an antisense phosphorothioate oligonucleotide to the Rel A subunit of NF- kappa B, as well as vitamin E and related antioxidants, significantly enhanced the differentiation of HL-60 leukemia cells when combined with low levels of 1 alpha, 25-dihydroxyvitamin D3 (vitamin D3) an effect accompanied by a marked inhibition of the transcription factor, NF-kappa B. Curcumin, a potent inhibitor of tumor promotion and of tumor cell growth, has also been shown to have antioxidant properties and to inhibit NF-kappa b. to ascertain whether curcumin would also enhance the differentiation of HL-60 leukemia cells produced by vitamin D3, presumably by interfering with NF- kappa B activity, the effects of curcumin on the differentiation of HL-60 cells produced by low levels of vitamin D3 were measured. Curcumin used alone did not produce a significant degree of differentiation of HL-60 cells; however, this agent markedly enhanced the expression of differentiation markers induced by low levels of vitamin D3. Curcumin also increased the differentiation of HL-60 cells when combined with vitamin D analogues (1,25-dihydroxy-16-ene-23-yne vitamin D3 and 1,25-dihydroxy-16-ene vitamin D3) that share the receptor binding properties of vitamin D3, whereas as vitamin D analogue (1,25-dihydroxy-16,23-diene vitamin D3) that caused significant calcium mobilization, but was less effective than vitamin d3 in binding the receptor, did not cause the differentiation of HL-60 cells in the presence or absence of curcumin. Several dietary compounds structurally related to curcumin (i.e., caffeic acid, chlorogenic acid, and ferulic acid) did not increase the differentiation of HL-60 cells produced by vitamin D3. However, the more lipophilic ethyl of ferulic and caffeic acid were capable of inducing the differentiation of HL-60 cells, as well as enhancing the maturation produced by vitamin D3. Curcumin caused a marked reduction in NF-kappa B activity in nuclear extracts of HL-60 cells exposed to this agent in the presence or absence of vitamin D3, supporting the possibility that NF-kappa B may be a factor in the regulation of the state of differentiation of leukemia cells.

Topics: Caffeic Acids; Calcitriol; Cell Differentiation; Cell Division; Chlorogenic Acid; Coumaric Acids; Curcumin; DNA-Binding Proteins; Drug Synergism; HL-60 Cells; Humans; Leukemia, Myeloid; Macrophage-1 Antigen; NF-kappa B; Oxidation-Reduction

The interaction between coffee (100 mg freeze-dried home brew/kg body weight) and dietary constituents was assessed for anti-genotoxic effects against cyclophosphamide, N-methyl-N-nitro-N- nitrosoguanidine (MNNG), N-nitroso-N-ethylurea, mitomycin C and urethane (URE) in the mouse bone marrow micronucleus test. Combinations of dietary constituents consisting of (1) chlorogenic acid, caffeic acid, ellagic acid and ferulic acid, (2) beta-carotene, curcumin and alpha-tocopherol, (3) chlorogenic acid, curcumin, alpha-tocopherol, anethole and eugenol, and (4) beta-carotene, curcumin, ellagic acid and chlorogenic acid were used in this study. Before the genotoxin was injected i.p., identical groups of mice were orally administered either vehicle control, coffee, dietary constituents, or coffee plus dietary constituents. Co-administration of coffee with the dietary constituents enhanced the anti-genotoxic effect compared with that of either coffee or the dietary constituents alone. Two-factor analysis of variance of the data suggests that there is a significant synergistic interaction between coffee and the dietary constituents for anti-genotoxic effects against MNNG (combination 1 and 2) and URE (combination 4).

Topics: Allylbenzene Derivatives; Animals; Anisoles; Antimutagenic Agents; Antioxidants; beta Carotene; Bone Marrow; Caffeic Acids; Carotenoids; Chlorogenic Acid; Coffee; Coumaric Acids; Curcumin; Diet; DNA Damage; Ellagic Acid; Eugenol; Flavoring Agents; Food-Drug Interactions; Male; Mice; Micronucleus Tests; Mutagens; Vitamin E

Topical application of curcumin, the yellow pigment in turmeric and curry, strongly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase activity, DNA synthesis, and tumor promotion in mouse skin (Huang et al., Cancer Res., 48: 5941-5946, 1988). Chlorogenic acid, caffeic acid, and ferulic acid (structurally related dietary compounds) were considerably less active. In the present study, topical application of curcumin markedly inhibited TPA- and arachidonic acid-induced epidermal inflammation (ear edema) in mice, but chlorogenic acid, caffeic acid, and ferulic acid were only weakly active or inactive. The in vitro addition of 3, 10, 30, or 100 microM curcumin to cytosol from homogenates of mouse epidermis inhibited the metabolism of arachidonic acid to 5-hydroxyeicosatetraenoic acid (5-HETE) by 40, 60, 66, or 83%, respectively, and the metabolism of arachidonic acid to 8-HETE was inhibited by 40, 51, 77, or 85%, respectively [IC50 (concentration needed for 50% inhibition) = 5-10 microM]. Chlorogenic acid, caffeic acid, or ferulic acid (100 microM) inhibited the metabolism of arachidonic acid to 5-HETE by 36, 10, or 16%, respectively, and these hydroxylated cinnamic acid derivatives inhibited the metabolism of arachidonic acid to 8-HETE by 37, 20, or 10%, respectively (IC50 greater than 100 microM). The metabolism of arachidonic acid to prostaglandin E2, prostaglandin F2 alpha, and prostaglandin D2 by epidermal microsomes was inhibited approximately 50% by the in vitro addition of 5-10 microM curcumin. Chlorogenic acid, caffeic acid, and ferulic acid (100 microM) were inactive. In vitro rat brain protein kinase C activity was not affected by 50-200 microM curcumin, chlorogenic acid, caffeic acid, or ferulic acid. The inhibitory effects of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on TPA-induced tumor promotion in mouse epidermis parallel their inhibitory effects on TPA-induced epidermal inflammation and epidermal lipoxygenase and cyclooxygenase activities.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Caffeic Acids; Chlorogenic Acid; Coumaric Acids; Curcumin; Dermatitis, Contact; Female; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Lipoxygenase; Mice; Peroxidases; Prostaglandin-Endoperoxide Synthases; Tetradecanoylphorbol Acetate

The effects of topically applied curcumin, chlorogenic acid, caffeic acid, and ferulic acid on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase activity, epidermal DNA synthesis, and the promotion of skin tumors were evaluated in female CD-1 mice. Topical application of 0.5, 1, 3, or 10 mumol of curcumin inhibited by 31, 46, 84, or 98%, respectively, the induction of epidermal ornithine decarboxylase activity by 5 nmol of TPA. In an additional study, the topical application of 10 mumol of curcumin, chlorogenic acid, caffeic acid, or ferulic acid inhibited by 91, 25, 42, or 46%, respectively, the induction of ornithine decarboxylase activity by 5 nmol of TPA. The topical application of 10 mumol of curcumin together with 2 or 5 nmol of TPA inhibited the TPA-dependent stimulation of the incorporation of [3H]-thymidine into epidermal DNA by 49 or 29%, respectively, whereas lower doses of curcumin had little or no effect. Chlorogenic acid, caffeic acid, and ferulic acid were less effective than curcumin as inhibitors of the TPA-dependent stimulation of DNA synthesis. Topical application of 1, 3, or 10 mumol of curcumin together with 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with 7,12-dimethylbenz[a]anthracene inhibited the number of TPA-induced tumors per mouse by 39, 77, or 98%, respectively. Similar treatment of mice with 10 mumol of chlorogenic acid, caffeic acid, or ferulic acid together with 5 nmol of TPA inhibited the number of TPA-induced tumors per mouse by 60, 28, or 35%, respectively, and higher doses of the phenolic acids caused a more pronounced inhibition of tumor promotion. The possibility that curcumin could inhibit the action of arachidonic acid was evaluated by studying the effect of curcumin on arachidonic acid-induced edema of mouse ears. The topical application of 3 or 10 mumol of curcumin 30 min before the application of 1 mumol of arachidonic acid inhibited arachidonic acid-induced edema by 33 or 80%, respectively.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Arachidonic Acid; Arachidonic Acids; Caffeic Acids; Catechols; Chlorogenic Acid; Cinnamates; Coumaric Acids; Curcumin; DNA; Edema; Female; Mice; Ornithine Decarboxylase; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate

The polycyclic aromatic hydrocarbon, benzo[a]pyrene, induced dose-related nuclear damage (micronuclei, pyknotic nuclei and karyorrhectic bodies) in colonic epithelial cells of C57BL/6J mice within 24 hr when administered intrarectally in single doses of 0-200 mg/kg body weight. This damage was reduced when mice ingested the plant phenols, caffeic, ferulic and ellagic acids, and quercetin at levels of 4% or BHA at 2% (w/w) in the diet for 1 wk prior to the benzo[a]pyrene challenge (100 mg/kg body weight). Benzo[a]pyrene-induced nuclear damage was not significantly inhibited by 4% curcumin under similar conditions. The inhibition of nuclear damage is consistent with reported antimutagenic effects for these agents in vitro and in longer term animal studies. The procedure described here may provide a rapid in vivo method for assessing the potential of natural products to inhibit the carcinogenic process.

Topics: Animals; Benzo(a)pyrene; Butylated Hydroxyanisole; Caffeic Acids; Cell Nucleus; Colon; Coumaric Acids; Curcumin; Dose-Response Relationship, Drug; Ellagic Acid; Epithelial Cells; Epithelium; Female; Mice; Mice, Inbred C57BL; Phenols; Quercetin