curcumin and Edema

In the present study, the improvement of diabetic microangiopathy and retinopathy was evaluated in 38 diabetic patients treated with a novel curcumin phospholipids delivery form (Meriva®).. Diabetes was diagnosed at least 5 years before inclusion and all patients had signs of retinal oedema and of peripheral microangiopathy. Meriva® was administered at the dosage of 2 tablets/day (each tablet containing 500 mg Meriva® corresponding to 100 mg curcumin) for a period of at least 4 weeks in addition to the standard management plan, while a comparable group of subjects (n = 39) followed the standard management plan alone.. All subjects (treatment and controls) completed the follow-up period, there were no dropouts and Meriva® showed an optimal tolerability. At 4 weeks, microcirculatory and clinical evaluations indicated an improvement of microangiopathy. In terms of peripheral microangiopathy, in the Meriva® group, there was a significant improvement in the venoarteriolar response (p<0.05) and a decrease in the score of peripheral oedema (p<0.05), a sign typically associated with the failure of the venoarteriolar response. At the retinal level, high-resolution, duplex scanning, used to measure retinal flow, showed improvements in the Meriva® treated patients. The evaluation of retinal oedema (Steigerwalt's scale) showed an improvement associated with improved visual acuity (Snellen scale). There were no clinical or microcirculatory effects in controls.. These preliminary observations, indicate the value of curcumin, when administered in a bioavailable form as with Meriva®, in the management of diabetic microangiopathy and retinopathy.

Topics: Curcumin; Diabetic Angiopathies; Diabetic Retinopathy; Drug Delivery Systems; Edema; Female; Humans; Laser-Doppler Flowmetry; Lecithins; Male; Microcirculation; Middle Aged; Pilot Projects; Regional Blood Flow; Retina

The aim of the present study was to evaluate the improvement of diabetic microangiopathy in patients suffering from this condition since at least five years, and whose disease was managed without insulin.. Curcumin, the orange pigment of turmeric, has recently received increasing attention because of its antioxidant properties, mediated by both direct oxygen radical quenching and by induction of anti-oxidant responses via Nrf2 activation. This aspect, combined with the beneficial effects on endothelial function and on tissue and plasma inflammatory status, makes curcumin potentially useful for the management of diabetic microangiopathy. To further evaluate this, Meriva, a lecithinized formulation of curcumin, was administered at the dosage of two tablets/day (1 g Meriva/day) to 25 diabetic patients for four weeks. A comparable group of subjects followed the best possible management for this type of patients.. All subjects in the treatment and control group completed the follow-up period; there were no dropouts. In the treatment group, at four weeks, microcirculatory and clinical evaluations indicated a decrease in skin flux (P<0.05) at the surface of the foot, a finding diagnostic of an improvement in microangiopathy, the flux being generally increased in patients affected by diabetic microangiopathy. Also, a significant decrease in the edema score (P<0.05) and a corresponding improvement in the venoarteriolar response (P<0.05) were observed. The PO2 increased at four weeks (P<0.05), as expected from a better oxygen diffusion into the skin due to the decreased edema. These findings were present in all subjects using Meriva, while no clinical or microcirculatory effects were observed in the control group.. Meriva was, in general, well tolerated, and these preliminary findings suggest the usefulness of this curcumin formulation for the management of diabetic microangiopathy, opening a window of opportunities to be evaluated in more prolonged and larger studies. The molecular mechanisms involved in the beneficial effects of curcumin on microcirculation and edema are also worth investigation.

Topics: Aged; Curcumin; Diabetic Angiopathies; Edema; Female; Foot; Humans; Male; Microcirculation; Middle Aged; Phytotherapy; Pilot Projects

A proprietary complex of curcumin with soy phosphatidylcholine (Meriva®, Indena SpA) was evaluated in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to 200 mg curcumin per diem.. OA signs/symptoms were evaluated by the WOMAC scores. Mobility was studied by walking performance (treadmill), and inflammatory status was assessed by measurements of C-reactive protein (CRP).. After three months of treatment, the global WOMAC score decreased by 58% (P<0.05), walking distance in the treadmill test was prolonged from 76 m to 332 m (P<0.05), and CRP levels decreased from 168 +/- 18 to 11.3 +/-. 4.1 mg/L in the subpopulation with high CRP. In comparison, the control group experienced only a modest improvement in these parameters (2% in the WOMAC score, from 82 m to 129 m in the treadmill test, and from 175 +/- 12.3 to 112 +/- 22.2 mg/L in the CRP plasma concentration), while the treatment costs (use of anti-inflammatory drugs, treatment and hospitalization) were reduced significantly in the treatment group.. These results show that Meriva® is clinically effective in the management and treatment of osteoarthritis and suggest that the increased stability and better absorption of curcumin induced by complexation with phospholipids have clinical relevance, setting the stage for larger and more prolonged studies.

Topics: Adult; C-Reactive Protein; Curcumin; Drug Synergism; Edema; Female; Glycine max; Humans; Inflammation; Male; Middle Aged; Osteoarthritis, Knee; Phosphatidylcholines; Treatment Outcome; Walking

Inflammation-related diseases are recognized as the major cause of morbidity around the globe. In this study, the anti-inflammatory potential of sericin, curcumin, and their mixture was investigated in vivo and in vitro. Edema was induced via 1% carrageenan and then sericin (0.03, 0.06, 0.09 mg/ml), curcumin (1%, 2%, 3%), and their mixture doses were applied topically. The paw circumference and thickness were measured after 1-, 2-, 3-, 4-, 5-, and 6-hour post-carrageenan injection. The levels of IL-4 and IL-10 were measured from the serum. In mice fibroblast cells, sericin (20, 40, 60 μg/ml), curcumin (5, 10, 20 μM), and mixture concentrations were applied and then stimulated with lipopolysaccharide (LPS). Afterward, the cells were used for the analysis of gene expression, and the supernatant was collected for protein expression of IL-1β, IL-4, and IL-10. Our results demonstrated that sericin and curcumin caused a dose-dependent reduction in edema, whereas the mixture-treated group reduced the paw thickness and circumference most significantly (p = .0001). Furthermore, the mixture treatment of carrageenan-inflicted group increased the levels of anti-inflammatory cytokines, IL-4 (650.87 pg/ml) and IL-10 (183.14 pg/ml), in comparison to the carrageenan control. The in vitro data revealed that among all the treatment doses, the mixture-treated group has effectively reduced the gene (1.13-fold) and protein (51.9 pg/ml) expression of IL-1β in comparison to McCoy cells stimulated with LPS. Moreover, mixture treatment elevated the expression of IL-4 and IL-10 at genes (4.3-fold and 3.7-fold, respectively) and protein levels (169.33 and 141.83 pg/ml, respectively). The current study reports the enhanced anti-inflammatory effects of the mixture of curcumin and sericin through modulating expressions of interleukins in vitro and in vivo. Thus, natural products (curcumin and sericin)-based formulations have greater potential for clinical investigations.

Topics: Animals; Anti-Inflammatory Agents; Burns; Carrageenan; Curcumin; Edema; Inflammation; Interleukin-10; Interleukin-4; Lipopolysaccharides; Mice; Sericins

Curcumin and its analogues exhibited anti-inflammatory activity in different experimental models. Recently, we synthesized (2E,3E)-3-buten-2-one-4-(4-hydroxy-3-methoxyphenyl)-2-(4-(4-methoxyphenyl)-2-thiazolyl)hydrazone (RI75), a curcumin analogue with a thiazolyl hydrazone moiety. In the present study, we investigated the effects induced by RI75 in different models of inflammation and pain in mice, as well as some underlying mechanisms. Pre-treatment with RI75 (40 mg/kg, intraperitoneal; i.p.) or curcumin (40 mg/kg, i.p.) reduced the mechanical allodynia and paw edema induced by intraplantar (i.pl) injection of carrageenan. RI75 antiallodynic activity was reduced by pre-treatment with naltrexone (5 and 10 mg/kg, i.p.) and cyproheptadine (10 mg/kg, i.p.), but not glibenclamide (20 and 40 mg/kg, i.p.). In a model of neuropathic pain, a single i.p. administration of RI75 (40 mg/kg) or curcumin (40 mg/kg) attenuated the ongoing mechanical allodynia induced by repeated administrations of paclitaxel. Pre-treatment with RI75 (40 mg/kg, i.p.) or curcumin (40 mg/kg, i.p.) also reduced tumor necrosis factor-α and interleukin-6 production and myeloperoxidase activity induced by carrageenan. The results of the present study demonstrate that RI75, a synthetic curcumin analogue, exhibits antiallodynic and antiedematogenic activities. Activation of opioidergic and serotonergic mechanisms and reduced production of inflammatory mediators and neutrophil recruitment may underlie RI75 activities.

Topics: Animals; Curcumin; Disease Models, Animal; Edema; Hyperalgesia; Inflammation; Interleukin-6; Mice; Neuralgia; Tumor Necrosis Factor-alpha

A silver nanoparticle obtained by reducing salts with solid dispersion of curcumin (130 nm, 0.081 mg mL. The edematogenic effect was evaluated by plasma extravasation in rat dorsal skin after injection of 50 µg per site of venom alone or preincubated with 1, 10, and 100 µL of AgNPs; the myotoxicity was evaluated by measuring the creatine kinase released into the organ-bath before the treatment and at the end of each experiment; and neurotoxicity was evaluated in chick biventer cervicis using the conventional myographic technique, face to the exogenous acetylcholine (ACh) and potassium chloride (KCl) added into the bath before the treatment and after each experiment. Preliminarily, a concentration-response curve of AgNPs was carried out to select the concentration to be used for neutralizing assays, which consists of neutralizing the venom-induced neuromuscular paralysis and edema by preincubating AgNPs with venom for 30 min.. The. AgNPs interact with constituents of

Topics: Animals; Chickens; Colubridae; Creatine Kinase; Curcumin; Dose-Response Relationship, Drug; Edema; Male; Metal Nanoparticles; Muscle Contraction; Muscle, Skeletal; Neurotoxins; Phrenic Nerve; Rats; Silver; Snake Venoms

A series of curcumin bis-conjugates 3a-q, 5a-k and 6a-k were synthesized in good yields utilizing an optimized reaction condition. We explored the effect of different amino acids and protecting groups on biological activities of curcumin. The conjugates were screened for anti-inflammatory, analgesic and antimicrobial properties. Some of the conjugates showed promising biological observations with a potency comparable with the standard references. The variations in biological properties concerning different amino acids and protecting groups are interesting observations. Effects of the synthesized conjugates on splenocytes and the production of nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages are correlated with the observed anti-inflammatory properties. We have also established the safety profile of the most active conjugates. Robust 2D-QSAR studies supported and validated biological data.

Topics: Amino Acids; Analgesics; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Candida albicans; Carrageenan; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Edema; Mice; Microbial Sensitivity Tests; Molecular Structure; Pain; Pseudomonas aeruginosa; Quantitative Structure-Activity Relationship; Rats; Salmonella typhi; Spleen; Staphylococcus aureus; Streptococcus pyogenes; Ulcer

Curcumin is a bioactive compound with proven antioxidant and anti-inflammatory activities, but has low water solubility and dermal absorption. The inflammatory process is considered as the biological response to damage induced by various stimuli. If this process fails to self-regulate, it becomes a potential risk of cancer. The objective of this work was to evaluate the anti-inflammatory activity of curcumin administered to mice with induced atrial edema using two topical vehicles: organogels and O/W-type nanogels at pH 7, Organogels and O/W-type nanogels at pH 7 were prepared, characterized and the anti-inflammatory activity was assessed. A histopathological analysis of mouse ears was performed and two gel formulations were selected. Thermograms of organogels indicated that increasing the gelling agent improved the stability of the system. Deformation sweeps confirmed a viscoelastic behavior characteristic of gels in both systems. During the anti-inflammatory activity evaluations, the nanogels demonstrated greater activity (61.8 %) than organogels; Diclofenac

Topics: Animals; Anti-Inflammatory Agents; Cardiomyopathies; Curcumin; Drug Carriers; Edema; Gels; Heart Atria; Mice; Phytotherapy

Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 μL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.

Topics: Animals; Anti-Inflammatory Agents; Arthralgia; Arthritis, Experimental; Cartilage, Articular; Collagen Type II; Curcuma; Cytokines; Disease Models, Animal; Edema; Female; Indomethacin; Inflammation; Iodoacetates; Joint Diseases; Knee Joint; Osteoarthritis; Pain; Plant Extracts; Rats; Rats, Wistar; Zingiber officinale

Rheumatoid arthritis (RA) is a chronic articular synovial inflammatory disease. The precise etiology underlying the pathogenesis of RA remains unknown. We aimed to investigate the inhibitory effect of curcumin analog FM0807 (curcumin salicylate monoester, 2-hydroxy-, 4-[(1E,6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxo-1,6-heptadien-1-yl]-2-methoxyphenyl ester) on experimental RA and investigate its possible mechanisms of action.. Rats with Freund's complete adjuvant (FCA)-induced arthritis (AIA) were administered aspirin (0.1 mmol.kg. Compared with AIA group, FM0807 reduced the AI and swelling of the injected hind paw in a dose-dependent manner, and inhibited increases in inflammatory cell infiltration, pannus formation and cartilage destruction. FM0807 also potently attenuated the increase in the expression of inflammatory factors TNF-α, IL-6 and IL-1β in synovial fluid, while IL-10 levels were also elevated. FM0807 significantly suppressed phosphorylation of extracellular-signal-regulated kinase (ERK) 1/2 (ERK1/2), c-Jun-N-terminal kinase (JNK) 1/2 (JNK1/2), p38MAPK, inhibitor of NF-κB kinase (IKK), IκB and NF-κB p65 protein, (all. FM0807 exerts its therapeutic effects on RA by inhibiting cartilage degeneration. FM0807 treatment might be an effective therapeutic approach for RA.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Aspirin; Curcumin; Disease Progression; Edema; Freund's Adjuvant; Gene Expression Regulation; Hindlimb; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; Male; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Rats; Rats, Sprague-Dawley; Tarsus, Animal; Tumor Necrosis Factor-alpha

Curcumin (CUR) is a hydrophobic polyphenol with anti-inflammatory activity. However, its low water-solubility and poor skin permeation limited its application in the treatment of dermititis. CUR-loaded micelles were prepared using thin membrane hydration method with methoxy poly (ethylene glycol)-block-poly (ε-caprolactone) (MPEG-PCL) as carrier material. The drug loading capacity and encapsulation efficiency were 12.14 ± 0.33 and 93.57 ± 1.67%, respectively. CUR-loaded micelles increased CUR's water-solubility to 1.87 mg/mL, being 1.87 × 10

Topics: Administration, Cutaneous; Animals; Curcumin; Dermatitis; Edema; Hydrogels; Mice; Micelles; Skin

Designing novel drug delivery systems to improve drug efficiencies have gained great interests in recent years. In this study, a new vesicular system has been prepared using thin film hydration method with slight modifications, hydrophobic drugs have been used in both lipophilic and hydrophilic phases and dry film was hydrated by hyaluronan polymeric solution, to overcome curcumin and quercetin formulation drawbacks. Briefly, different formulations were prepared according to Box-Behnken design to assess the effect of HLB value, cholesterol and hyaluronan contents on the properties of niosomes. Then, the best formulation was selected for further studies and compared with conventional niosomes. The results showed that both niosomes had spherical shapes according to Transmission Electron and Atomic Force Microscopic images. Results also showed that hyaluronan containing niosomes had smaller size and higher values of zeta potential and entrapment than conventional niosomes. The average size of hyaluronan containing niosomes was 260.37 ± 6.58 nm, the zeta potential was -34.97 ± 1.50 mv and the entrapment for curcumin and quercetin were 98.85 ± 0.55% and 93.13 ± 1.22%, respectively. The release kinetic of quercetin was best fitted to Peppas model for both conventional niosome and hyaluronan containing niosomes; while, the release kinetic of curcumin was best fitted with non-conventional order 2 and three second roots of mass for hyaluronan containing niosomes and conventional niosomes, respectively. Hyaluronan containing niosomes showed higher antioxidant and anti-inflammatory effects in comparison with conventional niosomes.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Drug Carriers; Drug Design; Drug Evaluation, Preclinical; Edema; Female; Hyaluronic Acid; Liposomes; Quercetin; Rats

This study aimed to determine the capacity of 7,7'-bromo-curcumin (CUR-Br), a curcumin analogue with higher chemical stability than curcumin (CUR), in the suppression of mouse ear edema. Male CD-1 mice were topically pre-treated with either CUR or CUR-Br for 30 min prior to an application of 12-O-tetradecanoylphorbol-13-acetate. After 6 h, mice were killed, and ear punches were measured for their weight and thickness as a marker of edema and inflammation. CUR-Br demonstrated a higher anti-inflammatory efficacy compared to CUR. CUR and CUR-Br at 1.0 μmol suppressed the TPA-induced increase in the ear weight by 26.0% and 57.2%, and decreased TPA-induced increase in the ear thickness by 22.2% and 84.7%, respectively. The inhibitory effects of Cur-Br were associated with decreased levels of inflammatory cytokines (IL-1β, IL-2, IL-6, KC/GRO, IL-10, IL-17, and IL-23). In addition, CUR-Br significantly downregulated expression of pro-inflammatory signaling proteins such as p-STAT3, STAT3, PI3K, AKT, p-p65, and COX-2. Overall, our results demonstrated that the curcumin analogue, CUR-Br, showed stronger anti-inflammatory properties than CUR in inhibiting TPA-induced inflammatory response in mouse skin.

Topics: Animals; Curcumin; Cytokines; Edema; Inflammation; Male; Mice; NF-kappa B; Signal Transduction; Skin; STAT3 Transcription Factor; Structure-Activity Relationship; Tetradecanoylphorbol Acetate

Curcumin has shown pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its numerous derivatives for diverse and improved therapeutic roles. In this study, we have synthesized curcumin derivatives containing isoxazole, pyrazoles, and pyrimidines and then the synthesized molecules were evaluated for their anti-inflammatory and antinociceptive activities in experimental animal models. Acute toxicity of synthesized molecules was evaluated in albino mice by oral administration. Any behavioral and neurological changes were observed at dose of 10 mg/kg body weight. Additionally, cyclooxygenase-2 (COX-2) enzyme inhibition studies were performed through in vitro assays. In vivo anti-inflammatory studies showed that curcumin with pyrimidines was the most potent anti-inflammatory agent which inhibited induced edema from 74.7% to 75.9%. Compounds 7, 9, and 12 exhibited relatively higher prevention of writhing episodes than any other compound with antinociceptive activity of 73.2%, 74.9%, and 71.8%, respectively. This was better than diclofenac sodium (reference drug, 67.1% inhibition). Similarly, COX-2 in vitro inhibition assays results revealed that compound 12 (75.3% inhibition) was the most potent compound. Molecular docking studies of 10, 11, and 12 compounds in human COX-2 binding site revealed the similar binding modes as that of other COX-2-selective inhibitors.

Topics: Administration, Oral; Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Binding Sites; Catalytic Domain; Curcumin; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Edema; Humans; Isoxazoles; Mice; Molecular Docking Simulation; Protein Binding; Pyrazoles; Pyrimidines; Stomach; Structure-Activity Relationship

Curcumin is the main curcuminoid found in turmeric rhizomes and is a strong candidate to formulate foodstuff with specific properties. Among various bioactive properties of curcumin, its antiinflammatory activity is remarkable; on the other hand, its low water solubility leads to low absorption. Thus, new formulations need to be developed to improve its efficacy, and encapsulation is a promising alternative strategy in this regard. The objective of the present study was to obtain curcumin-loaded polyvinylpyrrolidone (PVP) nanoparticles and evaluate their acute in vivo antiinflammatory activity. Nanoparticles were obtained by complexation using the solid dispersion technique, and the characterization of nanoparticles showed that curcumin and PVP formed an amorphous solid solution. Encapsulated curcumin was colloidally stable in distilled water; this was attributed to the formation of hydrogen bonds between curcumin hydroxyl and PVP carbonyl groups. Rats were treated orally with single doses of curcumin and curcumin-loaded PVP nanoparticles, and antiinflammatory activity was evaluated by an experimental model of carrageenan-induced paw edema, myeloperoxidase (MPO) activity, and microcirculation in situ. Treatment with nanoparticles at 12.5 mg kg

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Drug Carriers; Drug Evaluation, Preclinical; Edema; Humans; Hydrogen Bonding; Male; Nanoparticles; Particle Size; Rats; Rats, Wistar; Solubility

Resveratrol and curcumin, as natural flavones products, have good therapeutic effect in acute and chronic inflammation; on the other hand, tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well as anti-inflammatory function. In this paper, the anti-inflammatory effect of the tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and chronic inflammation was reported in vivo.. The dose of the combined three natural products was optimized based on the acute paw swelling mouse model with a Uniform Design methodology. The therapeutic effect of TRC combination on chronic inflammation was investigated by using the collagen-induced arthritis (CIA) rat model based upon the following indexes: the volume of paw swelling, arthritis score, serum mediators and histological examination as well as immunohistochemical staining. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were measured and the pathological sections of liver and kidney were analysed. LD. The results showed this formulation could provide a novel potent treatment for acute and chronic inflammation (RA) without side effect like gastric injury occurring in NSAIDs.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Aspartate Aminotransferases; Cartilage; Curcumin; Cytokines; Drug Combinations; Edema; Female; Inflammation; Joints; Kidney; Liver; Male; Mice; NF-kappa B; Phytotherapy; Plant Extracts; Pyrazines; Rats, Sprague-Dawley; Resveratrol; Stilbenes

Moringa oleifera Lam. is a tropical plant, used for centuries as food and traditional medicine. The aim of this study was to develop, validate and biochemically characterize an isothiocyanate-enriched moringa seed extract (MSE), and to compare the anti-inflammatory effects of MSE-containing moringa isothiocyanate-1 (MIC-1) with a curcuminoid-enriched turmeric extract (CTE), and a material further enriched in its primary phytochemical, curcumin (curcumin-enriched material; CEM). MSE was prepared by incubating ground moringa seeds with water to allow myrosinase-catalyzed enzymatic formation of bioactive MIC-1, the predominant isothiocyanate in moringa seeds. Optimization of the extraction process yielded an extract of 38.9% MIC-1. Phytochemical analysis of MSE revealed the presence of acetylated isothiocyanates, phenolic glycosides unique to moringa, flavonoids, fats and fatty acids, proteins and carbohydrates. MSE showed a reduction in the carrageenan-induced rat paw edema (33% at 500 mg/kg MIC-1) comparable to aspirin (27% at 300 mg/kg), whereas CTE did not have any significant effect. In vitro, MIC-1 at 1 μM significantly reduced the production of nitric oxide (NO) and at 5 μM, the gene expression of LPS-inducible nitric oxide synthase (iNOS) and interleukins 1β and 6 (IL-1β and IL-6), whereas CEM did not show any significant activity at all concentrations tested. MIC-1 (10μM) was also more effective at upregulating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) target genes NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase pi 1 (GSTP1), and heme oxygenase 1 (HO1) than the CEM. Thus, in contrast to CTE and CEM, MSE and its major isothiocyanate MIC-1 displayed strong anti-inflammatory and antioxidant properties in vivo and in vitro, making them promising botanical leads for the mitigation of inflammatory-mediated chronic disorders.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carrageenan; Cell Line; Curcuma; Curcumin; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Hindlimb; Inflammation; Isothiocyanates; Macrophages; Male; Moringa oleifera; Phytochemicals; Phytotherapy; Plant Extracts; Random Allocation; Rats, Sprague-Dawley; Seeds

This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Autophagy; Carrageenan; Cells, Cultured; Curcumin; Cyclooxygenase 2; Dose-Response Relationship, Drug; Edema; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Humans; Male; Mice; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase Type II; Structure-Activity Relationship

Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Carrageenan; Chemistry, Pharmaceutical; Curcumin; Disease Models, Animal; Drug Delivery Systems; Edema; Emulsions; Excipients; Inflammation; Male; Nanoparticles; Oils; Rats; Rats, Sprague-Dawley; Solubility

We describe several novel curcumin analogues that possess both anti-inflammatory antioxidant properties and thrombolytic activities. The therapeutic efficacy of these curcumin analogues was verified in a mouse ear edema model, a rat arterial thrombosis assay, a free radical scavenging assay performed in PC12 cells, and in both in vitro and in vivo ischemia/reperfusion models. Our findings suggest that their protective effects partially reside in maintenance of optimal mitochondrial function.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytochromes c; Disease Models, Animal; Edema; Enzyme-Linked Immunosorbent Assay; Free Radical Scavengers; Human Umbilical Vein Endothelial Cells; Interleukin-6; Mice; Microscopy, Fluorescence; Mitochondria; Muscle, Skeletal; Oxidative Stress; PC12 Cells; Quantum Theory; Rats; Reactive Oxygen Species; Reperfusion Injury; Tumor Necrosis Factor-alpha

Curcumin has diverse biological activities including antioxidant and anti-inflammatory activity. However, its clinical use for topical application is limited due to its poor aqueous solubility and thus, minimal cutaneous bioavailability. Elastic vesicles (EVs) of curcumin were prepared to improve its cutaneous bioavailability and to use it for topical anti-inflammatory effect. Ex vivo skin permeation and retention studies were performed to check if incorporation of curcumin into EVs could improve its permeation into and retention in the skin. Evaluation of acute and chronic anti-inflammatory effect was done using xylene-induced acute ear edema in mice and cotton pellet-induced chronic inflammation in rats, respectively. A significant improvement in flux (nine times) across murine skin was observed when aqueous dispersion of curcumin (flux - 0.46 ± 0.02 μg/h/cm(2)) was compared with curcumin-loaded EVs (flux - 4.14 ± 0.04 μg/h/cm(2)). Incorporation of these curcumin-loaded EVs into a hydrophilic ointment base resulted in higher skin retention (51.66%) in contrast to free curcumin ointment (1.64%) and a marketed formulation (VICCO® turmeric skin cream). The developed ointment showed an effect similar (p < 0.05) to the marketed diclofenac sodium ointment (Omni-gel®) in suppression of acute inflammation in mouse; a significant inhibition (28.8% versus 3.91% for free curcumin) of cotton pellet-induced chronic inflammation was also observed. Thus, curcumin-loaded EVs incorporated in hydrophilic ointment is a promising topical anti-inflammatory formulation.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Biological Availability; Chemistry, Pharmaceutical; Curcumin; Dermatologic Agents; Diclofenac; Drug Carriers; Edema; Female; Hydrophobic and Hydrophilic Interactions; Inflammation; Male; Mice; Ointments; Permeability; Rats; Rats, Wistar; Skin; Skin Absorption; Solubility

The curcumin (CUR)-loaded binary hydrogel was formulated using xanthan and galactomannan from Schizolobium parahybae (guapuruvu). The binary hydrogels presented gel characteristics, stable pH values and mechanical stress resistance even after 45 days of heat exposure (45 °C). The CUR-loaded hydrogel content was 98.6% for XGMC (xanthan and galactomannan with CUR-microemulsion) after the stability test. The in vitro cytotoxicity analysis suggested non-cutaneous membrane irritation, and the in vitro skin permeation analysis indicated 2.15 to 2.50 μg mL(-1) CUR at the stratum corneum, epidermal and dermal levels. The XGEC (xanthan and galactomannan with CUR solubilized in ethanol) and XGMC hydrogels presented 76.8 and 63.2% inhibition of topical inflammation, respectively. Chemical stability and non-cytotoxicity analysis confirm the safety of prolonged exposure of the skin during the topical treatment, offering long-lasting XGEC and XGMC action.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Cell Line; Cell Survival; Croton Oil; Curcumin; Drug Liberation; Drug Stability; Edema; Emulsions; Fabaceae; Galactose; Hot Temperature; Hydrogels; Hydrogen-Ion Concentration; Male; Mannans; Mice; Polysaccharides, Bacterial; Skin Absorption; Stress, Mechanical; Swine; Wound Healing

The polyphenolic compound, curcumin, is a natural yellow pigment component of turmeric. It exerts various biological effects, such as anti-inflammatory effects, and we have previously demonstrated that curcumin is a specific inhibitor of DNA polymerase λ. Curcumin is characterized by poor bioavailability as it is water-insoluble, is poorly absorbed and is systemically eliminated. In order to increase the bioavailability of curcumin, in this study, we produced a curcumin-loaded lipid nanoemulsion of various particle sizes (50, 100 and 200 nm). The curcumin lipid nanoemulsion was prepared by a modified thin-film hydration method followed by sonication. To identify the optimal particle size which exhibits the strongest physiological activity, we investigated the inhibitory effects of the obtained nanoemulsions against inflammatory and allergic activities. In in vitro cell culture experiments, the 100-nm curcumin lipid nanoemulsion showed the most prominent inhibitory effect on the production of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW264.7 murine macrophages, and on the release of β-hexosaminidase induced by the calcium ionophore, A23187, in rat basophilic leukemia RBL-2H3 cells. In an in vivo experiment, in which mice were administered the curcumin-loaded lipid nanoemulsion of various particle sizes, the 100-nm curcumin lipid nanoemulsion showed the most prominent anti-inflammatory and anti-allergic effects, inhibiting 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema and immunoglobulin E (IgE)-induced passive cutaneous anaphylactic (PCA) reaction. The effects of particle size on serum curcumin absorption were also assessed in mice, and the 100-nm lipid nanoemulsion showed the greatest absorption. The results from our study suggest that the physiological activities of curcumin lipid nanoemulsions differ depending on particle size. Our data indicate that the curcumin lipid nanoemulsion with a particle size of 100 nm has potential for use in enhancing the bioavailability and medical value of curcumin.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Curcumin; Drug Carriers; Edema; Emulsions; Macrophages; Male; Mice; Mice, Inbred ICR; Nanoparticles; Particle Size; Rats; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

Oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) was frequently associated with serious adverse effects. Inspired by curcumin-a naturally traditional Chinese medicine, a series of curcumin derivatives containing NSAIDs, used for transdermal application, were synthesized and screened for their anti-inflammatory activities in vitro and in vivo. Compared with curcumin and parent NSAID (salicylic acid and salsalate), topical application of A11 and B13 onto mouse ear edema, prior to TPA treatment markedly suppressed the expression of IL-1β, IL-6 and TNF-α, respectively. Mechanistically, A11 and B13 blocked the phosphorylation of IκBα and suppressed the activation of p65 and IκBα. It was found that A11 and B13 may be potent anti-inflammatory agents for the treatment of inflammatory diseases.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Ear; Edema; Inflammation; Interleukin-1beta; Interleukin-6; Mice; NF-kappa B; Tumor Necrosis Factor-alpha

The aim of the study was to investigate the safety and anti-inflammatory effects of polysaccharide fraction (F1) of Curcuma longa extract (NR-INF-02) in classical rodent models of inflammation. F1 was evaluated for its acute oral toxicity and found to be safe upto 5000 mg/kg body weight in rats. The anti-inflammatory activity of F1 was evaluated in acute (carrageenan - induced paw edema; xylene - induced ear edema) and chronic (cotton pellet - induced granuloma) models of inflammation. The results of the study demonstrated that F1 significantly (p ≤ 0.05) inhibited carrageenan-induced paw edema at 1 h and 3 h at doses of 11.25, 22.5 and 45 mg/kg body weight in rats. Also, F1 at doses of 15.75, 31.5 and 63 mg/kg significantly inhibited the xylene induced ear edema in mice. In a chronic model, F1 at 11.25, 22.5 and 45 mg/kg doses produced significant reduction of wet and dry weights of cotton pellets in rats. Overall results indicated that F1 of NR-INF-02 significantly attenuated acute and chronic inflammation in rodent models. This study emphasizes on the importance of Curcuma longa polysaccharide's role in acute and chronic inflammation.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Chemical Fractionation; Curcuma; Disease Models, Animal; Edema; Female; Granuloma; Humans; Male; Mice; Plant Extracts; Polysaccharides; Rats; Rats, Wistar; Xylenes

In the present work biocompatible quercetin and curcumin nanovesicles were developed as a novel approach to prevent and restore skin tissue defects on chronic cutaneous pathologies. Stable and suitable quercetin- and curcumin-loaded phospholipid vesicles, namely liposomes and penetration enhancer-containing vesicles (PEVs), were prepared. Vesicles were made from a highly biocompatible mixture of phospholipids and alternatively a natural polyphenol, quercetin or curcumin. Liposomes were obtained by adding water, while PEVs by adding polyethylene glycol 400 and Oramix®CG110 to the water phase. Transmission electron microscopy, cryogenic-transmission electron microscopy and small- and wide-angle X-ray scattering showed that vesicles were spherical, oligo- or multilamellar and small in size (112-220 nm). In vitro and in vivo tests underlined a good effectiveness of quercetin and curcumin nanovesicles in counteracting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced lesions and inflammation. Myeloperoxydase activity, used to gauge inflammation, was markedly inhibited by quercetin liposomes (59%) and curcumin liposomes and polyethylene glycol (PEG)-PEVs (∼ 68%). Histology showed that PEG-PEVs provided an extensive re-epithelization of the TPA-damaged skin, with multiple layers of thick epidermis. In conclusion, nanoentrapped polyphenols prevented the formation of skin lesions abrogating the various biochemical processes that cause epithelial loss and skin damage.

Topics: Animals; Curcumin; Disease Models, Animal; Edema; Female; Liposomes; Mice; Mice, Inbred ICR; Nanoparticles; Particle Size; Peroxidase; Quercetin; Regeneration; Scattering, Small Angle; Skin; Static Electricity; Sus scrofa; X-Ray Diffraction

Acute pain after surgery remains moderate to severe for 20% to 30% of patients despite advancements in the use of opioids, adjuvant drugs, and regional anesthesia. Depending on the type of surgery, 10% to 50% of patients experience persistent pain postoperatively, and there are no established methods for its prevention. Curcumin (diferuloylmethane) is one of the phenolic constituents of turmeric that has been used in Eastern traditional medicine as an antiseptic, antioxidant, anti-inflammatory, and analgesic agent. It may be effective for treating postoperative pain.. We used the hindpaw incision model with C57BL/6 mice. Sensitization to mechanical and thermal stimuli as well as effects on edema and temperature were measured up to 7 days after surgery. Spontaneous pain after incision was assessed by using conditioned place preference (CPP), and alterations in gait function were assessed using multiparameter digital gait analysis.. Curcumin (50 mg/kg) significantly reduced the intensity of mechanical and heat sensitization after hindpaw incision in mice. No effects of curcumin on baseline nociceptive thresholds were observed. Curcumin also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. In addition, perioperative curcumin treatment attenuated hyperalgesic priming due to incision when mice were subsequently challenged with hindpaw prostaglandin E2 application. Furthermore, while vehicle-treated mice had evidence of spontaneous pain 48 hours after incision in the CPP paradigm, no evidence of ongoing pain was observed in the mice treated with curcumin. Likewise, hindpaw incision caused changes in several gait-related indices, but most of these were normalized in the curcumin-treated animals. The peri-incisional levels of several pronociceptive immune mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor α, and macrophage inflammatory protein-1α were either not reduced or were even augmented 1 and 3 days after incision in curcumin-treated mice. The anti-inflammatory cytokine IL-10 was unchanged, while transforming growth factor-β levels were enhanced under the same conditions.. Our studies suggest that curcumin treatment is effective in alleviating incision-induced inflammation, nociceptive sensitization, spontaneous pain, and functional gait abnormalities. Augmented transforming growth factor-β production provides one possible mechanism. These preclinical findings demonstrate curcumin's potential as a preventative strategy in postoperative pain treatment.

Topics: Acute Pain; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomechanical Phenomena; Body Temperature; Conditioning, Operant; Curcumin; Cytokines; Edema; Foot Injuries; Gait; Hindlimb; Male; Mice; Mice, Inbred C57BL; Pain Measurement; Pain, Postoperative; Recovery of Function; Treatment Outcome

The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund's complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Biological Availability; Curcumin; Drug Therapy, Combination; Edema; Male; Oils; Rats; Rats, Sprague-Dawley

The present study was aimed to develop and optimize the microsponges of curcumin for colon specific drug delivery in a view to bypass the upper gastrointestinal tract (GIT) for enhanced therapeutic effect. Microsponges were developed by quasi emulsion solvent diffusion method using 3(2) full factorial design. Prepared microsponges were optimized in order to analyze the effects of independent variables (volume of ethanol and Eudragit L100) on the encapsulation efficiency, particle size, and drug release. The optimized formulation was subjected to in vivo study using acetic acid induced colitis model in rats. The F7 was selected as optimized formulation based on particle size of 41.63 μm, % entrapment efficiency of 78.13%, and % cumulative drug release of 84.12%, and desirability factor of 0.83. Release studies revealed that microsponges prevented the premature release of curcumin in upper GIT and specifically released the drug at colonic pH. The drug release profile of F7 formulation was subjected to different kinetic models and based upon the best correlation coefficient (r(2) = 0.9927) the release was found to follow Higuchi model, which suggested diffusion as the main mechanism of drug release. Pharmacodynamic study showed that curcumin loaded microsponges causes a significant decrease in edema, necrosis, and hemorrhage of colon as compared to free curcumin. This study proves that curcumin loaded microsponges may act as a promising drug delivery system for treatment of ulcerative colitis.

Topics: Animals; Colon; Curcumin; Drug Administration Routes; Drug Delivery Systems; Edema; Hemorrhage; Humans; Inflammatory Bowel Diseases; Male; Necrosis; Rats

Curcumin, a yellow pigment extracted from Carcuma longa, has been demonstrated to have extensive pharmacological activity in various studies, and it exhibits protective effects on injuries involving a number of human organs. The present study was designed to evaluate the potential effect and underlying mechanism of curcumin on the motor function and spinal cord edema in a rat acute spinal cord injury (SCI) model. The SCI model was induced by a heavy object falling. At 30min after the SCI was successfully induced, the animals were intraperitoneally given 40mg/kg curcumin. The Basso, Beattie and Bresnahan scores showed that curcumin moderately improved the recovery of the motor function in the injured rats, and hematoxylin-eosin staining demonstrated the role of this compound in reducing the hemorrhage, edema and neutrophil infiltration of the traumatic spinal cord. Furthermore, curcumin also inhibited the SCI-associated aquaporin - 4 (AQP4) overexpression and glial fibrillary acidic protein (GFAP) and repressed the unusual activation of the JAK/STAT signaling pathway. In conclusion, our data demonstrate that curcumin exhibits a moderately protective effect on spinal cord injury, and this effect might be related to the inhibition of overexpressed AQP4 and GFAP and the activated JAK/STAT signaling pathway. Curcumin may have potential for use as a therapeutic option for spinal cord injuries.

Topics: Animals; Aquaporin 4; Curcumin; Disease Models, Animal; Edema; Glial Fibrillary Acidic Protein; Janus Kinases; Male; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord Injuries; STAT Transcription Factors

The present study was aimed to investigate the antinociceptive and anti-inflammatory activity of the Curcuma zedoaria (family Zingiberaceae) ethanolic rhizome extract in laboratory using both in vitro and in vivo methods so as to justify its traditional use in the above mentioned pathological conditions.. Phytochemical screening was done to find the presence of various secondary metabolites of the plant. In vivo antinociceptive activity was performed employing the hot plate method, acidic acid induced writhing test and formalin induced writhing test on Swiss albino mice at doses of 250 and 500 mg/kg body weight. Anti-inflammatory activity test was done on Long Evans rats at two different doses (250 and 500 mg/kg body weight) by using carrageenan induced paw edema test. Finally in vitro anti-inflammatory test by protein-denaturation method was followed. Data were analyzed by one-way analysis of variance (ANOVA) and Dunnett's t-test was used as the test of significance. P value <0.05 was considered as the minimum level of significance.. Phytochemical screening revealed presence of tannins, saponins, flavonoids, gums & carbohydrates, steroids, alkaloids, reducing sugars and terpenoids in the extract. In the hot plate method, the extract increased the reaction time of heat sensation significantly to 61.99% and 78.22% at the doses of 250 and 500 mg/kg BW respectively. In acetic acid induced writhing test, the percent inhibition of writhing response by the extract was 48.28% and 54.02% at 250 and 500 mg/kg doses respectively (p < 0.001). The extract also significantly inhibited the licking response in both the early phase (64.49%, p < 0.01) and the late phase (62.37%, p < 0.01) in formalin induced writhing test. The extract significantly (p < 0.05, p < 0.01 and p < 0.001) inhibited carrageenan induced inflammatory response in rats in a dose related manner. In in-vitro anti-inflammatory test, the extract significantly inhibited protein denaturation of 77.15, 64.43, 53.04, 36.78 and 23.70% for doses of 500, 400, 300, 200 and 100 μg/mL respectively.. The results obtained from the tests indicate that the plant might have one or more secondary metabolite(s) having central and peripheral analgesic and anti-inflammatory activity.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Curcuma; Edema; Female; Humans; Male; Mice; Pain; Plant Extracts; Rats; Rats, Long-Evans; Rhizome

Curcumin, obtained from turmeric, has several biological properties to make it a desirable template for drug development. A lipophilic derivative of curcumin, diacetyl curcumin (DAC) and a hydrophilic derivative, diglutaryl curcumin (DGC) were synthesized and their in vivo analgesic and anti-inflammatory activities were compared with those of curcumin and aspirin. The in vitro anti-cancer activities of curcumin and the two derivatives against three cell cancer lines were compared with those against a non-cancerous cell line. The inhibitory effects were comparable to each other and nearing that of curcumin while they showed low inhibitory effect towards the non-cancerous cell line. The mouse tail flick assay showed that curcumin, DAC and DGC increased latency time. DGC was most effective as an analgesic, even more so than aspirin. The maximum percentage effect (MPE) was highest with DGC at 3 hours. The carrageenan induced paw edema model indicated anti-inflammatory activity of all three curcumin formulations. The percentage inhibition of paw edema was maximum for DAC, followed by aspirin and curcumin.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Aspirin; Cell Line; Cell Line, Tumor; Curcumin; Edema; Humans; Mice; Rats

Curcumin shows effective anti-inflammatory activities but is seldom used in clinic because of its poor solubility in water and vulnerablity to sunshine ultraviolet effect. Novel lipid vesicles have been developed as carriers for skin delivery. In this paper, lipid vesicles-propylene glycol liposomes (PGL), Ethosomes and traditional liposomes, were prepared as curcumin carriers respectively. Their morphology, particle size and encapsulation efficiency and drug release behavior in vitro were evaluated. Transdermal efficiency and deposition quantity in abdominal skin were also measured with Franz diffusion device. Carrageenan-induced paw edema was established to evaluate the anti-inflammatory effect. From the result, the particle size order of lipid vesicles was: PGL (182.4 ± 89.2 nm)Ethosomes>traditional liposomes. PGL had the best encapsulation efficiency of 92.74 ± 3.44%. From anti-inflammatory experiment, PGL showed the highest and longest inhibition on the development of paw edema, followed by Ethosomes and Traditional liposomes. With the elevated entrapment efficiency, good transdermic ability and sustained-release behavior, PGL may represent an efficient transdermal lipid vesicle for skin delivery.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Carrageenan; Chemistry, Pharmaceutical; Curcumin; Delayed-Action Preparations; Disease Models, Animal; Drug Stability; Edema; Female; Inflammation; Kinetics; Lipids; Liposomes; Male; Particle Size; Propylene Glycol; Rats, Sprague-Dawley; Skin; Skin Absorption; Solubility; Technology, Pharmaceutical

In the present study, we determined the anti-proliferative, anti-inflammatory and antioxidant effects of a curcumin analogue, 2,6-bis(3,4-dihydroxybenzylidene) cyclohexanone (designated as A2). In vitro studies showed that A2 had a stronger inhibitory effect on the growth of mouse macrophage RAW 264.7 cells than curcumin. A2 also showed a stronger inhibitory effect than curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in NF-κB activation and IL-1β expression as well as in aldose reductase activity. A2 was a stronger antioxidant than curcumin as determined by inhibition of lipid peroxidation, inhibition of 1,1-diphenyl-2-picryl-hydrazyl free radical formation, and inhibition of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical formation. In vivo studies indicated that A2 was more potent than curcumin for inhibiting TPA-induced ear edema and TPA-induced increases in IL-1β. In addition, oral administration of A2 at a dose of 2,000 mg/kg body weight did not cause acute toxicity in mice. Taken together, the results of our study indicate that the curcumin analogue A2 has stronger anti-proliferative, anti-inflammatory and antioxidant activities than curcumin.

Topics: Aldehyde Reductase; Animals; Anti-Inflammatory Agents; Antioxidants; Cell Proliferation; Curcumin; Edema; Female; Free Radicals; Interleukin-1beta; Lipid Peroxidation; Male; Mice; NF-kappa B; Tetradecanoylphorbol Acetate

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.

Topics: Animals; Curcumin; Diabetes Mellitus, Type 2; Edema; Hemorrhage; Infarction, Middle Cerebral Artery; Locomotion; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Metalloporphyrins; Minocycline; Neuroprotective Agents; NF-kappa B; Peroxynitrous Acid; Rats; Rats, Mutant Strains; Rats, Wistar

Chronic venous insufficiency (CVI) induces alterations that cause fibrosclerotic edema of the subcutaneous tissue. This study examined the effects of a complex naturopathic compound with vasoactive and antiedema activities (Lymdiaral®) administered intradermally.. 40 patients with signs and symptoms of CVI and associated fibrosclerotic edema of the subcutaneous tissue.. Efficacy was assessed by using clinical investigation, subjective and objective measures, and ultrasonography performed at baseline and after treatment.. Thirty-four patients completed the study; 6 of the original 40 (15%) had stopped for reasons unrelated to study treatment. The treatment was well tolerated. Fifteen adverse reactions were reported among a total of 378 doses administered (3.97%). None of these reactions were severe or required discontinuation of treatment. Subjective symptoms and objective measures improved, and ultrasonography showed statistically significant changes in hypodermal thickness of the medial aspect of the knees.. Its open-label design and small sample size notwithstanding, this study indicates that intradermal therapy, according to the recommendation of the Italian Society of Mesotherapy, may provide a valuable contribution to the treatment of CVI and related fibrosclerotic edema of the subcutaneous tissue by prolonging the local effect of the pharmacologically active compounds. Comparative studies are needed to identify the broader clinical and economic benefits of local therapy compared with other systemic therapies.

Topics: Adult; Chronic Disease; Conium; Edema; Female; Humans; Hydrastis; Leg; Mesotherapy; Phytolacca; Phytotherapy; Pilot Projects; Plant Preparations; Prospective Studies; Scilla; Treatment Outcome; Venous Insufficiency; Viscum album

A variety of novel aromatic and heterocyclic aromatic curcuminoids were synthesised, characterised and their anti-inflammatory activities (AIA) determined in vivo. Some of these compounds also were tested for inflammatory mediator production. The AIA of the main representatives of these compounds were assessed by oral administration to female Wistar rats using (a) acute carrageenan-induced paw oedema, (b) chronic adjuvant arthritis (therapeutic mode), and (c) anti-pyretic activity assessed in the yeast pyrexia. Gastric ulceration was determined in pre-inflamed rats. Natural curcumin showed modest aspirin-like anti-inflammatory activity which was enhanced when co-administered with the PGE(1) analogue misoprostol as a synergist. In contrast, four novel curcuminoids (RK-97, RK-103, RK-104 and RK-106) in which the bis-methoxy-phenyl group of curcumin was replaced with bis-dimethoxybutenolidyl-(ascorbate), bis-naphthyl, and bis-furanyl derivatives, respectively, had potent activity in the anti-arthritic assay with little gastric or systemic toxicity, compared with the vehicle-treated controls. Of the curcuminoids the furan RK-106 was the only compound to inhibit production of TNFα and IL-1β in a monocytic cell-line THP-1 in vitro. The inactivity of RK-106 on the production of PGE(2) may be related to its absence of gastrotoxicity. None of the curcuminoids exhibited anti-pyretic activity and this may also be related to its insensitivity to PGE(2). Thus, these novel curcuminoids, such as RK-106, may warrant the development of new low gastro-toxic anti-inflammatory agents with selective inhibitory activity of cytokine inflammatory mediators.

Topics: Administration, Oral; Alprostadil; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Carrageenan; Cell Line; Curcumin; Edema; Female; Heterocyclic Compounds; Humans; Interleukin-1beta; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats.

Topics: Animals; Antioxidants; Biomarkers; Body Weight; Chemical and Drug Induced Liver Injury; Curcumin; Edema; Erythrocytes; Female; Granuloma, Foreign-Body; Heart; Hemolysis; In Vitro Techniques; Lipid Peroxidation; Liver; Liver Function Tests; Male; Myocardium; Necrosis; Organ Size; Rats; Rats, Wistar

Dibenzoylmethane (DBM), a β-diketone structural analogue of curcumin, has been reported to exhibit anti-tumorigenic and chemopreventive activities. Due to the structural resemblance of DBM to the anti-inflammatory curcumin and an aspirin-like skeleton of DBM derivatives, we tested the anti-inflammatory effects of DBM and its derivatives, 1,3-bis-(2-substituted-phenyl)-propane-1,3-dione, on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion as well as TPA- and arachidonic acid-induced mouse ear edema in skin of CD-1 mice. Topical application of 10 μmol DBM together with TPA on the back of mice previously treated with 7,12-dimethylbenz[α]anthracene (DMBA) inhibited TPA-induced skin tumor promotion significantly. In addition, 1,3-bis-(2-acetoxy phenyl)-propane-1,3-dione was a superior anti-inflammatory agent to aspirin (80% of inhibition), on TPA-induced mouse ear edema and reduced the production of prostaglandin E2 (PGE(2)), comparable to aspirin. Taken together, 1,3-bis-(2-acetoxyphenyl-propane-1,3-dione merits a valuable anti-inflammatory agent substituting aspirin in therapeutic treatment as well prevention of cancer.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anti-Inflammatory Agents; Arachidonic Acid; Aspirin; Carcinogens; Curcumin; Dermatitis; Ear, External; Edema; Female; Ketones; Mice; Mice, Inbred Strains; Platelet Aggregation Inhibitors; Skin Neoplasms; Tetradecanoylphorbol Acetate

The purpose of this research was to develop a matrix-type transdermal therapeutic system containing herbal drug, curcumin (CUR), with different ratios of hydrophilic (hydroxyl propyl methyl cellulose K4M [HPMC K4M]) and hydrophobic (ethyl cellulose [EC]) polymeric systems by the solvent evaporation technique. Different concentrations of oleic acid (OA) were used to enhance the transdermal permeation of CUR. The physicochemical compatibility of the drug and the polymers was also studied by differential scanning calorimetry (DSC) and infrared (IR) spectroscopy. The results suggested no physicochemical incompatibility between the drug and the polymers. Formulated transdermal films were physically evaluated with regard to drug content, tensile strength, folding endurance, thickness, and weight variation. All prepared formulations indicated good physical stability. In vitro permeation studies of formulations were performed by using Franz diffusion cells. The results followed Higuchi kinetics, and the mechanism of release was diffusion-mediated. Formulation prepared with hydrophilic polymer containing permeation enhancer showed best in vitro skin permeation through rat skin as compared with all other formulations. This formulation demonstrated good anti-inflammatory activity against carrageenan-induced oedema in Wistar albino rats similar to standard formulation.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cellulose; Curcumin; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Delivery Systems; Drug Design; Drug Evaluation, Preclinical; Drug Incompatibility; Drug Stability; Edema; Excipients; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; In Vitro Techniques; Kinetics; Methylcellulose; Permeability; Pharmaceutical Vehicles; Rats; Rats, Wistar; Skin; Skin Absorption; Tensile Strength

The present study aimed to investigate potential effects of curcumin (CUR) and dexamethasone (DXM) on ischaemia-reperfusion (I/R) induced lung injury in rats. Experimental rats were pre-treated with a single i.p. dose of vehicle, CUR (50 mg.kg(-1) or 200 mg.kg(-1)) or DXM (5 mg.kg(-1)), 2 h before anaesthesia and subjected to left lung hilus clamping with 90-min ischaemia followed by 4 h of reperfusion. Pre-treatment with CUR (200 mg.kg(-1)) or DXM markedly attenuated I/R-induced barrier disruption, lung oedema, tissue inflammation, hypoxaemia 4 h after reperfusion, and overactivation of nuclear factor-kappaB, inflammatory cytokines, myeloperoxidase and malondialdehyde. It appears that curcumin attenuates acute lung injury, probably through improving oxidative stress and inhibiting nuclear factor-kappaB-mediated expression of inflammatory cytokines. Thus, curcumin may be an alternative therapy for improving the outcomes of ischaemia-reperfusion-induced lung injury.

Topics: Animals; Curcumin; Dexamethasone; Disease Models, Animal; Edema; Glucocorticoids; Lung; Microcirculation; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Treatment Outcome

The aim of the present investigation was to develop and study topical gel delivery of curcumin for its anti-inflammatory effects. Carbopol 934P (CRB) and hydroxypropylcellulose (HPC) were used for the preparation of gels. The penetration enhancing effect of menthol (0-12.5% w/w) on the percutaneous flux of curcumin through the excised rat epidermis from 2% w/w CRB and HPC gel system was investigated. All the prepared gel formulations were evaluated for various properties such as compatibility, drug content, viscosity, in vitro skin permeation, and anti-inflammatory effect. The drug and polymers compatibility was confirmed by Differential scanning calorimetry and infrared spectroscopy. The percutaneous flux and enhancement ratio of curcumin across rat epidermis was enhanced markedly by the addition of menthol to both types of gel formulations. Both types of developed topical gel formulations were free of skin irritation. In anti-inflammatory studies done by carrageenan induced rat paw oedema method in wistar albino rats, anti-inflammatory effect of CRB, HPC and standard gel formulations were significantly different from control group (P < 0.05) whereas this effect was not significantly different for CRB and HPC gels formulations to that of standard (diclofenac gel) formulation (P > 0.05). CRB gel showed better % inhibition of inflammation as compared to HPC gel.

Topics: Acrylates; Administration, Topical; Animals; Anti-Infective Agents, Local; Calorimetry, Differential Scanning; Carrageenan; Cellulose; Chemistry, Pharmaceutical; Curcumin; Drug Evaluation, Preclinical; Edema; Excipients; Forelimb; Gels; Histocompatibility; Inflammation; Menthol; Permeability; Rats; Rats, Wistar; Skin Absorption; Spectrophotometry, Infrared; Viscosity

Demethoxycurcumin and bisdemethoxycurcumin are the main active ingredients isolated from Curcumae Longae Radix. Recent studies demonstrated that both compounds exhibit antioxidative and anti-inflammatory effects as well as effects on cancer cell lines. In this study, we compared the activities of demethoxycurcumin and bisdemethoxycurcumin, and both compounds were evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), cycloxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB) activity in a RAW 264.7 macrophage cell line. The evaluation:results suggested that the anti-inflammatory properties of demethoxycurcumin and bisdemethoxycurcumin were attributed to the inhibition of iNOS and COX-2 expression, as initiated by the inhibition of NF-kappaB activity. Additionally, both of them significantly inhibited carrageenan-induced paw edema in mice. Taken together, all of the results showed that the suppressive effect of demethoxycurcumin was stronger than that of bisdemethoxycurcumin, indicating that the methoxy group had enhanced demethoxycurcumin's anti-inflammation effects.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cell Line; Curcumin; Cyclooxygenase 2; Diarylheptanoids; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Gene Expression Regulation, Enzymologic; I-kappa B Proteins; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Transfection

Curcuma xanthorrhiza Roxb. (Zingiberaceae) is a medicinal plant widely spread in South East Asia. In particular, it is commonly used not only for food and medicinal purposes in Indonesia, but also for the topical treatment of acne and skin inflammations as Thai traditional medicine. It was found that the methanol extract of C. xanthorrhiza inhibited significantly 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis of Salmonella typhimurium TA98 and TA100 in the presence of S9, and the mutagenesis induced by H2O2 and tert-butylhydroperoxide in S. typhimurium TA102, respectively. In addition, 12-O-tetradecanolyphorbol-13-acetate(TPA)-induced mouse ear edema was markedly inhibited by pretreatment with C. xanthorrhiza extract. C. xanthorrhiza extract dose-dependently reduced ODC expression in mouse skin with TPA-induced acute inflammation. Furthermore, repeated treatment with 0.1% C. xanthorrhiza extract reduced the average number of tumors per mouse and the percentage of tumor-bearing mice in a multistage mouse skin carcinogenesis induced by DMBA and TPA. These results demonstrate that the methanol extract of C. xanthorrhiza possesses cancer chemopreventive potential.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Curcuma; Dose-Response Relationship, Drug; Ear; Edema; Female; Humans; Methanol; Mice; Mice, Inbred ICR; Mutagenesis; Phytotherapy; Plant Extracts; Salmonella typhimurium; Skin Neoplasms; Tetradecanoylphorbol Acetate

From the methanolic extract of the rhizome of Curcuma zedoaria, we isolated anti-inflammatory sesquiterpene furanodiene (1) and furanodienone (2) along with new sesquiterpene compound 3 and known eight sesquiterpenes, zederone (4), curzerenone (5), curzeone (6), germacrone (7), 13-hydroxygermacrone (8), dehydrocurdione (9), curcumenone (10), and zedoaronediol (11). Their structures were elucidated on the basis of spectroscopic data. The anti-inflammatory effect of isolated components on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation of mouse ears were examined. Compounds 1 and 2 suppressed the TPA-induced inflammation of mouse ears by 75% and 53%, respectively, at a dose of 1.0 micromol. Their activities are comparable to that of indomethacin, the normally used anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents; Curcuma; Edema; Mice; Nuclear Magnetic Resonance, Biomolecular; Plant Extracts; Rhizome; Sesquiterpenes; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared

Alpinia oxphylla Miquel, which belongs to the ginger family (Zingiberaceae), has been used in Oriental herbal medicine. Our recent studies have revealed that the methanolic extract of A. oxyphylla suppresses mouse skin tumor promotion and induces apoptosis in cultured human promyelocytic leukemia cells. In the present work, we have assessed effects of yakuchinone A and yakuchinone B, phenolic diarylheptanoids derived from A. oxyphylla, on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and epidermal ornithine decarboxylase (ODC) activity as well as on skin tumor promotion in female ICR mice. Thus, topical application of 2 or 6 micromol of the diarylheptanoids prior to each topical dose of TPA significantly ameliorated 7,12-dimethylbenz[a]anthracene-initiated mouse skin tumor formation. In parallel with suppression of tumor promotion, topically applied yakuchinone A and B markedly inhibited TPA-induced epidermal ODC activity and ODC mRNA expression. In another experiment, yakuchinone A and B reduced production of tumor necrosis factor-alpha in TPA-stimulated mouse skin. Furthermore, both compounds inhibited the TPA-induced expression of cyclooxygenase-2 at both transcriptional and translational levels. These findings indicate that pungent diarylheptanoids from A. oxyphylla Miquel have an antitumor promotional activity that might be related to their anti-inflammatory properties.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diarylheptanoids; Edema; Guaiacol; Inflammation; Mice; Phytotherapy; Skin; Skin Neoplasms; Zingiber officinale

The inhibitory effects of curcumin and two tetrahydrocurcuminoids on tumor promoter-induced oxidative stress in vitro and in vivo were investigated. Curcumin, tetrahydrocurcumin (THC) and dihydroxytetrahydrocurcumin (DHTHC) exhibited significant inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced O2-generation in differentiated HL-60 cells. The inhibitory activity of THC was weaker than that of curcumin. This tendency was the inverse of the results of previous studies on in vitro antioxidative activity against lipid peroxidation. The curcuminoids inhibited TPA-induced intracellular peroxide formation in differentiated HL-60 cells. THC exhibited much weaker inhibition of intracellular peroxide formation than curcumin, suggesting that this inhibition might be attributable to the inhibition of O2-generation. The inhibitory effects of curcuminoids on TPA-induced H2O2 formation in female ICR mouse skin were further examined using the double-TPA-application model. Each TPA application induces two distinct biochemical events, 1) recruitment of inflammatory cells to the inflammatory regions and 2) activation of oxidant-producing cells. Double pretreatment of mice with curcuminoids before each TPA treatment significantly suppressed double TPA application-induced H2O2 formation in the mouse skin. Coadministrations of curcumin with either first or second TPA treatment significantly inhibited H2O2 formation. In addition, THC tends to show weaker inhibitory activities than curcumin in bioassays related to tumor promotion, i.e., inhibition of tumor promoter-induced inflammation in mouse skin and Epstein-Barr virus activation. These tendencies were parallel to those in the tumor-suppressive potential of curcumin and THC in mouse skin, as previously reported. Thus, we concluded that curcuminoids significantly suppress TPA-induced oxidative stress via both interference with infiltration of leukocytes into the inflammatory regions and inhibition of their activation.

Topics: Animals; Anticarcinogenic Agents; Antigens, Viral; Curcumin; Edema; Female; Fluorescent Antibody Technique, Indirect; Hydrogen Peroxide; Leukocytes; Mice; Mice, Inbred ICR; Oxidative Stress; Reactive Oxygen Species; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

Topics: Animals; Anthralin; Anti-Inflammatory Agents, Non-Steroidal; Croton Oil; Curcumin; Ear, External; Edema; Male; Masoprocol; Mice; Mice, Inbred Strains

The antioxidant spice principles curcumin and eugenol when given by gavage lowered the carrageenan-induced edema in the foot pads of rats. This lowering effect was dependent on the concentration, the time gap between the administration of spice principles and the induction of inflammation by carrageenan. Dietary lipids also influenced the extent of inflammation. Animals fed 10% cod liver oil [containing n-3 polyunsaturated fatty acids (PUFA)] for 10 weeks showed a significantly lower inflammation compared to that observed in animals fed diets supplemented with 10% groundnut oil (rich in n-6 PUFA) or 10% coconut oil (rich in medium-chain saturated fatty acids). Supplementation of diets with 1 weight% of curcumin did not affect the inflammatory responses of animals to carrageenan injection. However, supplementation of diets with 0.17 weight% eugenol further lowered inflammation by 16, 32 and 30% in animals fed coconut oil, groundnut oil and cod liver oil, respectively. Therefore, combinations of dietary lipids with spice principles like eugenol can help in lowering inflammation.

Topics: Administration, Oral; Animals; Antioxidants; Carrageenan; Curcumin; Dietary Fats; Dietary Fats, Unsaturated; Dose-Response Relationship, Drug; Edema; Eugenol; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Food, Fortified; Foot; Inflammation; Male; Rats; Rats, Wistar; Vitamin E

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

Topics: Animals; Anti-Inflammatory Agents; Catechols; Curcumin; Edema; Rats