naphthoquinones and Edema

The chemical study on the heartwoods extract of Ventilago harmandiana (Rhamnaceae) resulted in the isolation of ten previously undescribed pyranonaphthoquinones (ventilanones A-J), an undescribed anthraquinone (ventilanone K), together with eight known anthraquinone derivatives. Their structures were elucidated by extensive analysis of their spectroscopic data. The absolute configuration of ventilanone A was established from single crystal X-ray crystallographic analysis of its p-bromobenzenesulfonate ester derivative using Cu Kα radiation. The absolute configurations of the other related compounds were identified by comparison of their ECD data with those of ventilanone A and related known compounds. Cytotoxic and anti-inflammatory activities of some of the isolated compounds were evaluated. Ventilanone A and ventilanone C exhibited moderate cytotoxicity against P-388 cell line. Ventilanone D exhibited significant anti-inflammatory activity while ventilanone A and ventilanone C showed moderate activity.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents; Antineoplastic Agents; Cell Proliferation; Cell Survival; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Edema; Mice; Models, Molecular; Molecular Structure; Naphthoquinones; Rats; Rhamnaceae; Structure-Activity Relationship; Tumor Cells, Cultured

Topics: Adenosine Triphosphate; Animals; Caco-2 Cells; Carrageenan; Dose-Response Relationship, Drug; Edema; HEK293 Cells; Humans; Male; Mice; Molecular Structure; Naphthoquinones; Purinergic P2X Receptor Antagonists; Receptors, Purinergic P2X7; Structure-Activity Relationship

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Dinoprostone; Edema; Hyperalgesia; Magnoliopsida; Mice; Molecular Structure; Naphthoquinones; Plant Tubers

We report in vitro and in vivo anti-inflammatory activities of a series of copper(II)-lawsone complexes of the general composition [Cu(Law)2(LN)x(H2O)(2-x)]·yH2O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when LN = pyridine (1) and 2-aminopyridine (3) and x = 2 when LN = imidazole (2), 3-aminopyridine (4), 4-aminopyridine (5), 3-hydroxypyridine (6), and 3,5-dimethylpyrazole (7). The compounds were thoroughly characterized by physical techniques, including single crystal X-ray analysis of complex 2. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB) both by lipopolysaccharide (LPS) and TNF-alpha (complexes 3-7 at 100 nM level) in the similar manner as the reference drug prednisone (at 1 μM level). On the other hand, all the complexes 1-7 decreased significantly the levels of the secreted TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti-inflammatory potential via both NF-κB moderation and by other mechanisms, such as influence on TNF-alpha transcription and/or translation and/or secretion. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found at 100 nM dose in vitro. The ability to suppress the inflammatory response, caused by the subcutaneous application of λ-carrageenan, has been determined by in vivo testing in hind-paw edema model on rats. The most active complexes 1-3 (applied in a dose corresponding to 40 μmol Cu/kg), diminished the formation of edema simalarly as the reference drug indomethacine (applied in 10 mg/kg dose). The overall effect of the complexes, dominantly 1-3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Copper; Crystallography, X-Ray; Dose-Response Relationship, Drug; Edema; Humans; Inflammation; Male; Naphthoquinones; NF-kappa B; Rats; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization

Two chromone C-glucosides, biflorin (1) and isobiflorin (2), were isolated from the flower buds of Syzygium aromaticum L. (Myrtaceae). Here, inhibitory effects of 1 and 2 on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 macrophages were evaluated, and 1 (IC50 = 51.7 and 37.1 μM, respectively) was more potent than 2 (IC50 > 60 and 46.0 μM). The suppression of NO and PGE2 production by 1 correlated with inhibition of iNOS and COX-2 protein expression. Compound 1 reduced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression via inhibition of their promoter activities. Compound 1 inhibited the LPS-induced production and mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. Furthermore, 1 reduced p-STAT1 and p-p38 expression but did not affect the activity of nuclear factor κ light-chain enhancer of activated B cells (NF-κB) or activator protein 1 (AP-1). In a mouse model of LPS-induced endotoxemia, 1 reduced the mRNA levels of iNOS, COX-2, and TNF-α, and the phosphorylation-mediated activation of the signal transducer and activator of transcription 1 (STAT1), consequently improving the survival rates of mice. Compound 1 showed a significant anti-inflammatory effect on carrageenan-induced paw edema and croton-oil-induced ear edema in rats. The collective data indicate that the suppression of pro-inflammatory gene expression via p38 mitogen-activated protein kinase and STAT1 inactivation may be a mechanism for the anti-inflammatory activity of 1.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Edema; Endotoxemia; Flowers; Inflammation Mediators; Interleukin-6; Lipopolysaccharides; Macrophages; Male; Mice; Molecular Structure; Naphthoquinones; NF-kappa B; Nitric Oxide; p38 Mitogen-Activated Protein Kinases; Rats; STAT1 Transcription Factor; Syzygium; Transcription Factor AP-1; Tumor Necrosis Factor-alpha

Topics: Adult; Coloring Agents; Dermatitis, Allergic Contact; Edema; Humans; Male; Naphthoquinones; Tattooing

This study reports the in vivo anti-inflammatory and antioxidative effects of the methanolic extract of the aerial parts of Mitracarpus frigidus (MFM) and its chemical fingerprint.. The acute anti-inflammatory activity was performed using the carrageenan-induced paw oedema and peritonitis, ear oedema induced by croton oil and ethyl phenylpropiolate methods. Total COX, COX-1 and COX-2 expression was also evaluated. Chronic activity was determined by cotton pellet granuloma model. The antioxidative activity was assessed using liver tissue malondialdehyde, catalase and myeloperoxidase activities.. M. frigidus showed an intense acute anti-inflammatory action (100 and 300 mg/kg) in a nondose-dependent manner with selective inhibition of COX-2 expression. This activity may be also related to the strong antioxidative effect observed. By the other side, the chronic anti-inflammatory activity of MFM was not expressive. Kaempferol, kaempferol-O-rutenoside, rutin, ursolic acid and psychorubrin were identified in MFM.. The anti-inflammatory activity of MFM was probably due to inhibition of COX expression in a selective manner for COX-2. Other mechanisms, such as inhibition of inflammatory mediators and of the oxidative stress were possibly involved in the effects observed. To the best of our knowledge, it is the first time those activities are reported for M. frigidus.

Topics: Animals; Antioxidants; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Edema; Female; Inflammation; Inflammation Mediators; Kaempferols; Male; Mice; Naphthoquinones; Oxidative Stress; Phytotherapy; Plant Components, Aerial; Plant Extracts; Rats, Wistar; Rubiaceae; Rutin; Triterpenes; Ursolic Acid

Diospyros lotus L. is traditionally used in various diseases including pain and sleep disorders. The pain and inflammation are the common problems, which are treated with various synthetic analgesic drugs, and associated the side effects. The natural products have gained significant importance over synthetic drugs. The importance of phyto-medicine the current study has been designed with the aim to investigate the analgesic and anti-inflammatory effects of Diospyros lotus and bioassay guided isolation from its crude fractions. Seven known compounds; lupeol (1), 7-methyljuglone (2), β-Sitosterol (3), stigmasterol (4) betulinic acid (5), diospyrin (6; DS) and 8-hydroxyisodiospyrin (7; HDS) which were hitherto unreported from D. lotus. The chloroform fraction (CFDL) and isolated compounds DS and HDS were evaluated for anti-nociceptive, sedative and anti-inflammatory effects. The acetic acid induced writing was significantly (p<0.001) protected by CFDL (72.43%), DS (40.87%) and HDS (65.76%) at higher doses which exhibited peripheral and central analgesic effects in acetic acid and hot-plat pain paradigms. Regarding the anti-inflammatory effect the CFDL (77.43%), DS (80.54%) and HDS (75.87%) protected the carrageenan paw edema after 3rd h. The central analgesic effect was significantly antagonized with naloxone (0.5 mg/kg), showing opiodergic mechanism of action. The CFDL, DS and HDS were also proved sedative in open field animal models. In acute toxicity study the chloroform fraction [CFDL (50, 100 and 150 mg/kg)], DS (5 and 10 mg/kg) and HDS (5 and 10 mg/kg) were found safe. Our study concluded that CFDL, DS and HDS have marked anti-nociceptive, anti-inflammatory and sedative effect. The anti-nociceptive and anti-inflammatory effects of the roots of D. lotus are partially attributed due to the presence of analgesic constituents like diospyrin (DS), 8-hydroxyisodiospyrin (HDS) and strongly supports the ethno-pharmacological uses of D. lotus as anti-nociceptive, anti-inflammatory and sedative.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Chloroform; Diospyros; Drug Evaluation, Preclinical; Edema; Female; Hypnotics and Sedatives; Male; Mice, Inbred BALB C; Naphthoquinones; Plant Extracts; Toxicity Tests, Acute

The purpose of this study was to evaluate the anti-inflammatory and anti-arthritic activities of 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (β-lapachone; β-lap) and to elucidate its probable mode of action.. Carrageenan-induced paw edema, cell migration evaluation and production of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide were used for this study. Freund's complete adjuvant (FCA)-induced arthritis was used as a model of chronic inflammation. β-Lap was tested in doses of 40 and 60 mg/kg, orally.. In the paw edema test, the dose of 60 mg/kg gave a higher percentage inhibition of edema (49.3 %) than control. β-Lap inhibited neutrophil migration and reduced concentrations of TNF-α, IL-6 and NO in peritoneal exudates of animals with peritonitis. In the arthritis test, β-lap inhibited edema and NO production in the serum of treated animals.. Significant anti-inflammatory and anti-arthritic activities were observed in animals treated with β-lap. The effects of β-lap can be attributed in part to immunomodulation with reduction of pro-inflammatory cytokines and NO.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Edema; Female; Interleukin-6; Male; Mice; Naphthoquinones; Nitric Oxide; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Although various drugs for the treatment of rheumatoid arthritis (RA) have been used in clinics, RA is not completely curable to date. Thus, to seek new drugs for the treatment of RA has been a hotspot. Hydroxynaphthoquinones are the major anti-inflammatory active constituents in Arnebia euchroma (Royle) Johnst. The present study aims to evaluate the anti-arthritic activity of a hydroxynaphthoquinone mixture (HM) of A. euchroma (Royle) Johnst, including its anti-inflammatory and analgesic effects. The anti-arthritic efficacy of HM was examined using complete Freund's adjuvant- and bovine type II collagen-induced arthritic models. The paw edema, polyarthritis index and histopathological change were evaluated. The analgesic effect was assessed using the chemical and thermal models of nociception. Results found that HM administered prophylactically and curatively showed marked anti-arthritic activity by suppressing the paw swelling and development of inflammation, lowering the levels of TNF-α and IL-1β and protecting cartilage and bone from damage. The protection of HM was superior to that of reference drugs such as prednisone acetate or etanercept, and showed no direct deleterious effect. Similarly, HM showed significant analgesic effects. In summary, HM possessed potent anti-arthritic activity. It could relieve inflammatory symptoms and protect against joint destruction. These findings indicate that HM would be a potential therapeutic agent for arthritic disease, which provide pharmacological evidence for its clinical application.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Bone Diseases; Boraginaceae; Cartilage Diseases; Cattle; Collagen Type II; Edema; Etanercept; Freund's Adjuvant; Hot Temperature; Immunoglobulin G; Inflammation; Interleukin-1beta; Joint Diseases; Male; Naphthoquinones; Phytotherapy; Plant Extracts; Prednisone; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

Cipura paludosa (Iridaceae) is a plant that is distributed in the north region of Brazil. Its bulbs are used in folk medicine to treat inflammation and pain. Four naphthalene derivatives have been isolated from the bulbs of this plant. Three of them have been identified as the known naphthalene derivatives, eleutherine, iso-eleutherine, and hongkonin. The structure of the fourth and new component was determined as 11-hydroxyeleutherine by extensive NMR study. In addition, the IN VIVO effect of the two major compounds, eleutherine and iso-eleutherine, was evaluated in carrageenan-induced hypernociception and inflammation in mice. Eleutherine and iso-eleutherine (1.04-34.92 µmol/kg), dosed intraperitoneally (i.p.) or orally (p.o.), decreased the carrageenan-induced paw oedema (i.p. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively; p.o. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively). Iso-eleutherine, but not eleutherine, significantly reduced (inhibitions of 39 ± 4 %) the plasma extravasation induced by intradermal (i.d.) injection of carrageenan. Likewise, eleutherine and iso-eleutherine (1.04-34.92 µmol/kg, i.p. or p.o.) were also effective in preventing the carrageenan-induced hypernociceptive response (i.p. - inhibition of 59 ± 4 % and 63 ± 1 %, respectively; p.o. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively). It was also suggested that the anti-inflammatory and anti-hypernociceptive effects of eleutherine or iso-eleutherine partly depend on the interference with the synthesis or activity of mast cell products, kinins, cytokine, chemokines, prostanoids, or sympathetic amines. Our findings show that two major compounds of C. paludosa contain pharmacologically active constituents that possess antinociceptive and anti-inflammatory activity, justifying, at least in part, its popular therapeutic use for treating conditions associated with pain.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Brazil; Carrageenan; Drug Evaluation, Preclinical; Edema; Female; Inflammation; Injections, Intraperitoneal; Iridaceae; Magnetic Resonance Spectroscopy; Male; Mice; Molecular Structure; Naphthoquinones; Pain; Plant Roots; Plants, Medicinal

Temporary tattooing with black henna is known to cause contact dermatitis; however, this adverse effect is not considered to be life threatening. We report a female adolescent who used black henna as a hair dye and developed severe contact dermatitis with scalp, facial, and neck swelling causing hoarseness and stridor. A flexible bronchoscopy showed a normal epiglottis, and the patient was intubated, ventilated, and eventually recovered. We conclude that the use of black henna hair dye in sensitized patients can be life threatening.

Topics: Adolescent; Dermatitis, Allergic Contact; Edema; Female; Hair Dyes; Hoarseness; Humans; Naphthoquinones; Respiratory Sounds; Scalp Dermatoses

The effects of histochrome and mexidol on the morphology and function of the brain and behavior were studied in senescence-accelerated OXYS and Wistar rats. MRI showed that signs of neurodegenerative changes were present in OXYS rats at the age of 3 months and were pronounced at the age of 12 months. Histochrome (1 mg/kg, 5 days) more effectively than mexidol (4 mg/kg, 7 days) reduced anxiety and increased exploratory activity of 1-year-old OXYS rats. Both drugs improved the morphology and function of the brain. Their effects consisting in correction of diffuse changes in the white matter and reduction of edema were comparable; in addition, histochrome reduced the intensity of demyelinization processes.

Topics: Aging; Animals; Antioxidants; Anxiety; Brain; Demyelinating Diseases; Edema; Exploratory Behavior; Magnetic Resonance Imaging; Male; Naphthoquinones; Picolines; Rats; Rats, Wistar

In the present paper we studied the effect of shikonin on ear oedema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and determined the mechanisms through which shikonin might exert its topical anti-inflammatory action.. Acute ear oedema was induced in mice by topical application of TPA. The in vitro assays used macrophages RAW 264.7 cells stimulated with lipopolysaccharide. Cyclooxygenase-2, inducible nitric oxide synthase, protein kinase Calpha, extracellular signal-regulated protein kinase (ERK), phosphorylated ERK (pERK), c-Jun N-terminal kinase (JNK), pJNK, p38, p-p38, p65, p-p65, inhibitor protein of nuclear factor-kappaB (NF-kappaB) (IkappaBalpha) and pIkappaBalpha were measured by Western blotting, activation and binding of NF-kappaB to DNA was detected by reporter gene and electrophoretic mobility shift assay, respectively, and NF-kappaB p65 localization was detected by immunocytochemistry.. Shikonin reduced the oedema (inhibitory dose 50 = 1.0 mg per ear), the expression of cyclooxygenase-2 (70%) and of inducible nitric oxide synthase (100%) in vivo. It significantly decreased TPA-induced translocation of protein kinase Calpha, the phosphorylation and activation of ERK, the nuclear translocation of NF-kappaB and the TPA-induced NF-kappaB-DNA-binding activity in mouse skin. Moreover, in RAW 264.7 cells, shikonin significantly inhibited the binding of NF-kappaB to DNA in a dose-dependent manner and the nuclear translocation of p65.. Shikonin exerted its topical anti-inflammatory action by interfering with the degradation of IkappaBalpha, thus inhibiting the activation of NF-kappaB.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cell Nucleus; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; I-kappa B Proteins; Inflammation; Inhibitory Concentration 50; Macrophages; Mice; Naphthoquinones; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Protein Transport; Tetradecanoylphorbol Acetate

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) (PL) is a naturally occurring yellow pigment found in the plants of the Plumbaginaceae, Droseraceae, Ancistrocladaceae, and Dioncophyllaceae families. It has been reported that PL exhibits anticarcinogenic, anti-inflammatory, and analgesic activities. However, the mechanism underlying its anti-inflammatory action remains unknown. In the current study, we investigated and characterized the anti-inflammatory and analgesic effects of PL orally administrated in a range of dosages from 5 to 20 mg/kg. We also examined the role of nuclear factor κB (NF-κB) and proinflammatory cytokines and mediators in this effect. The results showed that PL significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan and various proinflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2). PL reduced the number of writhing episodes of mice induced by the intraperitoneal injection of acetic acid, but it did not reduce the writhing episode numbers induced by MgSO(4) in mice or prolong the tail-flick reaction time of rats to noxious thermal pain. Mechanistic studies showed that PL effectively decreased the production of the proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α. It also inhibited the expression of the proinflammatory mediators inducible nitric-oxide synthase and cyclooxygenase 2, whereas it did not inhibit the expression of cyclooxygenase 1. Further studies demonstrated that PL suppressed inhibitor of κBα phosphorylation and degradation, thus inhibiting the phosphorylation of the p65 subunit of NF-κB. This study suggests that PL has a potential to be developed into an anti-inflammatory agent for treating inflammatory diseases.

Topics: Abdominal Pain; Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bradykinin; Carrageenan; Cyclooxygenase 2; Dinoprostone; Edema; Foot; Gene Expression; Histamine; Hot Temperature; I-kappa B Proteins; Inflammation; Interleukin-1beta; Interleukin-6; Magnesium Sulfate; Male; Mice; Mice, Inbred ICR; Naphthoquinones; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase Type II; Pain Threshold; Phosphorylation; Rats; Rats, Sprague-Dawley; Serotonin; Transcription Factor RelA; Tumor Necrosis Factor-alpha

We report on a 14-year-old boy who was presented to the emergency department with an acute swelling of the face and scalp 3 days after using a new hair dye. The patient had applied a black henna tattoo 1 year earlier. Patch testing revealed an allergy to the potent skin sensitizer paraphenylenediamine, a common ingredient of hair dyes and also found in black henna tattoo. It is important for emergency physicians to be aware of the possibility of a delayed type-IV hypersensitivity reaction from black henna tattoos manifesting as an acute contact dermatitis. These patients may have gross facial swelling but should not be treated for angioedema.

Topics: Adolescent; Coloring Agents; Edema; Face; Hair Dyes; Humans; Hypersensitivity, Delayed; Male; Naphthoquinones; Phenylenediamines

The root extracts of Onosma leptanhtha were evaluated for their anti-iflammatory and cytotoxic activities. The cyclohexane extract, which appeared as the most active in both assays, has been further subjected to bioassay-directed fractionation to afford the naphthazarine derivatives: beta,beta-dimethylacrylshikonin (1), isovalerylshikonin (2) and acetylshikonin (3). The evaluation of the anti-inflammatory activity was performed on carrageenan-induced rat paw edema test. All the tested compounds proved to be active, while compound 3 showed the best anti-inflammatory effect. In addition, the cytotoxic activity of the extracts and isolated compounds, was also assayed against L1210 murine lymphoblastic leukemia cell line, and human fibrosarcoma HT-1080 cells. Compound 1 exhibited remarkable cytotoxic activity (390 nM for L1210 cells), which is superior to that of shikonin, which was used as control.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents; Antineoplastic Agents; Biological Assay; Boraginaceae; Carrageenan; Cell Line, Tumor; Cyclohexanes; Edema; Humans; Indomethacin; Inhibitory Concentration 50; Male; Naphthoquinones; Plant Extracts; Plant Roots; Rats; Rats, Wistar

Arnebia hispidissima ethanolic extract, after chromatography, yielded a number of shikonin derivatives, which were identified as arnebin-5, arnebin-6, teracryl shikonin, arnebinone and acetyl shikonin. All these compounds were firstly reported from this plant species and evaluated to the anti-inflammatory activity of ethanolic extract and isolated shikonin derivatives, models with carrageenan-induced paw edema and complete Freund's adjuvant (CFA)-induced chronic arthritis in rats were conducted. The observed results indicated that pre-treatment with arnebinone significantly inhibited the carrageenan-induced paw edema and also suppressed the development of chronic arthritis induced by CFA.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Boraginaceae; Edema; Ethanol; Male; Molecular Structure; Naphthoquinones; Plant Extracts; Plant Roots; Plants, Medicinal; Rats; Rats, Wistar

Alkannin and shikonin, two natural products from Alkanna tinctoria and Lithospermum erhythrorhizon (Boraginaceae), are used in folk medicine where they are claimed to possess, among other properties, wound healing and anti-inflammatory activity. We investigated, together with the structurally related naphthazarin, their in vitro antioxidant and hydroxyl radical scavenging activity as well as their in vivo antiinflammatory activity. I was found that all examined compounds significantly inhibited in vitro lipid peroxidation of ra hepatic microsomal membranes, competed with DMSO for free hydroxyl radicals, and reduced inflammation (mouse paw edema induced by FCA) very efficiently. The examined compounds proved equal or superior to the common reference compounds for each of these properties. I is concluded that the claimed and/or proven actions of alkannin and shikonin are attributable at least partly to their intervention in free radical processes.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dimethyl Sulfoxide; Edema; Female; Free Radical Scavengers; Freund's Adjuvant; Lipid Peroxidation; Naphthoquinones; Rats; Rats, Inbred F344

We have investigated the mechanisms of action of aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots.. Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of six animals.. Test compounds were applied topically in the mouse ear oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 pmol/pouch or 12.5-50 mg/kg p.o.).. LTB4 production was assayed in human neutrophils and COX-2 and iNOS activities in murine macrophages. Air pouches were induced subcutaneously in mice and injected with zymosan on the day six. Mouse ear oedema was induced by arachidonic acid. Dunnett's t-test was employed for statistical analysis.. We have observed potent inhibitory effects on human neutrophil LTB4 production without effects on COX or NOS activities. Aethiopinone is an in vitro inhibitor of 5-LO from human neutrophils (IC50 = 0.11 microM). In addition, aethiopinone reduced leukocyte accumulation and showed in vivo inhibitory activity on this enzyme.. Our results indicate that inhibition of 5-LO could participate in the anti-inflammatory properties of this natural product.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Ear; Edema; Humans; Inflammation; Isoenzymes; Leukotriene B4; Lipoxygenase Inhibitors; Macrophages, Peritoneal; Membrane Proteins; Mice; Naphthoquinones; Neutrophils; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phospholipases A; Prostaglandin-Endoperoxide Synthases

The effect of shikonin (SK) on granulation tissue formation was biochemically evaluated and the biological effect of SK on cotton pellet induced granulation tissue formation and the induction of hind paw edema was compared with that of lambda-carrageenan (carrageenan) in rats. The dry weight of granulation tissue formed was increased by SK. The amounts of hemoglobin and hydroxyproline in granulation tissue were also increased by SK. These results suggest that SK has an enhancing effect on the formation of granulation tissue, accompanied by the proliferation of capillaries and the increased production of collagen in rats. SK showed mild stimulation toward swelling when injected into the hind paws of rats, as did carrageenan, while it showed a marked enhancing effect on granulation tissue formation compared with carrageenan. These results suggest that the mechanism underlying the biological effect of SK on granulation tissue formation is different from that of carrageenan, though the mild stimulation by SK might still contribute in part to the enhancing effect on granulation tissue formation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Edema; Excipients; Granulation Tissue; Hindlimb; Male; Naphthoquinones; Rats; Rats, Wistar

2-Chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D1) produced a dose-dependent inhibition of the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. A comparable inhibitory profile was observed in mice to which PP1D1 was injected i.p. or applied orally. Unlike dexamethasone, PP1D1 had no effect on the liver glycogen content in fasting adrenalectomized mice. Ear edema caused by passive cutaneous anaphylactic reaction, or by subcutaneous injection of compound 48/80, histamine, serotonin, bradykinin or substance P was reduced by PP1D1 in a dose-dependent manner. In addition, topical application of PP1D1 suppressed the capsaicin- and arachidonic acid-induced ear edema. In compound 48/80-pretreated mice, the tissue histamine content was greatly reduced. Under these conditions, PP1D1 reduced the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine plus methysergide. These results suggest that the inhibitory effect of PP1D1 on the edematous response is due to the protection of the microvasculature from mediator challenge.

Topics: Animals; Anti-Inflammatory Agents; Bradykinin; Capillary Permeability; Edema; Mice; Mice, Inbred ICR; Naphthoquinones; Passive Cutaneous Anaphylaxis; Serotonin; Substance P

In the present study, the potential involvement of lipid peroxidation and disruption of lysosomal integrity in the pathogenesis of different experimental models of inflammation was examined. The chosen models were carrageenan-induced paw oedema, carrageenan granuloma pouch (acute phase) and Freund's adjuvant-induced arthritis in rats. The pharmacological and biochemical effects of naftazone, a lysosomal membrane stabilizer and indomethacin, a standard anti-inflammatory agent were evaluated with regard to paw oedema volume, serum and exudate activities of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG), in addition to serum and liver lipid peroxide (LP) levels. Intraperitoneal administration of the test drugs, in rats subjected to inflammation, produced: (1) a significant inhibition of carrageenan-induced paw oedema, (2) a marked reduction of the paw oedema of the Freund's adjuvant arthritis animals, (3) a remarkable decrease of lysosomal leakage of NAG into the exudate of carrageenan granuloma pouch, (4) a slight, but significant, reduction of NAG activity in the serum of rats subjected to carrageenan inflammation, and (5) a reduction of the serum level of LP that was elevated in adjuvant-induced arthritic rats. The level of liver LP was altered by either drugs in an opposite manner; while naftazone lowered hepatic LP, indomethacin markedly elevated its level. The results of the present investigation revealed that lipid peroxidation and disruption of lysosomal integrity are implicated in the pathogenesis of inflammatory processes, and the protection against these deleterious effects imparted both drugs significant anti-inflammatory activity.

Topics: Acetylglucosaminidase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Carrageenan; Edema; Foot; Freund's Adjuvant; Granuloma; Indomethacin; Inflammation; Lipid Peroxidation; Lysosomes; Male; Naphthoquinones; Rats; Rats, Sprague-Dawley

Crude ethanolic extract of Lawsonia inermis L. (0.25-2.0 g/kg) produced significant and dose-dependent anti-inflammatory, analgesic, and antipyretic effects in rats. The extract also produced significant increases in pentobarbitone-induced sleeping time. Using a liquid-liquid extraction procedure, the extract was fractionated into chloroform, butanol, and water fractions, and these were tested for the above activities. The butanol and chloroform fractions showed more potent anti-inflammatory, analgesic, and antipyretic effects than the crude extracts, while the aqueous extract showed significantly less effect. As compared with the other extracts, the butanolic extract (500 mg/kg) was the most effective in the analgesic test. From the chloroform extract, a pure compound was isolated and identified, using chromatographic and spectroscopic techniques, as 2-hydroxy-1,4-naphthaquinone (lawsone). The isolated compound was found to possess significant anti-inflammatory, analgesic, and antipyretic activity. It potentiated significantly the pentobarbitone-induced sleeping time. The anti-inflammatory effect of lawsone (500 mg/kg) was not significantly different from that of the reference drug phenylbutazone (100 mg/kg).

Topics: 1-Butanol; Administration, Oral; Analgesics, Non-Narcotic; Analysis of Variance; Animals; Anti-Inflammatory Agents; Antifungal Agents; Body Temperature; Butanols; Chemical Fractionation; Chloroform; Chromatography, Thin Layer; Dose-Response Relationship, Drug; Edema; Ethanol; Male; Naphthoquinones; Pain; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Sleep

Shikonin is one of the active components isolated from the dry root of Arnebia euchroma (Royle) Johnst (AERJ). It has been shown to have anti inflammatory activity on formaldehyde induced paw swelling in rats. Preparations of AERJ has been used clinically in curing phlebitis and vascular purpura. In the present study, sc administered shikonin was shown to have significant inhibitory effects on ear edema induced by croton oil in mice and paw swelling induced by yeast in rats. In order to investigate the influence of shikonin on biosynthesis of LTB4 and 5-HETE, an in vitro leukocyte incubation system was adopted. The results showed that shikonin has fairly strong inhibitory effects on LTB4 and 5-HETE biosynthesis. Its effects and concentrations fit a positive relationship within the range of 10(-7)-10(-4) mol.L-1. The equations of inhibition (Y) versus concentration (X, LogC) obtained by linear regression were Y = 166 + 18.7X (r = 0.9319) for LTB4 and Y = 173 + 18.7X (r = 0.9856) for 5-HETE. The IC50 were 6.2 x 10(-7) and 2.6 x 10(-7) mol.L-1, respectively. The results also indicate that natural shikonin derivatives have similar inhibitory effects on LTB4 biosynthesis. These results suggest that inhibition of LTB4 and 5-HETE may play a major role in the mechanism of anti inflammatory effects of shikonin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Croton Oil; Edema; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Male; Mice; Naphthoquinones; Rats; Rats, Wistar

Topics: Abscess; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Edema; Female; Foot; Male; Naphthoquinones; Phenylbutazone; Rats; Rats, Inbred Strains

Black walnut toxicosis was diagnosed in 10 horses at one stable. The time from exposure to shavings to development of clinical signs was 8 to 12 hours. Most common clinical signs were moderate to severe laminitis (Obel grade 2 or 3), pitting edema of the distal portion of the limbs, and rapid respiratory rate. Two horses had clinical signs of colic and 2 other horses had anorexia and lethargy. All 10 horses recovered without complications.

Topics: Animals; Anorexia; Colic; Edema; Horse Diseases; Horses; Lameness, Animal; Male; Naphthoquinones; Pigments, Biological; Plant Poisoning; Respiratory Insufficiency; Wood

SQ 26,490, (11 beta, 16 beta)-9-fluoro-1',2',3',4'-tetrahydro-11, 21-dihydroxypregna-1,4-dieno[16,17-b]naphthalene 3,20-dione hydrate (1 : 1), was a moderately potent inhibitor of edema formation in the rat. After extended topical application, SQ 26,490 totally inhibited edema formation without appreciable production of skin atrophy, measured under identical conditions. This atrophy was maintained at a low plateau level of 15-20% at doses beyond those necessary to achieve optimal anti-inflammatory activity. In contrast, the potent corticoids, fluocinolone acetonide and halcinonide, and the moderately potent corticoid, clobetasone butyrate, produced inhibition of edema with a concomitant dose-related atrophy. Hydrocortisone, a weakly potent corticoid, totally inhibited edema and produced at high doses a low atrophy. SQ 26,490 possesses the property for a greater separation of anti-inflammatory and atrophogenic activities than comparative corticoids.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Atrophy; Chemical Phenomena; Chemistry; Edema; Glucocorticoids; Male; Naphthoquinones; Rats; Rats, Inbred Strains; Skin Diseases

Topics: Animals; Edema; Female; Guinea Pigs; Histamine; Hyperemia; Injections, Intradermal; Male; Naphthoquinones; Skin