1-1-diphenyl-2-picrylhydrazyl and Pain

Topics: Analgesics; Animals; Antioxidants; Biphenyl Compounds; Isoxazoles; Mice; Molecular Docking Simulation; Pain; Picrates; Pyrazolones

Ethnopharmacological knowledge is important for the identification of active compounds from natural products. Pain may have different aetiologies with complex mechanisms. Tabernaemontana catharinensis A. DC. is well known for indole alkaloids, being used empirically in folk medicine, with antimicrobial and anti-inflammatory as well as antiofidic actions among others.. This work aims to evaluate the antinociceptive and antioxidant effect in mice of the alkaloids extract from leaves of Tabernaemontana catharinensis A. DC. (AITc).. The AITc was produced by ultrasound and acid-base extraction, and the chemical composition was evaluated by high resolution mass spectrometry. Male mice (Mus musculus), Swiss, were used for in vivo tests. The AITc was administrated at doses of 1.0, 5.0, and 10.0 mg/kg in acetic acid model, formalin, tail-immersion, hot plate, and open field tests, and compared to saline, morphine, or diazepam controls, depending on the test. The toxicological, biochemical, haemogram and antioxidant effect were evaluated in mouse organs such as liver, brain, kidneys, spleen and stomach.. In total, 10 compounds were identified in the AITc, being from the indole alkaloids from the ibogan and corynanthean classes. The extract in doses ranging from 5.0 to 10.0 mg/kg showed an antinociceptive effect for acetic acid, inhibiting by 47.7% and 61.6%. In the same line, reductions of 47.1% (first phase) and 43.6% (second phase) were observed for the 5.0 mg/kg dose in the formalin test. However, tail-immersion and hot plate tests did not show considerable modifications in the latency period, while in the open field test there was an inhibition of only 5.1%. It was observed no differences in NO levels and total antioxidant status of the mice in any of the studie tissues.. The results justify the use of this plant in traditional medicine. in vivo tests indicate that these compounds possess central and peripheral mechanisms of action. This is study that reports the nociceptive action of these alkaloids, also including toxicity tests, which are intended to guarantee the safety of use of extracts of this plant.

Topics: Acetic Acid; Alkaloids; Analgesics; Animals; Antioxidants; Biphenyl Compounds; Male; Mice; Pain; Picrates; Plant Extracts; Plant Leaves; Tabernaemontana; Toxicity Tests, Acute; Toxicity Tests, Subchronic

Ketoprofen belongs to one of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) but its clinical usefulness has been restricted due to the high incidence of gastrointestinal complications. The release of reactive oxygen species (ROS) in NSAIDs therapy plays a major role in causing gastric complications. Antioxidants not only prevent gastric ulceration and lipid peroxidation but also preserve glutathione-type peroxidase (GPO) activity. Therefore, the present study investigates the utility of combining anti-inflammatory and antioxidant properties of two different compounds in a single molecule to form a series of 16 ketoprofen-antioxidant mutual codrugs. The free carboxylic group, which is believed to be one of the reasons for gastric toxicity of ketoprofen, was masked temporarily by simple and double esterification with alcoholic/phenolic-OH of natural antioxidants. In simple esterification, ketoprofen is directly linked to natural antioxidants (IIa-h) in the hope to obtain drugs free of gastric side effects. In an attempt to improve the in vivo lability, as well as gastric side effects, the double ester codrugs, that is, ketoprofen-antioxidant through the glycolic acid spacer (-CH

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antioxidants; Biphenyl Compounds; Humans; Hydrolysis; Inflammation; Ketoprofen; Kinetics; Molecular Structure; Pain; Picrates; Rats; Stomach Ulcer

The aim of the current study was to evaluate the antinociceptive activity of the selected Pakistani medicinal plants (Chenopodium botrys, Micromeria biflora and Teucrium stocksianum) in-vivo followed by their antioxidant potential against 1,1-diphenyl-2-picrylhidrazyl (DPPH) in-vitro. The results demonstrated profound antinociceptive effect of both the crude methanolic extract of Chenopodium botrys (CBM) and subsequent aqueous fraction (CBW) of C. botrys with 80.76% and 84% pain relief in acetic acid induced writhing test at 100 mg/kg i.p respectively. Similarly the crude methanolic extract of Micromeria biflora (MBM) and its subsequent aqueous fraction (MBW) with 66.46% 78.08% pain reversal in acetic acid induced writhing test respectively at 100mg/kg i.p. However, the crude methanolic extract and isolated water fraction of Teucrium stocksianum (TS) did not show any significant effect at test doses. Both the crude extracts and aqueous fractions of selected medicinal plants exhibited marked scavenging effects on DPPH and therefore strongly support the antinociceptive activity. Phytochemical analysis indicated the presence of various classes of natural products (alkaloids, terpenoids, flavonoids etc.) and thus the current finding can be attributed to the presence of these compounds. In short, our findings provide a strong scientific background to the folk uses C. botrys and M. biflora in the management of various painful conditions.

Topics: Acetic Acid; Analgesics; Animals; Antioxidants; Biphenyl Compounds; Chenopodium; Disease Models, Animal; Dose-Response Relationship, Drug; Lamiaceae; Methanol; Mice, Inbred BALB C; Pain; Pakistan; Phytochemicals; Phytotherapy; Picrates; Plant Extracts; Plants, Medicinal; Solvents; Teucrium; Water

The leaves of Vitis vinifera is used in traditional medicine for diarrhea, hepatitis and stomachaches. The objective of this study was to investigate the anti-oxidant, anti-inflammatory, analgesic and antipyretic properties of the hydroalcoholic leaf extract of Vitis vinifera (EVV) on experimental models to provide scientific basis for its use.. The EVV was chemically characterized by LC-MS/MS analyses. The in vitro antioxidant activities of the EVV extract were measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and Ferric reducing antioxidant power assay (FRAP). Analgesic activity using acetic acid induced writhing and formalin test in mice, anti-inflammatory activity using carrageenan induced paw oedema and acetic acid-induced vascular permeability in mice, and antipyretic activity using Brewer's yeast induced pyrexia in rats were evaluated at 100mg/kg, 200mg/kg, and 400mg/kg doses of the extract.. The extract (EVV) was found to contain resveratrol, quercetin, catechin, flavone, flavonols, anthocyanin, gallic acid and epicatechin. EVV produced significant dose-response anti-inflammatory activity against carrageenan-induced paw edema. EVV at dosages of 100, 200 and 400mg/kgbw significantly reduced carrageenan-induced paw edema by 34.48% (P<0.05), 36.20% (P<0.05), and 41.37% (P<0.05) at 5h after carrageenan injection, respectively. Also EVV extract reduces significantly acetic acid-induced vascular permeability in mice dose dependently. EVV (100, 200 and 400mg/kgbw) produced significant dose-response analgesic activity in the formalin test. However, the low percentage inhibition (50%) suggests that it is not a centrally acting analgesic. Extract at dosages of 100, 200 and 400mg/kg bw, p.o. significantly reduced acetic acid-induced writhing by 48.15% (p<0.05), 57.97% (p<0.05), and 68.09% (p<0.05), respectively. The extract also caused marked dose-dependent inhibition of formalin-induced pain in the second phase (p<0.05). Statistical significant reduction in rectal temperatures was observed in standard group at 21 and 23h, and in 200mg/kg and 400mg/kg doses of the extract at 23h (p<0.05) compared with the 19h.. The results obtained indicated potential analgesic, anti-inflammatory and antipyretic effects of them hydroalcoholic leaf extract of V. vinifera observed at doses tested which support the claim for the traditional use of the plant in the treatment of various inflammatory and pain diseases.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Antipyretics; Behavior, Animal; Biphenyl Compounds; Body Temperature Regulation; Capillary Permeability; Carrageenan; Chromatography, Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Ethanol; Ferricyanides; Fever; Formaldehyde; Mice; Molecular Structure; Pain; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Plants, Medicinal; Saccharomyces cerevisiae; Solvents; Tandem Mass Spectrometry; Vitis

Inflammation is a common risk factor in the pathogenesis of conditions such as infections, arthritis, type 2 diabetes mellitus, obesity and cancer. An ethnobotanical survey of medicinal plants used traditionally to treat inflammation and related disorders such as pain, arthritis and stomach aches in southern Africa led to the selection of 25 plant species used in this study.. The antioxidant activities of acetone extracts were determined by measuring the free radical scavenging activity and ferric reducing ability, respectively. The anti-inflammatory activities of the extracts were determined by measuring the inhibitory effect of the extracts on the activities of the pro-inflammatory enzyme, lipoxygenase and inducible nitric oxide synthase.. Extracts of Peltophorum africanum had good antioxidant activity with IC50 values of 4.67 ± 0.31 μg/mL and 7.71 ± 0.36 μg/mL compared to that of the positive control ascorbic acid (2.92 ± 0.14 μg/mL and 13.57 ± 0.44 μg/mL), using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods, respectively. The metabolism of linoleic acid to leukotriene derivatives by 15-lipoxygenase (15-LOX) was also inhibited by the crude acetone extracts of Peltophorum africanum (IC50 = 12.42 μg/mL), Zanthoxylum capense (IC50 = 14.92 μg/mL) compared to the positive control quercetin (IC50 = 8.75 μg/mL). There was a poor correlation between the flavonoid content and 15-LOX inhibition by the extracts (R(2) = 0.05), indicating that flavonoids are not involved in LOX inhibition. Extracts of Clausena anisata, at a concentration of 6.25 μg/mL inhibited nitric oxide production by RAW 264.7 macrophage cell lines in vitro by 96 %. The extracts of Zanthoxylum capense were the least cytotoxic (IC50 > 1000 μg/mL) when the extract toxicity was determined against Vero (African green Monkey) kidney cell lines.. Some plant species used traditionally to treat pain have reasonable anti-inflammatory activity and flavonoids are probably not involved in this process.

Topics: Africa, Southern; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonate 15-Lipoxygenase; Biphenyl Compounds; Chlorocebus aethiops; Clausena; Fabaceae; Lipoxygenase Inhibitors; Medicine, African Traditional; Mice; Nitric Oxide; Oxidation-Reduction; Pain; Phytotherapy; Picrates; Plant Extracts; Plants, Medicinal; Rutaceae; Vero Cells; Zanthoxylum

The anti-nociceptive and antioxidant activities of the Anadenantheracolubrina stem bark aqueous extract (AEAC) were investigated. AEAC (30 μg/mL) reduced 94.8% of 2,2-diphenyl-1-picrylhydrazyl radical and prevented 64% (200 μg/mL) of lipid peroxidation caused by 2,2'-azobis(2-methylpropionamidine) dihydrochloride-induced peroxyl radicals. AEAC treatment (200 and 400 mg/kg) significantly (p < 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test. Nociception caused by glutamate was significantly (p < 0.001) reduced by up to 79% at 400 mg/kg, while 56-60% of the nociceptive behaviour induced by capsaicin was significantly inhibited by AEAC (100-400 mg/kg). Mice treated with AEAC did not show changes in motor performance in the Rota-rod apparatus. It appears that AEAC is of pharmacological importance in treating pain due to its anti-nociceptive effects, which were shown to be mediated by central and peripheral mechanisms.

Topics: Amidines; Analgesics; Animals; Antioxidants; Biphenyl Compounds; Capsaicin; Colubrina; Fabaceae; Glutamic Acid; Lipid Peroxidation; Male; Mice; Pain; Pain Measurement; Phytotherapy; Picrates; Plant Bark; Plant Extracts; Plant Stems

In the present study, the pharmacological effects of 2,8-dihydroxy-1,6-dimethoxyxanthone from the bark of Haploclathra paniculata were investigated in mice using in vivo inflammation and nociception models. Acetic acid-induced writhing, paw licking induced by formalin, hot plate, and carrageenan-induced paw edema tests were used to investigate the anti-inflammatory and antinociceptive activities of the xanthone compound. Xanthone, at both doses, inhibited abdominal writhing and the formalin test. At a dose of 20 mg/kg, the time of reaction to the hot plate increased, and significant effects were observed after 30, 60 and 90 min of treatment. At doses of 10 and 20 mg/kg p.o., the 2,8-dihydroxy-1,6-dimethoxyxanthone significantly reduced paw edema at 3 h after the stimulus. The tests also showed no acute toxicity of the xanthone compound in mice. 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability was also studied and confirmed the antioxidant activity of the xanthone. To propose the mechanism of action of anti-inflammatory activity of the xanthone, a molecular docking was performed using the isoenzymes cyclooxygenase 1 and 2 and the results indicate that the molecule is capable of inhibiting both the enzymes. Therefore, it can be concluded that 2,8-dihydroxy-1,6-dimethoxyxanthone from H. paniculata demonstrates analgesic, anti-inflammatory, and antioxidant activities.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Carrageenan; Clusiaceae; Cyclooxygenase 2 Inhibitors; Edema; Hot Temperature; Inflammation; Male; Pain; Pain Measurement; Phytotherapy; Picrates; Plant Bark; Plant Extracts; Prostaglandin-Endoperoxide Synthases; Rats, Wistar; Xanthones

Litchi chinensis has been traditionally used in folk medicine to treat several ailments. In this study, we investigated the chemical composition, antioxidant and antinociceptive activity of L. chinensis leaves.. The antioxidant capacity of the extract, fraction and compounds was evaluated using the 1,1-diphenyl-picrylhydrazyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, and the liposome model with peroxyl radicals generated by 2,2'-azobis (2-amidinopropane) dihydrochloride radical. The pharmacological models of acute nociception used in mice were: writhing test with acetic acid (AA), hotplate (HP), glutamate (GLU), capsaicin (CP) and formalin (FM) tests.. The main compounds isolated were procyanidin A2 (PA2), procyanidin B2 (PB2) and (-)-epicatechin. The biochemical features of the crude extracts and their ethyl acetate fraction (EtOAcFR) presented high antioxidant activity, and the antioxidant activity of PA2 and PB2 was remarkably high, with DPPH and ABTS. The crude methanol extract (MeOHEXTR), EtOAcFR and PB2 were effective in reducing nociception in FM and HP models. MeOHEXTR and EtOAcFR treatments also reduced pain induced by GLU and AA. In the CP model, only EtOAcFR and PB2 were effective.. The results demonstrate the antinociceptive and antioxidant of MeOHEXTR, EtOAcFR and PB2.

Topics: Analgesics; Animals; Antioxidants; Benzothiazoles; Biphenyl Compounds; Lipid Peroxidation; Litchi; Magnetic Resonance Spectroscopy; Male; Mice; Pain; Pain Measurement; Pain Threshold; Picrates; Plant Extracts; Plant Leaves; Sulfonic Acids

Psidium cattleianum Sabine is extensively used in Brazilian traditional medicine to treat several diseases including painful disorders. Aim of the study to investigate the toxicity and the possible analgesic activities of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine (ELPCS), to support its use in folk medicine. To screen the major phytochemical constituents of this extract and evaluate their antioxidant activity.. ELPCS was assessed for its antioxidant activity using the DPPH model. Its analgesic activity was examined using mouse models of acetic acid-induced writhing and hot plate paw licking models. The major phytochemical constituents of the extract were screened; their toxicity on LLC-MK2 mammalian cells was evaluated.. ELPCS exhibited significant peripheral analgesic activity at doses of 60, 80, 100, 200 and 400mg/kg in mice, but it did not display central analgesic activity and not was toxic to LLC-MK2 cell (LD50>400 µg/mL). The extract exhibited free radical scavenging activity as evidenced by IC50 values (15.9 µg/mL) obtained by the DPPH method. Phytochemical screening detected flavonoids, saponins, cardiac glycosides, anthraquinones, and tannins.. The results of the experimental studies proved the analgesic activity of ELPCS and supported the traditional use of this plant.

Topics: Acetic Acid; Analgesics; Animals; Antioxidants; Biphenyl Compounds; Cell Line; Ethanol; Hot Temperature; Macaca mulatta; Male; Mice; Pain; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Psidium; Solvents; Water

Ammannia baccifera L. has been reported as folklore remedy for the treatment of inflammation and tumor in the state of Rajasthan, India.. The present study was designed to investigate the antioxidant, anti-inflammatory and anti-nociceptive effects of the methanol extract from the aerial parts of Ammannia baccifera under in vitro and in vivo models.. The in vitro antioxidant activity of the extract was measured using DPPH, superoxide, hydroxyl and nitric oxide radicals. The anti-inflammatory activity was evaluated using carrageenan induced paw edema. Analgesic activity of the methanol extract was estimated against acetic acid-induced writhing and hot plate methods.. The IC(50) value for free radical scavenging activity of this extract was significantly superior over the positive standards butylated hydroxyl anisole (BHA) and rutin. The extract exhibited significant anti-inflammatory and analgesic activities at the dose of 100 and 200mg/kg p.o. The analgesic effect of the higher dose of the extract (200mg/kg) was comparable with the standard drugs aspirin and morphine.. The present study scientifically validated the traditional use of this plant against inflammation.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Behavior, Animal; Biphenyl Compounds; Carrageenan; Edema; Hot Temperature; India; Inflammation; Inhibitory Concentration 50; Lythraceae; Male; Medicine, Traditional; Mice; Mice, Inbred Strains; Pain; Phytotherapy; Picrates; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Reactive Oxygen Species

Cyathula prostrata (Linn) Blume (Amaranthaceae) is an annual herb widely used traditionally in the treatment of various inflammatory and pain related health disorders in Nigeria. The aim of this study is to evaluate the anti-inflammatory, analgesic and antioxidant activities of the methanolic extract of Cyathula prostrata (Linn) Blume.. The anti-inflammatory (phorbol 12-myristate 13-acetate (PMA)-induced reactive oxygen species (ROS), lipopolysaccharide (LPS) induced nitric oxide production in U937 macrophages, LPS-induced COX-2 expression, carrageenan-induced rat paw oedema, arachidonic acid-induced ear oedema and xylene-induced ear oedema), analgesic (acetic acid-induced writhing and hot plate tests) and antioxidant activities (DPPH [1,1-diphenyl-2-picrylhydrazyl] and lipid peroxidation assays) activities of the plant extract were investigated.. The methanolic extract of Cyathula prostrata did not show inhibitory activity in the in vitro PMA-induced reactive oxygen species, LPS-induced nitric oxide production and LPS-induced COX-2 expression assays. In the in vivo anti-inflammatory assays, the extract (50, 100 and 200mg/kg) showed a significant (P<0.05) dose-dependent inhibition in the carrageenan, arachidonic acid and xylene-induced tests. Cyathula prostrata produced a significant (P<0.05, 0.001) dose-dependent inhibition in the acetic acid and hot plate analgesic tests respectively. The plant extract did not exhibit any antioxidant activity in the DPPH and lipid peroxidation assays.. The results suggest that the methanolic extract of Cyathula prostrata possesses anti-inflammatory and analgesic activities and this authenticates the use of the plant in the traditional treatment of ailments associated with inflammation and pain.

Topics: Acetic Acid; Amaranthaceae; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Behavior, Animal; Biphenyl Compounds; Carrageenan; Cyclooxygenase 2; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hot Temperature; Humans; Inflammation; Inflammation Mediators; Lipid Peroxidation; Lipopolysaccharides; Macrophages; Male; Methanol; Mice; Motor Activity; Nitric Oxide; Oxidative Stress; Pain; Pain Threshold; Phytotherapy; Picrates; Plant Preparations; Plants, Medicinal; Rats; Rats, Wistar; Reactive Oxygen Species; Solvents; Tetradecanoylphorbol Acetate; U937 Cells; Xylenes

Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) is a common epiphytic lichen in the conifer-hardwood forest of Anatolia. This species is used in traditional medicine in Turkey as a treatment for wounds, eczema and hemorrhoids.. The present study was designed to investigate the active compounds from Pseudevernia. furfuracea, and the isolation studies yielded atraric acid (Aslan et al., 2006) as the major compound and a mixture of methyl hematommate (Baumann, 1960) and methyl chlorohematommate (Bayır et al., 2006). Furthermore, methanolic extract from thalli of Pseudevernia. furfuracea and its fractions and isolates (Aslan et al., 2006; Baumann, 1960; Bayır et al., 2006) were investigated for in vitro antimicrobial and antioxidant activities, and in vivo antinociceptive, anti-inflammatory and wound healing activities.. Antimicrobial activities of the samples were determined by using the disc diffusion technique. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used as a rapid TLC screening method to evaluate the antioxidant activity of Pseudevernia. furfuracea. The thiobarbituric acid (TBA) test was used to assess the efficacy of the extracts in protecting liposomes from lipid peroxidation. In vivo inhibitory effect of the extracts on the carrageenan-induced hind paw edema model in mice was studied for the assessment of anti-inflammatory activity. p-Benzoquinone-induced abdominal constriction test was used to explore the antinociceptive effects of the extracts. Moreover, the wound healing potential of the plant extracts that were evaluated by using in vivo incision and excision wound models on rats and mice, were comparatively assessed with a reference ointment Madecassol(®).. Significant antimicrobial activities were observed against Gram (+) microorganisms and Candida krusei and Candida. dubliniensis in dichloromethane (DCM) and ethyl acetate (EtOAc) extracts and isolates. The methanol (MeOH), DCM and EtOAc extracts of the lichen were found to possess moderate inhibitory activity on lipid peroxidation. Methanolic extract of the lichen was found to possess significant inhibitory activity on the carrageenan-induced hind paw edema model in mice whereas the other fractions did not show any activity. While DCM and EtOAc extracts and fractions showed notable anti-inflammatory activity on carrageenan-induced hind paw edema model without inducing any apparent acute toxicity or gastric damage. Moreover, topical application of the ointment prepared with MeOH extract and EtOAc fraction onto the incised wounds exerted remarkable wound healing activity.. The results of these experimental studies exhibited that nonpolar fractions of Pseudevernia. furfuracea have significant antimicrobial activity against especially Candida species and polar fractions (especially MeOH) display antioxidant, anti-inflammatory, antinociceptive and wound healing activities.

Topics: Analgesics; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antioxidants; Ascomycota; Bacteria; Behavior, Animal; Benzoquinones; Biphenyl Compounds; Candida; Carrageenan; Complex Mixtures; Edema; Lichens; Male; Mice; Microbial Sensitivity Tests; Pain; Picrates; Rats; Rats, Sprague-Dawley; Skin; Thiobarbituric Acid Reactive Substances; Wound Healing

Rosa davurica Pall. has been traditionally used to treat inflammatory diseases and tumors. Its dried leaves were extracted with absolute methanol, and the methanol extract was successively fractionated into n-hexane, chloroform, ethyl acetate, n-butanol, and aqueous fractions. Anti-angiogenic and anti-nociceptive activities were determined using the chick embryo chorioallantoic membrane (CAM) assay and acetic acid-induced writhing response, respectively. Anti-inflammatory activity was evaluated using two in vivo mouse models, acetic acid-induced vascular permeability and carrageenan-induced inflammation in the air-pouch. The methanol extract gave rise to significant inhibition in the CAM angiogenesis, and showed marked 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Among the fractions prepared from the methanol extract, the chloroform fraction exhibited highest inhibitory effect in the CAM angiogenesis. The chloroform fraction displayed anti-inflammatory activities in vascular permeability and air-pouch models. In the air-pouch model, it was able to diminish exudate volume, number of polymorphonulcear leukocytes, and nitrite content. It also showed anti-nociceptive activity in the writhing response model in mice. The leaves of R. davurica possess anti-angiogenic and related anti-inflammatory and anti-nociceptive activities, which would provide some therapeutic support on its traditional use.

Topics: Analgesics; Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Capillary Permeability; Chick Embryo; Chloroform; Chorioallantoic Membrane; Dose-Response Relationship, Drug; Free Radical Scavengers; Free Radicals; Male; Methanol; Mice; Mice, Inbred ICR; Pain; Picrates; Plant Extracts; Plant Leaves; Rosa

Minocycline (Mino) and doxycycline (Dox) are second generation tetracyclines known to present several other effects, which are independent from their antimicrobial activities. We studied in a comparative way the anti-inflammatory effects of Mino and Dox, on acute models of peripheral inflammation in rodents (formalin test and peritonitis in mice, and carrageenan-induced paw oedema in rats). Immunohistochemical assays for TNF-alpha and iNOS in rat paws of carrageenan-induced oedema were also carried out as well as in vitro assays for myeloperoxidase (MPO) and lactate dehydrogenase (LDH). Furthermore, antioxidant activities were evaluated by the DPPH assay.. In the formalin test although Mino and Dox (1, 5, 10 and 25 mg/kg, i.p.) inhibited the first phase, they acted predominantly on the second phase of the test, where inhibition of the licking time close to 80% were observed. Mino and Dox were very efficacious in reducing the carrageenan-induced paw oedema in rats (10, 25 and 50 mg/kg, i.p.) and carrageenan-induced leucocyte migration (1 and 5 mg/kg, i.p.) to mice peritoneal cavities. Besides, they also significantly inhibited MPO and LDH releases at doses ranging from 0.001 to 1 μg/ml. Thus, in general, the anti-inflammatory activity of Dox was higher as compared to that of Mino, although the radical scavenging activity of Mino was of a magnitude 10 times higher.. Our data indicate that anti-inflammatory and antioxidant effects, involve the inhibition of iNOS and TNF-alpha, among other properties, and these encourage clinical studies of these compounds for new therapeutic applications, especially those were inflammation plays a role.

Topics: alpha-Tocopherol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biphenyl Compounds; Carrageenan; Cell Movement; Doxycycline; Edema; Formaldehyde; Inflammation; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred Strains; Minocycline; Neutrophils; Nitric Oxide Synthase Type II; Oxidation-Reduction; Pain; Pain Measurement; Peritonitis; Peroxidase; Picrates; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Areca catechu, commonly known as betel nut, is very famous for its medicinal use in multiple disorders. It is also popular as a remedy against inflammatory disorders in the Unani (Greco-Arab) system of medicine.. This study was aimed at investigating the anti-inflammatory and analgesic activities of the crude extract of Areca catechu and its respective fractions.. Paw edema, formalin-induced nociception and acetic acid-induced writhing assays were carried out in vivo. Free radical scavenging activity of the plant extract was performed in vitro.. Preliminary experiments using a single dose (100 mg/kg) of Areca catechu and its respective fractions demonstrated an anti-inflammatory effect on carrageenan-induced edema in mice and rats, the aqueous fraction being distinctly more effective. When studied on prostaglandin E₂ (PGE₂), arachidonic acid, histamine, or serotonin (5HT)-induced edema in rats, Areca catechu and its aqueous fraction markedly repressed only the PGE₂ and arachidonic acid-induced inflammation. When studied for analgesic activity, the crude extract and its aqueous fraction produced a dose-dependent (10-100 mg/kg) inhibitory effect on formalin-induced nociception in mice and acetic acid-induced writhing in rats, similar to aspirin. In DPPH assay, Areca catechu and its aqueous fraction exhibited free radical scavenging activity with respective IC(50) values of 5.34 μg/ml (4.93-5.78, CI; 95%, n=5) and 7.28 μg/ml (6.04-7.95, n=4), like that of rutin with IC(50) value of 4.75 μg/ml (3.89-5.42, n=4).. These results indicate the anti-inflammatory and analgesic effects of Areca catechu and provide a rationale for its medicinal use in inflammatory disorders.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Areca; Aspirin; Behavior, Animal; Biphenyl Compounds; Carrageenan; Dose-Response Relationship, Drug; Edema; Mice; Mice, Inbred BALB C; Nuts; Pain; Phytotherapy; Picrates; Plant Extracts; Rats; Rats, Sprague-Dawley; Rutin

Since the leaves of olive have been recommended in the literature as a remedy for the treatment of diabetes and they also contain antioxidant agents, we decided to investigate the possible effects of olive leaf extract (OLE) on in vitro and in vivo models of diabetic pain neuropathy.. The high glucose-induced cell damage in naive and NGF-treated Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick test was used to access nociceptive threshold. Cell viability was determined by MTT assay. Biochemical markers of neural apoptosis were evaluated using immunoblotting.. We found that elevation of glucose (4 times of normal) sequentially increases functional cell damage and caspase-3 activation in NGF-treated PC12 cells. Incubation of cells with OLE (200, 400 and 600 μg/ml) decreased cell damage. Furthermore, the diabetic rats developed neuropathic pain which was evident from decreased tail-flick latency (thermal hyperalgesia). Activated caspase 3 and Bax/Bcl2 ratio were significantly increased in spinal cord of diabetic animals. OLE treatment (300 and 500 mg/kg per day) ameliorated hyperalgesia, inhibited caspase 3 activation and decreased Bax/Bcl2 ratio. Furthermore, OLE exhibited potent DPPH free radical scavenging capacity.. The results suggest that olive leaf extract inhibits high glucose-induced neural damage and suppresses diabetes-induced thermal hyperalgesia. The mechanisms of these effects may be due, at least in part, to reduce neuronal apoptosis and suggest therapeutic potential of olive leaf extract in attenuation of diabetic neuropathic pain.

Topics: Analgesics; Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Biphenyl Compounds; Blood Glucose; Caspase 3; Cell Line; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Free Radical Scavengers; Hyperalgesia; Male; Olea; Pain; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Spinal Cord

Aristotelia chilensis leaves (Elaeocarpaceae) are used in Chilean folk medicine to treat pain and inflammation. A bioguided study was carried out on serial extracts (hexane, dichloromethane, methanol, aqueous extract (INFU) and a crude mixture of alkaloids (ALK-MIX). All extracts were evaluated for (1) topical administration against both arachidonic acid and 12-deoxyphorbol-13-decanoate (TPA)-induced inflammation in mice and (2) per-os administration against inflammation by λ-carrageenan-induced paw oedema in guinea-pigs and (3) topical analgesia in tail flick and formalin models and per-os writhing test in mice.. Greater anti-inflammatory effects were obtained against TPA with dichloromethane extract and methanol extract (63.9 and 66.0%, respectively). INFU showed the most potent effect (56.2%) against arachidonic acid. Greater effects were obtained in the writhing test with hexane and dichloromethane extracts (89.2% both). In the topical analgesia models, all the extracts and ALK-MIX were active with exception of the hexane extract in the formalin assay. In tail flick test, ALK-MIX and the methanol extract were the most active (58.2 and 55.2%, respectively). In relation to the tail formalin assay, the methanol extract (74.1%) was the most active. Concerning antioxidant activity, both INFU and the methanol extract were the most active either in the inhibition of xanthine oxidase (52.9 and 62.7%, respectively) or in the DPPH free radical scavenging activity (EC50 (concentration that produced 50% of activity) = 12.1 and 9.7 µg/ml, respectively).. Aristoteline, aristone, serratoline and hobartinol were isolated from ALK-MIX. Ursolic acid, friedelin and quercetin 5,3'-dimethyl ether were present in the dichloromethane extract while quercetin 3-O-β-D-glucoside and kaempferol were present in the methanol extract. From INFU were isolated protopine, aristoteline and caffeic and ferulic acids.. The effects of A. chilensis are herein demonstrated, validating its use in traditional medicine. Protopine is reported for the first time in Elaeocarpaceae.

Topics: Administration, Topical; Alkaloids; Analgesia; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Behavior, Animal; Biphenyl Compounds; Carrageenan; Chile; Edema; Elaeocarpaceae; Female; Formaldehyde; Guinea Pigs; Inflammation; Male; Medicine, Traditional; Mice; Mice, Inbred Strains; Pain; Phorbol Esters; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Xanthine Oxidase

[corrected] The Taxillus liquidambaricola has been used to treat rheumatic arthralgia, threatened abortion and hypertension in the Chinese traditional medicine. However, there is no scientific evidence which supports the use in the literature. This study aimed to determine the antioxidant, and analgesic activities and the mechanism of anti-inflammatory activities of the ethanolic extracts of Taxillus liquidambaricola (ETL) in cell and animal models.. The following activities were investigated: free radical scavenging and antioxidant activities [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and DPPH (1, 1-diphenyl-2-picrylhydrazyl)], analgesic (writhing and formalin test), and anti-inflammatory [lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 macrophages and paw-edema induced by λ-carrageenan (Carr)]. We also investigate the anti-inflammatory mechanism of ETL via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the edema paw. Serum NO and tumor necrosis factor α (TNF-α) were also measured in vivo.. ETL showed the highest TEAC and DPPH radical scavenging activities, respectively. ETL also had highest contents of polyphenol and flavonoid contents. We evaluated that ETL and the reference compound of quercetin decreased the LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. Treatment of male ICR mice with ETL significantly inhibited the numbers of acetic acid-induced writhing response and the formalin-induced pain in the late phase. Administration of ETL showed a concentration dependent inhibition on paw edema development after Carr treatment in mice. The anti-inflammatory effects of ETL could be via NO and TNF-α suppression and associated with the increase in the activities of antioxidant enzymes. Western blotting revealed that ETL decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions.. Anti-inflammatory mechanisms of ETL might be correlated to the decrease in the level of MDA, iNOS, and COX-2 via increasing the activities of CAT, SOD, and GPx in the edema paw. Overall, the results showed that ETL demonstrated antioxidant, antinociceptive, and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Benzothiazoles; Biphenyl Compounds; Carrageenan; Catalase; Cell Line; Chromatography, High Pressure Liquid; Cyclooxygenase 2; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Edema; Endotoxins; Ethanol; Formaldehyde; Glutathione Peroxidase; Loranthaceae; Macrophages; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Nitric Oxide; Nitric Oxide Synthase Type II; Pain; Picrates; Plants, Medicinal; Solvents; Sulfonic Acids; Superoxide Dismutase; Thiazoles; Time Factors; Tumor Necrosis Factor-alpha

The present study investigated the antinociceptive, anti-inflammatory and antioxidant effects of the leaf essential oil (LEO) of Cymbopogon winterianus Jowitt (Poaceae). In the acetic acid-induced writhing and formalin tests, the LEO (50, 100, and 200 mg/kg, p.o.) significantly reduced (p < 0.05) the number of writhings and paw licking times in the first (0-5 min) and second (15-30 min) phases, respectively. In contrast, the LEO did not alter the latency time for mice licking the rear paws in hot-plate test. The LEO inhibited the carrageenan-induced neutrophil migration to the peritoneal cavity in a dose-dependent manner (35.5%, 42.8%, and 66.1% at doses of 50, 100, and 200 mg/kg, respectively, p < 0.001). Moreover, LEO exhibited higher scavenging activity toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals with an IC(50) (12.66 ± 0.56 μg/mL). Our present results demonstrated that the LEO has antinociceptive, anti-inflammatory, and antioxidant properties.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Carrageenan; Cymbopogon; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Hot Temperature; Male; Mice; Oils, Volatile; Pain; Pain Measurement; Phytotherapy; Picrates; Plant Leaves; Plant Oils; Rats; Rats, Wistar

We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Arachidonic Acids; Biphenyl Compounds; Brain; Cannabinoid Receptor Modulators; Carrageenan; Cell Proliferation; Edema; Endocannabinoids; Female; Formaldehyde; Free Radical Scavengers; Hydrazines; Hydrazones; Ligands; Male; Mice; Models, Molecular; Pain; Picrates; Polyunsaturated Alkamides; Pyridines; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Structure-Activity Relationship; Superoxides; T-Lymphocytes

Lindera angustifolia Chen is a folk medicine used for the treatment of contusions-induced swelling, rheumatic pains and bellyache in south and the middle part of China. Phytochemical studies showed that aporphine and benzyltetrahydroisoquinoline alkaloids are the characteristic constituents of this plant. In this study, we evaluated the antinociceptive and free radical scavenging properties of six aporphine and two benzyltetrahydroisoquinoline alkaloids isolated from the root of Lindera angustifolia. All alkaloids except magnocurarine exhibited remarkable radical scavenging effects (36-90% scavenging at 25-100microg/ml) in DPPH radical scavenging test, among them norisocorydine showed the hightest activity (SC(50): 14.1microg/ml). Antinociceptive activities were tested by using acetic acid-induced writhing and formalin test at dose of 20mg/kg. Norisocorydine exhibited the highest antinociceptive ability with 83.5% writhing inhibition. Boldine, norboldine showed significant antinociceptive activity with 76.3% and 74.6% writhing inhibition respectively. Indomethacin was used as positive control, which showed 67.8% writhing inhibition at dose of 10mg/kg. Most of the compounds, except N-ethoxycarbonyllaurotetanine and magnocurarine, could significantly inhibit the phase I reaction (P<0.01), and all of them inhibited the phase II reaction (P<0.001) in the formalin tests (indomethacin and morphine were used as positive drugs). The antinociceptive effects exhibited a structure-activity relationship similar to that of the free radical scavenging activities. Above results suggested that the alkaloids from the root of Lindera angustifolia possess both free radical scavenging and antinociceptive activities, and the antinociceptive activity seems to be related to the free radical scavenging effect.

Topics: Acetic Acid; Alkaloids; Analgesics; Animals; Biphenyl Compounds; Dose-Response Relationship, Drug; Formaldehyde; Free Radical Scavengers; Lindera; Mice; Pain; Pain Measurement; Phytotherapy; Picrates; Plant Extracts; Plant Roots