Effect of Brazilian propolis on scratching behavior induced by compound 48/80 and histamine in mice

We studied the effect of Brazilian propolis on scratching behavior induced by compound 48/80 and histamine in ICR mice. Propolis granular A.P.C dose-related inhibited scratching behavior induced by compound 48/80 and significant inhibition were observed at 1000 mg/kg. However, histamine-induced scratching behavior was not inhibited by propolis granular A.P.C even at 1000 mg/kg. Propolis ethanol extract at 10 microg/ml or more inhibited histamine release from rat mast cells induced by compound 48/80. In addition, it blocked increased vascular permeability induced by compound 48/80. The inhibitory effect of propolis on scratching behavior induced by compound 48/80 was gradually enhanced by repeated administration, and 500 mg/kg propolis granular A.P.C, which caused no effect through single administration, significantly inhibited scratching behavior after repeated administration for 4 weeks. From these findings, it is assumed that the inhibition of scratching behavior induced by propolis occurs through a mast cell-dependent mechanism.     

Evaluation of anti-inflammatory activity of chloroform extract of Bryonia laciniosa in experimental animal models

The anti-inflammatory effect of the leaves of Bryonia laciniosa was evaluated using carrageenan, dextran, histamine, serotonin induced rat paw oedema and cotton pellet induced granuloma (chronic) models in rats. In mice, carrageenan peritonitis test was performed for the extract by oral administration. The chloroform extract of Bryonia laciniosa (CEBL) exhibited significant anti-inflammatory effect at the dose 50, 100 and 200 mg/kg. Maximum inhibition (52.4%) was noted at the dose of 200 mg/kg after 3 h of drug treatment in carrageenan induced paw oedema, whereas the indomethacin (standard drug) produced 62.1% of inhibition. The extract exhibited significant anti-inflammatory activity in dextran induced paw oedema in a dose dependent manner. The extract also exhibited significant inhibition on the hind paw oedema in rats caused by histamine and serotonin respectively. In the chronic model (cotton pellet induced granuloma) the CEBL (200 mg/kg) and standard drug showed decreased formation of granuloma tissue by 50.1 and 57.3% (p<0.001) respectively. The extract also inhibited peritoneal leukocyte migration in mice. Thus, the present study revealed that the chloroform extract of Bryonia laciniosa exhibited significant anti-inflammatory activity in the tested models.     

Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle

Propolis is a bee product, which has long been used in folk medicine for the management of different diseases. In this study we evaluated the analgesic and anti-inflammatory effects of a standard ethanolic extract of Bulgarian propolis (Et-Blg) in mice and its in vitro effect on airway smooth muscle. Et-Blg inhibited acetic acid-induced abdominal contortions with an ID(50) = 7.4 +/- 0.7 mg. kg(-1). In the formalin test, the extract caused a significant reduction in pain in mice treated with 100 mg. kg(-1) Et-Blg during the neurogenic phase and for the inflammatory phase with all doses of the extract, with an ID(50) = 2.5 +/- 0.4 mg. kg(-1). Et-Blg inhibited also the capsaicin-induced ear edema in mice; however, this extract was ineffective when assessed in the tail-flick and hot-plate thermal assays. The analgesic effect of Et-Blg was associated with the inhibition of inflammatory responses and not to a simple irritation of nervous terminals. In vitro, this extract inhibited the contraction of trachea smooth muscle induced by histamine (IC(50) = 50 +/- 5 microg. mL(-1)), capsaicin (IC(50) = 26.8 +/- 3 microg. mL(-1)), 80 mM KCl (IC(50) = 27.8 +/- 3 microg. mL(-1)), and carbachol (IC(50) = 54 +/- 2 microg. mL(-1)).     

Evaluation of the anti-inflammatory property of the extract of <Emphasis Type="Italic">Combretum micranthum</Emphasis> G. Don (Combretaceae)

A methanol extract of Combretum micranthum leaves was studied for anti-inflammatory activity in rats and mice using the carrageenan-induced rat paw oedema and the acetic acid-induced vascular permeability in mice. The effect of the extract on cellular-type inflammation was also investigated in the cotton pellet granuloma in rats. The extract (50, 100 mg/kg) significantly (P < 0.05) inhibited oedema production induced by carrageenan in rats. Increased vascular permeability caused by acetic acid injection was also inhibited by the extract, within the same dose range. C. micranthum extract (100 mg/kg) inhibited granuloma formation in rats to a similar degree as indomethacin (5 mg/kg). These results provide evidence for the anti-inflammatory property of C. micranthum leaves.     

Anti-inflammatory Properties of Amaranthus spinosus Leaf Extract

The methanol extract of Amaranthus spinosus L. leaves was evaluated for anti-inflammatory activities in different animal models. The effect of the plant extract was also studied on castor oil–induced diarrhea and gastric mucosal integrity. The extract (25–100 mg/kg) inhibited the carrageenan-induced rat paw edema and produced significant (p < 0.05) inhibition of acetic acid–induced increased vascular permeability. Inhibition of the cotton pellet granuloma was also inhibited by 100 mg/kg of the plant extract. Analgesic activity was exhibited with the significant and dose-related reduction in the number of writhings induced with acetic acid, as well reduction in paw licking induced by injection of formalin in mice. The extract (50 and 100 mg/kg) produced gastric erosion in rats, following repeated administration for 4 days, and with 25–100 mg/kg of the extract, there was a statistically significant (p < 0.05) reduction in castor oil–induced diarrhea in rats. These results demonstrate the anti-inflammatory properties of the leaf extract of A. spinosus. It is also suggested that the plant extract probably acts by the inhibition of prostaglandin biosynthesis.     

Study of anti-inflammatory and antinociceptive activity of hydroalcoholic extract of Schima wallichii bark

Hydroalcoholic extract of Schima wallichii Choisy. (Ternstroemiaceae) bark (HESW) was investigated for its anti-inflammatory, antinociceptive, and antipyretic activities. The anti-inflammatory effects of the HESW were assayed by using carrageenan and dextran (acute model) induced paw edema and cotton pellet granuloma assay (chronic model) in experimental rats. Oral administration of HESW at the doses of 150 and 300?mg/kg caused dose-dependent inhibition of carrageenan and dextran induced inflammation. HESW at the doses of 150 and 300?mg/kg caused significant dose-dependent reduction of the granuloma tissue formation in experimental rats. The extract at the oral doses of 50 and 100?mg/kg body weight exhibited significant central and peripheral analgesic activity in acetic acid induced writhing test and hot-plate test respectively in experimental mice. Treatment with HESW at the oral doses of 150 and 300?mg/kg body weight significantly reduced the yeast-provoked elevated body temperature in experimental rats in a dose-dependent manner.     

Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin

The effects of a supercritical CO2 (SFE) extract, a dichloromethane (DCM) extract from Isatis tinctoria leaf and the alkaloidal constituent tryptanthrin were studied in acute and subchronic experimental models of inflammation. The SFE and DCM extracts showed anti-inflammatory activity in the carrageenan-induced acute mouse paw oedema (ED50 values of 78 mg/kg and 165 mg/kg P. O., respectively) and in the acute tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema in oral (62% and 32% oedema reduction at 100 and 125 mg/kg, respectively) and topical application (37% and 33% reduction of oedema at 0.5 mg/ear). In contrast, tryptanthrin showed no significant anti-inflammatory effect. The DCM extract inhibited oedema formation and neutrophil infiltration in subchronic inflammation in mice induced by repeated application of TPA. The extract showed activity after oral and topical administration by reducing the various parameters of the inflammatory response. The DCM extract (1 mg/ear) inhibited the delayed-type hypersensitivity (DTH) reaction induced by application of dinitrofluorobenzene (DNFB) after topical application. The response during the induction phase (24 h) was decreased by 48%, and the inflammatory phase (48 to 96 h) was reduced by 53 to 56%. The extract had no effect in this model when administered orally. The DCM extract (200 mg/kg P. O.) inhibited the acetic acid-induced writhing by 49%.     

Effect of propolis extract on D-galactosamine-induced hepatic injury in rats

The preventive effect of propolis extract on D-galactosamine-induced hepatic injury was examined in rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased at 24 h after intraperitoneal injection of D-galactosamine (400 mg/kg) in the animals. Propolis extract was administered orally three times in doses of 3 or 30 mg/kg at 18 h and 1 h before and 8 h after D-galactosamine injection. The extract itself and the vehicle alone (dextran) caused no significant changes in serum AST or ALT activities. Treatment with the extract dose-dependently prevented the increases in serum AST and ALT activities induced by D-galactosamine, and significant inhibition was observed at a dose of 30 mg/kg. These results suggested that propolis extract may have an ameliorating effect on hepatic dysfunction.     

Multiple treatment of propolis extract ameliorates carbon tetrachloride induced liver injury in rats

Propolis, a resinous wax-like beehive product has been used as a traditional remedy for various diseases due to a variety of biological activities of this folk medicine. In the present investigation, an attempt has been made to validate hepatoprotective activity of ethanolic extract of propolis (50-400mg/kg, p.o.) against carbon tetrachloride (CCl(4,) 0.5 ml/kg, p.o.) induced acute liver injury in rats. Silymarin, a known hepatoprotective drug was used as a positive control. Administration of CCl(4) altered various diagnostically important biochemical variables. Multiple treatment of propolis significantly prevented the release of transaminases, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, urea and uric acid in serum; improved the activity of hepatic microsomal drug metabolizing enzymes, i.e., aniline hydroxylase and amidopyrine-N-demethylase; significantly inhibited lipid peroxidation and markedly enhanced glutathione in liver and kidney as well as brought altered carbohydrate contents (blood sugar and tissue glycogen), protein contents (serum, microsomal and tissue protein) and lipid contents (serum and tissue triglycerides, serum cholesterol, total and esterified cholesterol in tissue) towards control. Propolis treatment also reversed CCl(4) induced severe alterations in histoarchitecture of liver and kidney in a dose dependent manner. Hepatoprotective activity of propolis at doses of 200 and 400 mg/kg was statistically compared to silymarin and found that propolis exhibited better effectiveness than silymarin in certain parameters, concluded its hepatoprotective potential.     

Anti-ulcer activity and mode of action of the polysaccharide fraction from the leaves of Panax ginseng.

The effects of a weakly acidic polysaccharide fraction, GL-4, from the leaves of Panax ginseng C. A. Meyer on various experimental gastric ulcer models in mice and rats have been studied. Oral administration of GL-4 at doses of 50 to 200 mg/kg inhibited the formation of the gastric lesions induced by necrotizing agents such as HCl/ethanol and ethanol in a dose-dependent manner. This protective effect was observed not only upon oral but also upon subcutaneous administration of GL-4 (50-100 mg/kg). GL-4 also inhibited the formation of gastric ulcers which were induced by water immersion stress, indomethacin, or pylorus-ligation. The contents of prostaglandin E2 in the gastric juice from rats were not influenced by oral administration of GL-4. The protective action of GL-4 against HCl/ethanol-induced gastric lesions was not abolished by pretreatment with indomethacin. When GL-4 (100 mg/kg, p.o.) was administered into pylorus-ligated rats, both gastric acidity and pepsin activity in the gastric juice decreased significantly.     

Suppressive effects of propolis in rat adjuvant arthritis

The effects of ethanolic extract (EEP) of propolis on chronic inflammation were evaluated using rat adjuvant arthritis. In the chronic inflammatory animal model, the arthritis index was suppressed by EEP treatments (50 mg/kg/day and 100 mg/kg/day, p.o.). Moreover, physical weakness, induced by the chronic disease state, was dose-dependently improved in the EEP-treated groups. Its analgesic effect, assessed using the tail-flick test, was comparable to prednisolone (2.5 mg/kg/day, p.o.) and acetyl salicylic acid (100 mg/kg/day, p.o.). In carrageenan rat hind paw edema, which was conducted to test the effects of subfractions of EEP, the petroleum ether sub-fraction (100 mg/kg, p.o.) showed an inhibitory effect on the paw edema whereas EEP (200 mg/kg, p.o.) showed a significant anti-inflammatory effect at 3 and 4 hrs after carrageenan injection. From these results, we conclude that the ethanolic extract of propolis had a profound anti-inflammatory effects on both chronic and acute inflammations.     

Natural Products: Anti-hyperalgesic Effect of an Ethanolic Extract of Propolis in Mice and Rats

Propolis, or bee glue, which contains a complex mixture of secondary metabolites, has long been used in many countries for the management of several diseases. The purpose of this study was to evaluate, by means of several pharmacological models, the anti-hyperalgesic effect of propolis collected in the south of Brazil. The abdominal constrictions induced in mice by intraperitoneal injection of acetic acid (0.6%), kaolin (50 mg kg^?1) or zymosan (40 mg kg^?1) were inhibited to different extents by an extract of propolis (1–60 mg kg^?1) administered intraperitoneally 30 min earlier; mean ID50 (concentrations resulting in 50% inhibition) values were 2.7, 10.8 and 10.7 mg kg^?1, respectively, and maximum inhibition was 58 ± 5, 57 ± 10 and 51 ± 5%, respectively. Given orally (25–200 mg kg^?1, 1 h previously) propolis also inhibited the abdominal constrictions induced by acetic acid (maximum inhibition 43 ±5%). When injected intraperitoneally (3–60 mg kg^?1, 30 min previously), propolis attenuated both the neurogenic (first phase) and inflammatory (second phase) pain responses and paw oedema caused by intraplantar injection of formalin (2.5%); maximum inhibition was 32 ±5, 43 ±6 and 19 ±2%, respectively. Oral administration of propolis (25–200 mg kg^?1, 1 h previously) inhibited both phases and reduced the oedema formation associated with the second phase of the formalin test (maximum inhibition 22±5, 33 ±6 and 26±3%) and extract of propolis (3–30 mg kg^?1 i.p. or 25–100 mg kg^?1 p.o., respectively 30 min and 1 h previously) significantly inhibited capsaicin-induced pain with maximum inhibition of 39±8 and 41 ±8%, respectively. When assessed in the Randall–Sellito test of pain, the extract of propolis (3–30 mg kg^?1, i.p., 30 min previously) significantly reversed the hyperalgesia induced by intraplantar injection of bradykinin (3 nmol per paw) in rats (P < 0.01). In contrast with morphine the extract of propolis (. 100 mg kg^?1, 30 min previously) was ineffective when assessed in the tail-flick and hot-plate thermal assays. Naloxone (5 mg kg^?1 i.p.) reversed (P < 0.01) the effect of morphine (5 mg kg^?1 s.c.) by 70 and 94% respectively in the first and second phases of the formalin test, but did not interfere with the analgesic effect of propolis (10 mg kg^?1 i.p., 30 min previously). These results show that ethanolic extract of propolis, given systemically, has significant anti-hyperalgesic action when assessed in chemical, but not thermal, models of nociception in mice and rats. Its analgesic action seems to be unrelated to release or activation of the opioid system.     

Suppression of interleukin 17 production by Brazilian propolis in mice with collagen-induced arthritis

Propolis is a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants. Propolis has been reported to have immunomodulatory activity. We hypothesized that propolis would be able to reduce the disease severity of rheumatoid arthritis. We evaluated the effect of Brazilian propolis ethanolic extract on the pathogenesis of collagen-induced arthritis (CIA) in mice. Mice fed propolis exhibited significant lower clinical arthritis scores than those fed the control diet. To investigate the mechanism of the effect of propolis on CIA mice, we examined interleukin-17 (IL-17) production in CIA mice fed propolis using an enzyme-linked immunospot assay and flow cytometric analysis. The numbers of IL-17-producing cells in the CIA mice fed propolis were significantly decreased. To determine direct influence of propolis on cytokine production, splenocytes were stimulated with phorbol myristate acetate in the presence of propolis extract in vitro. Concentration-dependent declines in IL-17 expression were observed by ELISA and real-time PCR methods. We further found that propolis significantly inhibited the differentiation of Th17 cells from murine splenocytes in a concentration-dependent manner. Taken together, our results may provide a new light on the potential mechanism of the immunosuppressive and anti-inflammatory effects of propolis.     

Anti-inflammatory effect of propolis through inhibition of nitric oxide production on carrageenin-induced mouse paw edema

The anti-inflammatory effect of propolis was compared with that of diclofenac, a non-steroidal anti-inflammatory drug, and L-N(G)-nitro arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, using carrageenin-induced mouse paw edema. When administered 10 min prior to carrageenin injection, propolis (1 : 1000, 1 : 100, p.o.), diclofenac (12.5, 50 mg/kg, p.o.) and L-NAME (10, 100 mg/kg, s.c.) showed a significant anti-inflammatory effect. The anti-inflammatory effects of propolis and L-NAME were significantly inhibited by L-arginine, a precursor of nitric oxide, but not by D-arginine. In contrast, the anti-inflammatory effect produced by diclofenac was not inhibited by either D-arginine or L-arginine. These results indicate that the anti-inflammatory effect of propolis on mouse paw edema acts via the inhibition of nitric oxide production, similar to that of L-NAME but not diclofenac.     

Propolis ameliorates cerebral injury in focal cerebral ischemia/reperfusion (I/R) rat model via upregulation of TGF-β1

Neuroprotective impact of transforming growth factor β1 (TGF-β1) is increasingly recognized in different brain injuries. Propolis exhibits a broad spectrum of biological and pharmacological properties including neuroprotective action. The objective of the investigation was to explore the involvement of TGF-β1 signaling in the neuroprotective mechanism of propolis in I/R rats. In this study, focal cerebral ischemia model was built by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The investigation was carried out on 48 rats that were arranged into four groups (n = 12): the sham group, I/R control group, I/R + propolis (50 mg/kg) group and I/R + propolis (100 mg/kg) group. The results revealed that propolis preserved rats against neuronal injury induced by cerebral I/R. It significantly reduced neurological deficit scores and improved motor coordination and locomotor activity in I/R rats. Propolis antagonized the damage induced by cerebral I/R through suppression of malondialdehyde (MDA) and elevation of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), brain-derived neurotropic factor (BDNF) and dopamine levels in the brain homogenates of I/R rats. Other ameliorations were also observed based on reduction of neurodegeneration and histological alterations in the brain tissues. These results also proposed that the neuroprotective effect of propolis might be related to upregulation of TGF-β1 and suppressed matrix metallopeptidase-9 (MMP9) mRNA expression.     

Inhibitory effects of the methanol extract of Ganoderma lucidum on mosquito allergy-induced itch-associated responses in mice

Recently, we showed that a methanol extract of Ganoderma lucidum inhibits scratching, an itch-related response, induced by intradermal injections of some pruritogens in mice. The present study investigated whether G. lucidum extract would inhibit allergic itch. In mice sensitized with an extract of salivary gland of mosquito (ESGM), an intradermal injection of ESGM elicited scratching, which was suppressed by oral administration of G. lucidum extract (100 and 300 mg/kg). The scratching was inhibited by the H? histamine-receptor antagonist azelastine, but not by the peripherally acting H?-antagonist terfenadine, at the oral dose of 30 mg/kg. In sensitized mice, ESGM increased the activity of cutaneous nerve, which was suppressed by G. lucidum extract (300 mg/kg). Although terfenadine (30 mg/kg) inhibited plasma extravasation induced by ESGM in the sensitized mice, G. lucidum extract (300 mg/kg) was without effect. These results suggest that G. lucidum extract relieves allergic itch through a peripheral action. The results support the idea that mast cells and H? histamine receptors are not the primary sites of the antipruritic action of G. lucidum extract.     

Reversal of acetaminophen induced subchronic hepatorenal injury by propolis extract in rats

The ethanolic extract of propolis (200mg/kg, p.o.) was evaluated against acetaminophen (APAP; 20mg/kg, p.o.) induced subchronic hepatorenal injury in rats. Administration of APAP significantly increased the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transpeptidase, bilirubin and serum proteins, whereas concomitantly decreased hemoglobin, blood sugar and albumin. Hepatorenal reduced glutathione and activities of superoxide dismutase and catalase, hepatic CYPs i.e., aniline hydroxylase and amidopyrine-N-demethylase were significantly decreased after APAP intoxication. Lipid peroxidation showed significant elevation in both organs significantly after APAP assault. Total proteins, glycogen contents and the activities of certain metabolic enzymes i.e., adenosine triphosphatase, alkaline phosphatase and acid phosphatase were altered after APAP administration. Propolis extract exhibited curative effects by reversing APAP induced alterations in blood biochemical variables, CYP enzymes and markers of oxidative stress. Histopathological analysis of liver and kidney was consistent with the biochemical findings and led us to conclude the curative potential of propolis against APAP induced hepatorenal injury.     

Preclinical pharmacology profile of CS-706, a novel cyclooxygenase-2 selective inhibitor, with potent antinociceptive and anti-inflammatory effects

We report here the preclinical anti-inflammatory profile of CS-706 [2-(4-ethoxyphenyl)-4-methyl-1-(4-sulfamoylphenyl)-1H-pyrrole], a novel cyclooxygenase-2 (COX-2) selective inhibitor. CS-706 selectively inhibited COX-2 in a human whole blood assay with an IC(50) of 0.31 microM, compared with an IC(50) of 2.2 microM for COX-1. The selectivity ratio of CS-706 was higher than those of the conventional non-steroidal anti-inflammatory drugs naproxen, indomethacin, and Diclofenac-Na, whereas it was lower than those of rofecoxib, valdecoxib and etoricoxib. It was similar to that of celecoxib. The pharmacokinetic profile of CS-706 showed rapid absorption and dose-proportional exposure after oral administration to rats. CS-706 inhibited prostaglandin E(2) production in inflamed tissue induced by yeast-injection in rats with potency similar to that of indomethacin. However, it inhibited gastric mucosal prostaglandin E(2) production in normal rats weakly compared with indomethacin. CS-706 ameliorated both yeast-induced inflammatory acute pain (ED(50)=0.0090 mg/kg) and adjuvant-induced chronic arthritic pain (ED(50)=0.30 mg/kg) in rats. CS-706 showed more potent antinociceptive activity than celecoxib and rofecoxib in these models. In an adjuvant-induced arthritic model in rats, CS-706 suppressed foot swelling prophylactically with an ID(50) of 0.10 mg/kg/day, and decreased foot swelling in the established arthritis therapeutically in a dose range of 0.040 to 1.0 mg/kg/day. Single administration of up to 100 mg/kg of CS-706 induced no significant gastric lesions in rats. In conclusion, CS-706 is a COX-2-selective inhibitor with a potent antinociceptive and anti-inflammatory activity and a gastric safety profile.     

Propolis reverses acetaminophen induced acute hepatorenal alterations: A biochemical and histopathological approach

The present study has been conducted to evaluate the curative effect of propolis extract, a honey bee-hive product, against acetaminophen (APAP) induced oxidative stress and dysfunction in liver and kidney. Animals were challenged with APAP (2 g/kg, p.o.) followed by treatment of propolis extract (100 and 200 mg/kg, p.o.) once only after 24 h. Release of transaminases, alkaline phosphatase, lactate dehydrogenase, and serum bilirubin were increased, whereas hemoglobin and blood sugar were decreased after APAP administration. Antioxidant status in both the liver and kidney tissues were estimated by determining the glutathione, malondialdehyde content and activities of the CYP enzymes, which showed significant alterations after APAP intoxication. In addition, activities of adenosine triphosphatase, acid phosphatase, alkaline phosphatase, and major cell contents (total protein, glycogen and cholesterol) were also altered due to APAP poisoning. Propolis extract successfully reversed the alterations of these biochemical variables at higher dose. Improvements in hepatorenal histoarchitecture were also consistent with biochemical observations. The results indicated that ethanolic extract of propolis has ability to reverse APAP-induced hepatorenal biochemical and histopathological alterations probably by increasing the antioxidative defense activities due to various phenolic compounds present in it.