The role of the phenethyl ester of caffeic acid (CAPE) in the inhibition of rat lung cyclooxygenase activity by propolis

In this study we investigated the effect of an ethanolic extract of propolis, with and without CAPE, and some of its components on cyclooxygenase (COX) activity. Propolis (0.00003-0.03%) significantly and concentration-dependently inhibited COX activity from lung homogenate of saline- or LPS-treated rats. Same results were obtained with CAPE (0.1-100 microM). COX activity from lung homogenate of saline- or LPS-treated rats was also inhibited by galangin (0.1-100 microM), although the inhibition induced by the lowest concentration was not significant. Caffeic, ferulic, cinnamic and chlorogenic acids and pinocembrin, (0.1-100 microM) did not affect COX activity. The inhibition curves showed that CAPE and propolis were equipotent inhibitors, whereas galangin was significantly (P<0.001) less potent than propolis and CAPE. In order to better investigate the role of CAPE, we tested the action of an ethanolic extract of propolis (0.00003-0.03%) without CAPE. This extract significantly and concentration-dependently inhibited COX activity from lung homogenate of saline- or LPS-treated rats, however, it resulted to be approximately 10 times less potent than the extract containing CAPE. The analysis of the inhibition curves of the extract with and without CAPE showed a significant (P<0.001) difference. These results suggest that both CAPE and galangin contribute to the overall activity of propolis, CAPE being more effective.     

Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin

Propolis, a natural product produced by the honeybee, has been used for thousands of years in folk medicine for several purposes. The extract contains amino acids, phenolic acids, phenolic acid esters, flavonoids, cinnamic acid, terpenes and caffeic acid. It possesses several biological activities such as antiinflammatory, immunostimulatory, antiviral and antibacterial. The exact mode of physiological or biochemical mechanisms responsible for the medical effects, however, is yet to be determined. In this work, we have investigated the antioxidant activity of a propolis extract deprived of caffeic acid phenethyl ester (CAPE). In addition, the activity of CAPE and galangin was also examined. Propolis extract (with and without CAPE) and its active components showed a dose-dependent free radical scavenging effect, a significant inhibition of xanthine oxidase activity, and an antilipoperoxidative capacity. Propolis extract with CAPE was more active than propolis extract without CAPE. CAPE, used alone, exhibited a strong antioxidant activity, higher than galangin. The experimental evidence, therefore, suggests that CAPE plays an important role in the antioxidant activity of propolis.     

Effect of a propolis extract and caffeic acid phenethyl ester on formation of aberrant crypt foci and tumors in the rat colon

We have studied the effect of propolis and its main active ingredient caffeic acid phenetyl ester (CAPE) on formation of aberrant crypt foci (ACF) and tumors in the rat colon in vivo. CAPE (50 mg/kg i.p.) reduced the formation of ACF and tumor induced by azoxymethane, while propolis ethanolic extract was without effect. These results suggest a potential anti-carcinogenesis of CAPE but not propolis.     

Anti-inflammatory activity of Syzygium cumini bark

The ethanolic extract of the bark of Syzygium cumini was investigated for its anti-inflammatory activity in animal models. The extract did not show any sign of toxicity up to a dose of 10.125 g/kg, p.o. in mice. Significant anti-inflammatory activity was observed in carrageenin (acute), kaolin-carrageenin (subacute), formaldehyde (subacute)-induced paw oedema and cotton pellet granuloma (chronic) tests in rats. The extract did not induce any gastric lesion in both acute and chronic ulcerogenic tests in rats. Thus, the present study demonstrated that S. cumini bark extract has a potent anti-inflammatory action against different phases of inflammation without any side effect on gastric mucosa.     

Anti-inflammatory activity of Dalbergia sissoo leaves

The possible anti-inflammatory activity of the 90% ethanolic extract of Dalbergia sissoo leaves (DSELE) was studied in different models of inflammation in rats after oral administration at doses of 100, 300 and 1000 mg/kg. DSELE significantly inhibited carrageenin, kaolin and nystatin-induced paw oedema, as well as the weight of granuloma induced by a cotton pellet. It also inhibited dye leakage in acetic acid-induced vascular permeability test in mice. DSELE was devoid of ulcerogenic effect on the gastric mucosa of rats in acute and chronic tests. In acute toxicity studies, it was found to be safe up to 10.125 g/kg, p.o. in the rat. It was concluded that the D. sissoo leaf extract possessed significant anti-inflammatory activity (in acute, sub-acute and chronic models of inflammation) without any side effect on gastric mucosa.     

In vitro permeation through porcine buccal mucosa of caffeic acid phenetyl ester (CAPE) from a topical mucoadhesive gel containing propolis

Recent studies have shown that propolis has on the oral cavity appreciable antibacterial, antifungal and antiviral actions, as well as anti-inflammatory, anaesthetic and cytostatic properties. In light of these studies, an assessment of the diffusion and permeation of caffeic acid phenetyl ester (CAPE) through porcine buccal mucosa was considered useful as a possible application in the stomatological field. To do so, a mucoadhesive topical gel was prepared to apply to the buccal mucosa. The gel was formulated in such a way as to improve the solubility of the propolis, conducting to an increase of the flux. The mucosal permeation of CAPE from the formulation was evaluated using Franz cells, with porcine buccal mucosa as septum between the formulation (donor compartment) and the receptor phase chamber. The diffusion through the membrane was determined by evaluating the amount of CAPE present in the receiving solution, the flux and the permeation coefficient (at the steady state) in the different formulations at set intervals. Qualitative and quantitative determinations were done by HPLC analysis. From the results, CAPE allowed a high permeability coefficient in comparison to the coefficient of other molecules, as expected from its physical-chemical structure. Moreover, the developed gel improved the CAPE flux approximately 35 times more with respect to an ethanol solution formulated at the same gel concentration. The developed gel was also tested in order to evaluate the mucoadhesive behaviour and comfort in vivo on 10 volunteers in a period of 8 h. The in vivo evaluation of mucoadhesive gel revealed adequate comfort and non-irritancy during the period of study and it was well accepted by the volunteers.     

Analgesic, anti-inflammatory and antipyretic activities of the ethanolic extract and its fractions of Cleome rutidosperma

Oral administration of the ethanolic extract (200 and 400 mg/kg, p.o) and its fractions (200 mg/kg each) of the aerial parts of Cleome rutidosperma produced significant analgesic activity in acetic acid-induced writhing and tail immersion tests, anti-inflammatory effect against carrageenin induced inflammation and adjuvant induced polyarthritis and antipyretic activity against yeast-induced pyrexia. Fractionation of the ethanolic extract potentiated the activities.     

Anti-inflammatory activity of Butea monosperma flowers

Methanolic extract of Butea monosperma flowers (MEBM) was studied for anti-inflammatory activity against carrageenin induced paw edema and cotton pellet granuloma in albino rats. In carrageenin induced paw edema, MEBM at oral doses of 600 mg/kg and 800 mg/kg, dose-dependently inhibited the paw edema. In cotton pellet induced granuloma, MEBM at the same doses was found to significantly inhibit granuloma tissue formation, including significant reduction in levels of serum lysosomal enzymes (SGOT, SGPT and ALP) and lipid peroxides as compared to control.     

Anti-nociceptive activity of the aqueous extract of Erythrina velutina leaves

Anti-nociceptive and anti-oedematogenic effects of the aqueous extract from the leaves of Erythrina velutina were tested through experimental models of nociception in mice and paw oedema induced by carrageenin in rats. The extract (300 and 600 mg/kg) did not change the carrageenin-induced paw oedema. In the hot plate test the extract also did not alter the latency time for mice liking the rear paws. Moreover, the extract (600 mg/kg) decreased by 96.5% the paw liking time in the second phase of the formalin test. This effect was antagonized by naloxone (5 mg/kg). In the acetic acid-induced writhing test, the extract (300 and 600 mg/kg) reduced the number of writhing by 88.8% and 96.4%, respectively. Our present results demonstrated that the crude extract from the leaves of E. velutina has anti-nociceptive but not anti-oedematogenic properties.     

Inhibitory effect of a propolis on Di-n-Propyl Disulfide or n-Hexyl salycilate-induced skin irritation,oxidative stress and inflammatory responses in mice

PurposeThermal imaging has been utilised, both preclinically and clinically, as a tool for assessing inflammation. Psoriasis is a chronic inflammatory skin disease characterised by hyperkeratosis, dermal inflammatory infiltrate and increased angiogenesis. The aim of the present study was to assess the usefulness of thermography in psoriatic lesion regression after topical treatment with bee propolis, recognised as potent antioxidants and anti-inflammatory agents.MethodsWe monitored the inflammation process induced by irritants such as n-Hexyl salycilate (HXS) or Di-n-Propyl Disulfide (PPD) by histopatological assessment of the skin, thermographic scanning, total number of inflammatory cells in the peritoneal cavity, differential analysis of cells in the peritoneal cavity, macrophage spreading index, haematological and biochemical parameters, frequencies of micronucleated reticulocytes, lipid peroxidation and glutathione assay in the skin.ResultsTopically applied ethanolic extract of propolis (EEP) with HXS or PPD reduced the lipid peroxidation in the skin and total number of inflammatory cells in the skin and peritoneal cavity, functional activity of macrophages, the number of micronuclei in mouse peripheral blood reticulocytes and enzymatic activity of ALP and AST.ConclusionThese results demonstrate that topical application of EEP may improve psoriatic-like skin lesions by suppressing functional activity of macrophages and ROS production. Taken together, it is suggested that EEP can safely be utilised in the prevention of psoriasis-related inflammatory changes without causing any toxic effect.     

Anti-inflammatory,analgesic and antipyretic properties of Clitoria ternatea root

Clitoria ternatea roots methanol extract when given by oral route to rats was found to inhibit both the rat paw oedema caused by carrageenin and vascular permeability induced by acetic acid in rats. Moreover, the extract exhibited a significant inhibition in yeast-induced pyrexia in rats. In the acetic acid-induced writhing response, the extract markedly reduced the number of writhings at doses of 200 and 400 mg/kg (p.o.) in mice.     

Analgesic and anti-inflammatory activity of Leonurus sibiricus

The methanolic extract of Leonurus sibiricus aerial parts injected intraperitoneally at dose of 250 and 500 mg/kg showed a significant analgesic effect in acetic acid-induced writhing in mice. Moreover, when given orally to rats at dose of 200 and 400 mg/kg, it showed a significant anti-inflammatory activity against carrageenin induced rat paw edema in rats.     

Propolis,an old remedy used in modern medicine

Propolis is one of the few natural remedies that has maintained its popularity over a long period of time. The pharmacologically active molecules in the propolis are flavonoids and phenolic acids and their esters. These components have multiple effects on bacteria, fungi and viruses. In addition, propolis and its components have anti-inflammatory and immunomodulatory activities. Moreover, propolis has been shown to lower blood pressure and cholesterol levels. However, clinical studies to substantiate these claims are required.     

Anti-inflammatory, antioxidant and antifungal furanosesquiterpenoids isolated from Commiphora erythraea (Ehrenb.) Engl. resin

The topical anti-inflammatory, free radical scavenging and antifungal activities of essential oils and extracts of Commiphora erythraea (Ehrenb.) Engl. resin were investigated. The hexane extract significantly inhibited oedema when applied topically in Croton oil-induced ear oedema assay in mice. The same extract showed antioxidant activity in DPPH radical scavenging assay. A bioguided separation of the hexane extract led to the isolation of furanosesquiterpenoids 1 and 2 that showed a weak antifungal activity, while compounds 3-5 resulted to be antioxidant (EC₅₀ 4.28, 2.56 and 1.08 mg/mL, respectively) and anti-inflammatory (30, 26 and 32% oedema reduction, respectively).     

Study of anti-inflammatory,analgesic and antipyretic activities of seeds of Hyoscyamus niger and isolation of a new coumarinolignan

A chemical and biological validation of the traditional use of Hyoscyamus niger seeds as anti-inflammatory drug has been established. The methanolic extract of seeds of H. niger (MHN) was evaluated for its analgesic, anti-inflammatory and antipyretic activities in experimental animal models at different doses. MHN produced significant increase in hot plate reaction time, while decreasing writhing response in a dose-dependent manner indicating its analgesic activity. It was also effective in both acute and chronic inflammation evaluated through carrageenin-induced paw oedema and cotton pellet granuloma methods. In addition to its analgesic and anti-inflammatory activity, it also exhibited antipyretic activity in yeast-induced pyrexia model. Furthermore, the bioactive MHN under chemical investigation showed the presence of coumarinolignans as major chemical constituent and yielded a new coumarinolignan, cleomiscosin A methyl ether (1) along with four known coumarinolignans, cleomiscosin A (2), cleomiscosin B (3), cleomiscosin A-9′-acetate (4) and cleomiscosin B-9′-acetate (5). The structure elucidation of 1 was done by spectroscopic data interpretation and comparative HPLC analysis. Cleomiscosin A, but not its isomer cleomiscosin B, reduced dry and wet weight of cotton pellet granuloma in mice. This suggests that cleomiscosin A is an important constituent of MHN responsible for anti-inflammatory activity.     

Studies on the anti-inflammatory properties of Entada abyssinica.

The defatted methanolic extract of Entada abyssinica was evaluated for anti-inflammatory activity in acute and chronic models of inflammation. The extract (50--200 mg/kg, p.o.) exhibited dose-dependent and significant inhibition of both the carrageenan-induced rat paw oedema and granuloma tissue formation in rats. The extract (50--200 mg/kg, p.o.) was also found to inhibit the acetic acid-induced vascular permeability in a dose-dependent fashion in mice. This study demonstrated the anti-inflammatory activity of Entada abyssinica.     

Anti-inflammatory activity of Butea frondosa leaves

In the carrageenan-induced rat paw oedema, the aqueous extract of Butea frondosa leaves showed dose-dependent (25–100 mg/kg, p.o.) anti-inflammatory activity which at the highest dose was almost comparable to ibuprofen (25 mg/kg, p.o.).The LD₅₀ was higher than 5 g/kg, p.o. in rats.     

Anti-inflammatory and anti-ulcer activity of Calligonum comosum in rats.

The 10% ethanol extract of the aerial parts of Calligonum comosum (50--400 mg/kg, i.p.) significantly reduced the increase in hind paw oedema induced by carrageenan in rats. Following sub-acute oral administration of the extract (50 and 100 mg/kg, daily for 14 days), a significant anti-inflammatory activity in the cotton pellet model was observed. Pre-treatment with the extract (100, 200 and 400 mg/kg) produced a significant and dose-dependent inhibition to the acute gastric ulcers induced by phenylbutazone, indomethacin, 0.2 N NaOH and 80% ethanol.     

Anti-inflammatory effect of (+)-pinitol

In the carrageenin-induced paw oedema in rats, (+)-pinitol (2.5-10 mg/kg, i.p.), isolated from Abies pindrow leaves, showed a significant anti-inflammatory effect, the highest dose being comparable to phenylbutazone (100 mg/kg, i.p.).     

Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of lycorine from Sternbergia fisheriana (Herbert) Rupr

The present study reports the potential antinociceptive, anti-inflammatory and hepatoprotective activities of lycorine from Sternbergia fischeriana (Herbert) Rupr. (Amaryllidaceae). Lycorine was evaluated on mice by using acetic-acid induced writhing and tail-flick tests. Lycorine exhibited stronger inhibition than aspirin in acetic-acid induced abdominal stretching at 1.0 mg/kg dose. Lycorine also showed antinociceptive activity at 1.0 mg/kg dose in tail-flick test. The anti-inflammatory activity of lycorine was not found to be significant at dose of 0.5 mg/kg. However, at doses of 1.0 mg/kg and 1.5 mg/kg, i.p. showed a significant reduction with 53.45% and 36.42%, respectively in rat paw oedema induced by carrageenan against the reference anti-inflammatory drug indomethacin (3 mg/kg, i.p.) (95.70%). The ED₅₀ of lycorine was determined as 0.514 mg/kg. Hepatoprotective activity of lycorine on carbon tetrachloride (CCl₄) induced acute liver toxicity following biochemical parameters were also evaluated. Rats were treated with lycorine at doses of 1.0 mg/kg and 2.0 mg/kg, i.p. Results of biochemical tests were confirmed by histopathological examination. Lycorine exhibited significant hepatoprotective effect at dose of 2.0 mg/kg i.p. dose.