Uncaria tomentosa (Willd. ex. Roem. & Schult.) DC. and Eucalyptus globulus Labill. interactions when administered with diazepam.

The safety of natural drugs is defined by their side effects and toxicity as well as any interactions that may occur if taken together with other drugs. In particular, it is essential to identify synergies, antagonisms and other types of interference with other drugs so that the correct choice can be made from the range of phytomedicines available. The aim of this work was to investigate changes in the pharmacological effect of diazepam (2 mg/kg) on the CNS when administered together with a medicinal plant: Eucalyptus globulus Labill. (eucalyptus 6 mg/kg and 3.25 mg/kg) or Uncaria tomentosa (Willd. ex Roem. & Schult). DC. (cat's claw, 7.14 mg/kg and 3.54 mg/kg). Various different psychopharmacological effects were evaluated through assessing exploratory behavior, muscle relaxation and spontaneous motor activity. Both phytodrugs interacted with the benzodiazepine. Eucalyptus had an inhibitory effect at both doses and could be useful at the highest dose in cases where the desired effect of the depressant is moderate anxiolytic activity without marked muscle relaxation. Cat's claw, at both doses, enhanced the action of diazepam on spontaneous motor activity and, at the lowest dose, exploratory ability. These herbal drugs could be useful for their antiinflammatory activity in musculoskeletal pathologies treated with benzodiazepines.

Hypocholesterolemic and hepatoprotective effects of "triguero" asparagus from andalusia in rats fed a high cholesterol diet.

The cultivated species of the wild autochthonous Asparagus officinalis in Andalusia in Spain is commonly called "triguero" asparagus. This vegetable has traditionally been very much appreciated for its organoleptic and nutritional characteristics. This study has been designed to evaluate the potential effect of different concentrations of freeze-dried asparagus (500, 250, and 125 mg/Kg of body weight/day) on oxidative status and lipid profile in rats fed a cholesterol-rich diet. After five weeks of treatment, doses of 250 and 500 mg/Kg of asparagus were able to significantly reduce total cholesterol and LDL cholesterol levels. Atherogenic index was also significantly reduced in a dose-dependent manner by administrating freeze-dried asparagus. A beneficial effect was observed in the HDL cholesterol levels in asparagus-fed groups although the increase was not significant. Consumption of asparagus also improved antioxidant status, assayed superoxide dismutase (SOD) and catalase (CAT) enzymes, and protected against lipid peroxidation. These results show that the intake of green asparagus from Andalusia (Spain) helps to regulate plasma lipid levels and prevents oxidative damage in hypercholesterolemic conditions.

Topical anti-inflammatory effect of tirucallol, a triterpene isolated from Euphorbia lactea latex.

Latex from Euphorbia lactea (Euphorbiaceae), a native Dominican medicinal plant, is claimed to be useful in the treatment of inflammation. Topical application of tirucallol, a tetracyclic triterpene isolated from Euphorbia lacteal latex, suppressed ear edema in the mouse model in a dose-dependent manner, as well as affecting the influx of polymorphonuclear cells in response to topical application of 12-O-tetradecanoylphorbol-acetate (TPA) in the mouse ear. In addition, the effect of tirucallol, on some macrophage functions was analyzed in vitro. Non-toxic concentrations of tirucallol potently inhibited nitrite production in lipopolysaccharide-stimulated macrophages. Western blot analysis showed that nitric oxide reduction was a consequence of the inhibition of inducible nitric oxide synthetase expression although tirucallol slightly affected to prostaglandin E(2) (PGE(2)) generation. The results of the study revealed that tirucallol (0.3%), present in Euphorbia lactea latex, exerts a topical anti-inflammatory effect in vivo, via a mechanism of action related to the neutrophil migration. On the other hand, it can be deduced that the mechanism of the anti-inflammatory activity of this triterpene is related to the control of the production of NO and its effect on the expression of iNOS.

Antimicrobial activity and phytochemical studies of some lichens from south of Spain.

The antimicrobial activity of some lichens from south Spain has been studied and some of plant constituents were identified. Activity against some Gram (+) bacteria has been observed in lichens containing usnic acid.

Antibacterial activity of essential oils of Pimenta racemosa var. terebinthina and Pimenta racemosa var. grisea.

The antibacterial activity of essential oils of Pimenta racemosa var. terebinthina and P. racemosa var. grisea was determined against Gram (+) and Gram (-) bacteria. P. racemosa var. grisea demonstrated a more pronounced activity. These data would indicate the potential usefulness of the variety grisea as a microbiostatic, antiseptic or disinfectant agent.

Phytochemical analysis and anti-allergic study of Agave intermixta Trel. and Cissus sicyoides L.

Agave intermixta Trel. (Maguey) and Cissus sicyoides L. (Bejuco caro) are Caribbean plant species from the Dominican Republic used locally in traditional popular medicine that have shown an antiinflammatory effect in experimental animal models. A phytochemical analysis on these species allowed us the isolation and identification of the steroidal sapogenins hecogenin and diosgenin from Maguey and the hydroxystilbene resveratrol from Bejuco caro. The effects of these plant extracts and their isolated constituents on compound-48/80-induced histamine release from peritoneal mast cells were investigated. Significant inhibition was produced by 0.5 mg mL(-1) of a methanolic extract of Bejuco (41.1%) and by its constituent resveratrol (82.4%) at a dose of 250 microM. However, none of the steroidal sapogenins from A. intermixta showed a significant inhibitory effect on histamine release from mast cells. From these results, it can be deduced that the in-vitro anti-allergic activity towards the release of histamine from mast cells shown by the methanolic extract of C. sicyoides may be mediated by its constituent resveratrol and might contribute to the antiinflammatory activity shown by this species.

Antinociceptive and anti-inflammatory effect of the aqueous extract from leaves of Pimenta racemosa var. ozua (Mirtaceae).

The leaves of Pimenta racemosa var. ozua (Urban & Ekman) Landrum L. (Myrtaceae) are used against the pain and the inflammation in popular medicine of the Caribe area. In the present work, the antinociceptive, anti-inflammatory effect, and acute toxicity of the aqueous extract from leaves of Pimenta racemosa have been investigated. The antinociceptive action was assayed in several experimental models in mice: acetic acid, formalin, and hot plate tests. The aqueous extract (125 and 250 mg/kg) significantly and in a dose-dependent manner reduced the nociception induced by the acetic acid intraperitoneal injection (P<0.001). In the formalin test, the extract also significantly reduced the painful stimulus in both phases of the test (P<0.001). On the contrary, the extract neither significantly increased the latency time of licking nor jumping in the hot plate test. In the anti-inflammatory study, the plant also showed an interesting effect. Aqueous extract (125 and 250 mg/kg) orally administered, significantly reduced the carrageenan-induced edema in rat paw at 1, 3, and 5 h (P<0.001). In the TPA test the edema was dose-dependent and significantly reduced by the extract (0.5, 1, and 3 mg per ear) when it was topically applied (P<0.01; P<0.001). The levels of myeloperoxidase enzyme also were reduced in the inflamed tissue by the extract. Acute toxicity also was investigated and the results indicated a moderate toxicity (LD50: 287 +/- 12.9 mg residue/kg; 1.854 +/- 0.083 g plant/kg). These results revealed that the extract from leaves of Pimenta racemosa var. ozua exerts an important antinociceptive activity, associated to an anti-inflammatory effect which to appear be markedly influenced by the inhibition of neutrophil migration into inflamed tissue and that lack of toxic effects at usual doses.

New insights into the mechanism of action of the anti-inflammatory triterpene lupeol.

The pentacyclic triterpene lupeol has been studied for its inhibitory effects on murine models of inflammation and peritoneal macrophage functions in-vitro. Lupeol (0.5 and 1 mg/ear) administered topically suppressed the mouse ear oedema induced by 12-0-tetradecanoyl-phorbol acetate (TPA), being less effective on ear oedema induced by arachidonic acid. Quantitation of the neutrophil specific marker myeloperoxidase demonstrated that its topical activity was associated with reduction in cell infiltration into inflamed tissues. When tested in-vitro, lupeol significantly reduced prostaglandin E2 (PGE2) production from A23187-stimulated macrophages, but failed to affect leukotriene C4 release. It was a weak inhibitor of nitrite release, but dose-dependently suppressed PGE2. Cytokine production (tumour necrosis factor-alpha and interleukin-1beta) was inhibited in the range 10-100 microM in lipopolysaccharide-treated macrophages. This study demonstrated that lupeol possessed anti-inflammatory activity which was likely to depend on its ability to prevent the production of some pro-inflammatory mediators.

Cytostatic activity of Achillea ageratum L.

The cytostatic activity of a chloroform extract and two isolated compounds from Achillea ageratum L. (Asteraceae) was determined in vitro against Hep-2 and McCoy cells. The chloroform extract exhibited a high degree of growth inhibition compared with the values obtained with the 6-mercaptopurine (positive control) against both cultures. Stigmasterol and beta-sitosterol, isolated from the chloroform extract, showed a high degree of growth inhibition.

Anti-inflammatory effect of Pimenta racemosa var. ozua and isolation of the triterpene lupeol.

Pimenta racemosa var. ozua (Myrtaceae) is a tropical plant, used in different inflammatory processes by the folk medicine of the Caribbean region. From the methanol extract of the leaves a terpenic compound identified as lupeol has been isolated for the first time in this species. The anti-inflammatory activity of the extract has been evaluated against two experimental models of acute inflammation: paw edema in rats, using carrageenan or dextran as phlogogen agents, and ear edema in mice, inducing the inflammation with 12-o-tetradecanoylphorbol acetate (TPA). Myeloperoxidase activity (MPO) was also assayed as an indicator of leukocytary migration in the inflamed ears. In the carrageenan test, the methanol extract (125 and 250 mg kg(-1) p.o.) had a dose-dependent and significant effect at different time intervals. On the contrary, when the dextran was injected in paw, the extract did not reduce the inflammation provoked. This behavior was similar to indomethacine (25 mg kg(-1)) used as a standard drug. In the TPA-induced ear edema, the methanol extract (0.5, 1 and 3 mg ear(-1)) significantly reduced the inflammation. In the MPO assay a significant inhibition of the enzyme was observed in the inflamed tissue in all the samples assayed. These results show that the methanol extract from the leaves of Pimenta racemosa var. ozua, is effective against acute inflammation processes, by oral route and when topically applied. The anti-inflammatory behavior of the extract was similar to that exhibited by the selective cyclo-oxygenase inhibitor, indomethacin. On the other hand, the reduction of MPO activity shows that the action mechanism is clearly related with the neutrophil migration.

Anti-inflammatory activity of abietic acid, a diterpene isolated from Pimenta racemosa var. grissea.

The anti-inflammatory activity of abietic acid, a diterpene isolated from Pimenta racemosa var. grissea (Myrtaceae), was evaluated in-vivo and in-vitro. This compound significantly inhibited rat paw oedema induced by carrageenan in a time- and dose-dependent manner, and mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate, after oral or topical administration. The inhibition of myeloperoxidase enzyme showed that its topical activity was influenced by neutrophil infiltration into the inflamed tissues (ears). In addition, the effect of abietic acid on some macrophage functions was analysed in-vitro. Non-toxic concentrations of abietic acid inhibited prostaglandin E2 (PGE2) production in lipopolysaccharide-treated macrophages, whereas nitrite, tumour necrosis factor alpha and interleukin-1beta production were only weakly affected by this diterpene. PGE2 production from A23187-stimulated macrophages was only inhibited at high doses (100 microM) and it failed to modify leukotriene C4 production. These results indicate that abietic acid exerts in-vivo anti-inflammatory activity after oral or topical administration and has partial ability to prevent the production of some inflammatory mediators.

Cytotoxic activity of Agave intermixta L. (Agavaceae) and Cissus sicyoides L. (Vitaceae).

The cytostatic activities of Agave intermixta L. (Agavaceae) and Cissus sicyoides L. (Vitaceae) have been determined. In the antimitotic assay, Agave intermixta L. showed complete inhibition of cell division at 24 h of treatment. Both species showed a moderate cytostatic activity against HEp-2 cells, Cissus sicyoides L. being the most active species.

Anti-inflammatory activity of Agave intermixta Trel. and Cissus sicyoides L., species used in the Caribbean traditional medicine.

Agave intermixta Trel. and Cissus sicyoides L. are two tropical plants originating from the Dominican Republic. Aqueous extracts from these species are used in traditional medicine. In contrast, biological activity and toxicity of these plants are not yet evaluated systematically. The aim of the present work is to investigate a potential anti-inflammatory activity, and to elucidate the toxicity of the extracts. No lethal effects were produced after oral administration of the extracts. The values of the medium lethal doses after intraperitoneal administration were quite high for both species, although A. intermixta seems to be rather more toxic than C. sicyoides. The anti-inflammatory effects have been investigated in two experimental in vivo models. The carrageenan-induced rat paw oedema was chosen as a model for general inflammation, and the mice ear oedema test using tetradecanoylphorbol acetate as inflammatory agent as a model of topical inflammation. Dry extracts from decoctions of A. intermixta leaves and C. sicyoides stems were administered in doses of 300 and 500 mg/kg (p.o.) in the general model, and in doses of 3 and 5 mg/mouse ear for both plants in the topical model. In the general anti-inflammation assay, the oral administration of both extracts produced a significant anti-inflammatory effect, most pronounced for A. intermixta than for C. sicyoides. In the topical model, the administration of both extracts produced similar inhibitions of the oedema, with a reduction of approximately 50% in comparison with the control group. In homogenated tissue samples from the inflamed areas, a distinct decrease in the level of myeloperoxidase enzyme was noted.

Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models.

Eryngium foetidum L. (Apiaceae) is a Caribbean endemic plant, used in folk medicine for the treatment of several antiinflammatory disorders. A preliminary phytochemical study showed that the hexane extract is rich in terpenic compounds. Chromatographic fractionation of this extract yielded: alpha-cholesterol, brassicasterol, campesterol, stigmasterol (as the main component, 95%) clerosterol, beta-sitosterol, delta 5-avenasterol, delta (5)24-stigmastadienol and delta 7-avenasterol. The topical antiinflammatory activity of the hexane extract and of stigmasterol was evaluated by auricular oedema, induced by 12-0-tetradecanoylphorbol acetate (TPA), in the mouse, using single and multiple applications of the phlogistic agent. Both reduced the oedema in a similar proportion in the two model assays (acute and chronic). Meloperoxidase activity was strongly reduced by both the extract and the compound, in the acute but not the chronic model. These results indicate that the leaves of Eryngium foetidum L may be effective against topical inflammation processes. Stigmasterol also exerts a significant topical antiinflammatory activity although it cannot be considered to be a major antiinflammatory agent, therefore other bioactive components are probably involved in the activity of the hexane extract.

Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models

Eryngium foetidum L. (Apiaceae) is a Caribbean endemic plant used in folk medicine for the treatment of several antiinflammatory disorders. A preliminary phytochemical study showed that the hexane extract is rich in terpenic compounds. Chromatographic fractionation of this extract yielded: alpha-cholesterol, brassicasterol, campesterol, stigmasterol (as the main component, 95 percent) clerosterol, beta-sitosterol, delta 5-avenasterol, delta (5) 24-stigmastadienol and delta 7-avenasterol. The topical antiinflammatory activity of the hexane extract and of stigmasterol was evaluated by auricular oedema, induced by 12-0-tetradecanoylphorbol acetate (TPA), in the mouse, using single and multiple applications of the phlogistic agent. Both reduced the oedema in a similar proportion in the two model assays (acute and chronic). Meloperoxidase activity was strongly reduced by both the extract and the compound, in the acute but not the chronic model. These results indicate that the leaves of Eryngium foetidum L may be effective against topical inflammation processes. Stigmasterol also exerts a significant topical antiinflammatory activity although it cannot be considered to be a major antiinflammatory agent, therefore other bioactive components are probably involved in the activity of the hexane extract.(AU)

Study of the topical anti-inflammatory activity of Achillea ageratum on chronic and acute inflammation models.

We have produced a chloroform extract from Achillea which includes stigmasterol and sitosterol. By comparing it with the pure compounds an anti-inflammatory effect (with mouse ears) is assumed. The topical anti-inflammatory effect of the chloroform extract from Achillea ageratum (Asteraceae) and of stigmasterol and beta-sitosterol, isolated of this extract has been evaluated, against to 12-0-tetradecanoylphorbol acetate (TPA)-induced mouse ear edema, using simple (acute model) and multiple applications (chronic model) of the phlogistic agent. Myeloperoxydase activity also was studied in the inflamed ears. In the acute model the extract exerted a dose-dependent effect. All the doses assayed (1, 3 and 5 mg/ear) significantly reduced the edema (50%, 66% and 82%, respectively). The isolated sterols stigmasterol and beta-sitosterol (with doses of 0.5 mg/ear) had similar effect as the extract with doses of 1 and 3 mg (59% and 65% respectively). In the chronic model the anti-inflammatory effect generally was a more moderate one. The highest dose of the extract decreased the edema reduction to 26% with the highest dose of the extract applied. With the compounds the effect decreased to 36% with stigmasterol, and 40.6% with beta-sitosterol. Myeloperoxydase activity (MPO) was reduced by the extract and the compounds in the acute model, however, in the chronic edema, the enzyme inhibition was very weak with all treatments even with the standard substance. These results indicate that the chloroform extract of Achillea ageratum and some of the its components stigmasterol and beta-sitosterol are more effective as topical anti-inflammatory agents in acute than in the chronic process and their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue.

Antinociceptive effects of the tubercles of Anredera leptostachys.

The tubercles of Anredera leptostachys are used as an antinociceptive and anti-inflammatory in the popular medicine of the Caribbean basin. In the present work, the anti-nociceptive and central nervous system depressant (CNS) effects of the methanolic extract from the tubercles of A. leptostachys have been evaluated. The antinociceptive activity was assayed in several experimental models in mice: acetic acid, formalin and hot plate tests. The methanolic extract (250 and 500 mg/kg) significantly and in a dose-dependent manner reduced the nociception induced by the acetic acid (P < 0.001). In the hot plate test, the extract significantly increased the latency time of jump although it slightly increased the licking time. The naloxone partially reversed the antinociception of the extract in the hot plate test. In the formalin test, the methanolic extract also significantly reduced the painful stimulus but the effect was not dose-dependent. In the study of the CNS-depressant effects, the extract was found to produce a significant reduction of the exploratory capacity with both doses assayed (P < 0.001). The muscular relaxation only decreased with the higher doses assayed (P < 0.001). The escape instinct was also significantly reduced (P < 0.001) by the two doses of the extract and both were more effective than standard drugs morphine and diazepam.

Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens.

Different species of the Scrophularia genus (Scrophulariaceae) have been reported to have bacteriostatic and anti-inflammatory properties. In previous studies the anti-inflammatory and antibacterial activity of different extracts from Scrophularia frutescens were investigated and p-coumaric, caffeic, ferulic gentisic, protocatechuic, syringic and isovanillic acids were isolated and identified. In this work the anti-inflammatory activity of these compounds, administered orally, has been studied against carrageenan-induced rat paw oedema and, administered topically, against tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema. The compounds' myeloperoxidase activity in inflamed ear was also investigated. Some of the phenolic acids were remarkably active in the TPA test (protocatechuic 71.59% inhibition, P < 0.001; syringic 74.43%, P < 0.001; ferulic 71.02% P < 0.001) and all significantly inhibited mouse ear oedema. They were only moderately active, or were without activity, in the carrageenan test. These results imply that the phenolic acids assayed are more effective topically than as oral anti-inflammatory agents and that their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue. This study has also enabled us to make some observations on the possible relationship between the chemical structure and anti-inflammatory activity of the compounds assayed.

Cytostatic activity of some compounds from the unsaponifiable fraction obtained from virgin olive oil.

Oleuropein, tyrosol, squalene and the fraction of sterols and triterpenoid dialcohols from the unsaponifiable fraction obtained from virgin olive oil have been tested for possible cytostatic activity against McCoy cells, using 6-mercaptopurine as a positive control. The samples of sterols and triterpenic dialcohols showed a strong activity.

Anti-inflammatory activity and acute toxicity of Anredera leptostachys.

Anredera leptostachys (Basellaceae) is a tropical plant, frequently found in the Dominica Republic. The decoction of the tubercles from this species are used in popular medicine, but there is no information on the biological activities of this species nor its toxicity. In the present work, the anti-inflammatory activity and the toxicity of an extract of tubercles from Anredera leptostachys have been studied. The antiinflammatory activity was investigated using two acute inflammation models: carrageenan induced-edema of the rat paw and tetradecanoylphorbol acetate (TPA) induced edema on the mouse ear. Indomethacin was used as standard drug. Myeloperoxidase activity (MPO) was also assessed as an indicator of leukocyte migration in the inflamed mouse ear. The extract given orally at doses of 250 and 500 mg/kg reduced the carrageenan induced edema in a dose-dependent manner: 27, 24, 25 and 10%; 44, 51, 61 and 57% at 2, 3, 4 and 5 h respectively. The extract applied topically, at doses of 3 and 5 mg/ear in the TPA test, produced an edema reduction of 14 and 20% respectively. The levels of myeloperoxidase enzyme were reduced in the inflammed tissue by 31 and 40% respectively. Acute toxicity also was investigated and the results indicated a low toxicity (LD(50):1043.38 ± 137.14 mg/kg; 61.07 ± 7.93 g plant/kg).