María Ángeles Álvarez Fernández

Antibacterial activity of the phenolic acids fractions of Scrophularia frutescens and Scrophularia sambucifolia

The phenolic fractions of aerial part of Scrophularia frutescens and S. sambucifolia (Scrophulariaceae) showed a potent antibacterial activity. Ferulic, isovanillic, p-hydroxycinnamic, p-hydroxybenzoic, syringic, caffeic, gentisic and protocatechuic acids were isolated from S. frutescens and ferulic, p-coumaric, vanillic, p-hydroxibenzoic and syringic acids were isolated from S. sambucifolia. Since phenolic acids have been shown in the literature to exert an antibacterial effect, the presence of these compounds in the two plants explains their antibacterial activity.

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‐O‐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‐α and interleukin‐1β) was inhibited in the range 10–100 μm 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.

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: α‐cholesterol, brassicasterol, campesterol, stigmasterol (as the main component, 95%) clerosterol, β‐sitosterol, Δ5‐ avenasterol, Δ524‐stigmastadienol and Δ7‐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.

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 α and interleukin‐1β production were only weakly affected by this diterpene. PGE2 production from A23187‐stimulated macrophages was only inhibited at high doses (100 μM) 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.

A pharmacological study of Cecropia obtusifolia Bertol aqueous extract

Cecropia obtusifolia (Cecropiaceae) is a species from tropical America and its leaves are used in traditional medicine for the treatment of diabetes and as an anti-inflammatory agent. In the present study, the analgesic, anti-inflammatory and central nervous system depressant effects of the aqueous extract from the leaves of C. obtusifolia were investigated in different experimental models, with the purpose of validating its ethnomedical uses. The results obtained with the extract from the leaves of C. obtusifolia reflect a low toxicity, a substantial central depressor effect and analgesic activity and significant motor incoordination and muscle relaxant activity. Concerning the analgesic activity, using the hot plate test, the extract did not produce any effect, however it showed a significant effect on the pain induced by chemical stimuli (acetic and formalin test); this suggests the peripheral analgesic effect of the extract. The extract also showed a topical and systemic anti-inflammatory effect. Thus this work could justify the popular use of C. obtusifolia in rheumatic and kidney inflammation pathologies and reveals that this plant is an interesting species.

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 β-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 β-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 β-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 β-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 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).