Irwin Rose Alencar de Menezes

Synergistic antibiotic activity of volatile compounds from the essential oil of Lippia sidoides and thymol

Lippia sidoides Cham. (Verbenaceae) is used in the folk medicine as topical antiseptic in skin and mucous membranes and its therapeutic effect is attributed to the thymol presence. The objective of this work was to verify the chemical composition and antibiotic modifying activity of the essential oil extracted from the leaves of L. sidoides and its major component thymol. The essential oil was obtained by hydrodistillation and analyzed by GC/MS. The synergistic activity was evaluated using gaseous contact method. The essential oil was obtained (yield of 1.06%) and the GC/MS analysis identified the main constituents: thymol (84.9%) and p-cymene (5.33%). The antibiotic modifying activity was verified using the minimal inhibitory dose method and gaseous contact. It verified the interference of essential oil and thymol against all tested aminoglycosides. There were no statistical differences between the activity of the essential oil and thymol against Pseudomonas aeruginosa, indicating this to be the responsible composition for such activity. However, the oil was shown more effective when compared to the thymol against Staphylococcus aureus. The essential oil of L. sidoides and its major component thymol influence the activity of aminoglycosides and may be used as adjuvant in antibiotic therapy against respiratory tract bacterial pathogens.

Topical anti-inflammatory effect of Caryocar coriaceum Wittm. (Caryocaraceae) fruit pulp fixed oil on mice ear edema induced by different irritant agents

AIM OF THE STUDY Caryocar coriaceum Wittm. fruit pulp fixed oil (CCFO) has been widely employed by communities from Brazil Northeastern in the treatment of skin inflammation, respiratory affections, wound healing and muscle pain. In this study, we evaluated the topical effect of CCFO against different irritant agents in vivo, in order to verify its antiedematous effect as well to unravel its tentative mechanisms of action. MATERIALS AND METHODS CCFO was obtained from Caryocar coriaceum fruits using ethyl acetate as solvent. Ear edema provoked by the application of Croton oil (single and multiple applications), arachidonic acid (AA), capsaicin, phenol and histamine to Swiss mice was used to evaluate the topical anti-inflammatory effect of CCFO. Histological analysis from mice ears sensitized with Croton oil and AA single application was also performed. RESULTS Crude CCFO (20μL/ear) demonstrated significant topical antiedematous effect against Croton oil single (inhibition of 32.0%; P<0.05) and multiple (41.4% after 9 days, P<0.001) applications, AA (inhibition of 49.7%; P<0.01) and phenol (inhibition of 38.8%; P<0.001). In contrast, CCFO did not antagonize the edema caused by topical treatment with capsaicin and histamine when compared to control group (P>0.05). Histological analysis also revealed that CCFO was able to reduce the edema and the influx of inflammatory cells in mice ears sensitized with Croton oil and AA. CONCLUSIONS CCFO exhibited a similar profile of topical anti-inflammatory activity to that of drugs that classically modulate the production of arachidonic acid metabolites. The study also indicates the potential application of CCFO as an important herbal medicine to be used against skin inflammatory diseases.

(-)-α-Bisabolol attenuates visceral nociception and inflammation in mice.

The study examined the antiinflammatory and antinociceptive effects of the sesquiterpene (-)-α-bisabolol (BISA). The antiinflammatory effect was evaluated on acute models of dermatitis induced by Croton oil, arachidonic acid, phenol and capsaicin, respectively, in mouse ear. BISA inhibited the dermatitis induced by all noxious agents, except capsaicin. BISA was assessed in two established mouse models of visceral nociception. Mice were pretreated orally with BISA, and the pain-related behavioral responses to intraperitoneal cyclophosphamide or to intracolonic mustard oil were analyzed. BISA showed a dose-unrelated significant antinociception. Collectively, the results suggest that BISA may be an topical antiinflammatory and visceral antinociceptive agent.

Topical antiinflammatory activity of essential oil of Lippia sidoides cham: possible mechanism of action.

This work reports the chemical composition of the essential oil of Lippia sidoides (EOLS) and evaluation of the topical effect of EOLS and thymol against different irritant agents in vivo. The essential oil was obtained by hydrodistillation, and gas chromatography/mass spectrometry analysis identified the main constituents: thymol (84.9%) and p‐cymene (5.33%). The antiinflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, phenol or histamine, and chronic inflammation induced by croton oil. The topical application of EOLS or thymol at a dose of 2 mg/ear significantly reduced (p < 0.001) ear edema induced with arachidonic acid by 45.1% and 47.4% and reduced ear edema induced with phenol by 33.2% (p < 0.05) and 54.7% (p < 0.01) in acute ear edema. However, a proinflammatory effect of EOLS and thymol was evidenced when it was applied for more than 1 day. There were no statistical differences in antiedematogenic activity between EOLS and thymol. In conclusion, the results indicate that thymol is the constituent responsible for the topical antiinflammatory activity of EOLS. Thus, these findings could justify the popular use of L. sidoides by alternative medicine, but chronic use has an inflammatory effect. Copyright

Ethnopharmacology of medicinal plants of carrasco, northeastern Brazil

ETHNOPHARMACOLOGICAL RELEVANCE The goal of this study was to conduct an ethnobotanical survey of medicinal species from the carrasco vegetation of the Araripe National Forest, state of Ceará, Brazil, as well as determining species with bioprospecting potential MATERIALS AND METHODS The ethnobotanical data were collected through semi-structured interviews and a free list. The relative importance of the plants cited was assessed, as well as species that stood out with respect to bodily systems, on the basis of informant consensus. RESULTS A total of 32 species belonging to 29 genera and 20 families were recorded. Of this total, six species (19%) showed great versatility regarding their uses in regard to up to seven bodily systems. The therapeutic indications were grouped into 14 categories of bodily systems. Circulatory and genitourinary disorders, endocrine, nutritional and metabolic diseases, and undefined pain or disease showed the greatest consensus between informants. CONCLUSIONS Ximenia americana, Himathantus drasticus, Stryphnodndron rotundifolium, Bowdichia virgilioides, and Hymenaea courbaril were the species warranting more in-depth study, on the basis of versatility and informant consensus on the uses of the species.

Anti-Trypanosoma cruzi and cytotoxic activities of Eugenia uniflora L.

Chagas disease is caused by Trypanosoma cruzi, being considered a public health problem. An alternative to combat this pathogen is the use of natural products isolated from fruits such as Eugenia uniflora, a plant used by traditional communities as food and medicine due to its antimicrobial and biological activities. Ethanolic extract from E. uniflora was used to evaluate in vitro anti-epimastigote and cytotoxic activity. This is the first record of anti-Trypanosoma activity of E. uniflora, demonstrating that a concentration presenting 50% of activity (EC(50)) was 62.76 μg/mL. Minimum inhibitory concentration (MIC) was ≤ 1024 μg/mL. Our results indicate that E. uniflora could be a source of plant-derived natural products with anti-epimastigote activity with low toxicity.

Modulation of the Antibiotic Activity by Extracts from Amburana cearensis A. C. Smith and Anadenanthera macrocarpa (Benth.) Brenan

The aim of this study was to verify the possible interactions between ethanol extracts of Amburana cearensis A. C. Smith and Anadenanthera macrocarpa (Benth.) Brenan, combined with six antimicrobial drugs against multiresistant strains of Staphylococcus aureus and Escherichia coli isolated from humans. The antibacterial activity of the extracts was determined using the minimum inhibitory concentration (MIC). The microdilution assay was performed to verify the interactions between the natural products and the antibiotics using a subinhibitory concentration. The activity of amikacin associated with the extract of Anadenanthera macrocarpa against EC 27 was enhanced, demonstrating an MIC reduction from 128 to 4 μg/mL. Among the β-lactams, no potentiation on its activity was observed, with exception to the antagonism of the natural products with ampicillin against S. aureus 358.

Biological Activities and Chemical Characterization of Cordia verbenacea DC. as Tool to Validate the Ethnobiological Usage

Knowledge of medicinal plants is often the only therapeutic resource of many communities and ethnic groups. “Erva-baleeira”, Cordia verbenacea DC., is one of the species of plants currently exploited for the purpose of producing a phytotherapeutic product extracted from its leaves. In Brazil, its major distribution is in the region of the Atlantic Forest and similar vegetation. The crude extract is utilized in popular cultures in the form of hydroalcoholic, decoctions and infusions, mainly as antimicrobial, anti-inflammatory and analgesic agents. The aim of the present study was to establish a chemical and comparative profile of the experimental antibacterial activity and resistance modifying activity with ethnopharmacological reports. Phytochemical prospecting and HPLC analysis of the extract and fractions were in agreement with the literature with regard to the presence of secondary metabolites (tannins and flavonoids). The extract and fraction tested did not show clinically relevant antibacterial activity, but a synergistic effect was observed when combined with antibiotic, potentiating the antibacterial effect of aminoglycosides. We conclude that tests of antibacterial activity and modulating the resistance presented in this work results confirm the ethnobotanical and ethnopharmacological information, serving as a parameter in the search for new alternatives for the treatment of diseases.

In vitro antimicrobial and modulatory activity of the natural products silymarin and silibinin.

Silymarin is a standardized extract from the dried seeds of the milk thistle (Silybum marianum L. Gaertn.) clinically used as an antihepatotoxic agent. The aim of this study was to investigate the antibacterial and antifungal activity of silymarin and its major constituent (silibinin) against different microbial strains and their modulatory effect on drugs utilized in clinical practice. Silymarin demonstrated antimicrobial activity of little significance against the bacterial strains tested, with MIC (minimum inhibitory concentration) values of 512 µg/mL. Meanwhile, silibinin showed significant activity against Escherichia coli with a MIC of 64 µg/mL. The results for the antifungal activity of silymarin and silibinin demonstrated a MIC of 1024 µg/mL for all strains. Silymarin and silibinin appear to have promising potential, showing synergistic properties when combined with antibacterial drugs, which should prompt further studies along this line.

Docking, characterization and investigation of β-cyclodextrin complexed with citronellal, a monoterpene present in the essential oil of Cymbopogon species, as an anti-hyperalgesic agent in chronic muscle pain model

BACKGROUND Citronellal (CT) is a monoterpene with antinociceptive acute effect. β-Cyclodextrin (βCD) has enhanced the analgesic effect of various substances. HYPOTHESIS/PURPOSE To evaluate the effect of CT both complexed in β-cyclodextrin (CT-βCD) and non-complexed, in a chronic muscle pain model (CMP) in mice. STUDY DESIGN The complex containing CT in βCD was obtained and characterized in the laboratory. The anti-hyperalgesic effect of CT and CT-βCD was evaluated in a pre-clinical in vivo study in a murine CMP. METHODS The complex was characterized through differential scanning calorimetry, derivative thermogravimetry, moisture determination, infrared spectroscopy and scanning electron microscopy. Male Swiss mice were pre-treated with CT (50mg/kg, po), CT-βCD (50mg/kg, po), vehicle (isotonic saline, po) or standard drug (tramadol4 mg/kg, ip). 60 min after the treatment and then each 1h, the mechanic hyperalgesia was evaluated to obtain the time effect. In addition, the muscle strength using grip strength meter and hyperalgesia were also performed daily, for 7 days. We assessed by immunofluorescence for Fos protein on brains and spinal cords of mice. The involvement of the CT with the glutamatergic system was studied with molecular docking. RESULTS All characterization methods showed the CT-βCD complexation. CT-induced anti-hyperalgesic effect lasted until 6h (p <0.001) while CT-βCD lasted until 8h (p <0.001vs vehicle and p <0.001vs CT from the 6th h). CT-βCD reduced mechanical hyperalgesia on all days of treatment (p <0.05), without changing muscle strength. Periaqueductal gray (p <0.01) and rostroventromedular area (p <0.05) showed significant increase in the Fos protein expression while in the spinal cord, there was a reduction (p <0.001). CT showed favorable energy binding (-5.6 and -6.1) to GluR2-S1S2J protein based in the docking score function. CONCLUSION We can suggest that βCD improved the anti-hyperalgesic effect of CT, and that effect seems to involve the descending pain-inhibitory mechanisms, with a possible interaction of the glutamate receptors, which are considered as promising molecules for the management of chronic pain such as CMP.