Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression.

Patients suffering from depression frequently display hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) resulting in elevated cortisol levels. One main symptom of this condition is anhedonia. There is evidence that exercise training can be used as a rehabilitative intervention in the treatment of depressive disorders. In this scenario, the aim of the present study was to assess the effect of an aerobic exercise training protocol on the depressive-like behavior, anhedonia, induced by repeated dexamethasone administration. The study was carried out on adult male Wistar rats randomly divided into four groups: the "control group" (C), "exercise group" (E), "dexamethasone group" (D) and the "dexamethasone plus exercise group" (DE). The exercise training consisted of swimming (1 h/d, 5 d/wk) for 3 weeks, with an overload of 5% of the rat body weight. Every day rats were injected with either dexamethasone (D/DE) or saline solution (C/E). Proper positive controls, using fluoxetine, were run in parallel. Decreased blood corticosterone levels, reduced adrenal cholesterol synthesis and adrenal weight (HPA disruption), reduced preference for sucrose consumption and increased immobility time (depressive-like behavior), marked hippocampal DNA oxidation, increased IL-10 and total brain-derived neurotrophic factor (BDNF; pro-plus mature-forms) and a severe loss of body mass characterized the dexamethasone-treated animals. Besides increasing testosterone blood concentrations, the swim training protected depressive rats from the anhedonic state, following the same profile as fluoxetine, and also from the dexamethasone-induced impaired neurochemistry. The data indicate that physical exercise could be a useful tool in preventing and treating depressive disorders.

Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens.

Dental caries and periodontal disease are associated with oral pathogens. Several plant derivatives have been evaluated with respect to their antimicrobial effects against such pathogenic microorganisms. Lippia sidoides Cham (Verbenaceae), popularly known as "Alecrim-pimenta" is a typical shrub commonly found in the Northeast of Brazil. Many plant species belonging to the genus Lippia yield very fragrant essential oils of potential economic value which are used by the industry for the commercial production of perfumes, creams, lotions, and deodorants. Since the leaves of L. sidoides are also extensively used in popular medicine for the treatment of skin wounds and cuts, the objective of the present study was to evaluate the composition and antimicrobial activity of L. sidoides essential oil. The essential oil was obtained by hydro-distillation and analyzed by GC-MS. Twelve compounds were characterized, having as major constituents thymol (56.7%) and carvacrol (16.7%). The antimicrobial activity of the oil and the major components was tested against cariogenic bacterial species of the genus Streptococcus as well as Candida albicans using the broth dilution and disk diffusion assays. The essential oil and its major components thymol and carvacrol exhibited potent antimicrobial activity against the organisms tested with minimum inhibitory concentrations ranging from 0.625 to 10.0 mg/mL. The most sensitive microorganisms were C. albicans and Streptococcus mutans. The essential oil of L. sidoides and its major components exert promising antimicrobial effects against oral pathogens and suggest its likely usefulness to combat oral microbial growth.

Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens

Dental caries and periodontal disease are associated with oral pathogens. Several plant derivatives have been evaluated with respect to their antimicrobial effects against such pathogenic microorganisms. Lippia sidoides Cham (Verbenaceae), popularly known as "Alecrim-pimenta" is a typical shrub commonly found in the Northeast of Brazil. Many plant species belonging to the genus Lippia yield very fragrant essential oils of potential economic value which are used by the industry for the commercial production of perfumes, creams, lotions, and deodorants. Since the leaves of L. sidoides are also extensively used in popular medicine for the treatment of skin wounds and cuts, the objective of the present study was to evaluate the composition and antimicrobial activity of L. sidoides essential oil. The essential oil was obtained by hydro-distillation and analyzed by GC-MS. Twelve compounds were characterized, having as major constituents thymol (56.7 percent) and carvacrol (16.7 percent). The antimicrobial activity of the oil and the major components was tested against cariogenic bacterial species of the genus Streptococcus as well as Candida albicans using the broth dilution and disk diffusion assays. The essential oil and its major components thymol and carvacrol exhibited potent antimicrobial activity against the organisms tested with minimum inhibitory concentrations ranging from 0.625 to 10.0 mg/mL. The most sensitive microorganisms were C. albicans and Streptococcus mutans. The essential oil of L. sidoides and its major components exert promising antimicrobial effects against oral pathogens and suggest its likely usefulness to combat oral microbial growth.

Antibacterial activity of the essential oil from Lippia aff. gracillis.

The essential oil of fresh leaves of Lippia aff. gracillis was analyzed by GC/MS and evaluated for its antibacterial effects. The results showed a moderate antibacterial activity and confirm the traditional uses of L. aff. gracillis.

Analgesic and anti-inflammatory effects of essential oils of Eucalyptus.

Many species of the genus Eucalyptus from the Myrtaceae family are used in Brazilian folk medicine for the treatment of various medical conditions such as cold, flue, fever, and bronchial infections. In the current investigation, we evaluated the analgesic and anti-inflammatory effects of essential oil extracts from three species of Eucalyptus employing various standard experimental test models. Using acetic acid-induced writhes in mice and hot plate thermal stimulation in rats, it was shown that the essential oils of Eucalyptus citriodora (EC), Eucalyptus tereticornis (ET), and Eucalyptus globulus (EG) induced analgesic effects in both models, suggesting peripheral and central actions. In addition, essential oil extracts from the three Eucalyptus species produced anti-inflammatory effects, as demonstrated by inhibition of rat paw edema induced by carrageenan and dextran, neutrophil migration into rat peritoneal cavities induced by carrageenan, and vascular permeability induced by carrageenan and histamine. However, no consistent results were observed for some of the parameters evaluated, both in terms of activities and dose-response relationships, reflecting the complex nature of the oil extracts and/or the assay systems used. Taken together, the data suggest that essential oil extracts of EC, ET, and EG possess central and peripheral analgesic effects as well as neutrophil-dependent and independent anti-inflammatory activities. These initial observations provide support for the reported use of the eucalyptus plant in Brazilian folk medicine. Further investigation is warranted for possible development of new classes of analgesic and anti-inflammatory drugs from components of the essential oils of the Eucalyptus species.

Analgesic and antiinflammatory effects of chalcones isolated from Myracrodruon urundeuva allemão.

The present work showed analgesic and antiinflammatory activities from a fraction containing three dimeric chalcones (chalcone enriched fraction - CEF), isolated from the stem-bark ethyl acetate extract of Myracrodruon urundeuva Allemao (Anacardiaceae). M. urundeuva is a popular medicinal plant used widely in Northeast Brazil, mainly as a topical female genital tract antiinflammatory. We observed that the CEF (5 and 10 mg/kg body wt., i.p. or p.o.) inhibited acetic acid-induced abdominal contractions in mice. In the formalin test, the CEF (5 and 10 mg/kg body wt.) was more effective intraperitoneally and inhibited predominantly the second phase of response. Naloxone reversed this effect, indicating an involvement of the opioid system. The CEF (10 and 20 mg/kg body wt.) also increased the reaction time to thermal stimuli in the hot-plate test in mice, after i.p. but not after p.o. administration. In the carrageenan-induced paw edema test in mice, the CEF (20 and 40 mg/kg body wt.) decreased paw volume significantly, after i.p. administration 2-4 hours after carrageenan injection. The CEF (40 mg/kg body wt.) was also active orally during the same period of time. The present work is the first report on peripheral and central analgesic effects and antiinflammatory activity of natural dimeric chalcones.

Antinociceptive properties of the essential oil of Ocimum gratissimum L. (Labiatae) in mice.

We have investigated the antinociceptive effects of the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) in two classical models of pain in male Swiss mice (25-35 g), the writhing test and the formalin test. At doses of 30, 100 and 300 mg/kg (po), EOOG produced a dose-dependent inhibition (from 58.3 4.4 to 40.7 6.3, 36.4 3.6 and 24.6 3.6, respectively; N = 8-10, P<0.05) of acetic acid-induced writhing, causing up to a ~60% inhibition at the highest dose used, comparable to that obtained with indomethacin (10 mg/kg, po). At the same doses, EOOG predominantly inhibited the late (inflammatory) phase of the formalin-induced pain response (from 59.3 8.3 to 40.4 4.8, 23.2 2.8 and 25.3 5.5, respectively; N = 6, P<0.05), with a maximal reduction of ~60% of the control, although a significant reduction of the initial (neurogenic) phase was also observed at 300 mg/kg (from 62.5 6.07 to 37 5.9; P<0.05). On the basis of these data, we conclude that EOOG possesses interesting antinociceptive properties in the writhing and formalin tests. Due to the relatively low toxicity of EOOG, further detailed examination is strongly indicated for a better characterization of its pharmacological properties and its potential therapeutic value.

Antinociceptive properties of the essential oil of Ocimum gratissimum L. (Labiatae) in mice

We have investigated the antinociceptive effects of the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) in two classical models of pain in male Swiss mice (25-35 g), the writhing test and the formalin test. At doses of 30, 100 and 300 mg/kg (po), EOOG produced a dose-dependent inhibition (from 58.3 ± 4.4 to 40.7 ± 6.3, 36.4 ± 3.6 and 24.6 ± 3.6, respectively; N = 8-10, P<0.05) of acetic acid-induced writhing, causing up to a 60 percent inhibition at the highest dose used, comparable to that obtained with indomethacin (10 mg/kg, po). At the same doses, EOOG predominantly inhibited the late (inflammatory) phase of the formalin-induced pain response (from 59.3 ± 8.3 to 40.4 ± 4.8, 23.2 ± 2.8 and 25.3 ± 5.5, respectively; N = 6, P<0.05), with a maximal reduction of 60 percent of the control, although a significant reduction of the initial (neurogenic) phase was also observed at 300 mg/kg (from 62.5 ± 6.07 to 37 ± 5.9; P<0.05). On the basis of these data, we conclude that EOOG possesses interesting antinociceptive properties in the writhing and formalin tests. Due to the relatively low toxicity of EOOG, further detailed examination is strongly indicated for a better characterization of its pharmacological properties and its potential therapeutic value

Anticonvulsant activity of essential oils and active principles from chemotypes of Lippia alba (Mill.) N.E. Brown.

In the present work we studied the anticonvulsive effects of the essential oils (EOs) from three chemotypes of Lippia alba (Mill.) N.E.Brown (Verbenaceae). Animals (female Swiss mice, 25 g) were treated with the EO and, 30 or 60 min after intraperitoneal (i.p.) or oral (p.o.) administration, respectively, injected with pentylenetetrazole (80 mg/kg, i.p.) and observed for 30 min. The results showed that EO I (200 and 400 mg/kg), EO II (100, 200 and 400 mg/kg), and EO III (400 mg/kg), i.p., produced an increased latency time for the first convulsion as related to controls. Death latency was greater in the groups receiving EO I (50 and 100 mg/kg), EO II (100 and 200 mg/kg), and EO III (200 mg/kg), i.p. Orally, while no effect was demonstrated with EOs at doses of 200 or 400 mg/kg, significant increases in the latency of convulsion and latency of death were observed with EO I at the highest dose (800 mg/kg). Similarly, EO III at this dose was also effective as far as latency of convulsion is concerned. Animals treated with citral (100 mg/kg, i.p.), beta-myrcene or limonene (200 mg/kg, i.p.), EOs chemical constituents, presented significant increases in the latency of convulsion and percentage of survival as compared to controls. After oral administration these effects were observed only with a higher dose (400 mg/kg). The association of EOs with diazepam significantly potentiated their effects, suggesting a similar mechanism of action and indicating that citral, beta-myrcene, and limonene are probably the EOs active compounds.

Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects.

PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

Antinociceptive effect of the essential oil from Cymbopogon citratus in mice.

The essential oil (EO) from leaves of Cymbopogon citratus increased the reaction time to thermal stimuli both after oral (25 mg/kg) and intraperitoneal (25-100 mg/kg) administration. EO (50-200 mg/kg, p.o. or i.p.) strongly inhibited the acetic acid-induced writhings in mice. In the formalin test, EO (50 and 200 mg/kg, i.p.) inhibited preferentially the second phase of the response, causing inhibitions of 100 and 48% at 200 mg/kg, i.p. and 100 mg/kg, p.o., respectively. On the other hand, the opioid antagonist naloxone blocked the central antinociceptive effect of EO, suggesting that EO acts both at peripheral and central levels.

Antinociceptive, anti-inflammatory and bronchodilator activities of Brazilian medicinal plants containing coumarin: a comparative study.

This work studied the antinociceptive, antiinflammatory and bronchodilator activities of hydroalcoholic extracts (HAEs) from Torresea cearensis, Justicia pectoralis, Eclipta alba, Pterodon polygaliflorus and Hybanthus ipecacuanha. These plants are largely used in north-eastern Brazil for respiratory tract diseases, and have in common coumarin, one of their active principles. The antinociceptive effects of all HAEs in mice were similar, and the inhibition of the acetic acid-induced writhing was 35-55% with 200 mg/kg, p.o. At this dose, the effect ranged from 41-77% with the formalin test in mice, and all the HAEs inhibited preferentially the 2nd phase of the response. In one case (P. polygaliflorus), the effect was partially reversed by naloxone. Except for the HAE from T. cearensis (200 mg/kg, p.o.) which inhibited carrageenan-induced edema by 47%, the others presented no effect orally but showed a significant activity intraperitoneally. On the other hand, T. cearensis was not active in the dextran model, while inhibitions with the other ones were lower than 30%. The bronchodilator activities of J. pectoralis and P. polygaliflorus HAEs as determined in isolated guinea-pig trachea were the most active.

Molluscicidal constituents of Marsypianthes chamaedrys.

Marsypianthes chamaedrys is a common herb that occurs in the North and Northeast regions of Brazil. Phytochemical studies showed this plant to be rich in triterpenoids. The hexane extract of M. chamaedrys yielded, after chromatographic separations, two mixtures: the first containing monohydroxylated-compounds (alpha-amyrin, beta-amyrin, lupeol and germanicol) and the second, dihydroxylated compounds (chamaedrydiol, castanopsol, 2alpha-hydroxylupeol and epigermanidiol). Molluscicidal tests were performed for the crude hexane extract and for mixtures I and II. Mixture II showed high activity.

Behavioral effects of essential oils from Lippia alba (Mill.) N.E. Brown chemotypes.

This work presents behavioral effects of three chemotypes of essential oils (EO) from Lippia alba (Mill.) N.E. Brown (Verbenaceae) on elevated plus maze, open field and rota rod tests and also on rectal temperature in mice. The results showed that all three EO increased significantly not only the number and percentage of entries, but also the time and percentage of time of permanence in the open arms. Greater effects were presented by EO II (50 mg/kg, i.p.) as related to controls for all parameters studied. In the open field test, while EO I (200 mg/kg, i.p.) decreased only the number of rearing as compared to controls, EO II and III (100 and 200 mg/kg, i.p., respectively) decreased both the number of rearing and grooming as compared to controls. None of them altered the number of crossings. In the rota rod test, only EO II (200 mg/kg, i.p.) decreased the time of permanence on the bar related to controls. All three EO decreased the rectal temperature at the doses of 100 and 200 mg/kg, i.p. EO I contains citral, beta-myrcene and limonene as the main constituents, while citral and limonene are present in EO II, and carvone and limonene in EO III. Citral and beta-myrcene seem to be the main active components of EO I and II. However, carvone and limonene are also active and probably responsible for the effects observed with EO III.

Antinociceptive and antiedematogenic effects of the hydroalcoholic extract and coumarin from Torresea cearensis Fr. All.

This work studied the antinociceptive and antiedematogenic effects of the hydroalcoholic extract (HAE) and coumarin (Coum) from T. cearensis in experimental models of nociception in mice, and carrageenan- and dextran-induced paw edema in rats. HAE (100 and 200 mg/kg, p.o.) and Coum (5-20 mg/kg, p.o.) reduced in a dose - dependent manner the nociception produced by acetic acid and formalin. In the hot plate test, HAE (100-400 mg/kg, p.o.) and Coum (5 and 10 mg/kg, p.o.) increased the latency time to the thermal stimulus 90 min after administration. While naloxone partially reversed the antinociceptive effect of the HAE but not that of Coum, L-arginine reversed the antinociceptive effect of Coum in the formalin test. HAE (200 mg/kg, p.o.) and Coum (10 and 20 mg/kg, p.o.) significantly inhibited the carrageenan-induced edemas in rats but not the dextran-induced edema. This antiedematogenic effect on the carrageenan model was supported by histological studies performed in sections of the rat paw. In conclusion, the antinociceptive effects of HAE and Coum occur by a mechanism at least in part dependent on the opioid system. The nitric oxide system possibly has also a role in the Coum nociception. In addition, the antiedematogenic activity is manifested in inflammatory processes dependent on polimorphonuclear cells.

A new triterpenoid saponin, bredemeyeroside B. from the roots of Bredemeyera floribunda.

A new triterpenoid saponin named bredemeyeroside B has been isolated from the roots of Bredemeyera floribunda and its structure elucidated as 3-O-beta-D-glucopyranosyl-2 beta, 3 beta, 27-trihydroxyolean-12-en-23,28-dioic acid 28-O-beta-D-xylopyranosyl-(1-->4)-[beta-D-apiofuranosyl-(1-->3)]-a lpha -L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->3] -beta-D-fucopyranoside by means of MS, NMR and chemical evidence. In addition rutin was also isolated. In laboratory tests bredemeyeroside B showed snake venom antidote activity.

[Antiseptic properties of essential oil of Lippia sidoides Cham. Application to the cutaneous microflora]. / Les propriétés antiseptiques de l'huile essentielle de Lippia sidoides Cham. Application à la microflore cutanée.

Two samples of essential oils of Lippia sidoides Cham. have been tested for their antibacterial and antifungal properties against some microorganisms living on the skin of feet and armpits. The essential oils and also their main components, thymol and carvacrol, show strong antagonistic activities. Corynebacterium xerosis developing axillary odour is specially inhibited. But on the other hand no specific activities have been observed upon the feet microflora.

Natural product chemistry in north-eastern Brazil.

The north-eastern region of Brazil comprises about one third of the country's territory. It is a semi-arid region with a flora rich in aromatic, toxic and medicinal plants. Screening of aromatic plants led to the investigation of about 2000 samples of essential oil from plants from the region and from abroad. Studies done by the Universidade Federal do Ceará and other research groups in the region discovered several new substances with distinct pharmacological activities. Recent examples are: schultezin, hydroxy-bisabolol, trans-annonene, (-)-hardwickic acid, trans-cascarillone, nor-cucurbitacins, oleanolic saponin and chalcone dimer. A social programme called the Living Pharmacy was created to teach poor people how to cultivate and use medicinal plants correctly. A project to develop interaction between the university and industry also arose from these studies.

Plants used in traditional medicine of China and Brazil.

Even though the rationale behind the use of medicinal plants in Brazil and China is different, twenty four species are used in both countries. Scientific name, vulgar name and uses in both countries along with their chemical constituents are listed.