Phylogenomic analyses of Sapindales support new family relationships, rapid Mid-Cretaceous Hothouse diversification, and heterogeneous histories of gene duplication.

Sapindales is an angiosperm order of high economic and ecological value comprising nine families, c. 479 genera, and c. 6570 species. However, family and subfamily relationships in Sapindales remain unclear, making reconstruction of the order's spatio-temporal and morphological evolution difficult. In this study, we used Angiosperms353 target capture data to generate the most densely sampled phylogenetic trees of Sapindales to date, with 448 samples and c. 85% of genera represented. The percentage of paralogous loci and allele divergence was characterized across the phylogeny, which was time-calibrated using 29 rigorously assessed fossil calibrations. All families were supported as monophyletic. Two core family clades subdivide the order, the first comprising Kirkiaceae, Burseraceae, and Anacardiaceae, the second comprising Simaroubaceae, Meliaceae, and Rutaceae. Kirkiaceae is sister to Burseraceae and Anacardiaceae, and, contrary to current understanding, Simaroubaceae is sister to Meliaceae and Rutaceae. Sapindaceae is placed with Nitrariaceae and Biebersteiniaceae as sister to the core Sapindales families, but the relationships between these families remain unclear, likely due to their rapid and ancient diversification. Sapindales families emerged in rapid succession, coincident with the climatic change of the Mid-Cretaceous Hothouse event. Subfamily and tribal relationships within the major families need revision, particularly in Sapindaceae, Rutaceae and Meliaceae. Much of the difficulty in reconstructing relationships at this level may be caused by the prevalence of paralogous loci, particularly in Meliaceae and Rutaceae, that are likely indicative of ancient gene duplication events such as hybridization and polyploidization playing a role in the evolutionary history of these families. This study provides key insights into factors that may affect phylogenetic reconstructions in Sapindales across multiple scales, and provides a state-of-the-art phylogenetic framework for further research.

Ligand screening assay for the enzyme kallikrein immobilized on NHS-activated Sepharose.

Human tissue kallikreins (KLKs) are serine proteases involved in various physiological and pathological conditions, including cancer and neurological disorders. These enzymes constitute attractive drug targets, which has stimulated the search for new KLK inhibitors. In this study, we have covalently immobilized porcine pancreas KLK on an NHS-activated Sepharose matrix, to obtain KLK-Sepharose-NHS. The immobilized enzyme showed high recovered activity and maintained the ability of free KLK to recognize the synthetic substrate Z-Phe-Arg-AMC (KMapp = 10.3 ±â€¯0.9 µM). As proof of concept, we used leupeptin as a reference inhibitor to perform inhibition studies for KLK-Sepharose-NHS and to determine the half-maximal inhibitory concentration (IC50 = 0.13 ±â€¯0.01 µM), the inhibition constant (Ki = 0.06 µM), and the leupeptin inhibition mechanism. We evaluated several complex matrixes (plant crude extract) by the same bioassay, to demonstrate their applicability. The species Solanum lycocarpum, Stryphnodendron adstringens, and Psychotria carthagenensis gave the best results. KLK-Sepharose-NHS was fully active after six consecutive reaction cycles and retained about 60 % of its initial activity after being used for at least five months, so the bioassay developed herein is a promising strategy to screen and to identify KLK ligands.

A tree nymph of the Brazilian Atlantic Forest: Dryades (Galipeinae, Rutaceae), a new neotropical genus segregated from Conchocarpus.

Subtribe Galipeinae (tribe Galipeeae) is the most diverse group of Rutaceae (the orange family) in the Neotropics, with 27 genera and ca. 130 species. The largest genus in the subtribe is Conchocarpus, with ca. 50 species, distributed from Central America to southern Brazil, and is particularly diverse in the Brazilian Atlantic Forest. The circumscription of the genus was recently changed to accommodate the species of Almeidea. However, even with this inclusion, Conchocarpus did not appear as monophyletic because the position of C. concinnus, which appeared in a clade with the other genera of Galipeinae rather than in the clade with the other species of Conchocarpus. The objective of the present study is to investigate the phylogenetic position of four other species of Conchocarpus (hereafter called "C. gauchaudianus group") that share morphological traits and geographical distribution with C. concinnus suggesting a close phylogenetic affinity. Phylogenetic analyses were based on morphological and molecular data from nuclear regions ITS-1 and ITS-2 as well as plastid regions trnL-trnF and rps-16, and were conducted with parsimony and Bayesian inference as optimization criteria. Results showed Conchocarpus as polyphyletic with its species divided in two clades, one, herein called "the Conchocarpus sensu stricto group," includes the type species C. macrophyllus, and the other "the Conchocarpus gaudichaudianus group" includes C. concinnus. The latter group is here recognized as a new genus, Dryades, the name given by Carl Friederich von Martius (1794-1868) to the Domain of the Atlantic Forest in Brazil, inspired by the tree nymphs in Greek mythology. Floral structure and leaf morphology provided further support to the findings of phylogenetic analysis. A description of the new genus, new combinations, a key to the species of the new genus, discussions of the affinities of the species are also provided, as well as data on the conservation status of the species of Dryades. Additionally, new data on floral structure of C. heterophyllus, C. macrophyllus and C. minutiflorus (all from the Conchocarpus sensu stricto group) are provided.

The ethanolic extract of Terminalia argentea Mart. & Zucc. bark reduces the inflammation through the modulation of cytokines and nitric oxide mediated by the downregulation of NF-κB.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia argentea Mart. & Zucc. (Combretaceae), popularly known as "capitão do campo", is native from the Brazilian cerrado, which is used in folk medicine to treat inflammatory diseases. AIM OF THE STUDY: We aimed to investigate the anti-inflammatory effects, toxicity and mechanisms of action regarding the use of the hydroalcoholic extract of T. argentea bark. MATERIALS AND METHODS: Toxicity was determinate in vitro using the macrophage lineage J774.1 without LPS. Cells were treated with 0.5; 2; 8; 32 and 125 µg/mL of the plant extract. Cell viability was assessed by MTT colorimetric assay. The production of nitrite and cytokines was also determined in the supernatants. A NF-κB reporter assay using RAW macrophages was employed to elucidate the impact of the plant extract on the expression of such molecule. In mice, toxicity was assessed by orally given an intermediate to high concentration of the plant extract on a single dose (1000 or 5000 mg/kg) or low and intermediate doses (300 or 1000 mg/kg) twice daily for 14 days. Blood samples were collected for biochemical analysis. The anti-inflammatory activity was assessed using the air-pouch model with or without pre-inoculation with the inflammatory stimuli LPS (0.5 µg/mL), followed by treatment with plant extract at 5, 60 or 300 mg/kg administered in the air pouch (subcutaneous injection). After 4 h, mice were euthanized and the air pouches washed with 2 mL heparinized PBS (10 IU/mL). Then, the local production in the air pouch wash of cytokines, total proteins and leukocytes was assessed. RESULTS: No signals of toxicity were observed either in cells or mice. Regardless the concentration used in vitro, the extract exhibited a significant anti-inflammatory activity, as perceived by the reduction of the inflammatory cytokines IL-1ß, TNF-α and IL-6 and nitrites on cell supernatants. This was concomitant with a downregulation in NF-κB and elevated levels of IL-10. In mice, similar effects were observed, especially when the plant extract was given at 300 mg/kg, inhibiting the release of IL-1ß, TNF-α, IL-6 and proteins, as well as increasing the release of IL-10. CONCLUSIONS: Altogether, our results demonstrated that the hydroalcoholic extract of T. argentea bark has anti-inflammatory activity without inducing toxicity in cells or living animals. This activity seems to be chiefly influenced by a downregulation in NF-κB, inflammatory cytokines and production of nitrite along with augmented concentration of IL-10.

Dalbergia ecastaphyllum (L.) Taub. and Symphonia globulifera L.f.: The Botanical Sources of Isoflavonoids and Benzophenones in Brazilian Red Propolis.

The Brazilian red propolis (BRP) constitutes an important commercial asset for northeast Brazilian beekeepers. The role of Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) as the main botanical source of this propolis has been previously confirmed. However, in addition to isoflavonoids and other phenolics, which are present in the resin of D. ecastaphyllum, samples of BRP are reported to contain substantial amounts of polyprenylated benzophenones, whose botanical source was unknown. Therefore, field surveys, phytochemical and chromatographic analyses were undertaken to confirm the botanical sources of the red propolis produced in apiaries located in Canavieiras, Bahia, Brazil. The results confirmed D. ecastaphyllum as the botanical source of liquiritigenin (1), isoliquiritigenin (2), formononetin (3), vestitol (4), neovestitol (5), medicarpin (6), and 7-O-neovestitol (7), while Symphonia globulifera L.f. (Clusiaceae) is herein reported for the first time as the botanical source of polyprenylated benzophenones, mainly guttiferone E (8) and oblongifolin B (9), as well as the triterpenoids ß-amyrin (10) and glutinol (11). The chemotaxonomic and economic significance of the occurrence of polyprenylated benzophenones in red propolis is discussed.

Chemosensitizing Effect of Cernumidine Extracted from Solanum cernuum on Bladder Cancer Cells in Vitro.

Cernumidine (CER) is a guanidinic alkaloid isolated from Solanum cernuum leaves. In this work, we investigated the cytotoxicity, chemosensitizing effect of cernumidine to cisplatin (cDDP) and the possible mechanism of action of the combination on bladder cancer cells. Cernumidine showed cytotoxicity and could sensitize bladder cancer cells to cisplatin. The combination of CER+cDDP inhibited cell migration on T24 cells. CER+cDDP down-regulated MMP-2/9 and p-ERK1/2, while it increased EGFR activity corroborating the observed cell migration inhibition. Down-regulation of Bcl-2 and up-regulation pro-apoptotic Bax and further depletion of the mitochondrial membrane potential (ΔΨm) indicates that mitochondria play a central role in the combination treatment inducing the mitochondrial signaling pathway of apoptosis in T24 cells. Our data showed that the alkaloid cernumidine is worthy of further studies as a chemosensitizing agent to be used in complementary chemotherapy.

Antiplasmodial evaluation of Anacardium occidentale and alkyl-phenols

Abstract The ethanol crude extract from cashew (Anacardium occidentale L. Anacardiaceae) displayed significant antiplasmodial activity (IC50 0.577 µg/ml). Liquid chromatography-high resolution Mass spectrometry analysis was performed to identify the main compounds existing in the ethanol extract. The occurrence of anacardic acids, cardols, and 2-methylcardols derivatives was confirmed in the extract. The IC50 obtained, when the main isolated compounds were evaluated in Plasmodium falciparum D6 strain, ranged from 5.39 µM to >100 µM. Tested here for the first time, the data showed that cardol triene 1 (IC50 = 5.69 µM) and 2-methylcardol triene 4 (IC50 = 5.39 µM) demonstrated good antimalarial activity. In conclusion, Anacardium occidentale nuts presented relevant biological potential, and further studies should be considered.

Chronic treatment with hydroalcoholic extract of Plathymenia reticulata promotes islet hyperplasia and improves glycemic control in diabetic rats / Tratamento crônico com extrato hidroalcoólico de Plathymenia reticulata promove hiperplasia de ilhotas e controle glicêmico em ratos diabéticos

ABSTRACT Objective: To investigate the anti-hyperglycemic effects of Plathymenia reticulata hydroalcoholic extract and related changes in body weight, lipid profile and the pancreas. Methods: Diabetes was induced in 75 adult male Wistar rats via oral gavage of 65mg/Kg of streptozotocin. Rats were allocated to one of 8 groups, as follows: diabetic and control rats treated with water, diabetic and control rats treated with 100mg/kg or 200mg/kg of plant extract, and diabetic and control rats treated with glyburide. Treatment consisted of oral gavage for 30 days. Blood glucose levels and body weight were measured weekly. Animals were sacrificed and lipid profile and pancreatic tissue samples analyzed. Statistical analysis consisted of ANOVA, post-hoc Tukey-Kramer, paired Student's t and χ2 tests; the level of significance was set at 5%. Results: Extract gavage at 100mg/kg led to a decrease in blood glucose levels in diabetic rats in the second, third (198.71±65.27 versus 428.00±15.25) and fourth weeks (253.29±47.37 versus 443.22±42.72), body weight loss (13.22±5.70 versus 109.60±9.95) and lower cholesterol levels (58.75±3.13 versus 80.11±4.01) in control rats. Extract gavage at 200mg/Kg led to a decrease in glucose levels on the fourth week in diabetic rats, body weight loss in the second, third and fourth weeks in control rats, and lower cholesterol levels in diabetic and control rats. Islet hyperplasia (p=0.005) and pancreatic duct dilation (p=0.047) were observed in diabetic and control rats. Conclusion: Plathymenia extract reduced blood glucose levels in diabetic rats, and body weight in control rats, and promoted pancreatic islet hyperplasia in diabetic and control rats.

RESUMO Objetivo: Avaliar o efeito anti-hiperglicêmico do extrato hidroalcoólico de Plathymenia reticulata, alterações no peso, lipídeos e efeito sobre o pâncreas. Métodos: O diabetes foi induzido pela administração de estreptozotocina 65mg/kg, em 75 ratos Wistar adultos machos, divididos em 8 grupos diferentes: ratos diabéticos e controle + água, ratos diabéticos e controle + 100mg/kg ou 200mg/kg de extrato, ratos diabéticos e controle + gliburida. O tratamento foi realizado por gavagem (oral) por 30 dias. Níveis de glicose e peso foram verificados semanalmente. Os animais foram sacrificados, e amostras de lipídeos e do pâncreas foram analisadas. A análise estatística incluiu ANOVA, post-hoc Tukey-Kramer, teste t de Student pareado e teste do χ2, com nível de significância de 5%. Resultados: O extrato 100mg/kg promoveu redução nos níveis de glicose sanguínea em ratos diabéticos na segunda, terceira (198,71±65,27 versus 428,00±15,25) e quarta semanas (253,29±47,37 versus 443,22±42,72), perda de peso (13,22±5,70 versus 109,60±9,95) e diminuição do colesterol (58,75±3,13 versus 80,11±4,01) em ratos controle. Com extrato de 200mg/kg, houve redução dos níveis de glicose na quarta semana, nos ratos diabéticos; de peso na segunda, terceira e quarta semanas, nos ratos controle; e de colesterol nos animais diabéticos e controle. Ocorreram hiperplasia de ilhotas (p=0,005) e dilatação dos ductos pancreáticos (p=0,047) em ratos diabéticos e controles. Conclusão: O extrato de Plathymenia reduziu os níveis de glicose em ratos diabéticos e de peso em ratos controle, além de ter promovido hiperplasia de ilhotas pancreáticas em diabéticos e controles.

Chemical Composition, Antibacterial, Schistosomicidal, and Cytotoxic Activities of the Essential Oil of Dysphania ambrosioides (L.) Mosyakin & Clemants (Chenopodiaceae).

We have investigated the chemical composition and the antibacterial activity of the essential oil of Dysphania ambrosioides (L.) Mosyakin & Clemants (Chenopodiaceae) (DA-EO) against a representative panel of cariogenic bacteria. We have also assessed the in vitro schistosomicidal effects of DA-EO on Schistosoma mansoni and its cytotoxicity to GM07492-A cells in vitro. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS) revealed that the monoterpenes cis-piperitone oxide (35.2%), p-cymene (14.5%), isoascaridole (14.1%), and α-terpinene (11.6%) were identified by as the major constituents of DA-EO. DA-EO displayed weak activity against Streptococcus sobrinus and Enterococcus faecalis (minimum inhibitory concentration (MIC) = 1000 µg/ml). On the other hand, DA-EO at 25 and 12.5 µg/ml presented remarkable schistosomicidal action in vitro and killed 100% of adult worm pairs within 24 and 72 h, respectively. The LC50 values of DA-EO were 6.50 ± 0.38, 3.66 ± 1.06, and 3.65 ± 0.76 µg/ml at 24, 48, and 72 h, respectively. However, DA-EO at concentrations higher than 312.5 µg/ml significantly reduced the viability of GM07492-A cells (IC50  = 207.1 ± 4.4 µg/ml). The selectivity index showed that DA-EO was 31.8 times more toxic to the adult S. mansoni worms than GM07492-A cells. Taken together, these results demonstrate the promising schistosomicidal potential of the essential oil of Dysphania ambrosioides.

Antischistosomal and Cytotoxic Effects of the Essential Oil of Tetradenia riparia (Lamiaceae).

This paper reports on the antischistosomal and cytotoxic effects of the essential oil obtained from Tetradenia riparia leaves (TR-EO). At concentrations of 50 and 100 µg/mL, TR-EO killed all the worms after 120 and 24 h of incubation, respectively. At a concentration equal to or higher than 50 µg/mL, this oil also separated the coupled pairs and decreased the adult worm motor activity after incubation periods higher than 72 h. In addition, at 120 h of incubation, TR-EO slightly decreased the number of eggs produced by Schistosoma mansoni adult worms and significantly reduced the percentage of developed eggs, in a dose-dependent manner. XTT-colorimetric assays showed that the tested TR-EO concentrations were not considerably cytotoxic to V79 cells (IC50 = 253.5 µg/mL). The effects of TR-EO on egg development were noteworthy; therefore, this essential oil deserves further investigation to identify the chemical constituents that elicit activity against S. mansoni.

Anthelmintic effects of the essential oil of fennel (Foeniculum vulgare Mill., Apiaceae) against Schistosoma mansoni.

Foeniculum vulgare Mill. (Apiaceae), known as fennel, is a widespread aromatic herbaceous plant, and its essential oil is used as additive in the food, pharmaceutical, cosmetic, and perfume industries. The in vitro antischistosomal activity and cytotoxic effects against V79 cells of the essential oil of F. vulgare cultivated in southeastern Brazil (FV-EO) was investigated. The FV-EO was obtained by hydrodistillation and characterized by GC-FID and GC/MS analyses. (E)-Anethole (69.8%) and limonene (22.5%) were identified as the major constituents. Its anthelmintic activity against Schistosoma mansoni was evaluated at concentrations of 10, 50, and 100 µg/ml, and it was found to be active against adult S. mansoni worms, although it was less effective than the positive control praziquantel (PZQ) in terms of separation of the coupled pairs, mortality, and decreased motor activity. However, FV-EO elicited an interesting dose-dependent reduction in the number of S. mansoni eggs. On their own, (E)-anethole and the limonene enantiomers were much less effective than FV-EO and PZQ. An XTT-cytotoxicity-based assay evidenced no FV-EO cytotoxicity against V79 cells. In summary, FV-EO displayed moderate in vitro schistosomicidal activity against adult S. mansoni worms, exerted remarkable inhibitory effects on the egg development, and was of low toxicity.

Antimicrobial Activity of the Essential Oil of Plectranthus neochilus against Cariogenic Bacteria.

This work used the broth microdilution method to investigate the antimicrobial activity of the essential oil obtained from the leaves of Plectranthus neochilus (PN-EO) against a representative panel of oral pathogens. We assessed the antimicrobial activity of this oil in terms of the minimum inhibitory concentration (MIC). PN-EO displayed moderate activity against Enterococcus faecalis (MIC = 250 µg/mL) and Streptococcus salivarus (MIC = 250 µg/mL), significant activity against Streptococcus sobrinus (MIC = 62.5 µg/mL), Streptococcus sanguinis (MIC = 62.5 µg/mL), Streptococcus mitis (MIC = 31.25 µg/mL), and Lactobacillus casei (MIC = 31.25 µg/mL), and interesting activity against Streptococcus mutans (MIC = 3.9 µg/mL). GC-FID and GC-MS helped to identify thirty-one compounds in PN-EO; α-pinene (1, 14.1%), ß-pinene (2, 7.1%), trans-caryophyllene (3, 29.8%), and caryophyllene oxide (4, 12.8%) were the major chemical constituents of this essential oil. When tested alone, compounds 1, 2, 3, and 4 were inactive (MIC > 4000 µg/mL) against all the microorganisms. These results suggested that the essential oil extracted from the leaves of Plectranthus neochilus displays promising activity against most of the evaluated cariogenic bacteria, especially S. mutans.

Chemical composition, antischistosomal and cytotoxic effects of the essential oil of Lavandula angustifolia grown in Southeastern Brazil

This paper reports on the chemical composition, the in vitro antischistosomal effects, and the cytotoxicity of the essential oil from the leaves of Lavandula angustifolia Mill., Lamiaceae, grown in the Southeastern Brazil. Borneol (22.4%), epi-α-muurolol (13.4%), α-bisabolol (13.1%), precocene I (13.0%), and eucalyptol (7.9%) were the major essential oil constituents. Incubation with essential oil at 200 μg/ml killed all the adult S. mansoni worms after 24 h (LC50 117.7 and 103.9 μg/ml at 24 and 120 h of incubation, respectively). At a concentration of 50 μg/ ml, the essential oil significantly decreased the motor activity and reduced the percentage of egg development after 120 h. In addition, the essential oil separated all the coupled S. mansoni worm pairs into individual male and female at 25 and 50 μg/ml within 120 and 24 h, respectively. This oil was cytotoxic to GM07492-A cells at only concentrations higher than 200 µg/ml (IC50 243.7 µg/ml). These data indicate that LA-EO exhibits moderate in vitro activity against adult S. mansoni and exerts remarkable effects on eggs development.

Antibacterial evaluation of Styrax pohlii and isolated compounds

The antibacterial activity of the compounds egonol (1) and homoegonol (2), of the crude ethanolic extract of Styrax pohlii (Styracaceae) aerial parts (EE), and of its n-hexane (HF), EtOAc (EF), n-BuOH (BF), and hydromethanolic (HMF) fractions was evaluated against the following microorganisms: Streptococcus pneumoniae (ATCC 6305), S. pyogenes (ATCC 19615), Haemophilus influenzae (ATCC 10211), Pseudomonas aeruginosa (ATCC 27853), and Klebsiella pneumoniae (ATCC 10031). The broth microdilution method was used for determination of the minimum inhibitory concentration (MIC) during preliminary evaluation of antibacterial activity. The EE yielded MIC values of 400 µg/mL for S. pneumoniae and P. aeruginosa and 300 µg/mL for H. influenzae. The HF and EF fractions exhibited enhanced antibacterial activity, with MIC values of 200 µg/mL against S. pneumoniae, but only EF displayed activity against H. influenzae (MIC 200 µg/mL). The best MIC value with compounds 1 and 2 (400 µg/mL) was obtained for (1) against S. pneumoniae and P. aeruginosa. Therefore, 1 exhibited weak antibacterial activity against these standard strains.

As atividades antimicrobianas das substâncias egonol (1) e homoegonol (2), do extrato etanólico das partes aéreas de Styrax pohlii (Styracaceae) (EE), bem como das frações n-hexano (HF), AcOEt (EF), n-BuOH (BF) e hidrometanólica (HMF) foram avaliadas frente aos seguintes microorganismos: Streptococcus pneumoniae (ATCC 6305), S. pyogenes (ATCC 19615), Haemophilus influenzae (ATCC 10211), Pseudomonas aeruginosa (ATCC 27853) e Klebsiella pneumoniae (ATCC 10031). O método de microdiluição em caldo foi utilizado para a determinação da concentração inibitória mínima (CIM) na avaliação preliminar da atividade antimicrobiana. EE mostrou valores de CIM de 400 µg/mL para S. pneumoniae e P. aeruginosa, e 300 µg/mL para H. influenzae. As frações HF e EF apresentaram melhora na atividade antimicrobiana, com valores de CIM de 200 µg/mL frente S. pneumoniae, mas apenas EF apresentou ação contra H. influenzae (200 µg/mL). Em relação às substâncias 1 e 2, o melhor valor de CIM (400 µg/mL) foi obtido por 1 frente a S. pneumoniae e P. aeruginosa, que exibiu fraca atividade antimicrobiana contra estas cepas padrões.

In vitro schistosomicidal effects of the essential oil of Tagetes erecta

The in vitro schistosomicidal effects of the essential oil obtained from Tagetes erecta L. Asteraceae, leaves (TE-EO) collected in Brazil against Schistosoma mansoni worms are reported in this paper. The oil caused a significant decrease in the motor activity at 50 µg/mL as minimal concentration after 24 h. This oil also caused death of all the parasites and the separation of coupled pairs into individual male and female at 100 µg/mL after 24 h. The viability of adult worm groups treated with the TE-EO at 100 µg/mL was similar to that of groups treated with praziquantel (positive control). In addition, the oil promoted the inhibition of eggs development at all the tested concentrations. These data indicate that the TE-EO could be considered as a promising source for the development of new schistosomicidal agents.

Chemical composition and in vitro schistosomicidal activity of the essential oil of Plectranthus neochilus grown in Southeast Brazil.

The chemical composition and the in vitro schistosomicidal effects of the essential oil of Plectranthus neochilus (PN-EO) grown in Southeast Brazil was studied. ß-Caryophyllene (1; 28.23%), α-thujene (2; 12.22%), α-pinene (3; 12.63%), ß-pinene (4; 6.19%), germacrene D (5; 5.36%), and caryophyllene oxide (6; 5.37%) were the major essential oil constituents. This chemical composition differed from that previously reported for specimens harvested in Africa. Concerning the in vitro schistosomicidal activity against adult Schistosoma mansoni worms, PN-EO was considered to be active, but less effective than the positive control praziquantel (PZQ) in terms of separation of coupled pairs, mortality, decrease in the motor activity, and tegumental alterations. However, PN-EO caused an interesting dose-dependent reduction in the number and the percentage of developed S. mansoni eggs. These results suggest that PN-EO might be very promising for the development of new schistosomicidal agents.

Schistosomicidal activity of the essential oil of Ageratum conyzoides L. (Asteraceae) against adult Schistosoma mansoni worms.

The in vitro schistosomicidal effects of the essential oil of Ageratum conyzoides L. (Ac-EO) against adult worms of Schistosoma mansoni is reported in this paper. Concerning this activity, Ac-EO was considered to be active, but less effective than the positive control (praziquantel, PZQ) in terms of separation of coupled pairs, mortality, decrease in motor activity, and tegumental alterations. However, Ac-EO caused an interesting dose-dependent reduction in the number of eggs of S. mansoni. Precocene I (74.30%) and (E)-caryophyllene (14.23%) were identified as the two major constituents of Ac-EO. These compounds were tested individually and were found to be much less effective than Ac-EO and PZQ. A mixture of the two major compounds in a ratio similar to that found in the Ac-EO was also less effective than Ac-EO, thus revealing that there are no synergistic effects between these components. These results suggest that the essential oil of A. conyzoides is very promising for the development of new schistosomicidal agents.

Comparative effects of lantadene A and its reduced metabolite on mitochondrial bioenergetics.

Lantana (Lantana camara Linn.) is a noxious weed to which certain medicinal properties have been attributed, but its ingestion has been reported to be highly toxic to animals and humans, especially in the liver. The main hepatotoxin in lantana leaves is believed to be the pentacyclic triterpenoid lantadene A (LA), but the precise mechanism by which it induces hepatotoxicity has not yet been established. This work addressed the action of LA and its reduced derivative (RLA) on mitochondrial bioenergetics. At the concentration range tested (5-25 microM), RLA stimulated state-4 respiration, inhibited state-3 respiration, circumvented oligomycin-inhibited state-3 respiration, dissipated membrane potential and depleted ATP in a concentration-dependent manner. However, LA did not stimulate state-4 respiration, nor did it affect the other mitochondrial parameters to the extent of its reduced derivative. The lantadenes didn't inhibit the CCCP-uncoupled respiration but increased the ATPase activity of intact coupled mitochondria. The ATPase activity of intact uncoupled or disrupted mitochondria was not affected by the compounds. We propose, therefore, that RLA acts as a mitochondrial uncoupler of oxidative phosphorylation, a property that arises from the biotransformation (reduction) of LA, and LA acts in other mitochondrial membrane components rather than the ATP synthase affecting the mitochondrial bioenergetics. Such effects may account for the well-documented hepatoxicity of lantana.