Chemical Constituents and Pharmacology properties of Aristolochia triangularis: a south brazilian highly-consumed botanical with multiple bioactivities.

Aristolochia triangularis Cham., is one of the most frequently used medicinal plant in Southern Brazil. Preparations containing the leaves and/or stems are traditionally used as anti-inflammatory, diuretic, as well as antidote against snakebites. This study screened A. triangularis extracts, fractions and isolated compounds for different bioactivities. A weak antiproliferative activity against human lung cancer cell line (A549) was observed only for chloroform fraction obtained from stems (CFstems - CC50: 2.93 µg/mL). Also, a moderate antimicrobial activity against Staphylococcus aureus was detected just for chloroform fraction obtained from leaves (CFleaves -13-16 mm inhibition zone). Additionally, two semi-purified fractions (CFstems-4 and CFleaves-4) selectively inhibited HSV-1 replication (IC50 values of 0.40 and 2.61 µg/mL, respectively), while only CFleaves showed promising results against Leishmania amazonensis. Fractionation of extracts resulted in the isolation of one neolignan (-) cubebin and one lignan (+) galbacin. However, these compounds are not responsible for the in vitro bioactivities herein detected. The presence of aristolochic acid I and aristolochic acid II in the crude ethanol extract of stems (CEEstems) and leaves (CEEleaves) was also investigated. The HPLC analysis of these extracts did not display any peak with retention time or UV spectra comparable to aristolochic acids I and II.

Synthesis and SAR of new isoxazole-triazole bis-heterocyclic compounds as analogues of natural lignans with antiparasitic activity.

Despite the impressive scientific and technological advances of recent decades, no effective treatment is currently available for Chagas disease. Our research group has been studying the design and synthesis of analogues of natural lignans aiming to identify compounds with antiparasitic activity. This article reports the synthesis of 42 novel bis-heterocyclic derivatives and the structure-activity relationship study conducted based on results of biological assays against Trypanosoma cruzi amastigotes. Thirty-seven compounds were active, and eight of them had GI50 values lower than 100 µM (GI50 88.4-12.2 µM). A qualitative structure activity relationship study using three dimensional descriptors was carried out and showed a correlation between growth inhibitory potency and the presence of bulky hydrophobic groups located at rings A and D of the compounds. Compound 3-(3,4-dimethoxyphenyl)-5-((4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)methyl)isoxazole (31) was the most active in the series (GI50 12.2 µM), showing, in vitro, low toxicity and potency similar to benznidazole (GI50 10.2 µM). These results suggest that this compound can be a promising scaffold for the design of new trypanocidal compounds.

Comparative central effects of the aqueous leaf extract of two populations of Passiflora edulis

ABSTRACTPassiflora edulis Sims, Passifloraceae, has been used in Brazilian traditional folk medicine to the treatment of anxiety and insomnia. P. edulis is commonly known for its economic interests in Brazil. This species exhibits significant variability in the fruit rind color, then two subpopulations has been described (P. edulis fo. flavicarpa O. Deg. (PEF); P. edulis fo. edulis (PEE)). This study compared phytochemical profile and biological actions of aqueous leaf extract of PEE and PEF. HPLC analysis showed marked distinct chromatograms to the P. edulisvarieties. However, in both extracts the major compounds observed were flavonoids C-glycosides. Behavioral studies showed that PEE (300 mg/kg, p.o.) and PEF (100 and 300 mg/kg, p.o.) reduced anxiety in the elevated plus maze test. PEE (300 and 1000 mg/kg, p.o.) and PEF (1000 mg/kg, p.o.) also induced antidepressant-like actions in the forced swimming test. PEE 1000 mg/kg significantly reduced distance moved, thus suggesting sedation. No alterations in sleeping time were observed with PEE and PEF extracts. In conclusion, despite the similarities between the biological actions observed for both P. edulis varieties, quite different phytochemical profile was herein reported. These data suggest that the anxiolytic and antidepressant actions are not due to a specific phytochemical component.

Seasonal variations in the amount of isoorientin and isovitexin in Cecropia glaziovii Sneth. leaves over a two-year period / Variación estacionaria en el contenido de isoorientina e isovitexina en hojas de Cecropia glaziovii Sneth. durante un período de dos años

Cecropia glaziovii Sneth. (Urticaceae) is a common tree from Southeast and South of Brazil, being widely used in traditional medicine to treat heart and respiratory conditions. C-glycosylflavonoids have being described as the major compounds for this genus, however, no seasonality studies of individual flavonoids was conducted for any Cecropia specie. In this work, the content of isoorientin and isovitexin in aqueous extract from the leaves of C glaziovii during a two-year period was determined by high-performance liquid chromatography with diode array detector (HPLC-DAD). Seasonal alterations in the content of these two majority C-glycosylflavonoids as well its possible correlation with the pluviosity in the period of January/2008 to January/2010 were determined. Isoorientin presented higher content in November/09 (6.04 mg/g of extract) and lower content in May/08 (1.01 mg/g of extract). The higher content of isovitexin was observed in March/09 and the lower in September/08 (11.42 and 4.47 mg/g of extract, respectively). Although they have distinct behaviors, it was not observed correlation between the values of pluviosity and the production of these C-glycosylflavonoids.

Cecropia glaziovii Sneth. (Urticaceae) es un árbol comúnmente encontrada en el Suroriente y Sur de Brasil, siendo ampliamente utilizada en la medicina tradicional para el tratamiento de problemas cardíacos y respiratorios. Flavonoides C-glucósidos vienen siendo descritos como los compuestos mayoritarios del género, sin embargo, ningún estudio de estacionalidad de flavonoides analizados de modo individual fue realizado con ninguna especie de Cecropia. En el presente trabajo, el contenido de isoorientina e isovitexina en el extracto acuoso de las hojas de C. glaziovii durante un período de dos años fue determinado por HPLC-DAD. Variaciones estacionarias en el contenido de esos dos flavonoides C-glucósidos así como la posible correlación con la pluviosidad en el periodo de Enero/2008 hasta Enero/2010 fueron determinados. Isoorientina presentó mayor contenido en Noviembre/09 (6,04 mg/g de extracto) y menos contenido en Mayo/08 (1,01 mg/g de extracto). El mayor contenido de isovitexina fue observado in Marzo/09 y el menor contenido in Septiembre/08 (11,42 y 4,47 mg/g de extracto, respectivamente). Aunque los flavonoides poseen distintos comportamientos, no fue observada correlación entre los valores de pluviosidad y la producción de esos compuestos.

Evaluation of impacts of climate change and local stressors on the biotechnological potential of marine macroalgae: a brief theoretical discussion of likely scenarios

Climate change can be associated with variations in the frequency and intensity of extreme temperatures and precipitation events on the local and regional scales. Along coastal areas, flooding associated with increased occupation has seriously impacted products and services generated by marine life, in particular the biotechnological potential that macroalgae hold. Therefore, this paper analyzes the available information on the taxonomy, ecology and physiology of macroalgae and discusses the impacts of climate change and local stress on the biotechnological potential of Brazilian macroalgae. Based on data compiled from a series of floristic and ecological works, we note the disappearance in some Brazilian regions of major groups of biotechnological interest. In some cases, the introduction of exotic species has been documented, as well as expansion of the distribution range of economically important species. We also verify an increase in the similarities between the Brazilian phycogeographic provinces, although they still remain different. It is possible that these changes have resulted from the warming of South Atlantic water, as observed for its surface in southeastern Brazilian, mainly during the winter. However, unplanned urbanization of coastal areas can also produce similar biodiversity losses, which requires efforts to generate long-term temporal data on the composition, community structure and physiology of macroalgae.

Short and long-term effects of Baccharis articulata on glucose homeostasis.

In this study, the in vivo effect of the crude extract and n-butanol and aqueous residual fractions of Baccharis articulata (Lam.) Pers. on serum glucose levels, insulin secretion and liver and muscle glycogen content, as well as in vitro action on serum intestinal disaccharidase activity and albumin glycation were investigated. Oral administration of the extract and fractions reduced glycemia in hyperglycemic rats. Additionally, the n-butanol fraction, which has high flavonoids content, stimulated insulin secretion, exhibiting an insulinogenic index similar to that of glipizide. Also, the n-butanol fraction treatment significantly increased glycogen content in both liver and muscle tissue. In vitro incubation with the crude extract and n-butanol and aqueous residual fractions inhibited maltase activity and the formation of advanced glycation end-products (AGEs). Thus, the results demonstrated that B. articulata exhibits a significant antihyperglycemic and insulin-secretagogue role. These effects on the regulation of glucose homeostasis observed for B. articulata indicate potential anti-diabetic properties.

Effects of Ilex paraguariensis A. St. Hil. (yerba mate) on herpes simplex virus types 1 and 2 replication.

The antiherpes effects of the crude extract obtained from Ilex paraguariensis leaves (yerba mate) and their purified fractions were investigated. The most active fraction was selected and assayed to determine the viral multiplication steps upon which it acted. In order to detect the major components of this fraction, thin layer chromatography (TLC) analysis was performed. The antiviral activity was evaluated against HSV-1 and HSV-2 by a viral plaque number reduction assay (IC(50) ) and the cytotoxicity by a MTT assay (CC(50) ). According to the obtained results, all tested samples showed antiherpes activity at noncytotoxic concentrations, and the ethyl acetate fraction was the most active (SI = CC(50) /IC(50) = 188.7 and 264.7 for HSV-1 and HSV-2, respectively). The results also demonstrated that this fraction exerts antiviral activity by the reduction of viral infectivity, the inhibition of virus entry into cells and cell-to-cell virus spread, as well as by the impaired levels of ICP27, ICP4, gD and gE proteins of HSV-1. The TLC analysis showed that this fraction contains monodesmosidic triterpenoid saponins, matesaponin-1 (a bidesmosidic one), caffeic and chlorogenic acids and rutin, which suggests that they could act synergistically and be responsible for the detected antiherpes activity.

Chemical and pharmacological aspects of the genus Cecropia.

The Cecropia genus consists of about 60 species distributed throughout Latin America, mostly in Brazil. These species are widely used in traditional medicine to treat cough, asthma, bronchitis, high blood pressure, inflammation, heart disease, and as a diuretic. In recent years, there has been an increase in research on Cecropia species, with several phytochemical and pharmacological reports. Concerning its chemical composition, C-glycosylflavonoids and proanthocyanidins have been described as the main constituents of C. glaziovii, C. hololeuca and C. pachystachya, while terpenoids and steroids have been reported in several species, including C. adenopus and C. pachystachya. Among the pharmacological properties described for the genus, the most frequently reported are hypoglycemic activity for C. obtusifolia and C. peltata, and hypotensive and central nervous system activity for C. glaziovii. The present review compiles the information available on this genus because of its ethnopharmacological relevance and the potential therapeutic uses of these species.

New cytotoxic cucurbitacins from Wilbrandia ebracteata Cogn.

Chemical investigation of the roots of Wilbrandia ebracteata Cogn. (Cucurbitaceae) led to the isolation of two new (1- 2) and four known (3- 6) cucurbitacins. Their structures were elucidated by NMR and MS and compared with related compounds. The in vitro cytotoxicity of isolated compounds was evaluated against RD, KB, HCT-8, and A549 cell lines showing strong activity.

Chemical and anti-ulcer evaluation of Jodina rhombifolia (Hook. & Arn.) Reissek extracts / Estudo químico e da atividade antiúlcera de Jodina rhombifolia (Hook. & Arn.) Reissek

Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) is a medicinal plant popularly used as an anti-ulcer medicine. The plant native from Southern Brazil was chemically investigated and tested for its in vivo gastric anti-ulcer property by chloride acid/ethanol model. The chromatographic analysis of the hydroethanol extract of its leaves revealed the presence of C-glycosylflavonoids. From the n-butanol fraction of the hydroethanol extract of its aerial parts, vicenin-2 was isolated as the main component and identified by spectroscopic methods; and, a direct comparison with authentic samples was made. This fraction afforded three other C-glycosylflavonoids: vitexin, orientin and swertisin; all of them identified by direct comparison with authentic samples. We found that the oral administration of aqueous and hydroethanolic extracts led to a significant decrease in the ulcer index.

Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) é uma espécie vegetal nativa do Sul do Brasil e usada externamente na medicina popular para o tratamento de úlcera na pele. Neste trabalho foi estudada a atividade antiúlcera gástrica em ratos usando como indutor ácido clorídrico/etanol. Os extratos hidroetanólico e aquoso apresentaram atividade antiúlcera no modelo utilizado. A análise cromatográfica do extrato hidroetanólico das folhas indicou a presença de C-glicosilflavonóides. Da fração n-butanólica obtida por extração seqüencial do extrato hidroetanólico foi isolada e identificada por métodos espectroscópicos a vicenina-2 como substância majoritária. Desta fração também foram identificados por CCD bidimensional, com auxílio de substâncias de referência, outros três C-glicosídeos: vitexina, orientina e swertisina.

Evaluation of antiviral activity of South American plant extracts against herpes simplex virus type 1 and rabies virus.

This paper describes the screening of different South American plant extracts and fractions. Aqueous and organic extracts were prepared and tested for antiherpetic (HSV-1, KOS and 29R strains) and antirabies (PV strain) activities. The evaluation of the potential antiviral activity of these extracts was performed by using an MTT assay for HSV-1, and by a viral cytopathic effect (CPE) inhibitory method for rabies virus (RV). The results were expressed as 50% cytotoxicity (CC(50)) for MTT assay and 50% effective (EC(50)) concentrations for CPE, and with them it was possible to calculate the selectivity indices (SI = CC(50)/EC(50)) of each tested material. From the 18 extracts/fractions tested, six extracts and four fractions showed antiviral action. Ilex paraguariensis, Lafoensia pacari, Passiflora edulis, Rubus imperialis and Slonea guianensis showed values of SI > 7 against HSV-1 KOS and 29-R strains and Alamanda schottii showed a SI of 5.6 against RV, PV strain.

Evaluation of anxiolytic activity of spray dried powders of two South Brazilian Passiflora species.

The Passiflora extracts have been used in folk medicine because of its reputed sedative and anxiolytic properties. The present study aimed to compare the potential anxiolytic activity of two Passiflora spray-dried powders obtained from P. alata and P. edulis, known in Brazil as 'maracujá'. Male adult Swiss rats were treated with 200, 400 and 800 mg/kg of spray-dried powders p.o. and anxiolytic activity was evaluated using the elevated plus-maze test. The spray-dried powders showed anxiolytic activity in doses of 400 and 800 mg/kg. Our results support the potential anxiolytic effect of Passiflora spray-dried powders (P. alata and P. edulis).

Triterpenoids from Brazilian Ilex species and their in vitro antitrypanosomal activity.

From the leaves of Ilex affinis and Ilex buxifolia, two adulterant species of "erva mate" (Ilex paraguariensis), three new triterpenoid glycosides were isolated. Affinoside 1 (3beta-O-[beta-D-glucopyranosyl-(1-->3)-[2-O-acetyl-(1-->2]]-alpha-L-arabinopyranosyl pomolic acid 28-O-beta-D-glucopyranosyl ester, 1) was isolated from I. affinis, while buxifolioside I (28-O-beta-D-glucopyranosyl ester of (20S)-3alpha,19alpha-dihydroxyurs-12-ene-23,28-dioic acid, 7) and buxifolioside II (28-O-beta-D-glucopyranosyl ester of (20S)-3beta,19alpha-dihydroxyurs-12-en-24,28-dioic acid, 8) were isolated from I. buxifolia. Along with these new compounds, ilexoside II (2), ursolic acid (3), 28-nor-ursolic acid (4), 3beta-O-acetylursolic acid (5), and uvaol (6) were also isolated. The observed results confirm the structural specificity of the I. paraguariensis triterpenoids and reinforce a previous proposal to detect mate adulteration by triterpenoid analysis. In addition, the in vitro antitrypanosomal activity of some Ilex triterpenoids is also reported.

A triterpene ozonide from Senecio selloi.

From the dried and fresh aerial parts of Senecio selloi Spreng, De Candolle (Asteraceae), the new triterpene ozonide 1 was isolated. Its structure was elucidated by NMR experiments, including inverse techniques HMQC and HMBC and by synthesis from the precursor 2 In contrast to natural peroxides, no antiplasmodial activity was detected for the ozonide 1.

Antioxidant activity of Baccharis articulata extracts: isolation of a new compound with antioxidant activity.

Baccharis articulata is traditionally used as diuretic and digestive in local folk medicine of south of Brazil, Uruguay and Argentina. The antioxidant activity of crude ethanol and aqueous extracts, together with ethyl acetate and n-butanol fractions obtained from aqueous extract of B. articulata was determined using TRAP and TBARS assays. The n-butanol fraction was found to be the most active and its major compound (BaII) was isolated, identified and assayed. The structure of the phenolic compound BaII was established by means of spectroscopic and chemical methods as 4'-O-beta-D-glucopyranosyl-3',5'-dimethoxybenzyl-caffeate. This previously unreported metabolite presented similar antioxidant capacity when compared to Trolox.

Saponins from maté (Ilex paraguariensis) amd other South American Ilex species: ten years research on Ilx saponins

Ilex paraguariensis is widely used in South Brazil, Argentinna, Paraguay and Uruguay as a beverage (maté) and also as a traditional medicinal plant. During the past ten years, we have systematically studied the saponins of the leaves of genuine maté (Ilex paraguariensis) and the other Ilex species reported as adulterants, searching for chemical differences. Here we give a brief account of the elucidated saponin structures. Ilex paraguariensis and Ilex dumosa can be considered as saponin rich species, containing between 5-10 per cent of crude saponins in the leaves, in opposition to other species that showed a lower saponin content. All the saponins from Ilex paraguariensis leaves identified up to now are glycosides of ursolic or oleanolic acid. From Ilex dumosa, the most frequently quoted maté adulterant, we have isolated and elucidated the structures of ten saponins, almost all of them being glycosides of oleanolic acid and one of 29-hydroxyoleanolic acid. In comparison, the saponin pattern for the other South American Ilex species investigated up to now is different. The saponins from I. pseudobuxus, I. argentina, I. taubertiana and I. theezans all have the aglycones derived from the 19alpha-hydroxyursolic acid. Saponins containing this type of aglycone were not found in the leaves of Ilex paraguariensis and Ilex dumosa. These are important features, that may have taxonomical significance. Furthermore, this knowledge is necessary to develop methodologies for quality control of maté products and to identify the compounds involved in the tast, flavor and pharmacological properties.