The Protective Role of Lychnophora ericoides Mart. (Brazilian Arnica) in 1,2-Dimethylhydrazine-Induced Experimental Colon Carcinogenesis

Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.

Antibacterial activity of 15-deoxygoyazensolide isolated from the stems of Minasia alpestris (Asteraceae) against oral pathogens

This work reports the isolation of the sesquiterpene lactone 15-deoxygoyazensolide from the stems of Minasia alpestris and the evaluation of its antimicrobial activity against the following oral pathogens: Enterococcus faecalis, Streptococcus salivarius, Streptococcus sobrinus, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, and Lactobacillus casei. Despite the cytotoxicity and genotoxicity of other sesquiterpene lactones of the furanoheliangolide-type, our results revealed that this compound exhibits low antibacterial activity against the evaluated oral pathogens; however, an interesting selectivity against E. faecalis (minimum inhibitory concentration [MIC] = 40 mu g mL(-1)) and S. sobrinus (MIC = 60 mu g mL(-1)) was observed.

Constituents of glandular trichomes of Tithonia diversifolia: Relationships to herbivory and antifeedant activity

The herbivory activity of the bordered patch larvae (Chlosyne lacinia, Lepidoptera) on leaves of a Brazilian population of Tithonia diversifolia and the antifeedant potential of its leaf rinse extract were investigated. The caterpillars fed only on the adaxial face, where the density of glandular trichomes is very low, and avoided the abaxial face, which contains high levels of trichomes. Deterrent activity against the larvae was observed in leaf discs treated with leaf rinse extract at concentrations of 1-5% of fresh leaf weight. High-performance liquid chromatography (HPLC) analysis indicated that sesquiterpene lactones are the main constituents of the glandular trichomes. Dichloromethane rinse extracts of the leaves and inflorescences were chemically investigated, and 16 compounds were isolated and identified: 14 sesquiterpene lactones, a flavonoid and a diterpenoid. In this study, five sesquiterpene lactones are described for the first time in the genus, including two lactones, one of which has an unusual seco-guaianolide skeleton. Our findings indicate that the caterpillars avoid the sesquiterpene-lactone-rich glandular trichomes, and provide evidence for the antifeedant activity of the dichloromethane leaf rinse extract. In addition, a study of the seasonal variation of the main constituents from the leaf surface throughout a year demonstrated that a very low qualitative but a very high quantitative variation occurs. The highest level of the main metabolite tagitinin C was observed between September and October and the lowest was from March to June, the later corresponding to the period of highest infestation by the larvae. (C) 2008 Elsevier Ltd. All rights reserved.

An approach to the synthesis of furanoheliangolides through Diels-Alder reactions

The core structure of the natural sesquiterpene lactones furanoheliangolides, an 11-oxabicyclo[6.2.1]undecane system, was synthesized through a pathway involving two Diels-Alder reactions. (c) 2007 Elsevier Ltd. All rights reserved.

Effects of phonophoresis with Arnica montana onto acute inflammatory process in rat skeletal muscles: An experimental study

This study aimed at verifying the effects of phonophoresis associated with Arnica montana on the acute phase of an inflammatory muscle lesion. Forty Wistar male rats (300 +/- 50 g), of which the Tibialis Anterior muscle was surgically lesioned, were divided into four groups (n = 10 each): control group received no treatment; the ultrasound group (US) was treated in pulsed mode with 1-MHz frequency, 0.5 W/cm(2) intensity (spatial and temporal average - SATA), duty cycle of 1: 2 (2 ms on, 4 ms off, 50%), time of application 3 min per session, one session per day, for 3 days; the phonophoresis or ultrasound plus arnica (US+A) group was treated with arnica with the same US parameters plus arnica gel; and the arnica group (A) was submitted to massage with arnica gel, also for 3 min, once a day, for 3 days. Treatment started 24 h after the surgical lesion. On the 4th day after lesion creation, animals were sacrificed and sections of the lesioned, inflamed muscle were removed for quantitative (mononuclear and polymorphonuclear cell count) and qualitative histological analysis. Collected data from the 4 groups were statistically analyzed and the significance level set at p < 0.05. Results show higher mononuclear cell density in all three treated groups with no significant difference between them, but values were significantly different (p < 0.0001) when compared to control group`s. As to polymorphonuclear cell density, significant differences were found between control group (p = 0.0134) and US, US+A and A groups; the arnica group presented lesser density of polymorphonuclear cells when compared (p = 0.0134) to the other groups. No significant difference was found between US and US+A groups. While the massage with arnica gel proved to be an effective anti-inflammatory on acute muscle lesion in topic use, these results point to ineffectiveness of Arnica montana phonophoresis, US having seemingly checked or minimized its anti-inflammatory effect. (C) 2008 Elsevier B. V. All rights reserved.

Effects of Goyazensolide during in Vitro Cultivation of Schistosoma mansoni

Goyazensolide, a component extracted of Eremanthus goyazensis showed a significant inhibitory effect on egg-laying of Schistosoma mansoni during in vitro cultivation of this parasite. Motility of the worms was also reduced under treatment with goyazensolide and 90% of mortality was reached with concentrations up to 4mg/ml. It has found that separated worms were more susceptible than worms pairing during drug exposition and female alone was significantly more susceptible than male worm in the same conditions of in vitro cultivation. Natural products isolated from plants represent potential sources for the identification of structures useful for the design of alternative molecules to be used as new drug substances against several infectious diseases

Identification and Characterization of Natural Anti-Breast Cancer Compound: Costunolide

Breast cancer is the most common cancer among women, 23% (1.3 million) of the total of new cases and the second leading cause of cancer death in women exceeded only by lung cancer. Natural medicines have been proven to be a central source of narrative agents with a pharmaceutical potential. Costunolide is sesquiterpene lactones consisting of diverse plant chemicals that exhibit anti cancer action through cytotoxic effects on various cancer cells. The objectives of present study were to explore the effects of natural compounds on the proliferation of MCF-7 cells and to determine the role of ROS in natural compounds-induced apoptosis in breast cancer cells with a therapeutic potential. Results showed that costunolide screened, possess potent anticancer properties against breast cancer MCF-7 cells, Costunolide was observed as strong anti-proliferative agent with IC50 = 50µM. The anti-proliferative effect of costunolide on MCF cells was confirmed by live/dead assay using fluorescent probes calcein AV/PI. The results demonstrated that treatment of cells with costunolide decreased the viability of MCF-7 cells in a dose-dependent manner. To determine the costunolide-induced apoptosis, flow cytometric analysis was carried out. The results showed that costunolide induced apoptosis in a dose-dependent manner in breast cancer MCF-7cells. ROS are well known mediators of intracellular signaling of cascades. The excessive generation of ROS can induce oxidative stress, loss of cell functioning, and apoptosis. In the present study, we assumed that costunolide might arouse ROS level, which could be involved in induction of apoptosis. Therefore, the intracellular ROS level was measured using the ROS-detecting fluorescence dye 2, 7-dichlorofluorescein diacetate (DCF-DA). Interestingly these effects were significantly abrogated when the cells were pretreated with N-acetyl- cysteine (NAC), a specific ROS inhibitor. Costunolide induces apoptosis through extrinsic pathway in MCF-7 breast cancer cells, In order to examine whether costunolide suppresses cell growth inducing apoptotic cell death, we analyzed DNA contents and apoptosis-related proteins expression level by flow cytometry and western blot, respectively in MCF-7 breast cancer cells we investigated whether costunolide activates extrinsic apoptotic pathway. We examined the expression levels of death receptor signaling-related proteins, caspase-3, and PARP. The results showed that procaspase-3 was cleaved to yield 17 and 20kDa fragments and activation of PARP in treated cells with 25 and 50μM of costunolide. Costunolide induce apoptosis through intrinsic mitochondria pathway in MCF-7 breast cancer Cells. We examined the expression levels of mitochondrial apoptotic pathway related proteins such as anti-apoptotic protein, B-cell lymphoma protein-2 (Bcl2), and pro-apoptotic protein Bax. Costunolide involved in the down regulation of Bcl-2 and up regulation of Bax. These results suggest that costunolide may have beneficial effects for the reduction of breast cancer growth, and new therapeutic strategy for the treatment of human cancers.

Um novo método para agrupar parâmetros quimiotaxonômicos

This work presents a new methodology for searching the present state of chemical evolution for different taxa, grouping five classes of secondary metabolites. Ocurrences of 10370 natural products isolated from Asteraceae were used to exemplify the method. Relationships among tribes are discussed.

Lychnophorinae (asteraceae): a survey of its chemical constituents and biological activities

This work reviews the current literature about the chemical constituents and the biological activities of the subtribe Lychnophorinae (Vernonieae, Asteraceae). The notable secondary metabolites are sesquiterpene lactones of furanoheliangolide (goyazensolide and eremantholide types) and flavonoids. Some of its most investigated activities include its anti-inflammatory, analgesic, antimicrobial and cytotoxic activities, specially for the Lychnophora and Eremanthus species. The data presented on this paper not only displayed the role played by the Lychnophorinae species as a source of bioactive compounds, but also reinforced the need of further studies involving the species of such subtribe.

Complete ¹H and 13C NMR structural assignments for a group of four goyazensolide-type furanoheliangolides

Four goyazensolide-type sesquiterpene lactones - lychnofolide, centratherin, goyazensolide and goyazensolide acetate - were thoroughly studied by NMR experimental techniques. ¹H NMR, 13C NMR {¹H}, COSY, HMQC, HMBC, J-res. and NOE experiments were performed to provide the needed structural information. Complete and unequivocal assignment, including the determination of all multiplicities, was obtained for each structure and the data collections are presented in tables.

Foliar anatomy and histochemistry in seven species of Eucalyptus

This work aimed to describe the foliar anatomy of seven species of Eucalyptus, emphasizing the characterization of secretory structures and the chemical nature of the compounds secreted and /or present in the leaves. Anatomical characterization and histochemical evaluation to determine the nature and localization of the secondary compounds were carried out in fully expanded leaves, according to standard methodology. Anatomical differences were verified among the species studied, especially in E. pyrocarpa. Sub-epidermal cavities were the only secretory structures found in the seven species studied, with higher density in E. pellita and lower in E. pilularis. The following compounds were histochemically detected: lipophilic compounds, specifically lipids of the essential or resin-oil type and sesquiterpene lactones found in the lumen of the cavities of the seven species; and hydrophilic compounds, of the phenolic compound type found in the mesophyll of all the species studied and on the epidermis of some of them. The results confirmed the complexity of the product secreted by the cavities, stressing the homogeneous histochemistry nature of these compounds among the species. However, the phenolic compounds results may be an indication of important variations in adaptations and ecological relations, since they show differences among the species.

Permeation of bioactive constituents from Arnica montana preparations through human skin in-vitro

This study investigated and characterised transdermal permeation of bioactive agents from a topically applied Arnica montana tincture. Permeation experiments conducted over 48 h used polyclimethylsiloxane (silastic) and human epidermal membranes mounted in Franz-type diffusion cells with a methanol-water (50:50 v/v) receptor fluid. A commercially available tincture of A. montana L. derived from dried Spanish flower heads was a donor solution. Further donor solutions prepared from this stock tincture concentrated the tincture constituents 1, 2 and 10 fold and its sesquiterpene lactones 10 fold. Permeants were assayed using a high-performance liquid chromatography method. Five components permeated through silastic membranes providing peaks with relative retention factors to an internal standard (santonin) of 0.28, 1.18, 1.45, 1.98 and 2.76, respectively. No permeant was detected within 12 h of applying the Arnica tincture onto human epidermal membranes. However, after 12 h, the first two of these components were detected. These were,shown by Zimmermann reagent reaction to be sesquiterpene lactones and liquid chromatography/diode array detection/mass spectrometry indicated that these two permeants were 11,13-dihydrohelenalin (DH) analogues (methacrylate and tiglate esters). The same two components were also detected within 3 h of topical application of the 10-fold concentrated tincture and the concentrated sesquiterpene lactone extract.

Bioactivity of Flavonoids Isolated from Lychnophora markgravii against Leishmania amazonensis Amastigotes

The bioactivity of the flavonoids pinostrobin (1), pinocembrin (2), tectochrysin (3), galangin 3-methyl ether (4), and tiliroside (5) isolated from Lychnophora markgravii aerial parts was investigated in vitro against amastigote stages of Leishmania amazonensis. The compounds were isolated by several chromatographic techniques and their chemical structures were established by ESI-MS and NMR spectroscopic data. The flavonoids 1 and 3 were the most active compounds; they markedly reduced the viability of Leishmania amastigotes.

A Ring Contraction Strategy toward a Diastereoselective Total Synthesis of (+)-Bakkenolide A

A diastereoselective route to (+)-bakkenolide A is presented from the readily available optically active Wieland-Miescher ketone. This novel synthesis of this sesquiterpene lactone features the following as key stereoselective transformations: (i) the ring contraction reaction of a octalone mediated by thallium(III) nitrate (TTN); (ii) a hydrogenation to create the cis-fused junction; and (iii) the formation of the C7 quaternary center through an enolate intermediate. Furthermore, during this work, the absolute configuration of a trinorsesquiterpene isolated from Senecio Humillimus was assigned.

In vitro activity of Artemisia annua L (Asteraceae) extracts against Rhipicephalus (Boophilus) microplus

A atividade de extratos vegetais sobre parasitas pode indicar grupos de substâncias de uso potencial no controle de Rhipicephalus (Boophilus) microplus. O objetivo do presente estudo foi investigar a ação in vitro de extratos de Artemisia annua sobre esta espécie. A concentração das lactonas sesquiterpênicas artemisinina e deoxiartemisinina presentes nos extratos vegetais, foi quantificada via cromatografia líquida de alta eficiência. Quatro extratos produzidos a partir do extrato bruto concentrado (EBC) foram avaliados sobre larvas pela metodologia do papel impregnado, com leitura após 24 horas de incubação. As fêmeas ingurgitadas foram imersas por cinco minutos no EBC e nos seus quatro extratos derivados, e incubadas para posterior análise dos parâmetros biológicos. Os extratos não tiveram eficácia sobre as larvas nas concentrações avaliadas (de 3,1 a 50 mg.mL-1). O EBC apresentou melhor eficácia sobre as fêmeas ingurgitadas (CE 50 de 130,6 mg.mL-1 e CE 90 de 302,9 mg.mL-1) que os extratos derivados. Esses resultados tendem a confirmar que a ação da artemisinina sobre as fêmeas ingurgitadas de R. (B.) microplus estaria condicionada à sua ingestão através do sangue. Nesse caso, os métodos in vitro seriam inadequados para a efetiva avaliação da ação de A. annua R.(B.) microplus.