LC-ESI/MS-phytochemical profiling with antioxidant and antiacetylcholinesterase activities of Algerian Senecio angulatus L.f. extracts.

Senecio angulatus L.f. is a flowering plant from the Asteraceae family that is native to South Africa and which was observed recently in the north and the east of Algeria. This study was aimed for the first time, to evaluate concomitantly phytochemical profiles, using LC-ESI/MS analysis, following by testing and assessing in vitro antioxidant and antiacetylcholinesterase activities of these specific species. The results indicated that the hydromethanolic and the acetate extracts have shown remarkable potent inhibitory effects on AChE with IC50 of (6.04 ± 0.05; 6.72 ± 0.10 µg/mL) respectively along with antioxidant potential of acetate for FRAP and phenanthroline methods with A0.5 of (11.15 ± 0.72; 5.72 ± 0.13 µg/mL) successively. Moreover, a high amount of cynarin and trans-ferulic acid was found in this extract whilst butanolic extract has recorded the highest amount of chlorogenic acid. Indeed phenolic compounds usually have a hydroxyl in their structure which may contribute significantly to the antioxidant activity.

A hydroalcoholic extract of Senecio nutans SCh. Bip (Asteraceae); its effects on cardiac function and chemical characterization.

ETHNOPHARMACOLOGY RELEVANCE: The plant Senecio nutans SCh. Bip. is used by Andean communities to treat altitude sickness. Recent evidence suggests it may produce vasodilation and negative cardiac inotropy, though the cellular mechanisms have not been elucidated. PURPOSE: To determinate the mechanisms action of S. nutans on cardiovascular function in normotensive animals. METHODS: The effect of the extract on rat blood pressure was measured with a transducer in the carotid artery and intraventricular pressure by a Langendorff system. The effects on sheep ventricular intracellular calcium handling and contractility were evaluated using photometry. Ultra-high-performance liquid-chromatography with diode array detection coupled with heated electrospray-ionization quadrupole-orbitrap mass spectrometric detection (UHPLC-DAD-ESI-Q-OT-MSn) was used for extract chemical characterization. RESULTS: In normotensive rats, S. nutans (10 mg/kg) reduced mean arterial pressure (MAP) by 40% (p < 0.05), causing a dose-dependent coronary artery dilation and decreased left ventricular pressure. In isolated cells, S. nutans extract (1 µg/ml) rapidly reduced the [Ca2+]i transient amplitude and sarcomere shorting by 40 and 49% (p < 0.001), respectively. The amplitude of the caffeine evoked [Ca2+]i transient was reduced by 24% (p < 0.001), indicating reduced sarcoplasmic reticulum (SR) Ca2+ content. Sodium-calcium exchanger (NCX) activity increased by 17% (p < 0.05), while sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) activity was decreased by 21% (p < 0.05). LC-MS results showed the presence of vitamin C, malic acid, and several antioxidant phenolic acids reported for the first time. Dihydroeuparin and 4-hydroxy-3-(3-methylbut-2-enyl) acetophenone were abundant in the extract. CONCLUSION: In normotensive animals, S. nutans partially reduces MAP by decreasing heart rate and cardiac contractility. This negative inotropy is accounted for by decreased SERCA activity and increased NCX activity which reduces SR Ca2+ content. These results highlight the plant's potential as a source of novel cardio-active phytopharmaceuticals or nutraceuticals.

New antimicrobial and cytotoxic benzofuran glucoside from Senecio glaucus L.

The ethyl acetate fraction of the dried aerial parts of Senecio glaucus L. exhibited significant antimicrobial activity against some of selected bacteria and fungi. Also, it showed potent cytotoxicity against PANC-1 cancer cell lines under glucose deficient medium. The ethyl acetate fraction was subjected to different chromatographic techniques for isolation of the bioactive compounds. A new benzofuran glucoside; 2,3-dihydro-3ß-hydroxyeuparin 3-O-glucopyranoside (1) was isolated. Additionally, two known flavonoid compounds isorhamentin 3-O-ß-D-glucoside (2), and isorhamentin 3-O-ß-D-rutinoside (3) were first identified in S. glaucus. Compound 1 exhibited potent antimicrobial activities against two Gram-positive bacteria, one Gram-negative bacteria, and two fungi. Also, it displayed potent cytotoxic activity against PANC-1 cancer cell lines under glucose deficient medium (IC50 7.5 µM). However, the isolated flavonoid glycosides (2 & 3) showed moderate antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria, four fungi, and did not show any cytotoxic activity against PANC-1.

Neuroprotective activity of natural products isolated from Senecio graciliflorus DC against corticosterone-induced impairment in SH-SY5Y cells.

Senecio graciliflorus DC root extract was studied for secondary metabolite composition following the bioactivity-guided isolation technique. The ethyl acetate extract of Senecio graciliflorus root yielded nine chemical constituents: 3,4-di-tert-butyl toluene, stigmasterol, ß-sitosterol, 2ß-(angeloyloxy)furanoeremophilane, gallic acid, 2ß-{[(Z)-2-hydroxymethylbut-2-enoyl]oxy}furanoeremophilane, 1-hydroxypentan-2-yl-4-methylbenzoate, sarcinic acid, and sitosterol 3-O-ß-D-glucopyranoside. The structures of the chemical constituents were elucidated on the basis of spectral data analysis in the light of literature. All the compounds are being reported for the first time from this plant. The isolated constituents were screened for neuroprotective effects against corticosterone-induced impairment in neuroblastoma cell lines (SH-SY5S cells). The viability of SH-SY5S cells was determined using MTT assay. Among various isolated compounds, three natural products (sarcinic acid, gallic acid, and ß-sitosterol) displayed robust neurotropic activity. The compounds increased neuronal cell survival in differentiated neuroblastoma cells (SH-SY5Y) from high-dose corticosterone (400 µM)-induced cell death. All the three constituents showed maximum AKT/ERK pathway activation at 20 µM concentration. The studies are aimed to explore small molecules for treating neurodegeneration underlying various neurological disorders to restore neuronal cell plasticity.

Effect of Senecio scandens ethanol extract on gut microbiota composition in mice.

The gut microbiota inhabits the animal intestinal tract, and dysbiosis of the gut microbiota may result in disease. Senecio scandens has pharmaceutical antibacterial activities and is regarded as a broad-spectrum antibiotic in traditional Chinese medicine. Extracts of S. scandens are reported to show strong antimicrobial activity, and quercetin significantly decreases some species in the caecal microflora. However, the bactericidal effects of the extracts on the gut microbiota remain obscure. Here, we supplied ethanol extract of S. scandens, which might possibly be used as an alternative for chemical antibiotics, to mice to investigate the state of the intestinal microbiota. Our studies included a control group, low-, moderate-, and high-dose ethanol extract groups, and cefixime capsule group. The ethanol extract groups did not present reduced diversity or differences in the gut microbiota balance. There were significant differences between the ethanol extract and cefixime capsule groups in terms of the gut microbiota. The control and ethanol extract groups contained similar bacteria, which suggested that the ethanol extract has no inhibitory effect on the gut microbiota in vivo. Bifidobacteriales and Lactobacillus acidophilus were significantly increased in the high-dose group. Both secretory immunoglobulin A and mucin 2 concentrations increased as the dose of ethanol extract increased. The functional prediction differences between the control and ethanol extract groups decreased with increasing extract doses, which indicated that the low-dose and high-dose extract treatments might regulate different pathways and functions of the gut microbiota. The results also highlighted the prevention of bacterial drug resistance in the ethanol extract groups.

Fatal pyrrolizidine alkaloid poisoning of infants caused by adulterated Senecio coronatus.

Senecio coronatus (known as izonkozonko and ubulibazi in Zulu) is commonly used in traditional medicine in South Africa as purification purgative and enemas for infants during weaning. We show for the first time that this species does not contain pyrrolizidine alkaloids and that reported cases of fatal hepatic sinusoidal obstruction syndrome in infants were caused by wrongly identified Senecio species containing large amounts of retrorsine-N-oxide. A validated ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the detection and quantitation of pyrrolizidine alkaloids is described.

Mosquito larvicidal potential of hydroxy-2-methyl-4H-pyran-4-one (MALTOL) isolated from the methanol root extract of Senecio laetus Edgew. and its in-silico study.

In the present study, hydroxy-2-methyl-4H-pyran-4-one was isolated from the methanol root extract of Senecio laetus and was identified by FT-IR, 1H, 13C NMR and GC-MS. The larvicidal potential of the compound 3-hydroxy-2-methyl-4H-pyran-4-one was evaluated against the 4th instar larvae of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus at concentrations ranging from 20 to 1.25 ppm under laboratory conditions. The compound showed 100% mortality at 20 ppm against all the tested mosquitoe species and the LC50 and LC90 values were 1.22 and 7.25 ppm (An. stephensi), 2.10 and 99.84 ppm (Ae. aegypti) and 3.88 and 12.47 ppm (Cx. quinquefasciatus), respectively after 24 h of exposure period. In silico molecular docking study results reflects that hydroxy-2-methyl-4H-pyran-4-one compound showed highest binding affinity with OBP of Cx. quinquefasciatus (Glide energy score - 7.3 kcal/mol-1). The larvicidal activity of hydroxy-2-methyl-4H-pyran-4-one against tested mosquito species appears interesting and may be developed after toxicological and field evaluation.

Pyrrolizidine alkaloids and beehive products: A review.

Pyrrolizidine alkaloids (PA) are secondary metabolites of plants, which are mostly found in the genus Senecio, Echium, Crotalaria, and Eupatorium. The presence of 1,2-unsaturated PA in foods is a concern to food regulators around the world because these compounds have been associated to acute and chronic toxicity, mainly in the liver. The intake foods with PA/PANO usually occur through accidental ingestion of plants and their derivatives, besides to products of vegetal-animal origin, such as honey. PA/PANO are transferred to honey by their presence in nectar, honeydew, and pollen, which are collected from the flora by bees. In addition to honey, other beekeeping products, such as pollen, royal jelly, propolis, and beeswax, are also vulnerable to PA contamination. In this context, this review provides information about chemical characteristics, regulation, and toxicity, as well as summarizes and critically discusses scientific publications that evaluated PA in honeys, pollens, royal jelly, and propolis.

Qualitative and quantitative analysis of pyrrolizidine alkaloids for the entire process quality control from Senecio scandens to Senecio scandens-containing preparations by high performance liquid chromatography-tandem mass spectrometry.

Senecio scandens as a commonly used traditional Chinese medicine that is used alone or in combination with other herbs in preparations such as QianBai BiYan tablets has attracted much attention because of its hepatotoxic pyrrolizidine alkaloids. Nowadays, most studies for pyrrolizidine alkaloids are only performed on herbs or a preparation, however, production of preparations is a dynamic process, control of toxic impurities for raw materials, or finished products cannot monitor the production process dynamically. Thus, in this study, qualitative and quantitative analysis of pyrrolizidine alkaloids for the entire process quality control from S. scandens to its preparations was carried out with HPLC-MS/MS for the first time, which was more comprehensive and dynamic than the previous single-layer analysis. First, the species of pyrrolizidine alkaloids in S. scandens were analyzed, and the characteristic fragmentation rules of pyrrolizidine alkaloids containing common parent nucleus were found, which can be used to identify these components rapidly in the future. Then, a quantitative method for S. scandens to QianBai BiYan tablets and other nine S. scandens-containing preparations was established, and after the medication safety speculation, all of them met the relevant safety requirements. After that, in order to ensure the stability and controllable of drug quality, the limit of pyrrolizidine alkaloids in preparations was determined according to the safe dosage that is stipulated to be the same as raw materials. Finally, the factors causing the content change of pyrrolizidine alkaloids in S. scandens from different source were studies, which can provide theoretical basis for selecting suitable raw materials for production.

[Quantification of hepatotoxic pyrrolizidine alkaloid adonifoline in traditional Chinese medicine preparations containing Senecionis Scandentis Herba].

Pyrrolizidine alkaloids(PAs) are a kind of natural toxins, which can cause severe hepatotoxicity, pulmonary toxicity, genotoxicity, neurotoxicity, embryotoxicity and even death. Therefore, international organizations and countries such as World Health Organization have paid great attention to herbal medicines and preparations containing PAs. PAs are widely distributed in Chinese herb medicines and contained in hundreds of traditional Chinese medicine preparations. The content of adonifoline, the main PAs in Senecionis Scandentis Herba, shall be less than 0.004% in herbal medicines as described in Chinese pharmacopeia. However, there is no guidance in preparations which contain Senecionis Scandentis Herba. In this study, 14 preparations were analyzed by an UPLC-MS method. Among them, 8 preparations were found to contain adonifoline much higher than the content limits of such countries as Germany, Netherlands and New Zealand. And the highest contents of adonifoline were found in Qianbai Biyan Tablets and Qianbai Biyan Capsules, which are officially recorded in Chinese Pharmacopeia. The contents of adonifoline varied in different batches of the same preparations. The highest content was 156.10 µg·g~(-1) Qianbai Biyan Tablets, whose daily intake of adonifoline was up to 1 030.26 µg according to the recommended dosage of the preparation. Our results showed the potential risk of these preparations, and the content limit of adonifoline shall be inspected Chinese medicine preparations containing Senecionis Scandentis Herba.

Effects of dietary Senecio scandens buch-ham extracts on growth performance, plasma biochemical, histology and the expression of immune-related genes in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀).

The study mainly aimed at the effects of dietary Senecio scandens buch-ham extract (SSBE) on the growth performance, body composition, plasma biochemical index, intestinal and liver histology and the expression of antioxidant, apoptosis and inflammatory related genes in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀). Basal diets supplemented with SSBE (10:1) 0%, 0.05%, 0.1%, 0.2% and 0.4% were fed hybrid grouper for 8 weeks. The results showed that WGR and SGR were significantly increased in the week 2 and week 4 in Diet 0.05% group (P < 0.05). The total protein, globulin and albumin significantly increased whereas alanine aminotransferase, triglyceride and alkaline phosphate in the plasma were significantly decreased in Diet 0.1% group (P < 0.05). The villi length, width, muscle thickness and the cross-sectional area of intestine were improved in Diet 0.05% and Diet 0.1% group. The expression levels of PPAR-α and CPT-1 in the liver of hybrid grouper were significantly increased following the supplementation of SSBE (P < 0.05). The expression levels of antioxidant related genes (CAT, GPX, GR and Keap1) and anti-inflammatory factor (IL-10) in liver, head kidney and spleen of hybrid grouper decreased significantly (P < 0.05). In addition, diets supplemented with 0.05%-0.1% SSBE had a good liver-protecting effect, but it would have a detrimental effect on hepatocytes when the content exceeds 0.2%. The above results indicated that the suitable additive amount of SSBE in hybrid grouper feed was 0.05%-0.1%.

In vitro ovicidal effect of a Senecio brasiliensis extract and its fractions on Haemonchus contortus.

BACKGROUND: Haemonchosis affects sheep husbandry and its treatment is often compromised due to the development of anthelminthic resistance. Plant-derived bioactive compounds have been studied as alternative to control Haemonchus contortus. The objective of this study was to evaluate the effect of Senecio brasiliensis extracts on H. contortus egg hatching and infective larvae migration. RESULTS: The aqueous extract from dried and fresh plant and alkaloid-enriched fraction of the previously dried leaves of S. brasiliensis inhibited H. contortus egg hatching. The main plant compound in alkaloid fraction was integerrimine, a pyrrolizidine alkaloid (PA). However, the aqueous extract from dried plant displayed higher efficacy when compared to their alkaloid enriched or non-polar fractions, meaning that, although PAs contributed to the ovicidal effect, other compounds in the plant can also contribute to their effect. Furthermore, the aqueous extract from dried plant also had higher efficacy than aqueous extract from fresh plant in larvae migration inhibition. Finally, extract from dried plant presented low in vitro cytotoxic effect. CONCLUSION: Taken together our results suggest a good anthelmintic effect of S. brasiliensis, especially when aqueous extract is prepared from dried plant. Further in vivo studies should be performed focused on forms of administration of this extract in rearing sheep.

Antihypertensive effects of the hydro-ethanol extract of Senecio serratuloides DC in rats.

BACKGROUND: Senecio serratuloides DC is used in folk medicine for treating hypertension, skin disorders, internal and external sores, rashes, burns and wounds. This study aimed at investigating the antihypertensive effects of the hydroethanol extract of S. serratuloides (HESS) in N-Nitro-L-arginine methyl ester (L-NAME) induced hypertension in rats. METHODS: Acute toxicity of HESS was first determined to provide guidance on doses to be used in this study. Lorke's method was used to determine safety of the extract in mice. Female Wistar rats were treated orally once daily with L-NAME (40 mg/kg) for 4 weeks and then concomitantly with L-NAME (20 mg/kg) and plant extract (150 and 300 mg/kg), captopril (20 mg/kg) or saline as per assigned group for 2 weeks followed by a 2-week period of assigned treatments only. Blood pressure was monitored weekly. Lipid profile, nitric oxide, renin and angiotensin II concentrations were determined in serum while mineralocorticoid receptor concentration was quantified in the kidney homogenate. Nitric oxide (NO) concentration was determined in serum and cardiac histology performed. RESULTS: HESS was found to be non-toxic, having a LD50 greater than 5000 mg/kg. Blood pressure increased progressively in all animals from the second week of L-NAME treatment. HESS treatment significantly and dose-dependently lowered systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.01), low density lipoprotein cholesterol (p < 0.01) and triglycerides (p < 0.01). It significantly prevented L-NAME induced decrease in serum angiotensin II (p < 0.01), high density lipoprotein cholesterol (p < 0.001) and serum nitric oxide concentrations (p < 0.001). HESS also significantly (p < 0.01) prevented collagen deposition in cardiac tissue. CONCLUSION: The hydro-ethanol extract of Senecio serratuloides showed antihypertensive, antihyperlipidemic and cardioprotective effects in rats thus confirming its usefulness in traditional antihypertensive therapy and potential for antihypertensive drug development.

Senecipyrrolidine, an unusual pyrrolidine alkaloid isolated from Jacobaea gigantea (Desf.) Pelser (Asteraceae).

Alkaloids and phenolic compounds are among the most biologically active natural products from the Jacobaea/Senecio genera (Asteraceae). To isolate original natural products directly from Jacobaea gigantea crude polar extracts, centrifugal partition chromatography (CPC) was used. Previously, we reported the phytochemical study of J. gigantea (syn. Senecio giganteus) n-butanol extract using various classical chromatographical techniques combined with CPC. Herein major constituents from the J. gigantea crude ethyl acetate extract and further compounds from the n-butanol extract were purified in only one step using this technique. A new pyrrolidine alkaloid, named senecipyrrolidine was isolated along with thirteen known compounds - chiro-inositol, three phenolic acids, six flavonoids, two quinones and emiline, another pyrrolidine alkaloid - from crude n-butanol or ethyl acetate extracts. Pyrrolidine alkaloids were isolated for the first time in the Jacobaea/Senecio genera and were probably biogenetically related to the two isolated quinones derivatives jacaranone and 3a-hydroxy-3,3a,7,7a-tetrahydrobenzofuran-2,6-dione, isolated in this species.

Antioxidant Activity and Phytochemical Characterization of Senecio clivicolus Wedd.

Antioxidant phytochemicals play a key role in oxidative stress control and in the prevention of related disorders, such as premature aging, degenerative diseases, diabetes, and cancer. The aim of this study was to investigate the potential antioxidant activity and the phytochemical profile of Senecio clivicolus Wedd., a perennial shrub, belonging to the Asteraceae family. Despite the wide interest of this family, this specie has not been investigated yet. S. clivicolus aerial parts were extracted with 96% ethanol. Then, the ethanol extract was fractionated by liquid/liquid extraction using an increasing solvents polarity. Total polyphenol and terpenoid contents were measured. Moreover, the antioxidant activity was evaluated by six different complementary in vitro assays. The Relative Antioxidant Capacity Index (RACI) was used to compare data obtained by different tests. The sample showing the highest RACI was subjected to characterization and quantitation of its phenolic composition using LC-MS/MS analysis. The ethyl acetate fraction, investigated by LC-MS/MS analysis, showed 30 compounds, most of them are chlorogenic acid and flavonoid derivatives. To the best of our knowledge, this is the first report about the evaluation of antioxidant activity and phytochemical profile of S. clivicolus, underlying the importance of this species as a source of health-promoting phytochemicals.

Process optimization of spray-dried fanhuncaoin powder for pulmonary drug delivery and its pharmacokinetic evaluation in rats.

The optimization of process parameters of spray-dried powder containing fanhuncaoin, a newly discovered anti-inflammatorily active phenolic acid isolated from Chinese herb, was conducted using response surface methodology (RSM). The experimental results were fitted into partial cubic polynomial model to describe and predict the response quality in terms of the final angle of repose, aerodynamic diameter, respirable fraction (RF), and yield. The recommended optimum spray-drying parameters for the development of fanhuncaoin powder with optimum quality were 110 °C inlet temperature, 0.50 m3/min aspiration speed, and 7.95 ml/min feed flow rate. The obtained optimum process parameters were employed for the production of spray-dried fanhuncaoin powder and to check the validity of the partial cubic model. Small and insignificant deviations were found between the predicted values and the experimental ones, showing the efficiency of the model in predicting the quality attributes of fanhuncaoin powder. The optimized powder was further examined for its pharmacokinetic properties in rats. A UPLC/MS assay was used to determine plasma fanhuncaoin concentration. Statistical analysis demonstrated that there was no significant difference in the t1/2 and dose-normalized Cmax and AUC as well as other pharmacokinetic parameters between the groups dosed differently following intratracheal administration (p > .05), indicating that fanhuncaoin followed linear kinetics. The pharmacokinetic parameters of fanhuncaoin after intratracheal administration differed significantly from the ones observed after intravenous administration (p < .05). The lower values of Cmax and AUC(0-∞) obtained following intratracheal administration may lead to effective drug concentrations at the target site with minimal systemic bioavailability and side effects.

Nutritional composition, antioxidant activity and isolation of scopoletin from Senecio nutans: support of ancestral and new uses.

Continuing with our study characterising Senecio nutans Sch. Bip., we have isolated and identified a simple coumarin, scopoletin, that could be relevant for the biological properties of the species related with the ancestral medical uses. This is the first report of scopoletin from S. nutans. In addition, the extract was analysed for its antioxidant activity using the ABTS and FRAP method as well as providing the first nutritional analyses of this plant from northern Chile highlands.

Chemical fingerprinting identifies Echium vulgare, Eupatorium cannabinum and Senecio spp. as plant species mainly responsible for pyrrolizidine alkaloids in bee-collected pollen.

Various studies have shown that bee-collected pollen sold as nutritional supplements may contain toxic pyrrolizidine alkaloids (PAs) and, thus, pose a potential health risk for consumers. The level of contamination may vary according to its geographical and botanical origin. Here, the PA content of pollen produced in Switzerland was studied and 32 commercially available bee-collected pollen supplements produced between 2010 and 2014 were analysed. In addition, at what time period bees collect PA-containing pollen was investigated. Hence, this study looked into the occurrence of PAs in pollen samples collected daily during two-to-three consecutive seasons. Furthermore, the PA spectrum in pollen was compared to the spectrum found in flower heads of PA-plants to unambiguously identify plants responsible for PA contamination of pollen. The PA concentration of commercial and daily collected pollen was determined by target analysis using an HPLC-MS/MS system, allowing the detection of 18 different PAs and PA N-oxides found in the genera Echium, Eupatorium and Senecio, while the comparison of the PA spectrum in pollen and flower heads was performed by LC-HR-MS, allowing the detection of all PA types in a sample, including saturated, non-carcinogenic PAs. Of the commercially available pollen, 31% contained PAs with a mean concentration of 319 ng/g, mainly Echium- and Eupatorium-type PAs, while the PA concentrations were below the limit of quantitation (LOQ) in 69% of the pollen samples. Bees collected pollen containing Echium-type PAs mainly in June and July, while they gathered pollen containing Eupatorium-type PAs from mid-July to August. Senecio-type PAs appeared from June to September. Comparison of the PA array in pollen and plants identified E. vulgare and E. cannabinum as the main plants responsible for PA contamination of Swiss bee-collected pollen, and to a lesser extent also identified plants belonging to the genus Senecio.

Senecio brasiliensis impairs eclosion rate and induces apoptotic cell death in larvae of Drosophila melanogaster.

Senecio brasilienis (Spreng) Less., is a species native from Brazil, popularly known as "Maria mole", and known to induce hepatotoxicity due to its high content of Pyrrolizidine alkaloids. Despite its toxicity, this plant is widely used in Brazilian folk medicine. Considering the antagonizing effects described for S. brasiliensis, we describe here molecular markers involved in the toxicity of hydroalcoholic extract from leaves of S. brasiliensis (HESB) in Drosophila melanogaster. Phytochemical analysis of HESB revealed the presence of phenolic acids and flavonoids. A significant antioxidant potential against ABTS+ and DPPH radical was found in parallel. Ingestion of extract did not alter the survival and locomotor activity of adult flies. However when ingested along the larval developmental phase, the eclosion rate of flies was interrupted at higher concentration of extract. To comprehend this phenomenon several analysis were conducted in larvae. HESB stimulated activity of antioxidant enzymes SOD and GST, and increased GSH/GSSG ratio and ROS production. Additionally, HESB caused a significant decrease of cell viability. The mRNA expression of Nrf2, TrxR, CAT, Drice and Dilp6 were also significantly up-regulated. HESB caused significant decrease on the phosphorylation of MAPKs and AKT. In parallel, PARP cleavage and caspases 3/7 activity were stimulated. In addition, glucose, glycogen and triglycerides levels were decreased. Taken together our study depicts a disruption in the eclosion of D. melanogaster possibly attributed to the inhibition of kinases implied in developmental process, energetic demand and induction of apoptotic cell death process.

Insect Antifeedant and Ixodicidal Compounds from Senecio adenotrichius.

Nine eremophilane sesquiterpenes 1 - 9, two flavonoids 11 and 12, and two known pirrolizidine alkaloids 13 and 14, were isolated from Senecio adenotrichius DC. Their structures were elucidated on the basis of spectroscopic data and by comparison with previously reported spectroscopic data of similar compounds. Compounds 5, 7, and 9 have not been previously reported as natural products. The antifeedant activity of these compounds was tested against Spodoptera litoralis and Myzus persicae. Eremophilanes 1, 3, and 8 were strong antifeedants to M. persicae, and 1 and 8 to Spodoptera littoralis. Their ixodicidal activity was tested against the tick Hyalomma lusitanicum, with eremophilanes 1, 3, and 8, being strong ixodicidal agents.