The essential oil of the leaves of Verbesina macrophylla (Cass.) S.F.Blake has antimicrobial, anti-inflammatory and antipyretic activities and is toxicologically safe.

ETHNOPHARMACOLOGICAL RELEVANCE: Verbesina macrophylla (Cass.) S.F.Blake is a medicinal plant from South America, popularly known as "asa de peixe", "asa de peixe branco", "cambará branco" or "cambará guaçu", being used by traditional communities for its healing powers in the form of teas, infusions, liqueurs and extracts, for the treatment of bacterial and fungal infections of the urinary and respiratory tracts, such as kidney problems, bronchitis, inflammation and fever. However, none of the ethnopharmacological properties has been scientifically evaluated. AIM OF THE STUDY: Based on the ethnopharmacological use of the species, this study investigated the chemical composition, and for the first time acute toxicity, hemolytic, antimicrobial, anti-inflammatory and antipyretic activities of the essential oil from leaves of V. macrophylla. MATERIAL AND METHODS: The essential oil was obtained from the leaves by hydrodistillation (HD), being characterized by gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography coupled to flame ionization detection (GC-FID). The antimicrobial activity was evaluated by the broth microdilution technique in bacteria and fungi that cause infections of the respiratory and urinary tract, and toxicological safety regarding hemolytic activity on human red blood cells (hRBCs), and acute toxicity in mice. The anti-inflammatory activity was evaluated by the model carrageenan-induced peritonitis with quantification of the levels of TNF-α and IL-1ß in the intraperitoneal fluid, and ear edema induced by croton oil. The antipyretic activity evaluated in mice with pyrexia induced by yeast. RESULTS: The extraction of essential oil by hydrodistillation (HD) showed a yield of 0.33 ±â€¯0.04%, with its composition constituted mainly by sesquiterpenes of hydrocarbons (94.00%). The essential oil demonstrated antibacterial and antifungal activity, with a low rate of hemolysis in human red blood cells (hRBCs) and no clinical signs of toxicity were observed in animals after acute treatment, which suggested that the LD50 is greater than 5000 mg/kg; p.o. The essential oil demonstrated anti-inflammatory activity reducing levels of pro-inflammatory cytokines TNF-α (38.83%, 72.42% and 73.52%) and IL-1ß (37.70%, 75.92% and 87.71%), and ear edema by 49.53%, 85.04% and 94.39% at concentrations of 4, 40 and 400 mg/kg, respectively. The antipyretic activity presented by the essential oil is statistically similar to dipyrone. CONCLUSION: The set of results obtained, validates the main activities attributed to the traditional use of Verbesina macrophylla (Cass.) S.F.Blake. These data add industrial value to the species, considering that the antimicrobial, anti-inflammatory and antipyretic activities present results similar to the drugs already used also presenting safety. The results suggest that essential oil from V. macrophylla may be used by industry for the development of drugs with natural antimicrobial, anti-inflammatory and antipyretic effect.

Uso en medicina tradicional de Verbesina sphaerocephala A. Gray (Asteraceae) en la comunidad de San Martin de las Flores, Jalisco, México / Use in traditional medicine of Verbesina sphaerocephala A. Gray (Asteraceae) in the community of San Martin de las Flores, Jalisco, Mexico

The community of San Martin de las Flores, Jalisco, México has a varied flora, part of which is used by its residents to treat their diseases. One of these wild species that grows in this community is Verbesina sphaerocephala A.Gray (Asteraceae). The objective of this research was to provide an overview of local knowledge about the traditional uses of this plant. A quantitative ethnobotanical method to analyse the value of traditional use of this species among the community, as well as, bibliographic information on the existing phytochemical and pharmacological properties of species of the genus Verbesina has been used. When examining the general knowledge of V. sphaerocephala among the community, it was concluded that the plant is used mainly in traditional medicine to treat eight different types of diseases, highlighting its use as a wound healing and anti-inflammatory.

La comunidad de San Martin de las Flores, Jalisco, posee una variedad de flora, la cual, gran parte de ella es utilizada por sus pobladores para el tratamiento de enfermedades. Una de estas especies silvestres que crece en esta comunidad es Verbesina sphaerocephala A. Gray (Asteraceae). El objetivo de esta investigación fue proporcionar una visión general del conocimiento local sobre los usos tradicionales de esta planta. Se ha utilizado un método etnobotánico cuantitativo para analizar el valor de uso tradicional de esta especie entre la comunidad, así como también se recopiló información bibliográfica sobre las propiedades fitoquímicas y farmacológicas existentes sobre especies del género Verbesina. Al examinar el conocimiento general de V. sphaerocephala entre la comunidad, se concluyó que la planta es utilizada fundamentalmente en medicina tradicional para tratar ocho diferentes tipos de enfermedades, destacándose su uso como cicatrizante y antiinflamatorio.

Antiprotozoal activity of major constituents from the bioactive fraction of Verbesina encelioides.

The bioactive petroleum ether fraction of Verbesina encelioides, previously studied by the authors, was chosen for the isolation of antiprotozoal metabolites. Pseudotaraxasterol-3ß-acetate (1), benzyl 2,6-dimethoxy benzoate (2), 16ß-hydroxy-pseudotaraxasterol-3ß-palmitate (3) and pseudotaraxasterol (4), in addition to ß-sitosterol glucoside (5) and ß-sitosterol galactoside (6) were isolated and identified based on one-dimensional and two-dimensional spectral analysis. This is the first report describing (3) and (6) in genus Verbesina. The isolated compounds were tested in vitro against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum. Cytotoxicity was evaluated on MRC-5 cells. Compound 1 showed moderate to weak activity against L. infantum T. brucei and P. falciparum and was inactive against T. cruzi. Compound 3 showed moderate activity against L. infantum, compound 4 revealed weak activity against T. cruzi, while 5 and 6 were inactive against all tested protozoa. All compounds were non-cytotoxic. The isolated constituents showed less antiprotozoal activity than the crude fraction.

SCANNING ELECTRON MICROSCOPIC CHANGES IN HABRONEMA MUSCAE AFTER IN VITRO EXPOSURE TO PLANT EXTRACT (VERBESINA ALTERNIFOLIA).

Scanning electron microscopy (SEM) was used to study the morphological alteration occurring in Habronema muscae adult female worms after in vitro exposure to different doses of Verbesina alternifolia oil extract. The half maximal lethal concentration (LC50) was reached 400 ppm after 24hrs, while LC100 was reached 600 ppm after 48hrs. Irreversible degenerative changes were recorded such as shrinking, detachment and distortion of the cuticle, cephalic and distal region. The cuticular surface had a wrinkled, corrugated appearance with longitudinal ridges and transverse thick folds. The lips and papillae were deformed and aggregated over each other. There is a direct relation between the level of the recorded degenerative changes and the increase in the dose and exposure time. In the same time no degen'erative changes were recorded in the control worm exposed to PBS till the end of the exposure period.

Verbesina encelioides: cytotoxicity, cell cycle arrest, and oxidative DNA damage in human liver cancer (HepG2) cell line.

BACKGROUND: Cancer is a major health problem and exploiting natural products have been one of the most successful methods to combat this disease. Verbesina encelioides is a notorious weed with various pharmacological properties. The aim of the present investigation was to screen the anticancer potential of V. encelioides extract against human lung cancer (A-549), breast cancer (MCF-7), and liver cancer (HepG2) cell lines. METHODS: A-549, MCF-7, and HepG2 cells were exposed to various concentrations of (10-1000 µg/ml) of V. encelioides for 24 h. Further, cytotoxic concentrations (250, 500, and 1000 µg/ml) of V. encelioides induced oxidative stress (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage in HepG2 cells were studied. RESULTS: The exposure of cells to 10-1000 µg/ml of extract for 24 h, revealed the concentrations 250-1000 µg/ml was cytotoxic against MCF-7 and HepG2 cells, but not against A-549 cells. Moreover, the extract showed higher decrease in the cell viability against HepG2 cells than MCF-7 cells. Therefore, HepG2 cells were selected for further studies viz. oxidative stress (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage. The results revealed differential anticancer activity of V. encelioides against A-549, MCF-7 and HepG2 cells. A significant induction of oxidative stress, ROS generation, and MMP levels was observed in HepG2 cells. The cell cycle analysis and comet assay showed that V. encelioides significantly induced G2/M arrests and DNA damage. CONCLUSION: These results indicate that V. encelioides possess substantial cytotoxic potential and may warrant further investigation to develop potential anticancer agent.

Chemical Composition and in vitro Antibacterial Activity of the Essential Oil of Verbesina negrensis from the Venezuelan Andes.

The composition and antimicrobial activity of the essential oil from Verbesina negrensis Steyerm. leaves is reported. Analysis was performed by GC/MS. Major constituents were α-pinene (43.1%), α-humulene (13.8%), Δ-cadinene (8.1%), limonene (4.6%) and bicyclogermacrene (4.2%). The essential oil showed in vitro activity against the Gram-positive bacteria Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212 (MIC 500 and 350 µL/mL respectively).

Anti-inflammatory and antiproliferative evaluation of 4ß-cinnamoyloxy,1ß,3α-dihydroxyeudesm-7,8-ene from Verbesina persicifolia and derivatives.

The anti-inflammatory and antiproliferative activities of 4ß-cinnamoyloxy,1ß,3α-dihydroxyeudesm-7,8-ene (1) and of three derivatives, namely diacetate (2), hydrogenate (3) and diacetate hydrogenate (4) were evaluated. All derivatives exert an anti-inflammatory effect significantly lower than that exerted by 1. Otherwise, both the lead compound and 2-4 showed a comparable antiproliferative activity on human tumor cell lines. The investigation of the mechanism of action accountable for cytotoxicity highlighted the capacity to impair mitochondrial functions through two different pathways, depending on chemical structure. In particular, the lead compound 1 and derivative 3 are able to induce mitochondrial permeability transition, while derivatives 2 and 4 inhibit Complex II in the respiratory chain.

An eudesman derivative from Verbesina persicifolia D.C. as a natural mild uncoupler in liver mitochondria. A new potential anti-obesity agent?

4ß-cinnamoyloxy,1ß,3α-dihydroxyeudesm-7,8-ene (CDE) extracted from Verbesina persicifolia induces bioenergetic collapse in rat liver mitochondria (RLM), monitored as a fall in the respiratory control index and ADP/O values. This fall in energy is accompanied by a protonophore effect and membrane potential (Δψ) collapse, demonstrating that CDE behaves as a typical uncoupling agent. However, when examining the effect of CDE in detail, we found that it acts as a "mild" uncoupler because it drops Δψ and increases respiratory state 4. The proposed mechanism is based on the interaction of CDE with membrane protein cytochrome C oxidase, which is implicated in proton permeability, and with the respiratory chain for the generation of reactive oxygen species which mediate and regulate the activity of the above membrane protein. Considering the energy collapse, "mild" uncoupling, and the fact that CDE is largely used in folk medicines, this extract may be viewed as a potentially effective anti-obesity drug and a natural lead compound for developing new natural uncouplers against obesity.

New antibacterial germacrene from Verbesina negrensis.

Several health benefits have been attributed to members of the Verbesina genus, including promotion of urinary and gastrointestinal health. Verbesina species are also reported to exhibit antibacterial, antiparasitic, and antioxidant activities. Although members of the Verbesina genus produce various pharmacologically relevant chemicals as secondary metabolites, including eudesmanes, flavonoids, guanidine alkaloids, acetylenic compounds, and germacrenes, the active compounds required for these benefits remain unknown. To investigate potential antimicrobial activities of Verbesina negrensis, crude extracts from plant aerial structures were evaluated. Following chemical fractionation, the chloroformic extract from Verbesina negrensis was subjected to bioassay-guided isolation using disk diffusion assays to determine antimicrobial activity. The active compound was characterized as 6ß-cinnamoyloxy-1ß-hydroxy-10α-metoxy-3-oxo-germacra-4,5Z-ene (1). Fractions containing 1 inhibited both Enterococcus faecalis (ATCC 29 212) and Staphylococcus aureus (ATCC 29213). The MIC for 1 was determined by microbroth dilution assay to be 64 µg/mL for both E. faecalis and S. aureus.

Laboratory evaluation of the effect of Egyptian native plants against some parasitic vectors.

OBJECTIVE: Four plant extracts possessing molluscicidal and insecticidal efficacy were evaluated under laboratory conditions versus Biomphalaria alexandrina, Lymnea cailliaudi snails, their egg masses and Culex pipiens larvae. These extracts included Grape seed, Eucalyptus, Pomegranate, Verbesina alcoholic extracts, as well as Eucalyptus oil. METHODS: Different mortalities in the exposed vectors were recorded due to the four plant extracts using different concentrations and exposure time. RESULTS: Total snail mortality LC < sub > 100 < /sub > was (100 ppm/12-24h) for Grape seed, (200 ppm/18-24h) for Eucalyptus, (100 ppm/12-18h) for Pomegranate, (100-200 ppm/24h) for Verbesina alcoholic extracts and (100-200 ppm/12h) for Eucalyptus oil. However, only Eucalyptus, Verbesina alcoholic extracts and Eucalyptus oil revealed snail ovicidal effects. LC < sub > 100 < /sub > was (100-200 ppm/24h), (100-200 ppm/24h) & (100-200 ppm/12-48h) respectively. Moreover, the same plant extracts were able to induce total Culex pipiens larvicidal mortality, LC < sub > 100 < /sub > was (200 ppm/48h). However, Grape seed and Pomegranate alcoholic extracts did not induce either snail ovicidal or Culex pipiens larvicidal total mortalities. Activities of the studied plant extracts were considered using reference molluscicidal (Copper sulfate) and insecticidal (Temephos) substances. CONCLUSION: Egyptian native plants continue to provide a wealth of potential sources for biologically active agents that may have a promising role in the production of safe, biodegradable eco-friendly and natural molluscicidal and insecticidal agents.

Phytochemical investigation of Verbesina turbacensis Kunth: trypanosome cysteine protease inhibition by (-)-bornyl esters.

The bark and leaf essential oils of Verbesina turbacensis were obtained by hydrodistillation and analyzed by GC-MS. The bark oil of the plant was composed mainly of monoterpene hydrocarbons (83.5-90.4%), predominately alpha-pinene, while the leaf oil was composed mainly of sesquiterpene hydrocarbons, dominated by germacrene-D (29.1-36.9%), and delta-elemene (21.7-22.1%). Three bornyl hydroxycinnamic esters isolated from the acetone bark extract were found to inhibit the cysteine protease, rhodesain. Molecular docking analysis to probe the inhibitory interactions of the esters was also carried out.

Verbesinosides A-F, 15,27-cyclooleanane saponins from the American native plant Verbesina virginica.

Verbesinosides A-F (1-6), six new 15,27-cyclooleanane-type triterpenoid saponins carrying different aromatic acyl moieties on the aglycon, were isolated from the leaves and flowers of Verbesina virginica. Their structures were established by interpretation of spectroscopic data and chemical methods. The representative major saponin, verbesinoside A (1), has the structure 21-trimethoxybenzoyl 15alpha,27-cycloolean-12-en-3beta,21beta-diol-28-oic acid 3-O-beta-D-xylopyranosyl(1-->4)-beta-D-xylopyranosyl(1-->2)-beta-D-glucopyranoside. This is the first report of triterpenoid saponins possessing the unique 15,27-cyclooleanane skeleton. The anisotropic effects of the aromatic acyl moieties on the triterpenoid skeleton are discussed.

Novel hypotensive agents from Verbesina caracasana: structure, synthesis and pharmacology.

The number and the pharmacological activities of drugs featuring a guanidine group is actually amazing. Many synthetic guanidine derivatives have attracted pharmacologists in search of new antihypertensive drugs for their ability to block adrenergic nerve activity through central and/or peripheral mechanisms. As a result, compounds such as guanethidine, guanabenz, guanfacine, and pinacidil have been introduced in antihypertensive drug therapy. A crude methanol extract of the Venezuelan plant Verbesina caracasana Fries (Compositae), intravenously administered to mice, was found to induce biological effects such as erection of hair, initial stimulation and subsequent blockade of breathing. Biologically controlled purification yielded a series of active guanidine derivatives, namely G1-G7, which were extensively studied with the focus on the following items: (1) The structure determination of the active compounds by spectral data and a set of reactions; (2) The confirmation of the structures by a biogenetically oriented synthesis; (3) The study of the pharmacological profiles of the isolated drugs; (4) The synthesis of analogous and homologous products in the effort to shed some light on the structure-activity relationship. The metabolites of V. caracasana were characterized, in anesthetized rats, as hypotensive drugs of high (G2), mild (G1, G7) and low (G3,G5,G6) potency, devoid of consistent actions in heart rate, and provided with moderate stimulatory effects on cardiac inotropism and breathing (at selected non-toxic intravenous doses). Autonomic neurogenic components and/or peripheral adrenergic and cholinergic receptor-related pathways were involved in the cardiovascular effects. Synthetic analogs and homologs of G1 and G5 were all shown to be hypotensive drugs of low-mild potency, not affecting appreciably cardiac inotropism and/or breathing. The pharmacodynamic differences among the studied compounds were likely to depend on their ability to cross the blood-brain barrier, lipophilicity and pharmacokinetics. Since most of the compounds did not induce reflex tachycardia and depression of myocardial contractility as the majority of the antihypertensive drugs, they might be useful in the treatment of arterial hypertension of various genesis.

Structure activity relationship studies of cinnamic acid derivatives as inhibitors of human neutrophil elastase revealed by ligand docking calculations.

Structure-activity relationship of cinnamic acid derivatives as inhibitors of the human neutrophil elastase is reported. Comparison of the inhibitory concentrations (IC50 values) with the results of the ligand docking calculations revealed that the structure element of the aromatic ortho-dihydroxy groups combined with a lipophilic residue seems to be a prerequisite for an optimal binding within the active site.