Antibacterial Activity and Reversal of Multidrug Resistance of Tumor Cells by Essential Oils from Fresh Leaves, Flowers, and Stems of Montanoa quadrangularis Schultz Bipontinus (Asteraceae) Collected in Mérida-Venezuela.

Essential oils obtained by hydrodistillation of Montanoa quadrangularis leaves, flowers, and stems were analyzed by GC and GC/MS techniques revealing myrcene, limonene, ß-phellandrene, and sabinene among the main components. The aim of the present study was to evaluate the MDR modulator activity on human MDR1 gene transfected mouse lymphoma cell line and the antimicrobial activity on the essential oils obtained from different parts of the species under investigation. The results revealed that MQL caused a similar increase in the fluorescence activity of the cells at 0.02 µL/mL comparing to the Verapamil® value. The antimicrobial assay was carried out according to the disc diffusion method. Five different bacterial strains (Staphylococcus epidermidis, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli AG 100, and Escherichia coli AG100A) were treated with the essential oils and the zones of inhibition were determined on TSA plates and TSA agar plates supplemented with Tween 20. MQF and MQL showed activity against B. subtilis, S. epidermidis, and E. coli AG 100A while MQS was only active against E. coli AG 100A on TSA agar plates experiment. In case of TSA agar plates supplemented with 0.1 v/v% Tween 20 detergent, MQF showed inhibition on B. subtilis, S. epidermidis, and E. coli AG 100A; MQL was active against B. subtilis, E. coli AG 100, and E. coli AG 100A while MQS was only active against E. coli AG 100A.

Distribución potencial de dos subespecies de Montanoa tomentosa (Asteracerae) en México / Potential distribution of two subspecies of Montanoa tomentosa (Asteracerae) in Mexico

Introducción: la Montanoa tomentosa es un recurso fitogenético con propiedades medicinales utilizado en México. A pesar de su relevancia botánica, la información específica de las distribuciones de taxones infraespecíficos y la los factores que influyen en su desarrollo aún son limitados. Objetivo: Informar el potencial geográfico distribución y las variables ambientales asociadas a nichos ecológicos de dos subespecies de M. tomentosa (M. tomentosa subsp. Tomentosa y M. tomentosa subsp. Xanthiifolia) en territorio mexicano. Métodos: A Se creó una base de datos de registros de herbario, se realizó una búsqueda sistemática in situ de ambas subespecies desde Octubre de 2015 a marzo de 2016, durante la temporada de floración y fructificación. Posteriormente, recorridos exploratorios (Guanajuato, Querétaro, Hidalgo, Ciudad de México, Estado de México, Puebla, Oaxaca y Chiapas). Un total de 181 Se muestrearon y georreferenciaron individuos, generando nuevos registros para la actualización de la base de datos. Tres hábitat modelos de idoneidad (complejo M. tomentosa, M. tomentosa subsp. tomentosa y M. tomentosa subsp. xanthiifolia) se generaron utilizando el software MaxEnt. Este software estima la probabilidad de distribución de especies. utilizando datos georreferenciados y características ambientales como predictores, mediante el logaritmo de entropía máxima y el método bayesiano. Resultados: De 22 variables ambientales utilizadas como predictores, cinco (estacionalidad de temperatura, isotermalidad, temperatura máxima del mes más cálido, precipitación del más cálido trimestre y precipitación del trimestre más húmedo) contribuyeron con el 70,2% de la contribución porcentual total. los El modelo mostró una distribución potencial de 77 688 km2, aproximadamente el 4% del territorio de la República Mexicana. Ambos La subespecie creció entre 500 y 2 500 m. Se asociaron a vegetación xerófila y heliófila, a veces también estaban ubicadas en la periferia o incrustadas en aberturas de bosques templados y subhúmedos. No estuvieron presentes regiones secas del norte del país. Conclusiones: estacionalidad de la temperatura, isotermalidad y la temperatura máxima del mes más cálido determinan la distribución de la especie. Precipitación del cuarto más cálido y la precipitación del cuarto más húmedo define el hábitat entre M. tomentosa subsp. tomentosa y M. tomentosa subsp. xanthiifolia. Estos hallazgos aclaran las preferencias ecológicas y la delimitación los taxones infraespecíficos de M. tomentosa.

Introduction: Montanoa tomentosa is a phytogenetic resource with medicinal properties used in Mexico. Despite its botanic relevance, the specific information of infraespecific taxa distributions and the environmental factors that influence their development is still limited. Objective: To report the potential geographic distribution and the environmental variables associated to ecological niches of two subspecies of M. tomentosa (M. tomentosa subsp. tomentosa and M. tomentosa subsp. xanthiifolia) in the Mexican territory. Methods: A database of herbarium records was created, an in situ systematic search of both subspecies was carried out from October 2015 to March 2016, during the flowering-fruiting season. After that, exploratory tours (Guanajuato, Querétaro, Hidalgo, Mexico City, State of Mexico, Puebla, Oaxaca and Chiapas) were realized. A total of 181 individuals were sampled and georeferenced, generating new records for the database upgrading. Three habitat suitability models (M. tomentosa complex, M. tomentosa subsp. tomentosa and M. tomentosa subsp. xanthiifolia) were generated using the MaxEnt software. These software estimates the probability of species distribution using geo-referenced data and environmental characteristics as predictors, through the maximum entropy logarithm and the Bayesian method. Results: From 22 environmental variables used as predictors, five (seasonality of temperature, isothermality, maximum temperature of the warmest month, precipitation of the warmest trimester and precipitation of the wettest trimester) contributed 70.2 % of the total percentage contribution. The model showed a potential distribution of 77 688 km2, approximately 4 % of the Mexican Republic territory. Both subspecies grew between 500 and 2 500 m. They were associated to xerophilous and heliophiles vegetation, sometimes they were located in the periphery or embed in openings of temperate and sub-humid forests too. They were not present dry regions from the North of the country. Conclusions: Temperature seasonality, isothermality and maximum temperature of the warmest month determine the distribution of the species. Precipitation of the warmest quarter and precipitation of wettest quarter defines the habitat between M. tomentosa subsp. tomentosa and M. tomentosa subsp. xanthiifolia. These findings clarify the ecological preferences and delimitation the infraspecific taxa of M. tomentosa.

Anxiolytic- and anxiogenic-like effects of Montanoa tomentosa (Asteraceae): Dependence on the endocrine condition.

ETHNOPHARMACOLOGICAL RELEVANCE: Montanoa tomentosa Cerv. (MT) is a native plant from Mexico used in traditional medicine as a remedy for reproductive impairments and relaxing effects. In previous studies, it has been shown that the endocrine state could modify the antianxiety-like actions of anxiolytic compounds. Although women are the primary user of MT, no studies have evaluated the potential impact of the endocrine milieu on its anti-anxiety actions. AIMS OF THE STUDY: Ascertain the antianxiety effects of M. tomentosa in rats with different hormonal conditions, and to analyze the participation of the GABAA receptor in ovariectomized rats treated with MT. MATERIALS AND METHODS: The animal model of anxiety used was the elevated plus-maze (EPM). Rats' endocrine conditions were: a) Low hormone levels (rats in diestrus I and II phases); b) High hormone levels (proestrus/estrus phases); c) No hormones (ovariectomized rats); and d) Rats under progesterone withdrawal (PW). To evaluate the participation of the GABAA receptor in the anxiolytic-like action of MT the antagonist picrotoxin was used. RESULTS: Results showed that MT induced dose-dependent anxiolytic-like actions in rats with low hormone level conditions. Also, MT reduced anxiety-like behavior in female rats under PW, in contrast to diazepam which was ineffective. MT's anxiolytic-like effect was blocked by picrotoxin, suggesting the participation of the GABAA receptor complex. However, increased anxiety-like behavior was observed in rats with a high hormone level condition and low doses of MT. CONCLUSIONS: Beneficial anxiolytic-like actions of MT are observed under low hormone conditions, particularly in the PW challenge (a condition that can be related to a premenstrual period). Furthermore, the participation of the GABAA receptor is evidenced. However, hormonal variations could induce the opposite effects, hence women should be cautious.

GABAA/benzodiazepine receptor complex mediates the anxiolytic-like effect of Montanoa tomentosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Montanoa tomentosa also named Cihuapatli is a native plant of Mexico that has been used in traditional medicine for the last five centuries mainly as a remedy for reproductive impairments. However, there are reports indicating that this plant was also consumed by Mexican ancient people for its relaxing properties. In order to corroborate this information, the present study was conducted to evaluate the effect of Montanoa tomentosa lyophilisate (MT) on rat׳s anxiety-like behavior and to analyze its mechanism of action. MATERIALS AND METHODS: The anxiolytic-like action of MT (1.5, 3.0, 6.0 and 12.0 mg/kg) was investigated in male Wistar rats tested in three animal models of anxiety: the burying behavior, the elevated plus maze and the hole-board tests. As a positive control, the anti-anxiety effects of different doses of the selective GABAA receptor agonist muscimol were also analyzed. In order to evaluate the participation of the GABAA and oxytocin receptors in the anxiolytic-like actions of MT, the GABAA receptors blockers picrotoxin (0.25 and 0.50 mg/kg), bicuculline (2.0 mg/kg) and flumazenil (5.00 and 10.0 mg/kg), the neurosteroid inhibitor finasteride (50.0 and 100 mg/kg) and the oxytocin receptor antagonist atosiban (0.25 µg) were used. Finally, to evaluate general activity, and motor coordination, the open field and rota-rod tests were used. RESULTS: MT at 3.0 mg/kg showed anxiolytic-like effects in the three anxiety paradigms without affecting reactivity, general motor activity or motor coordination; however, at higher doses sedative effects were observed. Picrotoxin (0.25 and 0.50 mg/kg), flumazenil (10.0 mg/kg) and finasteride (100 mg/kg) antagonized the anxiolytic-like actions of MT in the burying behavior test. In the plus maze and hole-board tests bicuculline (2.0 mg/kg) blocked the effects of the plant as well. Atosiban (0.25 µg) did not antagonize the anxiolytic-like actions of MT. CONCLUSIONS: The results corroborate the anxiolytic-like actions of Montanoa tomentosa and suggest that this effect is mediated through GABAA receptors but not oxytocin receptors.

Anti-fertility and other biological activities of zoapatle (Montanoa spp. )with biotechnological application / Anti-fertilidad y otras actividades biológicas del zoapatle (Montanoa spp. ) con aplicación biotecnológica

Species from the Montanoa genus have been used for hundreds of years in Mexican traditional medicine. The Náhuatl name given by Aztecs to this plant was “cihuapahtli”, meaning “woman’s medicine” (cihua, woman; pahtli, medicine), because M. tomentosa has been used to treat female health disorders since pre-Hispanic times due to its uterotonic properties. Later on, the Spanish pronunciation transformed the word into “zoapatle”, the name still used by herb sellers in México. Despite its use in folk medicine, intensive scientific research on this plant did not begin until the early 1970’s. The only two available reviews exclusively focused on the Montanoa species cover the period from 1529 to 1985. However, in the last two decades, important phytochemical, biochemical and biotechnological advances were achieved. This is a review of the history, botany, most relevant chemistry, biological activity and biotechnology of the secondary metabolites from the Montanoa genus so far.

Especies del género Montanoa han sido empleadas por siglos en la medicina tradicional Mexicana. El nombre asignado a esta planta por los Aztecas fue “cihuapahtli”, ó “medicina para la mujer” (cihua, mujer; pahtli, medicina). Específicamente, M. tomentosa es usada para tratar desordenes de la mujer desde tiempos prehispánicos por sus propiedades uterotónicas. La castellanización transformó esta palabra en “zoapatle”, este nombre sigue siendo usado por los curanderos en México. A pesar de su uso en la medicina folklórica, la investigación científica intensa en esta planta comenzó desde inicios de 1970. Las únicas dos revisiones disponibles y dedicadas exclusivamente a las especies de Montanoa cubren el periodo de 1529 a 1985. Sin embargo, en las últimas dos décadas, se han logrado importantes avances fitoquímicos, bioquímicos y biotecnológicos. Este trabajo presenta una revisión de la historia, botánica, química más relevante, actividades biológicas y biotecnología de los metabolitos secundarios del género Montanoa a la fecha.

Montanoa frutescens and Montanoa grandiflora extracts reduce anxiety-like behavior during the metestrus-diestrus phase of the ovarian cycle in Wistar rats.

In previous studies, the anxiolytic-like effects of Montanoa tomentosa and Montanoa frutescens were reported in male rats, but the potential anxiolytic-like effects of Montanoa plants during the different phases of the ovarian cycle in rats remain to be explored. The anxiolytic-like effects of the aqueous crude extracts of M. frutescens (25 and 50 mg/kg) and M. grandiflora (25 and 50 mg/kg) in the elevated plus maze were investigated in Wistar rats during the estrous cycle and compared with 2 mg/kg diazepam as a reference anxiolytic drug. To investigate any motor effect (i.e., hyperactivity, no changes, or hypoactivity) associated with the treatments, the rats were evaluated in the open field test. The M. frutescens (25 and 50 mg/kg) and M. grandiflora (50 mg/kg) extracts exerted anxiolytic-like effects during the metestrus-diestrus phase, similar to diazepam, without disrupting spontaneous motor activity. No significant effects of the extracts were detected in either behavioral test during the proestrus-estrus phase, whereas diazepam produced motor hypoactivity in the open field test. These results indicate that the M. frutescens and M. grandiflora extracts possess anxiolytic-like effects that depend on the ovarian cycle phase, supporting the Mexican ancient medicinal use of these plants to ameliorate anxiety disorders.

Increase of the ejaculatory potency by the systemic administration of aqueous crude extracts of cihuapatli (Montanoa genus) plants in spinal male rats.

In the present study, evidence on the aphrodisiac activity of Montanoa frutescens and Montanoa grandiflora and a comparison with the aphrodisiac activity of Montanoa tomentosa is presented. By using the fictive ejaculation model in spinal male rats, electromyographic recordings of the genital motor pattern of ejaculation were obtained in the bulbospongiosus muscles and analyzed after the intravenous injection of aqueous crude extracts of Montanoa tomentosa, Montanoa frutescens, and Montanoa grandiflora. Results showed that the systemic administration of the aqueous crude extracts of Montanoa plants elicits a significant increase in the ejaculatory capacity of spinal male rats with very robust ejaculatory motor patterns that included the expression of tonic penile erections and penile movements and the potent expulsion of urethral contents. In conclusion, Montanoa frutescens and Montanoa grandiflora increase the ejaculatory potency with aphrodisiac activity similar to Montanoa tomentosa.

The aqueous crude extract of Montanoa frutescens produces anxiolytic-like effects similarly to diazepam in Wistar rats: involvement of GABAA receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Cihuapatli is the Nahuatl name assigned to some medicinal plants grouped in the genus Montanoa, where Montanoa frutescens (Family: Asteraceae, Tribe: Heliantheae) is included. The crude extract from these plants has been used for centuries in the Mexican traditional medicine as a remedy for reproductive impairments and mood disorders. Experimental studies have systematically corroborated the traditional use of cihuapatli on reproductive impairments and sexual motivation, however, the effect on mood and "nervous" disorders, remains to be explored. MATERIALS AND METHODS: The anxiolytic-like effect of aqueous crude extract of M. frutescens (25, 50 and 75 mg/kg) was investigated in male Wistar rats evaluated in the elevated plus-maze and compared with several doses of diazepam (1, 2 and 4 mg/kg) as a reference anxiolytic drug. Picrotoxin (1 mg/kg), a noncompetitive antagonist of the GABA(A) receptor, was used in experimental procedures to evaluate if this receptor could be involved in the anxiolytic-like effects produced by M. frutescens. To discard hypoactivity, hyperactivity, or no changes associated with treatments, which could interfere with the behavioral activity in the elevated plus-maze, rats were subjected to the open field test. RESULTS: M. frutescens at 50 mg/kg showed anxiolytic-like activity similarly to 2 mg/kg of diazepam, without disrupts in general motor activity. The anxiolytic-like effect of M. frutescens detected in the elevated plus-maze was blocked by picrotoxin, indicating that GABA(A) receptors are involved in the modulation of this effect. CONCLUSIONS: The results corroborate the use of M. frutescens in folk Mexican ethnomedicine as a potential anxiolytic agent and suggest that this effect is mediated by the GABA(A) receptors. Additionally, some sedative effects with high doses of M. frutescens were detected in the present study.

Biosynthesis of uterotonic diterpenes from Montanoa tomentosa (zoapatle).

Montanoa tomentosa (zoapatle) is a Central American plant used in Mexico in traditional herbal medicine to ease childbirth labor and to cure certain female disorders. Recently, crude extracts of M. tomentosa have been reported to have an aphrodisiacal effect on male rats. The bioactive molecules are the uterotonic diterpenes kaurenoic acid (KA), grandiflorenic acid (GF), and monoginoic acid (MO). Roots of M. tomentosa contain all three diterpenes, whereas in leaves only kaurenoic and GF are present. However, despite the pharmacological importance of these compounds, specific information about their biosynthesis and localization in the plant is not available. In this investigation, we followed the metabolic transformation of a tritium-labeled diterpene-precursor via geranylgeranyl diphosphate into each of the three diterpenes. Inhibitors of gibberellin biosynthesis were used to elucidate the sequence of conversion of the intermediates. Our results suggest the biosynthetic conversion of KA into GF by a putative cytochrome P450-like desaturase. Partial characterization of the enzyme revealed that it requires NADPH and O2 but is inhibited by 50 microM paclobutrazol, suggesting a cytochrome P450 desaturase like enzyme (EC 1.14.14.-). Optimal reaction conditions are 32 degrees C and a pH of 7.6, respectively. Apparent kinetics parameters for KA gave a K(m,app) of 36.31 microM, and a V(max, app) of 13.6 nmol KA mg(1)protein h(-1). Based on the data presented, a putative biosynthetic pathway is proposed for the uterotonic diterpenes of M. tomentosa.

Montanoa tomentosa glandular trichomes containing kaurenoic acids chemical profile and distribution.

Montanoa tomentosa has been used in traditional medicine in Mexico to treat diverse female health disorders; it is particularly useful in inducing childbirth. Microscopic analysis of leaf surfaces of M. tomentosa revealed the presence of glandular trichomes. The chemical profile and distribution of glandular trichomes from different developmental stages of M. tomentosa leaves were investigated. Two diterpenic acids, kaurenoic and grandiflorenic were detected in glandular trichomes through the glandular microsampling technique and GC/MS analysis. In the glandular trichomes of the leaves also up to twenty-six volatile terpenes were identified, where beta-eudesmol and valencene were the most abundant terpenes.

Pro-ejaculatory effect of the aqueous crude extract of cihuapatli (Montanoa tomentosa) in spinal male rats.

In the present study, the pro-sexual effect of the cihuapatli (Montanoa tomentosa) and its possible pro-ejaculatory properties in spinal male rats were examined. Systemic administration of the aqueous crude extracts of Montanoa tomentosa exerted a pro-ejaculatory effect and produced an increase in the number of discharges in the ejaculatory motor patterns in the spinal rats. The cihuapatli-induced ejaculatory responses included the expression of penile erections and penile movements and the potent expulsion of urethral contents and in some cases the expulsion of seminal plugs. The cihuapatli-induced ejaculatory motor patterns were similar to that obtained after systemic oxytocin. Cihuapatli- and oxytocin-induced ejaculatory motor responses and the penile erections and movements were abolished by the pre-treatment with hexamethonium, a selective oxytocin antagonist. Present data show that the cihuapatli extract acts directly at the spinal system in charge of the expression of the ejaculatory motor patterns and suggest that the aqueous crude extract exerts its aphrodisiacs properties by increasing sexual potency acting as an oxytocic agent.

Photoperiodic induction of synchronous flowering near the Equator.

In tropical rainforests, 30-65% of tree species grow at densities of less than one individual per hectare. At these low population densities, successful cross-pollination relies on synchronous flowering. In rainforests with low climatic seasonality, photoperiodic control is the only reliable mechanism for inducing synchronous flowering. This poses a problem because there is no variation in day length at the Equator. Here we propose a new mechanism of photoperiodic timekeeping based on the perception of variation in sunrise or sunset time, which explains and predicts the annually repeated, staggered, synchronous and bimodal flowering of many tree species in Amazonian rainforests near the Equator.

A phylogeny of the ITS and ETS for Montanoa (Asteraceae: Heliantheae).

A phylogeny of the genus Montanoa based on the internal transcribed spacer (ITS) and the external transcribed spacer (ETS) is presented. Each of the two clades revealed by the Bayesian and parsimony analyses has approximately half of the number of species in the genus. One lineage is composed mostly of central and southern Mexican species whereas the other lineage contains those species endemic to Mesoamerica and South America. The molecular phylogeny is compared to previous phylogenetic hypotheses based on morphological characters. Key features in the structure of the capitulum such as pale morphology, heavily used in the past to construct hypotheses of relationship within the genus, are viewed as of minimal value to circumscribe natural groups. The relationships of Montanoa to other genera in the Heliantheae are briefly discussed.

Aphrodisiac properties of Montanoa tomentosa aqueous crude extract in male rats.

Cihuapatli, the Mexican zoapatle (Montanoa tomentosa) has an extensive ethnomedical history of use as a traditional remedy for reproductive impairments. During the study of the ejaculatory function in rats and by testing a set of Mexican plants with medicinal properties, we observed that crude extracts of M. tomentosa facilitated ejaculation. Thus, we decided to analyze the possibility that this plant possessed sexual stimulant properties. To that aim, copulatory behavior of sexually active male rats receiving doses of 38, 75 and 150 mg/kg of the aqueous crude extract of M. tomentosa, as it is prepared in traditional medicine, was assessed. In addition, we evaluated the effect of the 75-mg/kg dose of the extract on males with anesthetization of the genital area and on sexual behavior of sexually inactive male rats (noncopulators). Results showed that acute oral administration of crude extracts of M. tomentosa facilitates expression of sexual behavior in sexually active male rats, significantly increases mounting behavior in genitally anesthetized animals and induces the expression of sexual behavior in noncopulating males. Altogether, these data reveal a facilitatory action of this extract on sexual activity and particularly on sexual arousal. Present findings provide experimental evidence that the crude extract preparation of M. tomentosa, used as a traditional remedy, possesses aphrodisiac properties.

Sesquiterpene lactones from Montanoa hibiscifolia that inhibit the transcription factor NF-kappa B.

The reinvestigation of the aerial parts of Montanoa hibiscifolia afforded four new eudesmanolides (1-4), three of them with a rare endoperoxide structural element and the fourth with a rare carbonyl function. It also afforded three unusual montabibisciolides (5-7), two (5 and 7) of which are new natural compounds. Additionally, seven germacrolides (8-10 and 12-15) and one melampolide (11) could be isolated, including two new germacrolides (8 and 9). Their structures were elucidated using 1D and 2D NMR measurement as well as ESI, CIMS, and HRMS analyses. Low-energy conformations were obtained by molecular mechanics calculations. The (13)C NMR data of five compounds are reported for the first time. Six sesquiterpene lactones (4, 6, 10, 11, 12, and 14) were investigated for their inhibitory activity on DNA binding of the transcription factor NF-kappa B using Jurkat T cells as well as RAW 264.7 cells. Besides the alpha-methylene-gamma-butyrolactone moiety the epoxy group in the acyl residue might take part in the NF-kappa B inhibitory activity of sesquiterpene lactones.

Two new sesquiterpene lactones from Montanoa tomentosa ssp. microcephala.

Two new sesquiterpene lactones: 8alpha-(4'-acetoxymethacryloyloxy)-3alpha,9beta-dihydroxy-1(10)E,4Z,11(13)-germacratrien-12,6alpha-olide (1) and 8alpha-(2'E)-(2'-acetoxymethyl-2'-butenoyloxy)-3alpha,9beta-dihydroxy-1(10)E,4Z,11(13)-germacratrien-12,6alphaolide (2), together with the known zoapatanolide A were isolated from the aerial parts of Montanoa tomentosa Cerv. in La Llave et Lex ssp. microcephala (Sch. Bip. In K. Koch) V.A. Funk (Asteraceae). The structures of all compounds were established on the basis of 1D, 2D NMR, and EIMS analysis.

The zoapatle. XV. Activity of 16 alpha-hydroxy-ent-kauran-19-oic acid isolated from Montanoa hibiscifolia, and its methyl ester on rat and guinea pig uterus.

16 alpha-Hydroxy-ent-kauran-19-oic acid was isolated from Montanoa hibiscifolia. The effects of this acid and its methyl ester on the contractile activity of rat and guinea pig uterine horns were studied. Both inhibited spontaneous, oxytocin-induced and potassium-induced contractile activities. The inhibitory effect produced by the methyl ester was greater than that observed with the acid. The methyl ester was 2-5 times more potent than the acid upon spontaneous and potassium-induced contractions and 11-15 times more potent than the acid upon the contractile activity of uterine smooth muscle induced by oxytocin. Such effects were observed using bath concentrations of 6, 15, 30 and 60 microM of each compound.

The zoapatle XIV--the effect of oral administration of zoapatle upon progesterone plasma levels in pregnant rabbits.

Oral administration of zoapatle aqueous crude extract (ZACE) made from Montanoa tomentosa or frutescens at doses of 5 mg/day from days 3 through 17 of pregnancy in rabbit, did not modify the normal plasma levels of progesterone. Pregnancy and delivery were similar in controls and zoapatle-treated animals.

Studies on zoapatle. V. Correlation between in vitro uterine and in vivo pregnancy interruption effects in guinea pigs.

The zoapatle plant, Montanoa tomentosa, has an extensive ethnomedical history of use in fertility regulation. Several fractions and isolates of this plant were evaulated in in vitro and in vivo tests to identify and characterize active constituents which may be responsible for its antifertility effects. The guinea pig was the animal model. Two types of in vitro activity were observed, a uterotonic type effect and an inhibition of spontaneous contractions of the uterine muscle. The in vivo effects appear to correlate with the ability of a fraction/isolate to inhibit the spontaneous contractions in in vitro testing. The non-polar fractions/isolates accounted for the inhibition of spontaneous contraction effects and the in vivo activity. The more polar fractions/isolates accounted for the uterine stimulant activity.