Developmental exposure to Passiflora incarnata induces behavioural alterations in the male progeny.

Passiflora incarnata is marketed in many countries as a phytomedicine and is prescribed mainly as a sedative and anxiolytic. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. To evaluate the reproductive and developmental toxicity of P. incarnata, Wistar female rats were gavaged with 30 or 300 mg kg(-1) of this herb from gestational Day (GD) 0 to postnatal Day (PND) 21. P. incarnata treatment did not influence dams' bodyweight or food intake or their reproductive performance (post-implantation loss, litter size, litter weight). There was also no influence on the physical development of pups (bodyweight gain, day of vaginal opening or preputial separation) or their behaviour in the open-field at PND 22, 35 and 75. Sexual behaviour was disrupted in adult male pups exposed to 300 mg kg(-1) of P. incarnata; in this group, only 3 out of 11 pups were sexually competent. This behavioural disruption was not accompanied by alterations in plasma testosterone levels, reproductive-related organs and glands weights or sperm count. It is hypothesised that aromatase inhibition may be involved in the observed effect.

Toxicity and genotoxicity evaluation of Passiflora alata Curtis (Passifloraceae).

UNLABELLED: Passiflora alata is an official species of Brazilian Pharmacopoeia and its aerial parts are used as medicinal plant by local population as well as constitutes many phytomedicines commercialized in Brazil as sedative. AIMS OF STUDY: To evaluate the acute and sub-acute toxicity and genotoxicity of an aqueous spray-dried extract (PA) of Passiflora alata (2.6% flavonoids). MATERIALS AND METHODS: The acute and the sub-acute toxicity was evaluated in mice and rats, respectively. Behavioural, biochemical, hematological, histological and urine parameters were considered. Genotoxicity was assessed by using micronucleus test performed in peripheral blood and bone marrow cells and comet assay in peripheral blood leukocytes. RESULTS: Mice deaths were not observed up to 4800 mg/kg, p.o., single dose. Rats treated with aqueous extract at dose of 300 mg/kg, p.o., for 14 days did not present biochemical, hematological or histopathological significant alterations when compared to control group. However, these rats showed signs of irritability and did not show weight gain. In addition, mice acutely treated with extract 150, 300 and 600 mg/kg, p.o., presented DNA damage determined by comet assay in peripheral blood cells 3h after treatment. The effect of lower doses (12.5, 25 and 50mg/kg, p.o.) was evaluated at 3, 6 and 24h after treating. Only PA 50mg/kg (p.o.) induced significant damage at 3 and 6h. The maximum damage induction was observed at 6h. When the animals received PA 12.5, 25 or 50mg/kg/day during 3 days (i.e., 72h treatment) DNA damage (comet and micronucleus tests) increased significantly in a dose-dependent manner. CONCLUSION: In conclusion Passiflora alata presented genotoxic effect and deserves further toxicity evaluation in order to guarantee its safety for human use.

Evaluación de la toxicidad del extracto metanólico de hojas de Passiflora edulis Sims (maracuyá), en ratas / Passiflora edulis Sims (passion fruit) leaves methanol extract toxicity in rats

Objetivo: Determinar la toxicidad oral a dosis repetidas del extracto metanólico de las hojas de Passiflora edulis en ratas. Diseño: Estudio experimental. Institución: Instituto de Investigaciones Clínicas e Instituto de Patología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Ratas albinas, adultas hembras y machos, y hojas de Passiflora edulis. Métodos: Las hojas Passiflora edulis recolectadas en Trujillo fueron desecadas a 38ºC, pulverizadas y macerado con metanol. Se filtró, concentró y liofilizó. Se conformó dos grupos experimentales de 10 ratas (5 de cada sexo). Un grupo fue control, al cual se le administró agua destilada, y el otro fue grupo tratado, al cual se le administró extracto metanólico de las hojas de Passiflora edulis, en dosis de 200 mg/kg, una vez/día, vía oral, durante 28 días. Se hizo diariamente observaciones clínicas a los animales, se controló el peso cada semana. Al final del experimento se realizó las determinaciones hematológicas y de bioquímica clínica y necropsia. Se extrajo los órganos para la determinación de su peso y estudio histopatológico. Principales medidas de resultados: Peso corporal, e indicadores hematológicos, bioquímicos e histopatológicos. Resultados: No se observó mortalidad ni alteraciones clínicas o hematológicas. La alanina aminotransferasa se incrementó muy ligeramente hasta 55,4 ± 4,9 U/L, en machos (VN = 35,1-53,5), y 53,8 ± 3,9 U/L (VN = 28,8-46,0), en hembras. En el estudio histopatológico se observó en un caso microvesículas focal de hepatocitos y dos casos de focos de necrosis tubular. Conclusiones: La administración oral a dosis repetidas durante 28 días del extracto metanólico de las hojas de Passiflora edulis en ratas no es tóxica.

Objective: To determine oral toxicity of Passiflora edulis leaves metanol extract repeated doses in rats. Design: Experimental study. Setting: Institute of Clinical Research and Institute of Pathology, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological material: Adult female and male albino rats, and Passiflora edulis leaves. Methods: Passiflora edul is leaves harvested in Trujillo were dried at 38° C, powdered and macerated with methanol, filtered, concentrated and lyophilized. Two 10 rats (5 per sex) experimental groups were formed. One group was control that received distilled water and the other was the treated group that received Passiflora edulis leaves methanol extract in doses of 200 mg/kg once/day orally for 28 days. Clinical observations were done daily and the animals were weighed each week. At the end of the experiment we performed hematological, clinical biochemistry determinations and histology. Organs were extracted for determination of weight and histopathological study. Main outcome measures: Body weight, hematologic indicators, biochemical and histological analysis. Results: There was no mortality or clinical and hematological abnormalities. Alanine aminotransferase increased very slightly to 55,4 ± 4,9 U/L in males (VN = 35,1-53,5) and 53,8 ± 3,9 U/L (VN = 28,8-46,0) in females. Histopathology revealed one case of focal hepatocytes microvesicles and two cases of renal tubular necrosis foci. Conclusions: Repeated oral dose administration of Passiflora edulis leaves methanol extract in rats for 28 days is not toxic.

Preclinical toxicological assessment of a phytotherapeutic product--CPV (based on dry extracts of Crataegus oxyacantha L., Passiflora incarnata L., and Valeriana officinalis L.).

Associations of plants have been widely used, for centuries, in Ayurveda and in Chinese medicine and have been increasingly acknowledged in Western medicine. The objective of this study is to assess the level of toxicity of an association of three plants: Crataegus oxyacantha, Passiflora incarnata, and Valeriana officinalis (CPV extract). This association was administered to rats, mice, and dogs, both acute and chronically for 180 days. The tests used in the acute experiments were: observational pharmacological screening, LD(50), motor coordination and motor activity. Chronic tests carried out were: weight gain/loss and behavioral parameters in rats and in mice; estrus cycle, effects on fertility, and teratogenic studies in rats and of mutagenic features in mice, in addition to the Ames test. The following parameters were assessed in dogs: weight gain/loss, general physical conditions, water/food consumption and anatomopathological examination of the organs subsequent to the 180 days of treatment. All of the results were negative, showing that CPV administered in high doses and over a long period of time presents no toxicity, suggestive of the fact that this is an association devoid of risk for human beings.

Passiflora actinia Hooker extracts and fractions induce catalepsy in mice.

Leaves from several Passiflora species are largely employed in the Brazilian folk medicine for its anxiolytic and sedative properties. In behavioral studies, to analyze the tranquillizer action of Passiflora actinia Hooker, it was noteworthy that animals treated with the hydroethanol (HE) and methanol (ME) extracts presented an abnormal postural immobility compared to control animals. That observation led to an investigation of the effects of HE and its fractions on evaluation of catalepsy in mice. The results showed that HE extract, methanol extract, the sequent aqueous crude fractions (AF), and fa, fb and fc chromatographic fractions obtained from Passiflora actinia induced catalepsy in mice. Apparently, the active principles responsible for catalepsy are present in all of the fractions of the extract.

Passiflora incarnata L. y Senna alata (L) Roxo: Estudio toxicogenético que emplea 2 sistemas de ensayo a corto plazo / Passiflora incarnata L and Senna alata (L) Roxo: A toxicogenetic study using 2 short-term test systems

Con el objetivo de conocer el posible efecto toxicogenético de los extractos fluidos de Passiflora incarnata L. (pasiflora) y Senna alata (L.) Roxo (guacamaya francesa), se llevó a cabo un estudio mutagénico empleando 2 sistemas de ensayo a corto plazo, uno in vitro y otro in vivo: el modelo Aspergillus nidulans D-30 que detecta daño primario al ADN y el ensayo de inducción de micronúcleos en médula ósea de ratón el cual determina daño clastogénico y aneugénico. En el ensayo in vitro con el hongo Aspergillus nidulans D-30 (segregación mitótica) se evaluaron concentraciones del extracto fluido de Passiflora incarnata L.; desde 0,162 a 1,296 mg de sólidos totales/mL y para la Senna alata (L.) Roxo, concentraciones de 0,504 a 2,912 mg de sólidos totales/mL. En la prueba in vivo de inducción de micronúcleos se ensayaron para la Passiflora incarnata L. y para la Senna alata (L.) Roxo dosis de 0,607; 1,215; 2, 430 y 1 313,00; 2 625,00; 5 250,00 mg/kg de peso corporal (pc), respectivamente. En ambas baterías de ensayos genotóxicos ninguno de los 2 fitofármacos mostró daño celular ni actividad mutagénica(AU)