The Ethanolic Extract of Piper glabratum Kunth Is Teratogenic and Interferes with the Ossification Process of Swiss Mice Fetuses.

Piper glabratum Kunth is a plant traditionally used to treat pain and inflammation in the Mato Grosso do Sul, Brazil. Even pregnant women consume this plant. Toxicology studies of the ethanolic extract from the leaves of P. glabratum (EEPg) could establish the safety of popular use of P. glabratrum. Thus, the effects of the ethanolic extract of leaves of P. glabratum (EEPg) on the reproductive performance and embryofetal development of Swiss mice were evaluated. Pregnant female mice were treated with 100, 1000 and 2000 mg/kg throughout the gestational period by gavage (p.o). The control group received the EEPg vehicle (Tween 80-1%) in the proportion of 0.1 mL/10 g (p.o.). The results demonstrated that EEPg has low maternal toxic potential and does not alter the reproductive performance of females. However, it altered embryofetal development and caused fetal weight reduction (increasing the frequency of small-for-gestational-age fetuses) at the two highest doses. In addition, it interfered with placental weight, placental index and placental efficiency. The frequency of visceral malformations increased by 2.8 times for the lowest dose of EEPg, and skeletal malformations increased by 2.48, 1.89 and 2.11 times for doses of 100, 1000 and 2000 mg/kg of EEPg, respectively. It is noteworthy that 100% of the offspring treated with EEPg showed changes in the ossification process. Thus, it is considered that the EEPg has low maternal toxic potential; it does not alter the reproductive performance of females. However, it is teratogenic and interferes, mainly, in the ossification process, and therefore its use is contraindicated in the gestational period.

Effects of an ethanolic extract and fractions from Piper glabratum (Piperaceae) leaves on pain and inflammation.

In the state of Mato Grosso do Sul, Brazil, Piper glabratum leaves are used as a popular medicine for pain and inflammation. We performed a phytochemical analysis and evaluated the effects of ethanolic extract (EEPG) obtained from leaves of P. glabratum on toxicity as well as the effects of application of the hexanic fraction (HXPG) and the hydroalcoholic fraction (HAPG) obtained from the EEPG on inflammatory parameters and pain in mice. Swiss mice were treated with EEPG (30-300 mg/kg body weight (b.w.)), HXPG (19.5 mg/kg b.w.) or HAPG (83.37 mg/kg b.w.) and then subjected to carrageenan-induced pleurisy and paw oedema tests, the spontaneous pain, and zymosan-induced intra-articular inflammation. Wistar rats were treated with EEPG to assess acute toxicity. Phytochemical analysis of the fractions demonstrated the presence of phytol and mixture of stigmasterol and ß-sitosterol in the fractions. In the acute toxicity test, LD50 above 2000 mg/kg b.w. was observed. The treatments reduced oedema, cold and mechanical hyperalgesia, leukocyte migration and protein exudation. The antihyperalgesic and anti-inflammatory properties of EEPG and fractions were demonstrated in the present study. These results from EEPG and HXPG may be related, at least in part, to modulation of the inflammatory mediators by phytol, stigmasterol and ß-sitosterol.

Anti-inflammatory and toxicological evaluation of essential oil from Piper glabratum leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Although some of the species of the genus Piper exhibit interesting biological properties, studies on Piper glabratum Kunth are very limited. AIM OF THE STUDY: This study investigated the anti-inflammatory activity and the toxicological profile of the essential oil from P. glabratum leaves (OEPG) in mice. MATERIALS AND METHODS: The acute toxicity of OEPG was evaluated by oral administration to female mice as single doses of 500, 1000, 2000 or 5000mg/kg/body weight. In the subacute toxicity test, the females received 500 or 1000mg/kg/body weight of OEPG for 28 days. The anti-inflammatory potential of OEPG was evaluated using four models including pleurisy, edema, mechanical hyperalgesia and cold allodynia models in mouse paws. RESULTS: No clinical signs of toxicity were observed in animals after acute treatment, which suggested that the LD50 is greater than 5000mg/kg. The subacute exposure to OEPG produced no significant changes in the hematological or biochemical parameters. Similarly, the histology of the organs and the estrus cycle displayed no marked alterations. OEPG exhibited anti-inflammatory activity as indicated by inhibition of the leukocyte migration (100, 300, 700mg/kg) and the protein extravasation into the pleural exudates (700mg/kg). After intraplantar injection of carrageenan, it was observed that the 700mg/kg dose of OEPG reduced edema formation and decreased the sensitivity to mechanical stimulation and cold. CONCLUSIONS: These results demonstrate the anti-inflammatory potential of the essential oil of P. glabratum leaves in the absence of toxicity in female mice.