PMID- 24189034 OWN - NLM STAT- MEDLINE DCOM- 20140908 LR - 20131230 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 151 IP - 1 DP - 2014 TI - Evaluation of acute toxicity, antibacterial activity, and mode of action of the hydroethanolic extract of Piper umbellatum L. PG - 137-43 LID - S0378-8741(13)00718-6 [pii] LID - 10.1016/j.jep.2013.10.011 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Piper umbellatum L., Piperaceae, is a shrub that grows up to 3m high. It is commonly known as "capeba" or "pariparoba" in Brazil. Tea prepared using the leaves of this plant is employed in the treatment of infections and inflammatory processes in different countries. Approximately 50 compounds, notably from the flavonoid, alkaloid, terpene, and sterol classes, have been isolated from the leaves of Piper umbellatum. To evaluate the acute toxicity, antibacterial activity, and mode of action of the hydroethanolic extract of Piper umbellatum leaves (HEPu). MATERIALS AND METHODS: Acute toxicity of HEPu against CHO-K1 cells was evaluated using a cytotoxicity assay with Alamar Blue and that against mice was assessed by the Hippocratic test. Antibacterial activity of HEPu was tested using the broth microdilution method using a panel of clinically relevant bacteria, and the effects of HEPu on the bacterial membrane were analyzed in detail. A preliminary phytochemical analysis based on coloration/precipitation was performed according to procedure described in the literature. Secondary metabolites detected were analyzed and confirmed by thin layer chromatography (TLC), spectrophotometry, and high performance liquid chromatography (HPLC). RESULTS: Piper umbellatum did not appear to be toxic in the in vitro (IC50>200 microg/mL) cytotoxicity test. When administered in vivo at doses up to 2000 mg/kg p.o., HEPu did not cause any signs or symptoms of toxicity in mice. It demonstrated a good spectrum of antibacterial activity and its mode of action appeared to be associated with changes in the permeability of bacterial membranes; it led to increased entry of hydrophobic antibiotics, efflux of K(+), and nucleotide leakage. Preliminary phytochemical analysis revealed the presence of flavonoids, alkaloids, terpenes, and sterols in the extract. Spectrophotometric and HPLC analysis revealed the presence of the flavonoids rutin and quercetin. CONCLUSION: In summary, HEPu has antibacterial activity and low acute toxicity in vitro and in vivo. Its mode of action appears to be associated with changes in the permeability of the bacterial cell wall and cytoplasmic membrane, which can at least be partly attributed to the flavonoids present in the extract. CI - (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - da Silva, Ibere Ferreira Jr AU - da Silva IF Jr AD - Department of Basic Sciences in Health, Faculty of Medicine, Federal University of Mato Grosso (UFMT), Av. Fernando Correa da Costa, no. 2367, Coxipo, Cuiaba, Mato Grosso 78060-900, Brazil. FAU - de Oliveira, Ruberlei Godinho AU - de Oliveira RG AD - Department of Basic Sciences in Health, Faculty of Medicine, Federal University of Mato Grosso (UFMT), Av. Fernando Correa da Costa, no. 2367, Coxipo, Cuiaba, Mato Grosso 78060-900, Brazil. FAU - Mendes Soares, Ilsamar AU - Mendes Soares I AD - Federal University of Tocantins, Faculty of Food Engineering, Agroenergy Undergraduate Program, Av. NS 15, Block number III, 26 Room, Palmas, Tocantins 77020-210, Brazil. FAU - da Costa Alvim, Tarso AU - da Costa Alvim T AD - Federal University of Tocantins, Faculty of Food Engineering, Agroenergy Undergraduate Program, Av. NS 15, Block number III, 26 Room, Palmas, Tocantins 77020-210, Brazil. FAU - Donizeti Ascencio, Sergio AU - Donizeti Ascencio S AD - Federal University of Tocantins, Faculty of Food Engineering, Agroenergy Undergraduate Program, Av. NS 15, Block number III, 26 Room, Palmas, Tocantins 77020-210, Brazil; Federal University of Tocantins, Faculty of Medicine, Av. NS15, BALA Block, 11 C Room, Palmas, Tocantins 77020-210, Brazil. FAU - de Oliveira Martins, Domingos Tabajara AU - de Oliveira Martins DT AD - Department of Basic Sciences in Health, Faculty of Medicine, Federal University of Mato Grosso (UFMT), Av. Fernando Correa da Costa, no. 2367, Coxipo, Cuiaba, Mato Grosso 78060-900, Brazil.. Electronic address: domingos.tabajara@pq.cnpq.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131101 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Bacterial Agents) RN - 0 (Plant Extracts) RN - 059QF0KO0R (Water) RN - 3K9958V90M (Ethanol) RN - RWP5GA015D (Potassium) SB - IM MH - Animals MH - Anti-Bacterial Agents/chemistry/*pharmacology MH - Bacteria/drug effects MH - CHO Cells MH - Cricetinae MH - Cricetulus MH - Ethanol MH - Male MH - Mice MH - Microbial Sensitivity Tests MH - Piper/*chemistry MH - Plant Extracts/chemistry/*pharmacology/*toxicity MH - Potassium/metabolism MH - Water OTO - NOTNLM OT - Antibacterial activity OT - Flavonoids OT - Hydroethanolic extract OT - Mode of action OT - Piper umbellatum EDAT- 2013/11/06 06:00 MHDA- 2014/09/10 06:00 CRDT- 2013/11/06 06:00 PHST- 2013/05/15 00:00 [received] PHST- 2013/09/05 00:00 [revised] PHST- 2013/10/03 00:00 [accepted] PHST- 2013/11/06 06:00 [entrez] PHST- 2013/11/06 06:00 [pubmed] PHST- 2014/09/10 06:00 [medline] AID - S0378-8741(13)00718-6 [pii] AID - 10.1016/j.jep.2013.10.011 [doi] PST - ppublish SO - J Ethnopharmacol. 2014;151(1):137-43. doi: 10.1016/j.jep.2013.10.011. Epub 2013 Nov 1.