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Type: Artigo de periódico
Title: Inhibitory Effects Of Piper Umbellatum And Piper Peltatum Extracts Towards Myotoxic Phospholipases A2 From Bothrops Snake Venoms: Isolation Of 4-nerolidylcatechol As Active Principle
Author: Nunez V.
Castro V.
Murillo R.
Ponce-Soto L.A.
Merfort I.
Lomonte B.
Abstract: Phospholipases A2 (PLA2) are important constituents of snake venoms, being responsible for several of their toxic actions. Extracts from plants used in folk medicine were screened for inhibition of the enzymatic activity of myotoxin I, a PLA2 from Bothrops asper. Piper umbellatum and Piper peltatum extracts tested positive, and their fractionation resulted in the isolation of 4-nerolidylcatechol. Its inhibitory effects towards toxic activities of two Bothrops myotoxins, representing catalytically active (Asp49) and catalytically inactive (Lys49) types of group II PLA2s, respectively, were characterized. The enzyme activity of B. asper myotoxin I was completely inhibited by 4-nerolidylcatechol at an inhibitor:toxin ratio of 10:1 (wt/wt) with an IC50 of ∼1 mM. In addition, 4-nerolidylcatechol inhibited representatives of groups I and III of PLA2s. Its preincubation with Bothrops myotoxins significantly reduced their myotoxic and edema-inducing activities in animal experiments. However, when 4-nerolidylcatechol was administered in situ, immediately after toxin injection, its inhibitory ability was substantially lower or negligible. This might be explained by the rapid action of these toxins in vivo, together with the slow inactivation of PLA 2 activity observed in vitro. Electrophoretic and chromatographic analyses of myotoxins ruled out major changes in protein charge, hydrophobicity, or gross molecular mass being involved in the inhibition mechanism. Mass spectrometry determinations are consistent with the covalent modification of myotoxin by one molecule of 4-nerolidylcatechol. Finally, a novel compound was isolated from both Piper species, sharing the nerolidyl skeleton, but nevertheless not being inhibitory towards the PLA2s studied. © 2005 Elsevier Ltd. All rights reserved.
Rights: fechado
Identifier DOI: 10.1016/j.phytochem.2005.03.026
Date Issue: 2005
Appears in Collections:Unicamp - Artigos e Outros Documentos

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