Aim of the study: Sun-dried rind of the immature fruit of Punica granatum L. (Punicaceae)(Pg) is presently used as a herbal formulation (OMARIA) in Orissa, India, for the therapy and prophylaxis of malaria. The aims of this study were (i) to assess in vitro the antiplasmodial activity of the methanolic extract, of a tannin enriched fraction and of compounds/metabolites of the antimalarial plant, (ii) to estimate the curative efficacy of the Pg extracts and (iii) to explore the mechanism of action of the antiplasmodial compounds. Urolithins, the ellagitannin metabolites, were also investigated for antiplasmodial activity. Materials and methods: Chloroquine-susceptible (D10) and -resistant (W2) strains of Pf were used for in vitro studies and the rodent malaria model Plasmodium berghei-BALB/c mice was used for in vivo assessments. Recombinant plasmepsins 2 and 4 were used to investigate the interference of Pg compounds with the metabolism of haemoglobin by malaria parasites. Results: The Pg methanolic extract (Pg-MeOH) inhibited parasite growth in vitro with a IC50 of 4.5 and 2.8 mu g/ml, for D10 and W2 strain, respectively. The activity was found to be associated to the fraction enriched with tannins (Pg-FET, IC50 2.9 and 1.5 mu g/ml) in which punicalagins (29.1%), punicalins, ellagic acid (13.4%) and its glycoside could be identified. Plasmepsin 2 was inhibited by Pg-MeOH extract and by Pg-FET (IC50 7.3 and 3.0 mu g/ml), which could partly explain the antiparasitic effect. On the contrary, urolithins were inactive. Both Pg-MeOH extract and Pg-FET did not show any in vivo efficacy in the murine model. Conclusions: The in vitro studies support the use of Pg as antimalarial remedy. Possible explanations for the negative in vivo results are discussed.

Antiplasmodial activity of Punica granatum L. fruit rind / M. Dell’Agli, G. Galli, Y. Corbett, D. Taramelli, L. Lucantoni, A. Habluetzel, O. Maschi, D. Caruso, F. Giavarini, S. Romeo, D. Bhattacharya, E.A. Bosisio. - In: JOURNAL OF ETHNOPHARMACOLOGY. - ISSN 0378-8741. - 125:2(2009), pp. 279-285.

Antiplasmodial activity of Punica granatum L. fruit rind

M. Dell’Agli
Primo
;
G. Galli
Secondo
;
Y. Corbett;D. Taramelli;O. Maschi;D. Caruso;F. Giavarini;S. Romeo;E.A. Bosisio
Ultimo
2009

Abstract

Aim of the study: Sun-dried rind of the immature fruit of Punica granatum L. (Punicaceae)(Pg) is presently used as a herbal formulation (OMARIA) in Orissa, India, for the therapy and prophylaxis of malaria. The aims of this study were (i) to assess in vitro the antiplasmodial activity of the methanolic extract, of a tannin enriched fraction and of compounds/metabolites of the antimalarial plant, (ii) to estimate the curative efficacy of the Pg extracts and (iii) to explore the mechanism of action of the antiplasmodial compounds. Urolithins, the ellagitannin metabolites, were also investigated for antiplasmodial activity. Materials and methods: Chloroquine-susceptible (D10) and -resistant (W2) strains of Pf were used for in vitro studies and the rodent malaria model Plasmodium berghei-BALB/c mice was used for in vivo assessments. Recombinant plasmepsins 2 and 4 were used to investigate the interference of Pg compounds with the metabolism of haemoglobin by malaria parasites. Results: The Pg methanolic extract (Pg-MeOH) inhibited parasite growth in vitro with a IC50 of 4.5 and 2.8 mu g/ml, for D10 and W2 strain, respectively. The activity was found to be associated to the fraction enriched with tannins (Pg-FET, IC50 2.9 and 1.5 mu g/ml) in which punicalagins (29.1%), punicalins, ellagic acid (13.4%) and its glycoside could be identified. Plasmepsin 2 was inhibited by Pg-MeOH extract and by Pg-FET (IC50 7.3 and 3.0 mu g/ml), which could partly explain the antiparasitic effect. On the contrary, urolithins were inactive. Both Pg-MeOH extract and Pg-FET did not show any in vivo efficacy in the murine model. Conclusions: The in vitro studies support the use of Pg as antimalarial remedy. Possible explanations for the negative in vivo results are discussed.
Punica granatum; Dalima; Plasmodium; Ellagitannins; Malaria; Plasmepsin; Antiparasitic remedy
Settore BIO/10 - Biochimica
Settore MED/04 - Patologia Generale
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/15 - Biologia Farmaceutica
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0378874109004048-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 457.58 kB
Formato Adobe PDF
457.58 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/68931
Citazioni
  • ???jsp.display-item.citation.pmc??? 24
  • Scopus 81
  • ???jsp.display-item.citation.isi??? 65
social impact