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Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria.
Malar J. 2010;9:208
Publication Type
Mario Dell'agli
Germana V Galli
Michela Bulgari
Nicoletta Basilico
Sergio Romeo
Deepak Bhattacharya
Donatella Taramelli
Enrica Bosisio
Author Affiliation
Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti, 9 - 20133 Milano, Italy.
Malar J. 2010;9:208
Publication Type
Antimalarials - pharmacology
Biological Assay
Ellagic Acid - pharmacology
Gene Expression Regulation - drug effects
Hemeproteins - analysis
Hydrolyzable Tannins - pharmacology
Inflammation - drug therapy
Malaria, Cerebral - drug therapy
Matrix Metalloproteinase 9 - drug effects - metabolism - secretion
Matrix Metalloproteinase Inhibitors
NF-kappa B - drug effects - physiology
Plant Extracts - chemistry - pharmacology
Punicaceae - chemistry
RNA, Messenger - analysis - drug effects
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha - physiology
The sun-dried rind of the immature fruit of pomegranate (Punica granatum) is presently used as a herbal formulation (OMARIA, Orissa Malaria Research Indigenous Attempt) in Orissa, India, for the therapy and prophylaxis of malaria. The pathogenesis of cerebral malaria, a complication of the infection by Plasmodium falciparum, is an inflammatory cytokine-driven disease associated to an up-regulation and activity of metalloproteinase-9 and to the increase of TNF production. The in vitro anti-plasmodial activity of Punica granatum (Pg) was recently described. The aim of the present study was to explore whether the anti-malarial effect of OMARIA could also be sustained via other mechanisms among those associated to the host immune response.
From the methanolic extract of the fruit rind, a fraction enriched in tannins (Pg-FET) was prepared. MMP-9 secretion and expression were evaluated in THP-1 cells stimulated with haemozoin or TNF. The assays were conducted in the presence of the Pg-FET and its chemical constituents ellagic acid and punicalagin. The effect of urolithins, the ellagitannin metabolites formed by human intestinal microflora, was also investigated.
Pg-FET and its constituents inhibited the secretion of MMP-9 induced by haemozoin or TNF. The effect occurred at transcriptional level since MMP-9 mRNA levels were lower in the presence of the tested compounds. Urolithins as well inhibited MMP-9 secretion and expression. Pg-FET and pure compounds also inhibited MMP-9 promoter activity and NF-kB-driven transcription.
The beneficial effect of the fruit rind of Punica granatum for the treatment of malarial disease may be attributed to the anti-parasitic activity and the inhibition of the pro-inflammatory mechanisms involved in the onset of cerebral malaria.
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PubMed ID
20642847 View in PubMed
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