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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 Jul 19; 9:208.MJ

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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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Authors+Show Affiliations

Dell'agli M
Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti, 9 - 20133 Milano, Italy. mario.dellagli@unimi.it
Galli GV
No affiliation info available
Bulgari M
No affiliation info available
Basilico N
No affiliation info available
Romeo S
No affiliation info available
Bhattacharya D
No affiliation info available
Taramelli D
No affiliation info available
Bosisio E
No affiliation info available

MeSH

AntimalarialsBiological AssayEllagic AcidFruitGene Expression RegulationHemeproteinsHumansHydrolyzable TanninsInflammationLythraceaeMalaria, CerebralMatrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsNF-kappa BPhytotherapyPlant ExtractsRNA, MessengerReverse Transcriptase Polymerase Chain ReactionTumor Necrosis Factor-alphaUp-Regulation

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20642847

Citation

Dell'agli, Mario, et al. "Ellagitannins of the Fruit Rind of Pomegranate (Punica Granatum) Antagonize in Vitro the Host Inflammatory Response Mechanisms Involved in the Onset of Malaria." Malaria Journal, vol. 9, 2010, p. 208.
Dell'agli M, Galli GV, Bulgari M, et al. 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.
Dell'agli, M., Galli, G. V., Bulgari, M., Basilico, N., Romeo, S., Bhattacharya, D., Taramelli, D., & Bosisio, E. (2010). Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria. Malaria Journal, 9, 208. https://doi.org/10.1186/1475-2875-9-208
Dell'agli M, et al. 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 Jul 19;9:208. PubMed PMID: 20642847.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria. AU - Dell'agli,Mario, AU - Galli,Germana V, AU - Bulgari,Michela, AU - Basilico,Nicoletta, AU - Romeo,Sergio, AU - Bhattacharya,Deepak, AU - Taramelli,Donatella, AU - Bosisio,Enrica, Y1 - 2010/07/19/ PY - 2010/04/23/received PY - 2010/07/19/accepted PY - 2010/7/21/entrez PY - 2010/7/21/pubmed PY - 2010/8/20/medline SP - 208 EP - 208 JF - Malaria journal JO - Malar J VL - 9 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1475-2875 UR - https://www.unboundmedicine.com/medline/citation/20642847/Ellagitannins_of_the_fruit_rind_of_pomegranate__Punica_granatum__antagonize_in_vitro_the_host_inflammatory_response_mechanisms_involved_in_the_onset_of_malaria_ L2 - https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-9-208 DB - PRIME DP - Unbound Medicine ER -