Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria

• Published in: Malaria Journal
• Main Authors: Bhattacharya Deepak, Romeo Sergio, Basilico Nicoletta, Bulgari Michela, Galli Germana V, Dell'Agli Mario, Taramelli Donatella, Bosisio Enrica
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2010
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-9-208; https://doaj.org/article/22b77c65cfad48b596a89af6a6349b67

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.