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 2010-07, Vol.9 (1), p.208-208, Article 208
• Main Authors: Dell'agli, Mario, Galli, Germana V, Bulgari, Michela, Basilico, Nicoletta, Romeo, Sergio, Bhattacharya, Deepak, Taramelli, Donatella, Bosisio, Enrica
• Format: Article
• Language: English
• Subjects: Antimalarials - pharmacology; Antiparasitic agents; Ayurvedic medicine; Biological Assay; Care and treatment; Clinics; Constituents; Cytotoxicity; Defence mechanisms; Disease; Disease prophylaxis; Ellagic acid; Ellagic Acid - pharmacology; Fruit; Fruit juices; Fruits; Gelatinase B; Gene Expression Regulation - drug effects; Genetic aspects; Health aspects; Hemeproteins - analysis; Human diseases; Humans; Hydrolyzable Tannins - pharmacology; Immune response; Immune system; Immunity; Inflammation - drug therapy; Intestinal microflora; Intestine; Malaria; Malaria, Cerebral - drug therapy; Matrix Metalloproteinase 9 - drug effects; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase 9 - secretion; Matrix Metalloproteinase Inhibitors; Medical treatment; Metabolites; Metalloproteinase; NF-kappa B - drug effects; NF-kappa B - physiology; NF-κB protein; Pathogens; Physiological aspects; Phytotherapy; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plasmodium falciparum; Pomegranate; Prevention; Prophylaxis; Punica granatum; Punicaceae - chemistry; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; RNA, Messenger - drug effects; Secretion; Tannins; Transcription; Transcription factors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - physiology; Tumor necrosis factor-TNF; Up-Regulation; Vector-borne diseases
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/1475-2875-9-208

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.