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

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.Pomegranate (Punica granatum L., Punicaceae) is used in the traditional medicine of different Asian cultures for the treatment of a variety of ailments. In Ayurvedic medicine, the plant, described under its Sanskrit name "dalima" (fruit), is considered as a "blood tonic" and used to cure parasitic infections [1]. The decoction of the root was found beneficial in fevers and chronic debility due to malaria. Moreover, the fruit rind powder was found to possess immunomodulatory properties [2].The eastern province of Orissa (India) is an area endemic for both Plasmodium falciparum and Plasmodium vivax; malaria constitutes a major health problem for the population, in particular for those living in rural areas. Since 1998, malaria patients referring to the Ayurveda dispensary receive a herbal preparation named OMARIA, made of sun-dried rind of the immature P. granatum fruits (Pg). OMARIA (the acronym for Orissa Malaria Research Indigenous Attempt) is dis