Punica granatum Leaf Lipophilic Fraction Favours Mortality by Attenuating Inflammation in Mice with Polymicrobial Sepsis

Punica granatum L. possesses known antimicrobial and anti-inflammatory actions. Preparations of different parts of this plant have been commonly used in the folk medicine to prevent and treat infections; and studies have supported the use of P. granatum extracts for this purpose. However, little is known of the effects of P. granatum-derived fractions in severe infectious diseases such as sepsis. Here, we investigated the actions of the hexane fraction (HF), rich in lipophilic compounds, obtained from the leaves of this plant, in a murine model of polymicrobial sepsis. Oral pre-treatment with HF increased mortality in septic mice. The same animals presented with lower levels of interleukin-6, nitric oxide and hydrogen peroxide in their peritoneal lavage samples than vehicle mice. HF also increased polymorphonuclear cell accumulation in to the peritoneum of mice with sepsis. Macrophage-derived nitric oxide upon lipopolysaccharide stimuli was markedly reduced by incubation with HF. Diterpenes, triterpenes, phytosterols, vitamin E and ascorbyl palmitate were detected in the HF. These results indicate that P. granatum leaf lipophilic fractions may worsen sepsis outcome. This effect may be associated with its bioactive compounds which act synergistically or not, increasing sepsis mortality in vivo.