Malaria is a disease that causes millions of clinical episodes annually. Therefore, the discovery and development of preventive, therapeutic agents are considered necessary to control and manage the disease. While research in this area has achieved considerable progress, the problem of emerging parasite drug-resistant has also created additional challenges, making the mission more difficult. The beneficial role of medicinal plants in regulating malaria parasite infections has recently been shown [25–27]. Furthermore, malaria infection is associated with the release of proinflammatory cytokines including IL-1?, TNF-?, iNOS, and IFN?, which play vital roles in mediating the severity of the disease [28]. Moreover, these proinflammatory cytokines are implicated in the pathogenesis and immunopathological reactions of the host-parasite interaction. Here, we propose that P. granatum treatment has beneficial effects on murine malaria-induced splenic injury and oxidative stress. For centuries, pomegranate has been considered as one of the candidate plants that shows potential therapeutic effects against numerous ailments as documented in different cultures [29]. The ameliorative effect of PPE in mice infected with the P. chabaudi parasite was investigated in this study. Mice infected with the P. chabaudi parasite achieved maximal parasitemia on day 6 p.i. during which the parasite induced the splenic responses. However, our findings showed that the parasitemia level decreased by 50 % following treatment with PPE. This observation illustrated the efficacy of PPE treatment compared to vehicle treatment and was in agreement with the results of our previous study [25].
Although malaria infection is characterized by splenic rupture and splenomegaly, the spleen is known as a key organ in the immune response development, and it senses infected RBCs [3, 4]. To evaluate the effect of PPE on the spleen, the thickness of the spleen capsules of uninfected mice, as well as those that were infected with or without treatment, was examined. The findings confirmed the beneficial effect of PPE, which conspicuously restored the spleen capsule thickness compared to that of the untreated group. This observation indicates that pomegranate inhibited the development of the P. chabuadi parasite in the host and perhaps acted by reducing the splenic inflammation. This suggests that the protective effect of PPE involves diminishing the oxidative destruction.
This is in accordance with the data of different studies that show that pomegranate peel and its biological properties are principally associated with the presence of flavonoids and tannins, and pomegranates have higher antioxidant properties than other fruits do [30–33]. Moreover, it has been reported that PPE reduces the production of NO and MDA while hindering the infection-induced loss of catalase activity [16]. Our data supported this notion by revealing that the supplementation of PPE to infected mice induced a superior recovery response from the oxidative stress-associated metabolites including H2O2, NO, and MDA compared to that of the untreated mice.
Furthermore, the modulatory effect of PPE on splenic injury and oxidative stress was also shown to be associated with the proinflammatory cytokines, IL-1?, TNF-?, iNOS, and IFN?. The effects of PPE on the expression levels of IL-1?, TNF-?, iNOS, and IFN? mRNA were investigated, and we obtained remarkable results. The results showed an upregulation of the mRNA levels of the proinflammatory cytokines in the untreated infected group of mice compared to the controls. However, the PPE-treated group of infected mice showed significantly downregulated mRNA levels compared to the untreated mice.
The cellular immune response arm of the adaptive immunity is known to degrade the pRBC by activating intracellular cytotoxicity mechanisms and IFN? plays a key role in this process. Nonetheless, the increased level of IFN? expression stimulates the responses of the local Th1/Th2 cell, which favor Th1 [6, 7]. In addition, IL-12 has been shown to be a proinflammatory Th1 cytokine that is promoted by the upregulation of IFN? expression [34].
These findings suggest that PPE has anti-inflammatory activity and attenuates the inflammatory response of the innate immunity. Similar findings were obtained by Dkhil et al. [35] who reported the anti-inflammatory effect of berberine in mice infected with Eimeria papillata.