Therapeutic Potential of Natural Products in the Treatment of Schistosomiasis

Abstract

It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are Schistosoma Mansoni, S. japonicum, and S. haematobium, each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.

Keywords: essential oil; molecular tools; natural compounds; schistosomiasis.

Figure 1

Chemical structures of natural products with antischistosomal activity demonstrated either in in vitro assays and/or murine models of infection.

Figure 2

Main mechanisms of action of natural products against adult worms of S. mansoni. In general, natural products induced tegument damage in schistosomes associated with body deformation, morphological disfiguring of the oral and ventral suckers, extensive sloughing, loss of tubercles, and shrinking (1). In addition, some natural products, such as licochalcone A, promoted swelling and degeneration of mitochondria and nuclear chromatin condensation, which correlated with increased superoxide anion levels and decreased superoxide dismutase activity (2). Some natural products, mainly chalcones, inhibited S. mansoni ATPase and ADPase activity (3). The reactive oxygen species (ROS) are mainly produced at the electron transport chain (ETC) in the mitochondria, which are formed by transmembrane protein complexes (I–IV). During transportation, leaked electrons interact with oxygen to form superoxide anions (O₂-) at complexes I and III. These complexes are the major source of superoxide and hydrogen peroxide (H₂O₂) since the O₂- released can be reduced into H₂O₂ through a reaction catalyzed by superoxide dismutase (SOD) (Tirichen et al., 2021 [40]; Brand, 2016 [41]). The overproduction of superoxide anions leads to oxidative stress and activates transcription factors such as NF-κB and AP-1. Moreover, increased ROS in mitochondria can induce the release of transmembrane proteins such as cytochrome c, an electron carrier between complexes III and IV, into the cytosol that triggers the apoptotic machinery of the cell (Tirichen et al., 2021 [40]; Guerra-Castellano, 2018 [42]).

Figure 3

Main outcomes of in vivo treatments with natural products. Following intraperitoneal or oral administration, natural products have demonstrated an ability to reduce Schistosoma egg deposition in tissue and worm burden, leading to a reduction in the size of hepatic granulomas and fibrotic areas. Some compounds, such as nerolidol and piplartine, were observed to induce tegument damage as a mechanism of worm elimination. Moreover, plumbagin, curcumin, and other natural products exhibited different immunomodulatory properties by modulating cytokine production associated with Th1, Th2, and Th17 profiles.