Aqueous extract of<i>Phyllanthus niruri</i>protects against severe malaria by blocking erythrocyte invasion and modulating the host immune response

<jats:title>ABSTRACT</jats:title><jats:p><jats:italic>Plasmodium falciparum</jats:italic>parasites are the major cause of malaria across Africa. Due to the appearance of multi-drug resistant parasites, new antimalarial drugs are needed. The medicinal plant<jats:italic>Phyllanthus niruri</jats:italic>is being used to treat fever and other symptoms of malaria in Nigeria; however, little is known about its antimalarial mechanisms. Here, we show that aqueous extract of<jats:italic>P. niruri</jats:italic>(PE) has multiple antimalarial effects, including anti-parasitic and host immunomodulatory activity. We found that co-culture of<jats:italic>P. falciparum</jats:italic>with PE drastically reduced parasite number, but PE did not inhibit parasite development or rupture; rather, it blocked erythrocytes invasion. In addition, we identified Astragalin as one of the antimalarial compounds which are contained in PE. Moreover, we found that PE suppresses the inflammatory activity and apoptosis of immune cells (T cells) and astrocytes and neurons in the central nervous system (CNS). Furthermore, we confirmed that oral administration of PE to mice suppressed parasite growth, excessive inflammation, CNS dysfunction, and the development of experimental cerebral malaria in an<jats:italic>in vivo</jats:italic>murine malaria model. Our findings demonstrate that PE has multiple effects on malaria progression, targeting both parasite and host cells.</jats:p>