The combination of apigenin and ursolic acid reduces the severity of cerebral malaria in Plasmodium berghei ANKA-infected Swiss Webster mice

Abstract

Cerebral malaria (CM) is a complication of severe malaria characterized by reduced consciousness and other neurological symptoms resulting from Plasmodium falciparum infection. Apigenin and ursolic acid have antimalarial activity in vitro and in vivo in both P. falciparum culture and murine models. So this study evaluated the combination of apigenin and ursolic acid in inhibiting experimental CM in Plasmodium berghei Antwerpen-Kasapa (ANKA)- infected mice. Mice that were infected with P. berghei and showed neurological symptoms (ECM score ≥3) were treated orally for 4 days with 0.5% hydroxypropyl methylcellulose (HPMC) control; 20 mg/kg chloroquine; 75, 100, and 125 mg/kg apigenin; 50, 75, and 100 mg/kg ursolic acid; a combination of 50 mg/kg apigenin + 50 mg/kg ursolic acid and 75 mg/kg apigenin + 50 mg/kg ursolic acid. The percentage inhibition of parasites, neurological assessment, mean survival time (MST), and the measurement of the integrity of the blood-brain barrier (BBB) was recorded. The combination of 75 mg/kg apigenin + 50 mg/kg ursolic acid inhibited parasite growth, extended the MST, reduced neurological symptoms, and protected the BBB in mice with CM. In conclusion, combining apigenin and ursolic acid can reduce the severity of CM in P. berghei ANKA-infected mice.