In vivo anti-plasmodial activity of alpha-onocerin and artesunate combination against Plasmodium berghei infected mice

Alpha-onocerin is a triterpenoid derived from Huperzia phlegmaria which is used in ethnomedicine for the treatment of fever, headaches, pains and malaria. This study was conducted to evaluate the safety, antipyretic and anti-plasmodial activity of alpha-onocerin and artesunate (ART) co-administration in ICR mice for use in traditional medicine. The anti-plasmodial effects of alpha-onocerin (10, 30, 100, 300 mg/kg) and ART (1, 2, 4, 8, 16 mg/kg) were assessed in P. berghei-infected mice. Alpha-onocerin /ART were administered with a fixed dose combination of their median effective doses (ED50s) to determine the experimental ED50 (Zexp). An isobologram was developed to identify the nature of the interaction by comparing Zexp with the theoretical ED50 (Zadd). Alpha-onocerin (300 mg/kg) showed a similar chemosuppression (93.51 ± 2.15%) to ART (2 mg/kg, i.p.) of 97.02 ± 0.27% in the 4-day suppressive test as well as in the prophylactic test with chemosuppression at 54.94% and 69.76% for alpha-onocerin (300 mg/kg) and artesunate (2 mg/kg, i.p.) respectively. All doses of alpha-onocerin significantly (p < 0.05) reduced pyrexia in 1 h and 2 h after their administration in the baker’s yeast test. ED50s for ART and alpha-onocerin were 1.33 ± 0.11 and 13.64 ± 0.22 mg/kg, respectively. The Zadd, Zexp and interaction index for alpha-onocerin /ART co-administration were 7.49 ± 3.46, 1.61 ± 0.78 and 0.22 respectively. The Zexp for alpha-onocerin /ART laid below the additive isobole indicating significant (p < 0.001) synergistic activity with ART. Alpha-onocerin showed analgesic effects, antipyretic and synergistic anti-plasmodial effects in P. berghei-infected mice. © 2025 Elsevier B.V., All rights reserved.