Abstract:
Background: Increasing resistance to current anti-malarial therapies requires a renewed effort in searching for
alternative therapies to combat this challenge, and combination therapy is the preferred approach to address this. The
present study confirms the anti-plasmodial effects of two compounds, cryptolepine and xylopic acid and the relation‑
ship that exists in their combined administration determined.
Methods: Anti-plasmodial effect of cryptolepine (CYP) (3, 10, 30 mg kg−1) and xylopic acid (XA) (3, 10, 30 mg kg−1)
was evaluated in Plasmodium berghei-infected male mice after a 6-day drug treatment. The respective doses which
produced 50% chemosuppression (ED50) was determined by iterative fitting of the log-dose responses of both drugs.
CYP and XA were then co-administered in a fixed dose combination of their ED50s (1:1) as well as different fractions
of these combinations (1/2, 1/4, 1/8, 1/16 and 1/32) to find the experimental E D50 (Zexp). The nature of interaction
between cryptolepine and xylopic acid was determined by constructing an isobologram to compare the Z
exp with
the theoretical ED50 (Zadd). Additionally, the effect of cryptolepine/xylopic acid co-administration on vital organs asso‑
ciated with malarial parasiticidal action was assessed.
Results: The Zadd and Zexp were determined to be 12.75 ± 0.33 and 2.60 ± 0.41, respectively, with an interaction
index of 0.2041. The Zexp was significantly (P < 0.001) below the additive isobole indicating that co-administration of
cryptolepine and xylopic acid yielded a synergistic anti-plasmodial effect. This observed synergistic antiplasmodial
effect did not have any significant deleterious effect on the kidney, liver and spleen. However, the testis were affected
at high doses.
Conclusion: The co-administration of cryptolepine and xylopic acid produces synergistic anti-malarial effect with
minimal toxicity.
