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BackgroundIncreasing 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 relationship that exists in their combined administration determined.MethodsAnti-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 ED50 (Zexp). The nature of interaction between cryptolepine and xylopic acid was determined by constructing an isobologram to compare the Zexp with the theoretical ED50 (Zadd). Additionally, the effect of cryptolepine/xylopic acid co-administration on vital organs associated with malarial parasiticidal action was assessed.ResultsThe 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.ConclusionThe co-administration of cryptolepine and xylopic acid produces synergistic anti-malarial effect with minimal toxicity.

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Context: Various parts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) have been used in Ghanaian and African traditional medicine as an analgesic. However, there are little scientific data to support the anti-nociceptive effects of the hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) as well as the possible mechanisms involved in its anti-nociceptive effects. Purpose: To predict possible nociceptive pathways involved in the anti-nociceptive effects of EthE. Materials and methods: The effect of EthE (30, 100 and 300 mg/kg) on intraplantar injection of pain mediators such as interleukin-1b, tumour necrosis factor-a, prostaglandin E 2 and bradykinin was evaluated in male Sprague Dawley rats using Randall-Selitto test for 5 h. The effect of specific antagonists to the opioidergic, adenosinergic, ATP-sensitive K þ channels, nitric oxide, serotonergic, muscarinic, adrenergic and voltage-gated calcium channel on the anti-nociceptive effect of EthE (100 mg/kg) was evaluated using the formalin test in male imprinting control region (ICR) mice for 1 h. Results: Pretreatment of the rats with EthE significantly reversed the hypernociception induced by intraplantar injection of TNF-a (F 4,120 ¼ 10.86, p < 0.0001), IL-1b (F 4,120 ¼ 14.71, p < 0.0001), bradykinin (F 4,80 ¼ 12.52, p < 0.0001) and prostaglandin E 2 (F 5,144 ¼ 6.165, p ¼ 0.0001). The anti-nociceptive effect exhibited by EthE in the formalin test was reversed by systemic administration of N G -L-nitro-arginine methyl ester, naloxone, theophylline and glibenclamide. Conclusions: EthE inhibits hypernociception induced by TNF-a, IL-1b, bradykinin and prostaglandin E 2 . EthE exhibited anti-nociceptive effects possibly mediated through opioidergic, adenosinergic, ATP-sensitive potassium channels and nitric oxide cyclic GMP pathways. ARTICLE HISTORY