BackgroundCryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives.MethodsThe in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane’s test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd.ResultsCPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Zadd of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg−1po) and in combination with ART (4 mg kg−1) showed no significant difference compared to the control group.ConclusionThe combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.

The aim of present study was to investigate the possible protective effects of an ethanolic stem bark extract of Terminalia ivorensis on gentamicin -induced nephrotoxicity and hepatotoxicity in male Sprague-Dawley rats. Groups of animals received either gentamicin alone or in combination with 100, 300 or 1000 mg/kg of extract for a period of 14 days. On the 15 th day, the modulatory effect of Terminalia ivorensis was examined by assessing biochemical and renal markers of hepatic and renal damage. Markers of oxidative injury including reduced glutathione, superoxide dismutase, catalase and lipid peroxidation were assessed. Histology of the kidneys and the liver were also processed for analysis. The extract at a dose of 100-1000 mg/kg significantly reduced elevations in creatinine, urea and serum enzymes evokedby gentamicin. Additionally, the low levels of reduced glutathione and the antioxidant enzymes from the gentamicin treatment were significantly improved in the extract-treated animals. The results correlated well with the histopathological findings as the extract reversed the severe architectural distortions of the kidneys and liver caused by gentamicin. We conclude from the study that, the ethanolic stem bark extract of Terminalia ivorensis protects the liver and the kidneys against gentamicininduced renal and hepatic damage.

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