Evaluation of 6-Gingerol and its modified analogues as therapeutic candidates against Schistosoma mansoni phosphofructokinase

The African most prevalent tropical disease after malaria is schistosomiasis and this disease in the developing countries is a massive socio-economic and public health burden. The disease also caused over 200,000 deaths. The development and design of new and novel antischistosomal drugs is now very important, as there are no vaccines currently and there is only one drug at the moment for the treatment of schistosomiasis. In this article, 6-gingerol was docked against the Schistosoma mansoni phosphofructokinase and the docking result was compared to those obtained from the docking of its modified analogues against the same enzyme. The chemical structure of 6-gingerol was obtained from the PubChem database while the modified analogues were designed using the ChemAxon software. The molecular docking procedure was carried out with the aid of the AutoDock Vina software while polar interactions which were eventually used in predicting the amino acid residues at the Schistosoma mansoni phosphofructokinase active site were visualized using the Pymol software. The Schistosoma mansoni phosphofructokinase 3D crystallized structure was modeled using the Swiss Model server. The molecular docking result showed that the modifications made on 6-gingerol had a positive effect on the binding energy of the compound to the enzyme active site as an appreciable increase was observed. 6-Gingerol and its modified analogues also violated none of the Lipinski's rule with suggests that the experimental compounds are drug-like. The C2H5 analogue of 6 gingerol was selected as the ideal therapeutic agent based on the pharmacokinetics study and the exhibited binding energy(AU)

La enfermedad tropical con más prevalencia en África después de la malaria es la esquistosomiasis; en los países en vías de desarrollo constituye una carga socio-económica y de salud pública enorme. La enfermedad ha ocasionado más de 200.000 muertes anuales. El desarrollo y diseño de nuevas y novedosas drogas antiesquistosomales es muy importante, ya que actualmente no existe vacuna disponible y solo hay una sola droga licenciada para su tratamiento. En esta investigación, el compuesto 6-gingerol se acopló a la enzima fosfofructoquinasa de Schistosoma mansoni y se comparó con los resultados obtenidos a partir de las interacciones de sus análogos modificados a la misma enzima. La estructura química del 6-gingerol se obtuvo de la base de datos PubChem, mientras que los análogos modificados se diseñaron utilizando el software ChemAxon. El procedimiento de acoplamiento molecular se llevó a cabo con la ayuda del software AutoDockVina, mientras las interacciones polares eventualmente utilizadas para predecir los residuos de aminoácidos en el sitio activo de la enzima fosfofructoquinasa de Schistosoma mansoni se visualizaron empleando el software Pymol. La estructura cristalizada tridimensional de la enzima fosfofructoquinasa de Schistosoma mansoni se modeló utilizando el programa Swiss Model. Se demostró que las modificaciones realizadas en el 6-gingerol tuvieron un efecto positivo en la energía de unión del compuesto al sitio activo de la enzima, tras observarse un aumento apreciable de dicha energía. El compuesto 6-Gingerol y sus análogos modificados tampoco violaron ninguna de las reglas de Lipinski, lo que sugiere que estos compuestos experimentales tienen propiedades similares a los medicamentos. El análogo C2H5 de 6-gingerol se seleccionó como el agente terapéutico ideal, basados en el estudio de farmacocinética y la energía de enlace demostrada(AU)

Effect of Chloroform-Ethanol Extracts of Cashew (Anacardium occidentale) Kernel on Electrolyte Imbalance in Castor Oil-induced Diarrhea Rats.

Diarrhea results from an imbalance between the absorptive and secretary mechanisms in the intestinal tract, accompanied by watery bowel movement resulting in excess fluid and electrolytes in faeces. This study was undertaken to evaluate the effect of chloroform-ethanol extracts of Cashew (Anacardium occidentale) kernel at the dose of 21 mg/kg and 84 mg/kg body weight on electrolyte imbalance in castor oil induced diarrheal rats. Acute toxicity and lethality (LD50) and phytochemical constituents of the extracts where also evaluated. The results showed the extract significantly (P<0.05) reduced the concentration of sodium and potassium ion in the intestinal solution compared to the control animals induced with castor oil only. The results of the qualitative phytochemical analysis showed that the chloroform-ethanol extract (ethanol, chloroform and middle layers) tested positively to flavonoids, alkaloids saponin, reducing sugars, glycosides and steroids while, chloroform layer and middle layer tested positive to fat and oil. Acute toxicity and lethality studies on chloroform-ethanol extracts revealed an oral LD50 equal to or more than 5000mg/kg body weight in mice. These results showed that kernels of A. occidentale possess anti-diarrheal properties through inhibition reduction of the intestinal electrolyte secretion which can substantiate its use in the treatment of diarrhea in traditional medicine.

Acute toxicity investigation and anti-diarrhoeal effect of the chloroform-methanol extract of the leaves ofpersea americana

Persea americana is a plant used by traditional medicine practitioners to treat ailments including diarrhoea and diabetes mellitus in Nigeria. Hence, the chloroform and the methanol fractions of the chloroform-methanol extract of the leaves of P. americana were evaluated for their acute toxicity as well as anti-diarrhoeal effects in Wistar rats to substantiate this claim. The chloroform and methanol fractions [at graded doses of 100 and 200 mg/Kg body weight [b.w] of each] were studied for their anti-diarrhoeal effects in terms of the reductions in the wetness of faeces and the frequency of defaecation of castor oil-induced diarrhoea. To understand the mechanism of their anti-diarrhoeal effects, their actions were further evaluated on castor oil-induced enteropooling [intestinal fluid accumulation]. The median lethal dose [LD[50]] of the methanol fraction was found to be less than 5000 mg/Kg b.w. At the two doses, the chloroform and the methanol fractions showed dose-dependent significant [p < 0.05] reductions in the wetness of faeces and the frequency of defaecation with the 200 mg/Kg b.w of the chloroform fraction being the most effective. Results of the fractions were comparable with those of the standard anti-diarrhoeal drug, hyoscine butylbromide [3 mg/Kg b.w]. Both fractions produced remarkable [p < 0.05] dose-related inhibition of castor oil-induced enteropooling as shown by the significant [p < 0.05] decreases in the weight and volume of the intestinal contents. Experimental findings show that the chloroform-methanol extract of the leaves of P. americana possesses significant anti-diarrhoeal effect and may be a potent source of anti-diarrhoeal drug[s] in future