This study was to justify the acclaimed antidiarrhoeal activity of ethanol extract of Spondias mombin leaves (EESML) and to suggest probable mechanism of action.EESML was screened for its secondary metabolites. The diarrhoeal models involved randomized Wistar rats in 5 groups of 6 animals each. Animals in groups A&B (negative and positive control) were treated with normal saline and loperamide respectively while those in groups C, D and E received 100, 200 and 400 mg/kg body weight of EESML respectively.EESML contained saponins, alkaloids, flavonoids, tannins, steroids, phenolics and glycosides. EESML lengthened the onset time of diarrhoea and as well caused reductions in the number, fresh weight and total number of wet feaces; and increase in the inhibition of defecations. EESML increased the intestinal activity of Na+–K+ ATPase; the concentrations of intestinal Na+, K+, Cl-, total protein and glucose but decreased the concentration of nitric oxide of the diarrhoeal rats. The intestinal fluid concentrations of Na+, K+, Cl- were dose dependently increased by EESML. EESML also increased the length of the small intestine.EESML possess antidiarrhoeal activity owing to the secondary metabolites, ability to enhance Na+–K+ATPase activity and electrolytes as well as suppression of nitric oxide.

Globally used pesticides contains zinc phosphide (ZnP) which are toxic. This present study was carried out to investigate the potency of bioactive curcumin in ameliorating the toxicity of zinc phosphide on biochemical enzymes present in kidney and liver of Wistar rats. A total of 30 (120–150 g) male adult Wistar rats were used. Experimental animals were divided into five groups and treated as follows for a period of 21 days: Group I rats, serving as the control, orally received 1 ml/kg body weight of corn oil with administration of same volume of saline. Group II rats were orally administered Zinc phosphide at a dose of 4.57 mg/kg body weight (one-tenth LD50) in corn oil. Group III rats orally received curcumin at a dose of 100 mg/kg body weight. Groups IV and V rats were orally administered curcumin at graded doses of 100 and 200 mg/kg body weight respectively, 2 hours before administration of Zinc phosphide. At the end of the time interval, experimental animals were anesthesized with diethylether and organs (kidney and liver) were harvested for biochemical assays. The oral administration of Zinc phosphide at 4.57 mg/kg body weight for 21 days resulted in a significant increase in hepatic and nephridial malondialdehyde. This index of lipid peroxidation, was accompanied by decreased activity of the antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) followed by a drastic reduction in the non-enzymatic antioxidant indices of reduced glutathione when compared to control. Pre-administration of Curcumin significantly ameliorated zinc phosphide-induced hepatic and nephrotic effects by subduing oxidative stress indices and improving antioxidant status. The result of the present study shows that curcumin has a protective effect against zinc phosphide induced liver and kidney damage in male Wistar rats.

Histone deacetylases have been recognized as a potential target for epigenetic aberrance reversal in the various strategies for cancer therapy, with HDAC6 implicated in various forms of tumor growth and cancers. Diverse inhibitors of HDAC6 has been developed, however, there is still the challenge of iso-specificity and toxicity. In this study, we trained a Random forest model on all HDAC6 inhibitors curated in the ChEMBL database (3,742). Upon rigorous validations the model had an 85% balanced accuracy and was used to screen the SCUBIDOO database; 7785 hit compounds resulted and were docked into HDAC6 CD2 active-site. The top two compounds having a benzimidazole moiety as its zinc-binding group had a binding affinity of -78.56kcal/mol and -78.21kcal/mol respectively. The compounds were subjected to exhaustive docking protocols (Qm-polarized docking and Induced-Fit docking) in other to elucidate a binding hypothesis and accurate binding affinity. Upon optimization, the compounds showed improved binding affinity (-81.42kcal/mol), putative specificity for HDAC6, and good ADMET properties. We have therefore developed a reliable model to screen for HDAC6 inhibitors and suggested a series of benzimidazole based inhibitors showing high binding affinity and putative specificity for HDAC6.

Background The prevalence of diarrhoea remains high despite efforts by governments and NGOs to reverse trend. This study investigated the antidiarrhoeal activity and mechanism of Spondias mombin leaf fraction rich in quercetin-3-O-β-D-glucopyranoside (Q3G-RF) because of the acclaimed therapeutic efficacy. Secretory, osmotic, and infectious diarrhoea models using castor oil, magnesium sulphate, and Shigella flexneri respectively were evaluated at the doses of 100, 200, and 400 mg/kg in Wistar rats. Enteropathy was induced with castor oil and magnesium sulphate, while gastrointestinal motility was determined with charcoal meal. Results Findings showed no mortality after 14 days of experimental period and no significant changes in behaviour, food, and water consumption. Relative to control, Q3G-RF inhibited the three models of diarrhoea, enteropathy, and gastrointestinal motility; bacterial colonies were reduced by Q3G-RF, while it improved the relative body weight of the animals. Q3G-RF also increased the intestinal concentration/activity of glucose, total protein, and Na+–K+ ATPase but reduced the concentration of TNF-α, PGE2, IL-1β, nitric oxide, Na+, K+, and Cl− in the diarrhoeal models. The intestinal fluid level of K+, Na+, and Cl− was significantly decreased by Q3G-RF in the enteropathy model. Length of the small intestine in the motility model was also increased by Q3G-RF, while peristaltic index and inhibition of peristalsis were reduced. Conclusion Overall, quercetin-3-O-β-D-glucopyranoside from Spondias mombin leaves demonstrated efficacy against infectious, secretory, and osmotic form of diarrhoeal and further justified its traditional use in the treatment of diarrhoea due to its antimotility, antisecretory, and antimicrobial properties by mechanism related to enhanced Na+–K+ ATPase, repressed nitric oxide, and suppressed prostaglandins.