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Objective:The aim was to study the in vitro and in silico interactions of cleistanthin A and B on the adrenergic and cholinergic receptors using isolated animal tissues and bioinformatics tools.Materials and Methods:The alpha adrenergic receptor activities of cleistanthin A and B were studied in vitro using a guinea pig vas deferens preparation. The beta adrenergic receptor activities of cleistanthin A and B on an isolated rat heart were studied in vitro using a modified Langendorff apparatus. The effects of cleistanthin A and B on the nicotinic and muscarinic cholinergic receptors were studied in vitro using rabbit vas deferens and rabbit jejunum, respectively. All the drug responses were recorded using a data acquisition system through a variable force transducer. The receptor–ligand interactions of cleistanthin A and B with adrenergic and cholinergic receptor proteins were determined using the ArgusLab molecular modeling and drug docking program.Results:Cleistanthin A and B significantly inhibited the actions of the alpha adrenergic receptor and the nicotinic cholinergic receptor. Cleistanthin A and B shifted the dose–response curve to the right with an increased EC50 value of phenylephrine and acetylcholine. Both cleistanthin A and B did not have any significant effect on the beta adrenergic and muscarinic cholinergic receptors.Conclusion:Cleistanthin A and B block the alpha adrenergic and nicotinic cholinergic receptors, but these compounds do not interact at all with the beta adrenergic and muscarinic cholinergic receptors.

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To study the diuretic effects of cleistanthin A and cleistanthin B, phytoconstituents were isolated from the leaves of Cleistanthus collinus in Wistar rats. The in vivo diuretic effects of cleistanthins A and B were determined according to the Lipschitz test. Prior to the experiment, the animals were fasted for 5 h and placed individually in metabolic cages. Cleistanthins A and B (12.5, 25, and 50 mg/kg) and furosemide (5 mg/kg) were suspended in 0.5% w/v carboxymethyl cellulose and administered orally. The urine was collected up to 5 h after administration and subsequently up to 24 h after administration. The acidity and urine volume were measured immediately. The urinary sodium and potassium levels were determined using a flame photometer, and the chloride level was determined by argentometric titration. The diuretic index and diuretic activity were calculated mathematically. While cleistanthins A and B showed a diuretic index of more than one, the diuretic activity of these compounds was less than one, indicating inferior activity compared with furosemide. Both cleistanthin A and B produced a significant increase in the urine volume and alterations in urinary electrolyte levels. However, the effect of the compounds was not dose dependent. Cleistanthin A and cleistanthin B exert diuretic effects in male Wistar rats without affecting the urinary acidity.

ObjectiveTo investigate the toxicological effects of cleistanthin A and cleistanthin B using sub-chronic toxicity testing in rodents.MethodCleistanthins A and B were isolated from the leaves of Cleistanthus collinus. Both the compounds were administered orally for 90 days at the concentration of 12.5, 25 and 50 mg/kg, and the effects on blood pressure, biochemical parameters and histology were assessed. The dose for sub-chronic toxicology was determined by fixed dose method according to OECD guidelines.ResultSub-chronic toxicity study of cleistanthins A and B spanning over 90 days at the dose levels of 12.5, 25 and 50 mg/kg (once daily, per oral) revealed a significant dose dependant toxic effect in lungs. The compounds did not have any effect on the growth of the rats. The food and water intake of the animals were also not affected by both cleistanthins A and B. Both the compounds did not have any significant effect on liver and renal markers. The histopathological analysis of both cleistanthins A and B showed dose dependent morphological changes in the brain, heart, lung, liver and kidney. When compared to cleistanthin A, cleistanthin B had more toxic effect in Wistar rats. Both the compounds have produced a dose dependent increase of corpora amylacea in brain and induced acute tubular necrosis in kidneys. In addition, cleistanthin B caused spotty necrosis of liver in higher doses.ConclusionThe present study concludes that both cleistanthin A and cleistanthin B exert severe toxic effects on lungs, brain, liver, heart and kidneys. They do not cause any significant pathological change in the reproductive system; neither do they induce neurodegenerative changes in brain. When compared to cleistanthin A, cleistanthin B is more toxic in rats.

The antioxidant and cytotoxic properties of four major parts of methanolic extracts of Tephrosia purpurea including leaves, root, stem and seed were investigated and compared. In vitro antioxidant activity of T. purpurea extracts was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), reducing power assay and antihemolytic assay. In vitro cytotoxic effect of T. purpurea extracts on SW620 colorectal cancer cell line was studied using 3-(4, 5-dimethylthiazolyl -2,5-diphenyl-tetrazolium bromide (MTT) assay. Folin-ciocalteu and aluminium chloride methods were used to determine the total phenolic and flavonoid contents respectively. Among the four extracts studied, leaves extract showed the highest antioxidant activity, DPPH: 186.3 ± 14.0 μg/mL, FRAP: 754.2 ± 50.9 μmol Fe(II)/mg and reducing power activity: 65.7 ± 4.2 μg/mg of quercetin equivalent (QE/mg) and there was no significant difference observed in antihemolytic activity. Leaves extract showed effective cytotoxicity on colorectal cancer cells (IC50: 95.73 ± 9.6 μg/mL) and also had the higher total phenolic (90.5 ± 6.7 μg/mg of gallic acid equivalent (GAE/mg) and flavonoid content (21.8 ± 5.4 μg QE/mg). These results suggest higher antioxidant and cytotoxic activities of leaves extract in comparison with other extracts and these activities could be due to the presence of rich phenolic and flavonoid content.

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