In silico molecular modeling and simulations of black tea theaflavins revealed theaflavin-3'-gallate as putative liver X receptor-beta agonist.

The low constitutive activation of Liver X receptor, an endogenous nuclear receptor with two subtypes (α and ß), is a condition lying at the crossroad of cancer and cardiovascular disease. Both natural and synthetic Liver X receptor agonists have reportedly shown remarkable antiproliferative and atheroprotective effects but the repeated doses of its synthetic ones are also paradoxically associated with hyperlipidaemic effects and neurotoxicity, though attributed to the alpha subtype. This highlights the need for novel, safe, and potent LXR-beta-selective agonists. Hypocholesterolaemic effects of black theaflavins have been widely reported, but data on the exact theaflavin compound (s) responsible for these effects is currently lacking. Neither is information on the possible modulatory effects of the compound (s) on LXR-beta nor its possible implications in the context of drug development for cardiovascular diseases and cancers is explored. On this account, we investigated the potential interaction of four main theaflavin monomers (TF1, TF2A, TF2B & TF3) with human LXR-beta through robust computational modelling that entails molecular docking, free energy calculations and molecular dynamics simulations. The ligands were further profiled (in silico) for absorption, distribution, metabolism, excretion, and toxicological properties. Our result revealed theaflavin TF2B as a putative LXR-beta agonist, possibly responsible for the widely observed hypocholesterolaemic effect in black tea. This finding, while encouraging, needs to be experimentally verified in wet studies.Communicated by Ramaswamy H. Sarma.

Experimental validation and molecular docking to explore the active components of cannabis in testicular function and sperm quality modulations in rats.

BACKGROUND: Data available support that ninety percent of male infertility cases are due to low sperm counts. There is a scarcity of data on the medicinal effects of cannabis on fertility. This study evaluated testicular function and sperm quality modulation with cannabis in rats. METHODOLOGY: Twenty-five male Wistar rats were randomly grouped into five: A, B, C, and D, each group have 5 rats. A (control): 0.2 ml 2% DMSO, B (vitamin C): 90 mg/kg body weight, C, D, and E were administered: 5 mg/kg, 10 mg/kg and 20 mg/kg body weight of ethanolic leaf extract of cannabis (ELEC) respectively. The rats were sacrificed 24 h after the last day of the 60 day oral administrations. Flavonoids were the predominant phytochemical present in the extract while quercetin, kemferol, silyman and gallic acid were identified. RESULTS: The results showed a significant improvement (p < 0.05) in sperm quality and a significant increase in the concentrations of follicle-stimulating hormone, luteinizing hormone, triglycerides, cholesterol, and total protein determination compared to the normal control. Similarly, there was a significant increase (p < 0.05) in the activities of acid phosphatase, alkaline phosphatase, and superoxide dismutase compared to the normal control. RAC-alpha serine/threonine-protein kinase (AKT1)-silymarin complexes (-8.30 kcal/mol) and androgen receptor (AR)-quercetin complexes (9.20 kcal/mol) had the highest affinity. CONCLUSION: The antioxidant effects of the flavonoids in the ethanolic extract of cannabis may have protected testicular and sperm cells from oxidative damage. Biochemical processes and histopathological morphology were preserved by cannabis. The docking prediction suggests that the bioactive principle of cannabis may activate the androgenic receptors. The androgenic receptor modulation may be attributed to silymarin and quercetin.