A multidisciplinary approach to the antioxidant and hepatoprotective activities of Arbutus pavarii Pampan fruit; in vitro and in Vivo biological evaluations, and in silico investigations.

The Libyan Strawberry, Arbutus pavarii Pampan (ARB), is an endemic Jebel Akhdar plant used for traditional medicine. This study presents the antioxidant and hepatoprotective properties of ARB fruit-extract. ARB phytochemical analysis indicated the presence of 354.54 GAE and 36.2 RE of the phenolics and flavonoids. LC-MS analysis identified 35 compounds belonging to phenolic acids, procyanidins, and flavonoid glycosides. Gallic acid, procyanidin dimer B3, ß-type procyanidin trimer C, and quercetin-3-O-glucoside were the major constituents of the plant extract. ARB administration to paracetamol (PAR)-intoxicated rats reduced serum ALT, AST, bilirubin, hepatic tissue MDA and proinflammatory markers; TNF-α and IL-6 with an increase in tissue GSH level and SOD activity. Histological and immunohistochemical studies revealed that ARB restored the liver histology and significantly reduced the tissue expression of caspase 3, IL-1B, and NF-KB in PAR-induced liver damage. Docking analysis disclosed good binding affinities of some compounds with XO, COX-1, 5-LOX, and PI3K.

Chronobiology in nephrology: the influence of circadian rhythms on renal handling of drugs and renal disease treatment.

INTRODUCTION: Chronobiology studies the phenomenon of rhythmicity in living organisms. The circadian rhythms are genetically determined and regulated by external synchronizers (the daylight cycle). Several biological processes involved in the pharmacokinetics and pharmacodynamics of drugs are subjected to circadian variations. Chronopharmacology studies how biological rhythms influence pharmacokinetics, pharmacodynamics, and toxicity, and determines whether time-of-day administration modifies the pharmacological characteristics of the drug. Chronotherapy applies chronopharmacological studies to clinical treatments, determining the best biological time for dosing: when the beneficial effects are maximal and the incidence and/or intensity of related side effects and toxicity are minimal. Most water-soluble drugs or drug metabolites are eliminated by urine through the kidney. The rate of drug clearance in the urine depends on several intrinsic variables related to renal function including renal blood flow, glomerular filtration rate, the ability of the kidney to reabsorb or to secrete drugs, urine flow, and urine pH, which influences the degree of urine acidification. Curiously, all these variables present a circadian behavior in different mammalian models. CONCLUSION: The circadian rhythms have influence in the renal physiology, pathophysiology, and pharmacology, and these data should be taken into account in clinical nephrology practice.