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Ceterach officinarum  Willd is a plant widespread throughout Europe and used in southern Italy as a diuretic. Beliefs in the benefits of  C .  officinarum  aqueous extract in the treatment of calcium oxalate kidney stones are widely held. Little is known, however, about the actual mechanism of its antilithiatic action. Our results in this  in vitro  study corroborate  C .  officinarum  aqueous extract as a good source of antioxidants with a high antioxidant effects. Our results also demonstrate a major impact of  C .  officinarum  aqueous extract on  in vitro  induced calcium oxalate crystallization kinetics and crystal morphology, showing its critical role in kidney stone formation and/or elimination. We show that progressively increasing doses of  C .  officinarum  aqueous extract cause a sequence of effects. A powerful inhibitory action on calcium oxalate monohydrate (COM) growth and aggregation is first observed.  C .  officinarum  aqueous extract also appears highly effective in stimulating nucleation increasing the number and reducing the size of COM crystals, which become progressively thinner, rounded and concave in a dose-dependent manner. These shape-modified COM crystals are known to be less adherent to renal tubular cells and more easily excreted through the urinary tract preventing kidney stone formation. Further,  C .  officinarum  aqueous extract promotes the formation of calcium oxalate dihydrate (COD) rather than the monohydrate so that, at the highest concentrations used, only COD crystals are observed, in significant greater numbers with a clear reduction in their size, in a dose-dependent manner. Furthermore, AFM analyses allowed us to reveal the presence of  C .  officinarum  component(s) on the surfaces of COD and modified COM crystals. The crystal surface adsorbed component(s) are shown to be similarly active as the total aqueous extract, suggesting a trigger factor which may direct crystal modification towards COD forms. In urolithiasis pathogenesis COD crystals are less dangerous than the COM forms due to their lower affinity for renal tubular cells. Our results are important in understanding the mechanisms which guide the modification induced by  C .  officinarum  on the crystallization process. Based on these data, together with no adverse toxic effect being observed on the  in vitro  model of human intestinal enterocytes,  C .  officinarum  aqueous extract could represent an attractive natural therapy for the treatment of urolithiasis.

plos one

In vitro effects on calcium oxalate crystallization kinetics and crystal morphology of an aqueous extract from Ceterach officinarum: Analysis of a potential antilithiatic mechanism