† These authors contributed equally.
We evaluated the influence of an antioxidant-rich extract of Filipendula ulmaria L. on anxiety levels induced by nano-sized particles of different calcium phosphates. Rats in experimental groups were administered with either nano-sized hydroxyapatite, tricalcium phosphate, or amorphous calcium phosphate in the presence of Filipendula ulmaria extract. Appropriate behavioral tests were performed to assess anxiety levels, while oxidative status and apoptosis parameters were determined in the hippocampus samples. The applied calcium phosphates increased oxidative stress markers in hippocampal tissue, accompanied by an enhanced pro-apoptotic mechanism. Moreover, the hippocampal immunoreactivity for brain-derived neurotrophic factor and GABAergic-A receptors was significantly lower following calcium phosphate nanoparticles intake. The observed functional and morphological alterations in the rat hippocampus occurred simultaneously with the anxiogenic response estimated in behavioral testing. The neuroprotective effect of Filipendula ulmaria was markedly manifested by the attenuation of oxidative damage induced by amorphous calcium phosphate and enhanced anti-apoptotic action in the rat hippocampus. The increased hippocampal immunoreactivity for brain-derived neurotrophic factor, GABAergic-A receptors and significant anxiolytic-like effects of Filipendula ulmaria may suggest a beneficial role of antioxidant supplementation in preventing anxiogenic response to nano-sized calcium phosphates.