Valeriana officinalis Counteracts Rotenone Effects on Spreading Depression in the Rat Brain in vivo and Protects Against Rotenone Cytotoxicity Toward Rat Glioma C6 Cells in vitro .

Astrocytes can protect neurons against oxidative stress and excitability-dependent disorders, such as epilepsy.Valeriana officinalishas been used as anticonvulsant and can exert an antioxidant effect, which may underlie its opposing action against the toxic effects of the pesticide rotenone. We investigated theV. officinalis/rotenone interaction in the cortical spreading depression (CSD), a phenomenon that depends upon brain excitability (in vivo model). In addition, we analyzed the protective action ofV. officinalisagainst the cytotoxic effects of rotenone in cultures of rat C6 glioma cells (in vitromodel). For the CSD study, Wistar rats received eitherV. officinalis(250 mg/kg/day via gavage for 15 days;n= 8) or 10 mg/kg/day rotenone via subcutaneous injections for 7 days (n= 7), or they received both substances (n= 5). Two control groups received either saline (vehicle forV.officinalis;n= 8) or 1% Tween-80 aqueous solution (vehicle for rotenone;n= 9). After treatment, CSD was recorded for 4 h. The rotenone- andV. officinalis-treated groups presented, respectively, with lower (2.96 +/- 0.14 mm/min), and higher CSD propagation velocity (3.81 +/- 0.10 mm/min) when compared with the controls (Tween-80, 3.37 +/- 0.06 mm/min and saline, 3.35 +/- 0.08 mm/min;p< 0.05). The rotenone plusV. officinalis-treated group displayed a CSD velocity (3.38 +/- 0.07 mm/min) that was similar to controls. In line with these results,in vitroexperiments on rat glioma C6 cells revealed a protective effect (MTT assay) ofV. officinalisagainst rotenone-induced cytotoxicity. These results suggest the therapeutic potential ofV. officinalisfor treating neurological diseases involving redox imbalance and astrocyte dysfunction.