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

Abstract

Astrocytes can protect neurons against oxidative stress and excitability-dependent disorders, such as epilepsy. Valeriana officinalis has 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 the V. 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 of V. officinalis against the cytotoxic effects of rotenone in cultures of rat C6 glioma cells (in vitro model). For the CSD study, Wistar rats received either V. 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 for V. officinalis; n = 8) or 1% Tween-80 aqueous solution (vehicle for rotenone; n = 9). After treatment, CSD was recorded for 4 h. The rotenone-and V. officinalistreated 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 plus V. officinalis-treated group displayed a CSD velocity (3.38 ± 0.07 mm/min) that was similar to controls. In line with these results, in vitro experiments on rat glioma C6 cells revealed a protective effect (MTT assay) of V. officinalis against rotenoneinduced cytotoxicity. These results suggest the therapeutic potential of V. officinalis for treating neurological diseases involving redox imbalance and astrocyte dysfunction.

Ameliorative Effects of the Sesquiterpenoid Valerenic Acid on Oxidative Stress Induced in HepG2 Cells after Exposure to the Fungicide Benomyl

“…The oxidative potential of benomyl in cellular and ER environments has been previously shown in human bronchial epithelial cells via IRE1, CHOP, and PERK induction, a fact that supports our results, although in a different cell model [ 17 ]. While there are studies suggesting the ameliorative effects of extracts originating from V. officinalis against cellular stress induction, the molecular mechanisms to which this biological action is attributed when measuring the expression levels of genes coding for key molecules have not been in depth examined [ 8 , 52 , 53 , 54 ]. It has been demonstrated that V. officinalis , and specifically VA, is a protective agent against rotenone-induced oxidative stress in neuroblastoma cells (SH-SY5Y cells), since it enhances the expression of genes coding for the antioxidant defense playing a crucial role in protection against Parkinson’s disease [ 42 ].…”

Multifunctional role of natural products for the treatment of Parkinson’s disease: At a glance

“…Valeriana officinalis (Valerian) is a sedative and antispasmodic herb that has long been used for sleeplessness, anxiety, and restlessness. In SH-SY5Y cells, valerian has been shown to inhibit rotenone-induced cell death ( Amaral de Brito et al, 2020 ). Furthermore, valerian extract was effective in reducing rotenone toxicity in Drosophila melanogaster , as evidenced by the normalization of superoxide dismutases-SOD and catalase mRNA expression, implying that valerian’s effects are, at least in part, due to the plant’s antioxidant properties due to its phenolic and flavonoid constituents ( Sudati et al, 2013 ).…”

"Valeriana officinalis" – a review

“…In vitro studies on rat C6 glioma cells showed a protective effect against rotenone-induced cytotoxicity. 37 Shi et al showed in their in vitro study that valerian extract reduces breast cancer cell proliferation. This could make valerian a therapeutic agent for breast cancer.…”