Antioxidant, anti-inflammatory and neuroprotective effect of kaempferol on rotenone-induced Parkinson’s disease model of rats and SH-S5Y5 cells by preventing loss of tyrosine hydroxylase

Abstract

• Kaempferol prevented the loss of tyrosine hydroxylase. • Kaempferol reduced lipid peroxidation and the levels of TNF-α and IL-6. • Kaempferol increased GSH, SOD, Gpx and catalase. • Kaempferol increased 5-HT, 5-HIAA and noradrenaline. • Kaempferol reduced ROS. The present study investigated the antioxidant and neuroprotective effect of kaempferol against rotenone-induced Parkinson’s disease (PD). Kaempferol inhibits apomorphine-induced rotational behavior and inhibited lipid peroxidation and interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while antioxidant markers were increased in a PD rat model and SH-S5Y5 cells. Kaempferol increased levels of monoamine in striatum and substantia nigra region of brain. Histopathological analyses showed that kaempferol inhibited apoptosis. Intracellular reactive oxygen species (ROS) and apoptosis were also inhibited by more than 50%. The mRNA expression of tyrosine hydroxylase was increased 0.45- and 1.04-fold at 25 and 50 µM kaempferol respectively, and protein expression of tyrosine hydroxylase was also increased. In addition, In silico molecular docking study confirmed the binding interaction between tyrosine hydroxylase and kaempferol. These results show that kaempferol act as neuroprotective agent against rotenone-induced PD model of rats and SH-S5Y5 cells by preventing the loss of tyrosine hydroxylase expression.