Amelioration of oxidative stress in differentiated neuronal cells by rutin regulated by a concentration switch.

Increasing studies have implicated superfluous production of reactive oxygen species (ROS) as a significant factor in the progress of neurodegenerative disorders ranging from ischemic stroke to amyotrophic lateral sclerosis. The possible mechanisms relating to oxidative stress and neurodegeneration are yet to be thoroughly understood. Rutin, a flavonoid, has been well documented for its beneficial and pharmacological activities against diverse targets. However, the mechanism involved in the beneficial effects of rutin against neurodegeneration still remains unclear. Our study investigates the concentration switch effects of rutin on differentiated human neuroblastoma cells (IMR32) in vitro to unveil the possible mechanism of its action. IMR32 cells were differentiated using retinoic acid and challenged with different doses of rutin for 24 h duration to study the influence of ROS on differentiated neuronal cells and ROS-mediated apoptosis. The study showed that the high (100 μM) and low (100 nM and 10μM) rutin concentrations significantly avert ROS generation by two different mechanisms, by enhancing apoptosis through the modulation of levels of Bcl2, Caspase-3, survivin and its antioxidant activity via stress-related proteins, JNK and p38 MAPK. Our study suggests that rutin is a multi-targeted therapeutic and preventive agent that may act as an adjuvant complementary therapeutic molecule to treat oxidative stress-mediated neurodegeneration.