Bacopa monnieri alleviates paraquat induced toxicity in Drosophila by inhibiting jnk mediated apoptosis through improved mitochondrial function and redox stabilization.

Paraquat (PQ) is an organic chemical compound and a member of redox active family of heterocycles. In spite of its high toxicities, it is used as one of the potent herbicide throughout the world. Though its toxic manifestations are observed in different organs, its principal toxic effect is manifested in the brain leading to the development of Parkinsonian symptoms. PQ exposure adversely affects dopaminergic (DA-ergic) neuron-rich region in the substantia nigra pars compacta (SNPC) of brain in the animal models of Parkinson's disease (PD), thereby mimicking PD like symptoms. Currently, lack of a potential drug to counter the toxic effect of PQ makes the management difficult. Bacopa monnieri extract (BME) has been shown to have promising effect against neurodegenerative disorders. Therefore, the present study evaluated the role of BME against PQ induced toxicity in Drosophila model of PD, the results of which are reproducible in higher animal models including human subjects. Here, we showed that BME treatment attenuates acute PQ induced toxicity in Drosophila by decreasing mortality and improving climbing ability. BME functions by optimizing redox equilibrium, mitochondrial function and depreciating apoptosis level. The underlying mechanisms were attributed to optimization of active JNK and cleaved Caspase-3 activity along with transcriptional stabilization of the genes regulating oxidative stress and apoptosis (jnk, caspase-3, damb and nrf-2). These results showed therapeutic efficacy of BME against PQ toxicity in the brain. Our results pave the way for further detailed analysis of BME to combat the development of Parkinson's like symptoms following exposure to PQ toxicity in the brain of higher animal models.