Combinatorial Chemistry & High Throughput Screening - Online First

Parkinson’s disease (PD) is the age-associated, second most advanced neurodegenerative illness. Rotenone is an extensively used pesticide to study PD pathology and inhibits mitochondrial complex I. Reports indicate that rotenone exerts neurotoxicity by its capability to produce reactive oxygen species (ROS), which eventually leads to neuronal apoptosis.

Sanggenol L (SL) is an eminent flavonoid present in the Morus alba root bark, which exhibits neuroprotective, anticancer, and antioxidant properties. Materials and Methods: Hence, we assessed the neuroprotective activity of SL (5 and 10 µM/ml) on rotenone-stimulated SK-N-SH neuroblastoma cells and elucidated the effect of the P13K/AKT/mTOR signalling.

The anti-PD action of SL on proliferation, oxidative stress (OS), intracellular ROS, apoptosis, Bax, cleaved Caspase-12, -9, -3, and Cyt-c, Bcl-2 and P13K/AKT/mTOR signaling was determined by MTT assay, biochemical analysis, DCFDA, AO/EB staining and western blot. It was found that SL (5 and 10 µM/ml) reduced rotenone-triggered OS, ROS levels, and apoptosis in a concentration-related way. SL alleviates Bax, cleaved caspase-12, -9, -3, and Cyt-c, while reducing Bcl-2. Furthermore, SL safer mitochondria by increase MMP and suppresses phosphorylation of P13k/AKT/mTOR pathway, thereby regulating apoptotic signalling.

Our findings indicate that SL showed protective effects against rotenone-induced OS, mitochondrial complex-I in neuronal cell damage, which suggests that SL might potentially serve as an anti-PD remedial candidate for PD treatment.