Zhi-Shi-Huang-Wu slows Parkinson’s progression in transgenic C. elegans models

Abstract Parkinson’s disease (PD) is the second most progressive degenerative disorder of the brain due to dopaminergic (DA) neuron degenerations and alpha-synuclein (α-Syn) accumulations. At present, the disease has no effective treatment. Therefore, the current study objective is to identify a novel anti-PD formula (Zhi-Shi-Huang-Wu Formula, F-2) computed at 8:4:2:1 ratio from HSP 70 promoter activators Valeriana jatamansi (V), Acori talarinowii (A), Scutellaria baicalensis (S), Fructus Schisandrae (F). Traditionally, V is used to cure memory impairments, A treats mental disorders, and chronic mild stress, S for neuroprotection, and F showed multiple therapeutic actions to treat insomnia. This study investigated the neuroprotective potential of the V, A, S, F, formula F-2 and its underlying molecular mechanisms in transgenic Caenorhabditis elegans models. A, S, F, and F-2 successfully restored 6-hydroxydopamine intoxicated DA neuron degenerations, reduced food-sensing behavior disabilities, and attenuated α-Syn aggregations. Moreover, activates the lipid deposition and proteasome expressions to confirm α-Syn degradations at the cellular level. Reactive oxygen species (ROS) cause oxidative stress, and A, S, F, and F-2 repressed ROS and raised SOD-3 expressions. Overall, these data indicate that V, A, S, F combined into F-2 (22.3%) are more effective against PD progression-like symptom than individual drugs V (0.7%), A (11.4%), S (9.6%), and F (12.6%). These improved neuroprotective actions of F-2 possibly due to following the antioxidative pathway. Competing Interest Statement The authors have declared no competing interest. List of abbreviations - PD - Parkinson’s disease - TCM - Traditional Chinese Medicine - α-Syn - Alpha-synuclein - 6-OHDA - 6-hydroxydopamine - CGC - Caenorhabditis Genetics Centre - NGM - Nematode growth medium - OD - Optical density - ROS - Reactive oxygen species - DA Neuron - Dopaminergic Neuron - SNPc - substantia nigra pars compacta - SOD - Superoxide dismutase - UPS - Ubiquitin-like Proteasome System