Neuroprotective effect of modified Chungsimyeolda-tang, a traditional Korean herbal formula, via autophagy induction in models of Parkinson׳s disease

Abstract

Aim of the studyPrevious studies in our laboratory revealed the neuroprotective effect of modified Yeoldahanso-tang (MYH) in models of Parkinson׳s disease (PD). In this study, we investigated another traditional Korean herbal formula, modified Chungsimyeolda-tang (termed DG), as a potential treatment for PD. Chungsimyeolda-tang has been used in Korea to treat cerebrovascular diseases, such as stroke. Here, we verify the neuroprotective and autophagy-inducing effects of DG to evaluate any potential anti-parkinsonian properties. Materials and methods1-Methyl-4-phenylpyridinium (MPP+) and rotenone were used to induce cytotoxicity in nerve growth factor (NGF)-differentiated rat pheochromocytoma (PC12) cells. Cell viability was measured using an MTT assay. Induction of autophagy by DG in NGF-differentiated PC12 cells was measured using an immunoblotting assay with an LC3 antibody. The proteasomal inhibitor lactacystin was used to induce ubiquitin-proteasome system (UPS) dysfunction in NGF-differentiated PC12 cells. DG-mediated clearance of aggregated proteins was measured using an immunoblotting assay with a ubiquitin antibody. Results and conclusionsOur findings indicate that DG robustly protects NGF-differentiated PC12 cells against the neurotoxic effects of MPP+ and rotenone in an in vitro model. Furthermore, DG protects NGF-differentiated PC12 cells against lactacystin-induced cell death. This effect is partially mediated by an increased autophagy associated with the enhanced degradation of aggregated proteins. This study suggests that DG is an attractive candidate drug for inducing autophagy and, therefore, may represent a promising strategy to prevent diseases associated with misfolded/aggregated proteins in various neurodegenerative disorders, including Parkinson׳s disease.