Neuroprotective effect of modified Chungsimyeolda-tang, a traditional Korean herbal formula, via autophagy induction in models of Parkinson׳s disease. (15th January 2015)

• Record Type: Journal Article
• Authors: Bae, Nayoung; Chung, Sungkwon; Kim, Hee Ju; Cha, Jin Wook; Oh, Hyungun; Gu, Ming-Yao; Oh, Myung Sook; Yang, Hyun Ok
• Is Part Of: Journal of ethnopharmacology. Volume 159(2015)
• Page Start: 93
• Page End: 101
• Publication Date: 2015-01-15
• Subjects: DG modified Chungsimyeolda-tang -- MYH modified Youldahanso-tang -- SCM Sasang Constitutional Medicine -- PD Parkinson׳s disease -- UPS ubiquitin-proteasome system -- ALP autophagy-lysosomal pathway -- MPP+ 1-methyl-4-phenylpyridinium -- NGF nerve growth factor -- PC12 rat pheochromocytoma cells -- LC3 light chain 3 -- 3MA 3-methyladenine -- Baf A1 bafilomycin A1 -- SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis.; DG -- Parkinson׳s disease -- Neuroprotection -- Autophagy -- Lactacystin -- PC12 cells; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2014.11.007
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Aim of the study: Previous 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 methods: 1-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 conclusions: Our 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. Graphical abstract: Induction of autophagy by DG in NGF-differentiated PC12 cells. Protein levels of LC3-I and LC3-II were investigated by western blotting in protein lysates of cells pretreated with DG by the dose and time dependent manner.