Planta Med 2014; 80 - P2B107
DOI: 10.1055/s-0034-1394984

Neuroprotective effect of a traditional Korean herbal formula via autophagy induction in models of Parkinson's disease

N Bae 1, 2, S Chung 3, JW Cha 1, H Oh 3, HJ Kim 1, MY Gu 1, MS Oh 4, J Kim 1, HO Yang 1
  • 1Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, 210 – 340, Korea
  • 2Dept. of Sasang Constitution Medicine, Pusan National University School of Korean Medicine, Yangsan, 626 – 870, Korea
  • 3Dept. of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University, School of Medicine, Suwon 440 – 746, Korea
  • 4Department of Life and Nanopharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130 – 701, Korea

Chungsimyeolda-tang, a traditional Korean herbal formula which contains 17 kinds of medicinal plants, has been used to treat cerebrovascular disease including stroke in Korea. In this study, we made efforts to explore if our modified Chungsimyeolda-tang (termed DG), containing three selected medicinal plants such as Angelica tenuissima Nakai, Polygala tenuifolia and Dimocarpus longan Lour from original prescription, has the possibility as a treatment for Parkinson's disease (PD). Here, we verified the neuroprotective and autophagy inducing effects of DG. 1-methyl-4-phenylpyridinium (MPP+) was 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 treatment up to 300 µg/ml concentration 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 dysfunction in NGF-differentiated PC12 cells. Clearance of aggregated proteins by DG was measured using an immunoblotting assay with an ubiquitin antibody. Our findings indicate that DG robustly protects NGF-differentiated PC12 cells against the neurotoxic effects of MPP+ in an in vitro model. Furthermore, DG provides neuroprotection against lactacystin-induced NGF-differentiated PC12 cell death. This effect is partially mediated by increased autophagy associated with enhanced degradation of aggregated proteins. These studies suggest that DG is an attractive candidate as an autophagy-inducing drug and may play a beneficial role in preventing diseases associated with misfolded/aggregated proteins, including PD.

Keywords: DG, parkinson's disease, neuroprotection, autophagy, MPP, lactacystin