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Ginsenoside Re Rescues Methamphetamine-Induced Oxidative Damage, Mitochondrial Dysfunction, Microglial Activation, and Dopaminergic Degeneration by Inhibiting the Protein Kinase Cδ Gene

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Abstract

Ginsenoside Re, one of the main constituents of Panax ginseng, possesses novel antioxidant and anti-inflammatory properties. However, the pharmacological mechanism of ginsenoside Re in dopaminergic degeneration remains elusive. We suggested that protein kinase C (PKC) δ mediates methamphetamine (MA)-induced dopaminergic toxicity. Treatment with ginsenoside Re significantly attenuated methamphetamine-induced dopaminergic degeneration in vivo by inhibiting impaired enzymatic antioxidant systems, mitochondrial oxidative stress, mitochondrial translocation of protein kinase Cδ, mitochondrial dysfunction, pro-inflammatory microglial activation, and apoptosis. These protective effects were comparable to those observed with genetic inhibition of PKCδ in PKCδ knockout (−/−) mice and with PKCδ antisense oligonucleotides, and ginsenoside Re did not provide any additional protective effects in the presence of PKCδ inhibition. Our results suggest that PKCδ is a critical target for ginsenoside Re-mediated protective activity in response to dopaminergic degeneration induced by MA.

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Acknowledgments

This study was supported by a grant (no. 110113-3) from the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (IPET), Republic of Korea. Thuy-Ty Lan Nguyen was supported by BK21 PLUS project. The English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see: http://www.textcheck.com/certificate/ECwpMn and http://www.textcheck.com/certificate/01ZHRL.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 200-701, Republic of Korea

    Eun-Joo Shin, Seung Woo Shin, Thuy-Ty Lan Nguyen, Dae Hun Park & Hyoung-Chun Kim

  2. Department of Oriental Medicine Materials, Dongshin University, Naju, 520-714, Republic of Korea

    Dae Hun Park

  3. School of Veterinary Medicine, Kangwon National University, Chunchon, 200-701, Republic of Korea

    Myung-Bok Wie

  4. Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea

    Choon-Gon Jang

  5. Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, Republic of Korea

    Seung-Yeol Nah

  6. Department of Systems Biotechnology, Chung-Ang University, Anseong, 456-756, Republic of Korea

    Byung Wook Yang

  7. Department of Oriental Medical Food & Nutrition, Semyung University, Jecheon, Choongbuk, 390-711, Republic of Korea

    Sung Kwon Ko

  8. Department of Regional Pharmaceutical Care & Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya, 468-8503, Japan

    Toshitaka Nabeshima

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  1. Eun-Joo Shin
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  10. Toshitaka Nabeshima
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  11. Hyoung-Chun Kim
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Corresponding authors

Correspondence to Sung Kwon Ko or Hyoung-Chun Kim.

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Shin, EJ., Shin, S.W., Nguyen, TT.L. et al. Ginsenoside Re Rescues Methamphetamine-Induced Oxidative Damage, Mitochondrial Dysfunction, Microglial Activation, and Dopaminergic Degeneration by Inhibiting the Protein Kinase Cδ Gene. Mol Neurobiol 49, 1400–1421 (2014). https://doi.org/10.1007/s12035-013-8617-1

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