Neuroprotective effects of Go-sha-jinki-Gan in a Parkinson's disease model

• Project/Area Number: 17K09299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Osaka University
• Principal Investigator: Baba Kousuke 大阪大学, 医学系研究科, 特任講師(常勤) (90750159)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経疾患 / 牛車腎気丸 / 神経炎症 / 漢方薬 / 中枢神経 / パーキンソン病 / 実験的脊髄炎 / 実験的自己免疫性脊髄炎 / 実験的自己免疫性脊髄炎モデル / 漢方 / 神経保護

Outline of Final Research Achievements

We examined the anti-neuroinflammatory effects of Go-sha-jinki-Gan (GJG), a herbal medicine used in clinical practice, using a model of central nervous system disease. Using two animal models with different pathological mechanisms, a drug-induced Parkinson's disease model and a experimental autoimmune myelitis model, we confirmed biochemically and pathologically that GJG suppresses the expression of the proinflammatory cytokine TNFα by inhibiting p38 phosphorylation, and then inhibits the activation and aggregation of microglia and astrocytes. These results indicate that GJG inhibits neuroinflammation in the central nervous system by suppressing the phosphorylation of p38 in microglia through oral administration. These results were published in the journal Neurotherapeutics.

Academic Significance and Societal Importance of the Research Achievements

これまで臨床現場で使用されてきた牛車腎気丸（GJG）が神経障害に効果を有することは経験的に知られてきた。本研究でその機序を生化学的に明らかにしすることで科学的な裏付けが示す事が出来たと考える。また、今回の研究成果から経口投与で中枢神経系での炎症反応を抑制することが示され、本剤の臨床応用の可能性を拡げたと考える。

Research Products

• [Journal Article] Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System (2020)
  • Author(s): Shiying Jiang, Kousuke Baba, Tatsusada Okuno, Makoto Kinoshita, Chi-Jing Choong, Hideki Hayakawa, Hiroshi Sakiyama, Kensuke Ikenaka, Seiichi Nagano, Tsutomu Sasaki, Munehisa Shimamura, Yoshitaka Nagai, Keisuke Hagihara, Hideki Mochizuki
  • Journal Title: Neurotherapeutics Volume: 17 Issue: 1 Pages: 1-14
  • DOI: 10.1007/s13311-020-00948-w
  • Peer Reviewed / Open Access
• [Journal Article] Structurally Distinct α‐Synuclein Fibrils Induce Robust Parkinsonian Pathology (2019)
  • Author(s): Hayakawa Hideki、Nakatani Rie、Ikenaka Kensuke、Aguirre Cesar、Choong Chi‐Jing、Tsuda Hiroshi、Nagano Seiichi、Koike Masato、Ikeuchi Takeshi、Hasegawa Masato、Papa Stella M.、Nagai Yoshitaka、Mochizuki Hideki、Baba Kousuke
  • Journal Title: Movement Disorders Volume: 35 Issue: 2 Pages: 256-267
  • DOI: 10.1002/mds.27887
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Go-sha-jinki-gan (GJG), increases muscle weight in severe muscle dystrophy model mice. (2017)
  • Author(s): Takemoto Y, Inaba S, Zhang L, Baba K, Hagihara K, Fukada S.
  • Journal Title: Clinical Nutrition Experimental Volume: 16 Pages: 13-23
  • Peer Reviewed
• [Presentation] GO-SHA-JINKI-GAN (GJG) prevent inflammation in MPTP induced Parkinson’s disease model mice. (2019)
  • Author(s): Jiang S, Baba K, Hayakawa H, Hagihara K, Mochizuki H.
  • Organizer: 6th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress (MDS-AOS 2019)
  • Int'l Joint Research
• [Presentation] GO-SHA-JINKI-GAN (GJG) Palliates Progression of EAE Mice by Anti-inflammatory Mechanism (2018)
  • Author(s): Shiying Jiang, Kousuke Baba, Tatsusada Okuno, Hideki Hayakawa, Chiharu Shiomoto, Kensuke Ikenaka, Tsutomu Sasaki, Seiichi Nagano, Yoshitaka Nagai, Keisuke Hagihara, Hideki Mochizuki
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] GO-SHA-JINKI-GAN (GJG) Palliates Inflammation In Experimental Autoimmune Encephalomyelitis (EAE) Mice (2017)
  • Author(s): Shiying Jiang, Kousuke Baba, Tatsusada Okuno, Hideki Hayakawa, Chiharu Shiomoto, Kensuke Ikenaka, Tsutomu Sasaki, Seiichi Nagano, Yoshitaka Nagai, Keisuke Hagihara, Hideki Mochizuki
  • Organizer: XXIII World Congress of Neurology (WCN 2017), Kyoto, Japan
  • Int'l Joint Research