Human Cell

, Volume 31, Issue 2, pp 95–101 | Cite as

Therapeutic activity of plant-derived alkaloid conophylline on metabolic syndrome and neurodegenerative disease models

  • Kazuo Umezawa
  • Itaru Kojima
  • Siro Simizu
  • Yinzhi Lin
  • Hitomi Fukatsu
  • Naoki Koide
  • Yukiomi Nakade
  • Masashi Yoneda
Review Article


Increasing metabolic syndromes including type-2 diabetes mellitus, obesity, and steatohepatitis are serious problems in most countries in the world. Neurodegenerative diseases such as Alzheimer, Parkinson’s, and Huntington’s diseases are increasing in many countries. However, therapy for these diseases is not sufficient yet. Thus, effective chemotherapy for these diseases is being expected. Conophylline is an alkaloid isolated from the leaves of Ervatamia microphylla and related plants. It was found to induce beta-cell differentiation in the precursor pancreatic cells. Oral administration of this compound ameliorated type-2 diabetes mellitus model in mice and rats. Later, fibrosis of the pancreatic islets was found to be greatly reduced by conophylline in the pancreatic islets. It also inhibited chemically induced liver cirrhosis. Further study indicated that conophylline inhibited non-alcoholic steatohepatitis in the model mice. On the one hand, loss of autophagy often causes protein aggregation to give neural cell death. Conophylline was found to activate autophagy in cultured neural cells. Activation of autophagy ameliorated cellular models of Parkinson’s and Huntington’s diseases. Thus, conophylline is likely to be useful for the development of chemotherapy for metabolic and neurodegenerative diseases.


Conophylline Diabetes mellitus Fibrosis Non-alcoholic steatohepatitis (NASH) Parkinson’s disease 



This work was financially supported in part by JSPS Kakenhi Grant Number 17K01967, the Anti-HBV project fund from Japan Agency for Medical and Research Development (AMED), and the Aichi Medical University Research Unit Fund.

Compliance with ethical standards

Conflict of interest

K. U. belongs to the donated fund laboratory supported by Shenzhen Wanhe Pharmaceutical Co., Ltd, Brunese Co., Ltd, and Meiji Seika Pharma Co., Ltd. M. Y. received lecture fee from Otsuka Pharmaceutical Co., Jansen Pharma Co. and Sumitomo Dainippon Pharm Co., and research funding from Bristol Myers Co. and Abbvie GK. The other authors declare no conflict of interest.


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Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Molecular Target MedicineAichi Medical University School of MedicineNagakuteJapan
  2. 2.Institute for Molecular and Cellular RegulationGunma UniversityMaebashiJapan
  3. 3.Department of Applied Chemistry, Faculty of Science and TechnologyKeio UniversityYokohamaJapan
  4. 4.Department of Microbiology and ImmunologyAichi Medical University School of MedicineNagakuteJapan
  5. 5.Division of Gastroenterology and Hepatology, Department of Internal MedicineAichi Medical University School of MedicineNagakuteJapan

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