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

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)95-101
Number of pages7
JournalHuman Cell
Volume31
Issue number2
DOIs
Publication statusPublished - 2018 Apr 1

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

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