Therapeutic activity of plant-derived alkaloid conophylline on metabolic syndrome and neurodegenerative disease models |
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Authors: | Kazuo Umezawa Itaru Kojima Siro Simizu Yinzhi Lin Hitomi Fukatsu Naoki Koide Yukiomi Nakade Masashi Yoneda |
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Institution: | 1.Department of Molecular Target Medicine,Aichi Medical University School of Medicine,Nagakute,Japan;2.Institute for Molecular and Cellular Regulation,Gunma University,Maebashi,Japan;3.Department of Applied Chemistry, Faculty of Science and Technology,Keio University,Yokohama,Japan;4.Department of Microbiology and Immunology,Aichi Medical University School of Medicine,Nagakute,Japan;5.Division of Gastroenterology and Hepatology, Department of Internal Medicine,Aichi Medical University School of Medicine,Nagakute,Japan |
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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. |
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