TY - JOUR
T1 - Therapeutic activity of plant-derived alkaloid conophylline on metabolic syndrome and neurodegenerative disease models
AU - Umezawa, Kazuo
AU - Kojima, Itaru
AU - Simizu, Siro
AU - Lin, Yinzhi
AU - Fukatsu, Hitomi
AU - Koide, Naoki
AU - Nakade, Yukiomi
AU - Yoneda, Masashi
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
KW - Conophylline
KW - Diabetes mellitus
KW - Fibrosis
KW - Non-alcoholic steatohepatitis (NASH)
KW - Parkinson’s disease
UR - http://www.scopus.com/inward/record.url?scp=85038093170&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038093170&partnerID=8YFLogxK
U2 - 10.1007/s13577-017-0196-4
DO - 10.1007/s13577-017-0196-4
M3 - Review article
C2 - 29249016
AN - SCOPUS:85038093170
VL - 31
SP - 95
EP - 101
JO - Human Cell
JF - Human Cell
SN - 0914-7470
IS - 2
ER -