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Discovery of a Potent 9‐Deazaxanthine‐based Agent for the Treatment of Obesity‐Related Non‐alcoholic Fatty Liver Disease
Author(s) -
Chen Jinying,
Ma Liang,
Huang Li,
Xie Caifeng,
Pei Heying,
He Linhong,
Fu Suhong,
Chen Lijuan
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12429
Subject(s) - fatty liver , disease , obesity , anti obesity , alcoholic liver disease , medicine , pharmacology , chemistry , cirrhosis
A series of deazaxanthine‐based derivatives were rationally prepared and evaluated. 8g exhibited the most potent glucose‐lowering effect on H ep G 2 cell line and modulated adiponectin and leptin expression in 3 T 3‐ L 1 adipocytes. Oral administration of 8g at 25 mg/kg/day for 4 weeks manifested therapeutic effects on high‐fat diet‐induced non‐alcoholic fatty liver disease (NAFLD) by decreasing the weights of the body, liver, and fat. 8g also modulated the serum levels of fasting glucose and adiponectin, triglycerides, low‐density lipoprotein‐cholesterol, and alanine aminotransferase, as well as the hepatic concentrations of triglycerides, total cholesterol. Moreover, 8g significantly decreased steatosis and blocked the increase of adipocytes and the size of adipose tissues from NAFLD . In the DIO mice model, 8g ameliorated the obesity‐related symptoms and normalized serum biomarkers.