| First Author | Zhang M | Year | 2020 |
| Journal | Mol Cell Endocrinol | Volume | 513 |
| Pages | 110867 | PubMed ID | 32422400 |
| Mgi Jnum | J:296877 | Mgi Id | MGI:6469205 |
| Doi | 10.1016/j.mce.2020.110867 | Citation | Zhang M, et al. (2020) Andrographolide modulates HNF4alpha activity imparting on hepatic metabolism. Mol Cell Endocrinol 513:110867 |
| abstractText | Hepatic nuclear factor 4 alpha (HNF4alpha) drives the expression of apolipoprotein B (ApoB), microsomal triglyceride transfer protein (MTP) and phospholipase A2 G12B (PLA2G12B), governing hepatic very-low-density lipoprotein (VLDL) production and secretion. Andrographolide (AP) is a major constituent isolated from Andrographis paniculata. We found that AP can disrupt the interaction between HNF4alpha and its coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1alpha). Virtual docking and mutational analysis indicated that arginine 235 of HNF4alpha is essential for binding to AP. As a consequence of antagonizing the activity of HNF4alpha, AP suppresses the expression of ApoB, MTP and PLA2G12B and reduces the rate of hepatic VLDL secretion in vivo. AP additionally reduced gluconeogenesis via down-regulating the expression of HNF4alpha target genes phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pc). Collectively, our results suggest that AP affects liver function via modulating the transcriptional activity of HNF4alpha. |
