The extract of Scutallariae baicalensis as the potential therapeutics for diabetes targeting Pck-1

Abstract

The phosphoenolpyruvate carboxykinase (PEPCK, encoded by the Pck-1 gene) is the enzyme mainly controlling the hepatic gluconeogenesis. The cytosolic form of Pck-1 enzyme catalyzes the oxaloacetate to form phosphoenolpyruvate and water. Accumulating studies have delineated the relationship between overexpression of Pck-1 with diabetes, obesity, fatty liver diseases, as well as liver cancer. Therefore, the objective of this study is to systematically identifya lead compound targeting on Pck-1 gene, and further elucidate its effect on pre-diabetic animal model. Methods: Pck-1:eGFP reporter zebrafish was used to screen for the drug candidate form hundreds of Chinese herbal medicine and its derivatives. High fatdiet-fed rodent model was used to validate the efficacy of the screened drug. Several clinical symptoms of pre-diabetes such as net changes of fasting blood glucose, and systemic sensitivity to glucose and insulin were assessed. The hepatic Pck-1 expression changes was further determined. Results: High-throughput screening using zebra fish observed that the extract of Scutellariae baicalensis (HuangQin in Chinese, HQE) potently reduced Pck-1 expression. Further validation using high-fat diet rodent model observed that oral administration of HQE significantly improved the systemic sensitivity to insulin compared to control mice group. As well, HQE treatment reduced hepatic Pck-1 gene expression in diet-fed mice, suggested the potent inhibitory effect of HQE on diabetic rodent model. Conclusion: Altogether, our results demonstrate the efficacy of Scutellariae baicalensis in reducing insulin resistance via targeting the hepatic Pck-1 gene and its potential applications on other Pck-1-overexpressed diseases.