Protopine-Enriched Dactylicapnos Scandens Root Fraction Improves Glucose Homeostasis in Cell and Mouse Models Via AMPK/PEPCK/G6Pase Modulation.

Dactylicapnos scandens (D. Don) Hutch is popular among traditional healthcare providers in Nagaland, North-East India and Bai communities in China. Current investigation analyses traditional claims of Dactylicapnos scandens root tuber extract to control diabetes through down-regulation of hepatic gluconeogenesis and oxidative stress in diabetes mellitus (Type 2) in both in vitro (cell culture) and in vivo (animal model) systems. Potential of Dactylicapnos scandens against diabetes was demonstrated in free fatty acid (FFA)-induced CC1 liver cells and streptozotocin-induced diabetic male Swiss albino mice. Enriched bioactive fraction was prepared through activity guided fractionation and major component was identified to be protopine. Enriched fraction of Dactylicapnos scandens root tuber and its isolated compound, protopine increased glucose uptake by the liver cells in FFA-induced condition. Further, the enriched fraction down regulated gluconeogenesis enzymes (Glucose-6-phosphatase and phosphoenolpyruvate kinase) through AMP-activated protein kinase (AMPK) modulation in both CC1 liver cells and liver tissues of diabetic mice. Moreover, in vivo experiment with enriched fraction containing protopine enhanced the tolerance of glucose as well as insulin level in plasma. Antidiabetic activity of enriched fraction containing protopine as a major component was also supported by histopathological analysis. Overall, protopine containing root tuber enriched fraction of Dactylicapnos scandens regulates antihyperglycemic efficacy in CC1 liver cells and in Swiss albino mice induced with diabetes via ameliorating AMPK/PEPCK/G6Pase signalling pathway.