Characteristic components from Rehmannia radix and their effects on insulin resistance through PI-3K/AKT signaling pathway in HepG2 Cells

Rehmannia radix is a kind of food and medicinal material, riched in monoterpenoids, phenylethanol glycosides, triterpenes, flavonoids, and other kinds of chemical compounds, among which monoterpenoids such as iridoids and ionones, and phenylethanol glycosides are the characteristic components of R. radix, with various biological activities. To excavate more characteristic active ingredients, the chemical compositions were identified from the 75% ethanol extract by v a variety of column methods and their hypoglycemic activities were evaluated in HepG2 cells. As a consequence, 13 compounds (1-13) were identified, including 4 iridoid compounds, 3 ionones, and 6 phenylethanol compounds, among them compound 3 was a new iridoid. The hypoglycemic activity showed that 7 compounds (1~2, 4~7 and 13) could promote glucose uptake of IR-HepG2 cells. And compound 6 could significantly upregulate protein levels of PI-3K, p-GSK3β, p-AKT and GLUT4, and significantly downregulated protein levels of PEPCK and G6Pase. These results revealed that compound 6 improved insulin resistance in HepG2 cells probably by activating PI-3K/AKT signaling pathway and inhibiting gluconeogenesis. These results succeeded in enriching the chemical composition of R. radix and provided an important scientific basis for the application of Rehmannia in the treatment of diabetes.