Antidiabetic Activity of a Flavonoid-Rich Extract From Sophora davidii (Franch.) Skeels in KK-Ay Mice via Activation of AMP-Activated Protein Kinase

Abstract

The present study was undertaken to investigate the hypoglycemic activity and potential mechanisms of action of a flavonoid-rich extract from Sophora davidii (Franch.) Skeels (SD-FRE) through in vitro and in vivo studies. Four main flavonoids of SD-FRE namely apigenin, maackiain, leachianone A and leachianone B were purified and identified. In vitro, SD-FRE significantly promoted the translocation and expression of glucose transporter 4 (GLUT4) in L6 cells, which was significantly inhibited by Compound C (AMPK inhibitor), but not by Wortmannin (PI3K inhibitor) or Gö6983 (PKC inhibitor). These results indicated that SD-FRE enhanced GLUT4 expression and translocation to the plasma membrane via the AMPK pathway and finally resulted in an increase of glucose uptake. In vivo, using a spontaneously type 2 diabetic model, KK-Ay mice received intragastric administration of SD-FRE for 4 weeks. As a consequence, SD-FRE significantly alleviated the hyperglycemia, glucose intolerance, insulin resistance and hyperlipidemia in these mice. Hepatic steatosis, islet hypertrophy and larger adipocyte size were observed in KK-Ay mice. However, these pathological changes were effectively relieved by SD-FRE treatment. SD-FRE promoted GLUT4 expression and activated AMPK phosphorylation in insulin target tissues (muscle, adipose tissue and liver) of KK-Ay mice, thus facilitating glucose utilization to ameliorate insulin resistance. Regulation of ACC phosphorylation and PPARγ were also involved in the antidiabetic effects of SD-FRE. Taken together, these findings indicated that SD-FRE has the potential to alleviate type 2 diabetes.

Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line

“…MK is known for its multiple biological activities [ 34 ]. In this study, we used pharmacologic and transgenic C. elegans models to confirm that treatment with MK can ameliorate the degeneration of dopaminergic neurons induced by 6-OHDA, thus recovering the food-sensing behavior and life-span of worms as well as improving human α-synuclein protein accumulation in a dose-dependent manner.…”

Ethanolic Extract of Folium Sennae Mediates the Glucose Uptake of L6 Cells by GLUT4 and Ca2+

“…The global prevalence of DM is on the rise, especially in developing countries [ 3 ]. T2DM is the most prevalent form of DM and accounts for more than 90% of the cases of DM [ 4 ]. Insulin resistance is the typical feature of T2DM, which causes cells to stop responding adequately to the standard role of insulin.…”

“…The increase in PM GLUT4 leads to glucose uptake [ 10 ]. Previous studies have reported that defective GLUT4 translocation is a feature of insulin resistance and an essential precursor of T2DM [ 4 , 7 , 11 ]. Thus, GLUT4 as a key regulatory target for glucose homeostasis is widely used in antidiabetic drug research.…”

Phytochemicals Content, Antioxidant and Antibacterial Activities of Sophora viciifolia

“…and also have the effect of clearing heat and relieving heat, used for heat and polydipsia. [2,3] At present, the use of S. viciifolia is mainly concentrated in the feed industry, [4] ecological reconstruction, [5] and soil restoration. [6] The research on the composition of S. viciifolia is mainly concentrated on the flowers and roots.…”

“…Tai and Cai [8] evaluated the antioxidant activity of different polar extracts of S. viciifolia and identified flavonoids in its flowers. The hypoglycemic effect of roots rich in flavonoids has been studied by Huang et al [3] However, there has been no previous study on the leaves of S. viciifolia, and no comparative studies have been reported on the types and contents of active substances, antioxidant activities and antimicrobial activities in extracts from the flowers, leaves, and fruits of S. viciifolia.…”