Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells

Abstract

Background Paliurus spina-christi Mill. (PSC) fruit is frequently used in the treatment of diabetes mellitus in Mediterranean regions. Here, we investigated the effects of various PSC fruit extracts (PSC-FEs) on glucose consumption and some key mediators of insulin signaling pathways in high glucose and high insulin-induced insulin-resistant HepG2 cells. Methods The effects of methanolic, chloroform and total extracts on cell proliferation were assessed by the MTT assay. The potential of non-toxic extracts on glucose utilization in insulin-resistant HepG2 cells was checked using a glucose oxidase assay. AKT and AMP-activated protein kinase (AMPK) pathway activation and mRNA expression levels of insulin receptor (INSR), glucose transporter 1 (GLUT1), and glucose transporters 4 (GLUT4) were determined by western blotting and real-time PCR, respectively. Results We found that high concentrations of methanolic and both low and high concentrations of total extracts were able to enhance glucose uptake in an insulin-resistant cell line model. Moreover, AKT and AMPK phosphorylation were significantly increased by the high strength of methanolic extract, while total extract raised AMPK activation at low and high concentrations. Also, GLUT 1, GLUT 4, and INSR were elevated by both methanolic and total extracts. Conclusions Ultimately, our results shed new light on methanolic and total PSC-FEs as sources of potential anti-diabetic medications, restoring glucose consumption and uptake in insulin-resistant HepG2 cells. These could be at least in part due to re-activating AKT and AMPK signaling pathways and also increased expression of INSR, GLUT1, and GLUT4. Overall, active constituents present in methanolic and total extracts of PCS are appropriate anti-diabetic agents and explain the use of these PSC fruits in traditional medicine for the treatment of diabetes.

Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis

“…Studies show that it could enhance insulin secretion and manage high-glucose levels during hyperglycemia ( 13 – 15 ), although its mechanism of action in pancreatic β cells is not known. Previous studies on various plant extracts and a few bioactive compounds have reported their anti-diabetic properties with respect to increasing GLUT expression ( 16 – 18 ). Considering that the expressed GLUTs must be trafficked and functional for effective glucose absorption, expression alone is insufficient.…”

Molecular Docking Studies and In Vitro Activity of Paliurus spina-christi Mill Extracts as Pancreatic Lipase Inhibitors

“…The antidiabetic activity of the plant was extensively investigated both in vitro, through the assessment of the e α-glucosidase and α-amylase inhibitory potential of the fruit extracts and some pure isolated components [6], and in vivo, on diabetic rats induced by streptozotocin [13]. The fruits extract was also demonstrated to improve the glucose uptake and to activate the insulin signaling pathways in HepG2 insulin-resistant cells [15]. Previous studies conducted to determine the phytochemical profile of this plant have demonstrated the presence of flavonoids in all its parts [16].…”