α-Methyl artoflavanocoumarin from Juniperus chinensis exerts anti-diabetic effects by inhibiting PTP1B and activating the PI3K/Akt signaling pathway in insulin-resistant HepG2 cells

Abstract

Diabetes mellitus is one of the greatest global health issues and much research effort continues to be directed toward identifying novel therapeutic agents. Insulin resistance is a challenging integrally related topic and molecules capable of overcoming it are of considerable therapeutic interest in the context of type 2 diabetes mellitus (T2DM). Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling transduction and is regarded a novel therapeutic target in T2DM. Here, we investigated the inhibitory effect of α-methyl artoflavanocoumarin (MAFC), a natural flavanocoumarin isolated from Juniperus chinensis, on PTP1B in insulin-resistant HepG2 cells. MAFC was found to potently inhibit PTP1B with an IC of 25.27 ± 0.14 µM, and a kinetics study revealed MAFC is a mixed type PTP1B inhibitor with a K value of 13.84 µM. Molecular docking simulations demonstrated MAFC can bind to catalytic and allosteric sites of PTP1B. Furthermore, MAFC significantly increased glucose uptake and decreased the expression of PTP1B in insulin-resistant HepG2 cells, down-regulated the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307), and dose-dependently enhanced the protein levels of IRS-1, phosphorylated phosphoinositide 3-kinase (PI3K), Akt, and ERK1. These results suggest that MAFC from J. chinensis has therapeutic potential in T2DM by inhibiting PTP1B and activating insulin signaling pathways.

A systematic analysis of anti-diabetic medicinal plants from cells to clinical trials

“…Monosaccharides from Anemarrhena asphodeloides Bunge exhibited hypoglycemic effects by activating PI3K/Akt, IRS-1signaling pathway, and inhibiting α-glucosidase activities in insulin-resistant-HepG2 cells ( Chen et al, 2022 ). A natural flavonocoumarin (α-Methylartoflavonocoumarin) isolated from Juniperus chinensis was reported to activate PI3K/Akt pathway in insulin-resistant HepG2 cells ( Jung et al, 2017 ). Thus, effects are evident both at the level of gene expression and activity mediated by a range of extracts.…”

Evaluation of anticancer effects of Juniperus communis extract on hepatocellular carcinoma cells in vitro and in vivo

“…Juniperus communis has been extensively used in traditional medicine. Extract deriving from different parts of the J. communis tree have been proven to have anti-inflammatory [8,9], antidiabetic [10][11][12], antioxidant [13,14], and antimicrobial activities [15,16] as well as anticancer properties [17][18][19][20]. Currently, the antitumor properties of J. communis extract (JCo extract) and the underlying molecular mechanisms remain unknown in the case of hepatocellular carcinoma.…”