Abstract
ObjectivesThe study aimed to examine the anti-diabetic effects of Gynura divaricata (GD) and the underlying mechanism.MethodsInformation about the chemical compositions of GD was obtained from extensive literature reports. Potential target genes were predicted using PharmMapper and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). To validate the results from bioinformatics analyses, an aqueous extract of GD was administered to type 2 diabetic rats established by feeding a high-fat and high-sugar diet followed by STZ injection. Key proteins of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway were investigated by immunoblotting.ResultsThe blood glucose of the rats in the GD treatment group was significantly reduced compared with the model group without treatment. GD also showed activities in reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (CREA). The levels of urine sugar (U-GLU) and urine creatinine (U-CREA) were also lowered after treatment with GD. Bioinformatics analysis showed that some pathways including metabolic pathways, insulin resistance, insulin signaling pathway, PPAR signaling pathway, bile secretion, purine metabolism, etc. may be regulated by GD. Furthermore, GD significantly increased the protein expression levels of PKM1/2, p-AKT, PI3K p85, and GLUT4 in the rat liver. In addition, the expression levels of key proteins in the fatty acid metabolism signaling pathway including AMPK, p-AMPK, PPARα, and CPT1α were significantly upregulated. The anti-apoptotic protein BCL-2/BAX expression ratio in rats was significantly upregulated after GD intervention. These results were consistent with the bioinformatics analysis results.ConclusionsOur study suggests that GD can exert hypoglycemic effects in vivo by regulating the genes at the key nodes of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway.
Highlights
Diabetes mellitus (DM) is a complex chronic disease affecting >425 million people worldwide[1,2], with 114 million in China[3,4]
Screening of the active constituents of Gynura divaricata (GD) The diabetes-related active ingredients were determined by their abundance and a large number of reported literature
Our study demonstrated that GD upregulates the expression levels of PKM1/2, PI3Kp85, p-AKT, and glucose transporter type 4 (GLUT4) and reducing the blood glucose level, improving diabetic symptoms, and protecting the liver and kidneys
Summary
Diabetes mellitus (DM) is a complex chronic disease affecting >425 million people worldwide[1,2], with 114 million in China[3,4]. Due to the drastic increase in diabetes prevalence rate, diabetes has become a serious health issue in China. Gynura divaricata (GD), a perennial herb, has been used in treating diabetes, hypertension, and hyperlipidemia[5,6,7] in Nutrition and Diabetes. Xu et al Nutrition and Diabetes (2020)10:31. Numerous pharmacological studies have shown that extracts of GD can significantly decrease blood glucose levels, improve lipid metabolism, and promote islet β-cell repair[8,9]. Precise anti-diabetic mechanisms of GD still need to be elucidated
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