Bioactive Phytochemicals Isolated from Akebia quinata Enhances Glucose-Stimulated Insulin Secretion by Inducing PDX-1

Abstract

Chocolate vine (Akebia quinata) is consumed as a fruit and is also used in traditional medicine. In order to identify the bioactive components of A. quinata, a phytosterol glucoside stigmasterol-3-O-β-d-glucoside (1), three triterpenoids maslinic acid (2), scutellaric acid (3), and hederagenin (4), and three triterpenoidal saponins akebia saponin PA (5), hederacoside C (6), and hederacolchiside F (7) were isolated from a 70% EtOH extract of the fruits of A. quinata (AKQU). The chemical structures of isolates 1–7 were determined by analyzing the 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data. Here, we evaluated the effects of AKQU and compounds 1–7 on insulin secretion using the INS-1 rat pancreatic β-cell line. Glucose-stimulated insulin secretion (GSIS) was evaluated in INS-1 cells using the GSIS assay. The expression levels of the proteins related to pancreatic β-cell function were detected by Western blotting. Among the isolates, stigmasterol-3-O-β-d-glucoside (1) exhibited strong GSIS activity and triggered the overexpression of pancreas/duodenum homeobox protein-1 (PDX-1), which is implicated in the regulation of pancreatic β-cell survival and function. Moreover, isolate 1 markedly induced the expression of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), insulin receptor substrate-2 (IRS-2), phosphoinositide 3-kinase (PI3K), and Akt, which regulate the transcription of PDX-1. The results of our experimental studies indicated that stigmasterol-3-O-β-d-glucoside (1) isolated from the fruits of A. quinata can potentially enhance insulin secretion, and might alleviate the reduction in GSIS during the development of T2DM.

Methyl Caffeate Isolated from the Flowers of Prunus persica (L.) Batsch Enhances Glucose-Stimulated Insulin Secretion

“…Polypeptide-p isolated from Momordica charantia , a bioactive natural ingredient from herbal medicine, has been reported to act as insulin [ 6 ], and epicatechin isolated from Pterocarpus marsupium induces pancreatic islet β-cell regeneration [ 7 ]. S-methylcysteine sulfoxide isolated from Allium cepa [ 8 ], Momordicoside U isolated from Momordica charantia [ 9 ], stigmasterol-3- O -β- d -glucoside isolated from the fruit of Akebia quinata [ 10 ], formononetin isolated from Astragalus membranaceus [ 11 ], and hypoxylonol F isolated from Annulohypoxylon annulatum [ 12 ] have been reported as bioactive compounds that increase insulin secretion from pancreatic islet β-cells. These bioactive natural ingredients that increase insulin secretion also enhance the expression of proteins related to the regulation of pancreatic β-cell survival and function, such as peroxisome proliferator-activated receptor-γ (PPARγ), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1).…”

PDX-1: A Promising Therapeutic Target to Reverse Diabetes

“…Silymarin can induce the expression of PDX-1 gene to increase serum insulin levels and decrease serum glucose levels [ 146 ]. Andrographolide, naringin, and Akebia quinata can also enhance insulin secretion and alleviate β-cell dysfunction by targeting PDX-1 [ 147 , 148 , 149 ].…”

Jiedu Tongluo Tiaogan Formula Protects Pancreatic Islet Cells Against Dysfunction by Relieving Endoplasmic Reticulum Stress and Excessive Autophagy via Regulating CaMKKβ/AMPK Pathway

“…In T2DM, dysfunctional pancreatic β-cells exhibit reduced insulin secretion, an indicator of disease progression. PDX-1 and MafA genes are involved in development of pancreatic β-cells and transcription of the insulin gene [6]. To further analyze protective effects of JTTF treatment on pancreatic β cells, INS-1 cells were exposed to high-glucose conditions.…”

“…Importantly, numerous studies have demonstrated that longterm exposure of pancreatic β-cells to high glucose (HG) levels induces cell dysfunction and apoptosis, thus impairing insulin secretion function and promoting eventual development of T2DM [5]. Aside from strategies to reduce insulin resistance or promote GSIS by increasing hepatic glucose output, maintenance of healthy pancreatic β cell function is another strategy for preventing T2DM [6], since dysregulated pancreatic β-cells play critical roles in T2DM pathogenesis [7] . Recently, Traditional Chinese Medicine (TCM) has gained attention as an important source of potential bioactive compounds for use in preventing or treating T2DM.…”