Antidiabetic Activity of Gold Nanoparticles Synthesized Using Wedelolactone in RIN-5F Cell Line

Abstract

We synthesized the gold nanoparticles (AuNPs) using wedelolactone (WDL) and characterized them using UV-visible spectroscopy, fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopic (SEM), transmission electron microscopic (TEM), energy dispersive X-ray diffraction, and atomic force microscopic (AFM) studies. The electronic spectrum exhibited an absorption peak at 535 nm. The FT-IR results proved that WDL was stabilized on the surface of AuNPs by acting as a capping or reducing agent. The crystalline structure was affirmed by XRD pattern and the spherical shape of WDL-AuNPs was evidenced by SEM, TEM, and AFM. The synthesized WDL-AuNPS were evaluated for anti-diabetic activity in pancreatic RIN-5F cell lines. In vitro results showed that WDL-AuNPs did not only improve the insulin secretion affected by di-(2-ethylhexyl) phthalate (DEHP), but also the cell viability in RIN5F cells. WDL-AuNPs treatment modulates the pro-apoptotic proteins and anti-apoptotic proteins expression to prevent the cells undergoing apoptosis in DEHP-exposed RIN-5F cells. The exposure of DEHP causes an increase in ROS production and lipid peroxidation levels. The free radical scavenging and antioxidant properties of WDL-AuNPs increase the deleterious effect caused by DEHP. On the other side, WDL-AuNPs increase mRNA expressions of insulin-signaling proteins in RIN-5F cells. This study concludes that WDL-AuNPs can be successfully used to regulate the expression of Bcl-2 family proteins, reduce lipid peroxidation, and to improve the secretion of antioxidants and insulin through the GLUT2 pathway in RIN-5F cell lines.

Screening of Relevant Metabolism-Disrupting Chemicals on Pancreatic β-Cells: Evaluation of Murine and Human in Vitro Models

“…For example, studies performed on the rat insulinoma cell line INS-1 have shown that cells exposed to DEHP for 24 h at different concentrations in the micromolar range [44, 45] exhibited decreased insulin secretion. A similar response was found in the murine β-cell line Rin 5F [46]. Under in vivo conditions, DEHP has also been shown to negatively affect pancreatic β-cell function and, accordingly, glucose homeostasis [47–51].…”

“…A similar response was found in the murine -cell line Rin 5F [46]. Under in vivo conditions, DEHP has also been shown to negatively affect pancreatic -cell function and, accordingly, glucose homeostasis [47][48][49][50][51].…”

Nanoformulation of Plant-Based Natural Products for Type 2 Diabetes Mellitus: From Formulation Design to Therapeutic Applications

“…The treatment of di (2-ethylhexyl) phthalate plasticizer-exposed cells with nanoparticles (10, 20, 40, and 80 µmol/L) for 24 hours improved cell viability, increased secretion of insulin, decreased levels of reactive oxygen species, and restored antioxidant enzymes, indicating its ability to reduce oxidative stress, which is beneficial in the treatment of type 2 DM. 28 …”

“…The majority of synthesized nanoformulations have been evaluated in only preclinical studies, 80 primarily using cell culture models 28 and other in vitro models. 31 In addition, almost all of the studies included in this review were of only acute or subacute duration and did not attempt to elucidate anti-DM mechanisms.…”

Nanoparticle Effects on Stress Response Pathways and Nanoparticle–Protein Interactions

“…The transcription factor Nrf2 mediates the cellular response to oxidative stress by binding to the antioxidant response element in the promoters of genes for various antioxidant proteins and enzymes such as heme oxygenase-1 (HO-1), SOD1, CAT, GPx1, and NADPH quinone dehydrogenase 1 (NQO1), and inducing their expression [ 284 ]. Nuclear factor erythroid 2-related factor 2 is regulated by binding to Kelch-like ECH-associated protein 1 (Keap1) as well as by microRNA-27a, which is redox-sensitive.…”