Glycation derived AuNPs bioconjugated novel herbal drug isoferulic acid: As a potential anti-glycation, anti-diabetic and antineoplastic agent

Abstract

Based on the significance and impact of serum protein glycation and the possibility that AGEs play a role in diabetes-related complications and cancer, this study examined the anti-glycation, anti-cancer, and α-amylase inhibition activities of isoferulic acid (IFA) and its gold nanoparticle (IFA-AuNPs) bioconjugated formulations. In comparison to the control (glycated) samples, IFA and IFA-AuNPs were found to show a significant reduction in the KM moieties, carbonyl content, and HMF content that were produced during the glycation, demonstrating that the glycation reaction generated less superoxide radicals, had fewer intermediates, and did not cause as many structural perturbations to BSA. The IFA and IFA-AuNPs treated samples had a higher proportion of unreacted lysine and arginine deposits than the control (glycated) samples, suggesting that the inhibitors prevented the association of negatively charged arginine deposits with 2′-Deoxyribose. Purified IFA (IC50 = 4.3 mM) decreased α-amylase activity insignificantly compared to acarbose (IC50 = 0.118 mM). Therefore, IFA may not be suited for targeting α-amylase. However, IFA and its analogs have been reported to inhibit several malignancies, including leukemia, breast, colon, and lung cancer. Therefore, the cytotoxicity study was conducted using human keratinocytes (HaCat cells), and the IC50 values for IFA and IFA-AuNPs were determined to be 6062.4 µM and 151.6 µM, respectively. Their cytotoxic effects on human lung cancer epithelial cells (A549), however, were estimated to be 5593 µM and 117.5 µM. Our study confirmed that IFA-treated A549 cells at a greater concentration (5593 µM) caused less disruption of mitochondrial membrane potential (ΔΨm) and production of ROS burst than IFA-AuNPs at a significantly lower concentration (117,5 µM). When ΔΨm was disrupted, Cyt-c-mediated apoptosis was elicited, which then allowed IFA and AuNPs to work synergistically to degrade DNA. It was discovered that IFA-AuNPs target cancer cells through different pathways, with AuNPs potentiating the effect of IFA.