Advanced glycation end products (AGEs) are harmful molecules formed through non-enzymatic reactions between proteins, lipids, and reducing sugars, contributing to diseases such as diabetes, Alzheimer’s disease, and cardiovascular conditions. This study investigates the inhibitory mechanisms of CMP-LSOPC nanoparticles (NPs) on AGEs release during gastrointestinal digestion. CMP-LSOPC NPs were synthesized by complexing carboxymethyl pachymaran (CMP) with lotus seedpod oligomeric procyanidins (LSOPC), and its structure confirmed via Fourier transform infrared (FTIR), ultraviolet-visible (UV-Vis), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses. In simulated gastrointestinal conditions, CMP-LSOPC NPs exhibited a significant reduction in AGE formation, achieving up to lowering AGE release by 48.5% compared to LSOPC alone. Furthermore, associated mechanisms are explored, including CMP-LSOPC NPs improving the stability and antioxidant activity of LSOPC, inhibiting the activity of related hydrolase enzymes in the gastrointestinal environment. The CMP-LSOPC NPs exhibited 4.1% higher LSOPC content during the gastric phase compared to LSOPC alone, indicating that CMP-LSOPC NPs with better stability. The antioxidant activity, measured through DPPH, ABTS⁺, and hydroxyl radical scavenging assays, demonstrated that CMP-LSOPC NPs enhanced antioxidant capacity, with a 35% increase in DPPH radical scavenging and 29% increase in ABTS⁺ radical scavenging compared to LSOPC alone. Enzyme inhibition assays showed a protective effect, with a 22% decrease in trypsin activity and 19% reduction in pepsin activity. Meanwhile, mass spectrometry revealed the presence of more long-chain glycopeptides in the CMP-LSOPC NPs group, which may exert beneficial influence on adiminishing the absorption of harmful AGEs. However, the potential risks of accumulating long glycated peptides in the colon should not be overlooked. Overall, CMP-LSOPC NPs effectively inhibited AGE release, which may offer a promising strategy for reducing the dietary risk of AGEs.

Advanced glycosylated end products (AGEs) can cause a variety of chronic metabolic diseases such as diabetic kidney disease, Alzheimer’s disease, atherosclerosis and osteoarthritis by causing reactive oxygen species (ROS) generation and activating oxidative stress. So advanced glycation end products have long been considered potently toxic molecules that promote host cell death and contribute to organ damage in humans. Polyphenols are common secondary metabolites in nature. They have diverse structures and biological activities such as antioxidant, anti-inflammatory and anti-bacterial functions. Natural polyphenols can reduce the formation of AGEs and inhibit related diseases by capturing free radicals, blocking inflammatory signaling pathways, and interacting with microorganisms. This paper reviews the inhibitory effects of polyphenols on AGEs and related diseases, expecting to provide scientific reference for further research on the inhibition of AGEs by polyphonel.