Deglycosylated alfalfa saponins enhance antioxidant capacity and gene expression in obese mice

Alfalfa (<i>Medicago sativa</i> L.) saponins (AS) and their deglycosylated derivatives (DAS), naturally occurring dietary bioactive compounds, show potential for managing metabolic challenges linked to high-fat diets (HFD). In C57BL/6 mice fed an HFD, dietary supplementation with AS/DAS significantly improved metabolic markers compared to HFD controls, including reduced body weight, daily feed intake and blood glucose levels. Notably, DAS demonstrated enhanced bioactivity, elevating antioxidant capacity (superoxide dismutase and catalase activities) while reducing lipid peroxidation (malondialdehyde levels). The DAS modulated intestinal gene expression by enhancing nutrient absorption regulators (liver X receptor and glucagon-like peptide-2) and suppressing diet-induced inflammatory markers (nuclear factor kappa-B p50, tumour necrosis factor-α and interleukin-6). Thus, AS and DAS are dual-function dietary components that boost feed efficiency while reducing gut inflammation. These properties support their use as nutraceuticals against obesity-linked metabolic dysfunctions, warranting further study on functional food applications.<b>Impact Statement</b>This work advances the utilization of plant-derived saponins in functional foods by demonstrating the enhanced efficacy of deglycosylated alfalfa saponins in modulating oxidative stress and inflammatory pathways, contributing to sustainable strategies against diet-induced metabolic diseases.<b>Practitioner Relevance Statement</b>This study demonstrates that deglycosylated alfalfa saponins (DAS) can serve as a natural feed additive to enhance antioxidant capacity and alleviate metabolic inflammation in obese subjects. These findings provide practical support for nutritionists and functional food developers in creating effective nutraceutical solutions for managing obesity-related metabolic disorders.